{ "schemaVersion": 1, "entries": { "peptide:bpc-157": { "id": "peptide:bpc-157", "path": "/peptides/bpc-157.html", "title": "BPC-157", "summary": "A 15-amino-acid fragment of the gastric body-protection compound, the most widely self-administered healing peptide for tendon, ligament, muscle, and gut injuries.", "aliases": [ "BPC-157 acetate", "PL 14736", "Bepecin", "Pentadecapeptide BPC 157", "Arg-BPC-157 (stable version)" ], "kind": "peptide", "categories": [ "recovery-healing" ], "legacy": { "name": "BPC-157", "full_name": "Body Protection Compound 157", "aliases": [ "BPC-157 acetate", "PL 14736", "Bepecin", "Pentadecapeptide BPC 157", "Arg-BPC-157 (stable version)" ], "categories": [ "recovery-healing" ], "tagline": "A 15-amino-acid fragment of the gastric body-protection compound, the most widely self-administered healing peptide for tendon, ligament, muscle, and gut injuries.", "status": "Research chemical / not FDA-approved. Tested in a handful of small human trials under the name PL 14736 (rectal enemas for ulcerative colitis); most other human use is off-label self-administration.", "origin": "A fragment of a larger gastric-juice protein called Body Protection Compound. It occurs naturally in the human GI tract, and older Croatian tissue-distribution work found it expressed at low levels in lung, kidney, and skin too.", "mechanism": "It doesn't bind classical receptors: dopamine, serotonin, histamine, adrenergic, muscarinic, and adenosine receptors have all been screened and show no affinity. Its effects instead run through upregulated growth-factor receptor expression (including growth hormone receptor in tendon fibroblasts), nitric-oxide modulation, and strong pro-angiogenic signaling. In animal models it consistently speeds fibroblast activity, blood vessel formation, and collagen organization at injury sites while suppressing scar tissue.", "research_summary": "The published evidence base is large, over 200 papers, but almost entirely rodent and in-vitro. Repeated findings include faster healing of tendon, ligament, muscle, and nerve transections; faster healing of skin incisions, burns, and GI fistulas; protection against and healing of gastric ulcers; and a strong anti-inflammatory effect across multiple models. Human data is limited to Phase I/II trials of a rectal enema formulation (PL 14736) in healthy volunteers and ulcerative colitis patients in the early 2000s: well tolerated, with a statistically significant improvement in disease-activity scores versus placebo, and essentially no systemic absorption from the rectal route. No modern human dosing, efficacy, or long-term safety trials exist for the injectable or oral forms people use. One red flag: essentially every animal study on BPC-157 reports a positive result, which points to publication bias. Treat individual studies as suggestive, not proof. One in-vitro plasma-stability study found roughly 36% of BPC-157 still intact after 60 minutes, implying a plasma half-life in the range of 40 minutes — short, consistent with why community protocols favor frequent small doses over infrequent large ones.", "reported_benefits": [ "Faster recovery from tendon, ligament and muscle strains reported anecdotally and in animal studies", "Reduced joint and connective-tissue pain in long-standing injuries", "Improved gut symptoms (reflux, IBD-type symptoms, leaky-gut complaints) reported by oral users", "General anti-inflammatory effect described by long-term users" ], "dosing_protocols": [ { "route": "Subcutaneous injection (most commonly used for systemic/peripheral healing)", "protocol": "A frequently cited compounding-pharmacy protocol is 300 mcg once daily for 30 days. A very common self-administered pattern in online communities is 250 mcg injected subcutaneously into belly fat, twice daily. Conservative starting point: 100 mcg once daily, increasing slowly while watching for reactions." }, { "route": "Oral (capsules or reconstituted drops)", "protocol": "500 mcg, twice daily is a commonly reported oral dose. The 'stable' arginine-salt version (Arg-BPC-157) survives low stomach pH far better than the acetate salt and is generally preferred for oral use, though orally dosed BPC-157 is too large a molecule to be meaningfully absorbed intact — any systemic effect from oral dosing is unproven and the community consensus is that oral use is mainly reported to help local GI complaints, not peripheral joint or tendon injuries." }, { "route": "Local/near-injury injection", "protocol": "Some experienced users inject near (not into) an injury site on the theory of a local concentration effect; mainstream practice is simple subcutaneous injection into abdominal fat, which is easier, safer, and has the deepest anecdotal track record." } ], "side_effects": [ "Injection-site irritation, stinging, occasional bruising", "Drowsiness / increased sleep need reported in the first 1-2 weeks by some users", "Rare reports of headache or lightheadedness", "No established maximum tolerated human dose; animal toxicology found no lethal dose up to very high doses, but this has not been replicated in modern controlled human trials" ], "safety_notes": "Legal status is grey-market in most countries: possessing the research chemical is typically not illegal, but it's sold 'not for human consumption' and falls outside any regulatory framework. No long-term human safety data exists for the doses and routes people use. People with active cancer should be cautious: BPC-157's strong pro-angiogenic activity is exactly what makes it good at healing tissue, and in theory could also feed a tumor's blood supply. This hasn't been directly studied.", "community_notes": "One of the most discussed peptides in self-experimentation communities (notably r/Peptides), with unusually consistent reporting: people using injectable BPC-157 on stalled tendon, ligament, or joint injuries report it 'restarting' healing within days to a few weeks, often alongside noticeably increased sleepiness the first week. Users with connective tissue disorders (EDS/HSD) who stack it with GH secretagogues like CJC-1295/Ipamorelin report stronger, more durable results than BPC-157 alone. Oral users consistently report GI benefit but are far less confident about peripheral joint or tendon benefit; the community's strong prior is that injection is needed for systemic connective-tissue effects, while oral is a cheaper option purely for gut issues.", "related": [ "tb-500", "ghk-cu", "kpv", "ara-290", "ipamorelin" ], "citations": [ { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study", "authors_year": "Biçer et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "authors_year": "Tewari et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management", "authors_year": "Yuan et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41898733/" }, { "title": "Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing", "authors_year": "McGuire et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40789979/" } ], "mixing_notes": { "clinic_combos": [ "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "ghrp-6", "hexarelin", "ipamorelin", "kpv", "mgf", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "hcg", "igf-1-lr3" ], "reported_avoid": [ "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:bpc-157", "title": "BPC-157", "summary": "Synthetic pentadecapeptide studied in animal models for connective tissue and gut healing. No approved human indication.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "The published evidence is large, over 200 papers, but almost entirely in rodents and cell models. Repeated findings include faster healing of tendon, ligament, muscle and nerve injuries, faster healing of skin wounds and gut damage, protection against gastric ulcers, and anti-inflammatory effects. Human data is very limited: small early trials of a rectal formulation in ulcerative colitis, and a few pilot studies. Recent reviews note that most publications are animal work, that preparation standards vary, and that almost all animal studies report positive results, which points to publication bias. It is not an approved medicine.", "verdict": { "benefits": [ "Over 200 papers report faster healing of tendon, gut and skin injuries, almost all in rodents or cells" ], "risks": [ "Not an approved medicine anywhere", "Nearly all animal studies report positive results, which reviewers read as publication bias", "In a rat tendon study the main histology scores did not reach significance; preparation standards vary", "Human data is very limited: small early trials of a rectal form in ulcerative colitis and a few pilots" ], "bottomLine": "An unapproved peptide with a large animal literature, minimal human data and likely publication bias." }, "originalLinks": [ { "title": "PubMed: BPC-157 literature", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=BPC+157" }, { "title": "ClinicalTrials.gov: BPC-157", "url": "https://clinicaltrials.gov/search?term=BPC-157" } ], "links": [ { "title": "Peptide Wiki: BPC-157", "url": "https://vespassassina.github.io/peptide-wiki/peptides/bpc-157.html" }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine (Tewari et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management (Yuan et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41898733/" }, { "title": "Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing (McGuire et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40789979/" } ], "protocols": [ { "population": "32 male Sprague-Dawley rats after Achilles tendon transection and repair, 8 per group", "regimen": "BPC-157 10 µg/kg a day intraperitoneally, against control, TB-500 and the two combined", "duration": "four weeks after surgery", "outcome": "The BPC-157 group had numerically better histology and failure load than controls, but total Bonar and Movin scores did not reach significance.", "source": { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, "origins": [ "evidence.json#/catalog:peptide:bpc-157/protocols/0" ] } ], "community": [ { "description": "Forum participants describe a protocol of 500 micrograms once daily or 250 micrograms every other day via subcutaneous injection, with combination therapy alongside TB500.", "source": { "title": "Best ways to mix and dose BPC-157", "url": "https://www.elitefitness.com/forum/threads/best-ways-to-mix-and-dose-bpc-157.1514654/" }, "origins": [ "evidence.json#/catalog:peptide:bpc-157/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:bpc-157/community/0", "url": "https://www.elitefitness.com/forum/threads/best-ways-to-mix-and-dose-bpc-157.1514654/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 5, "lowerHours": 4, "source": "Preclinical PK; human data limited", "upperHours": 6 } } ], "related": [ "peptide:ara-290", "peptide:ghk-cu", "peptide:ipamorelin", "peptide:kpv", "peptide:tb-500" ], "conflicts": [ { "status": "unresolved", "origins": [ "peptides.json#/bpc-157/research_summary", "audit/catalogue-authored.json#catalog:peptide:bpc-157/template/halfLife" ], "text": "Half-life estimates differ: the legacy summary reports approximately 40 minutes from an in-vitro plasma-stability study; the imported template reports 4-6 hours with a preclinical source note. These are not interchangeable measurements. Both accounts are retained; neither is newly verified here." } ], "sourceRefs": [ "pmid:42542926", "pmid:42578445", "pmid:41898733", "pmid:40789979", "https://vespassassina.github.io/peptide-wiki/peptides/bpc-157.html", "https://pubmed.ncbi.nlm.nih.gov/?term=BPC+157", "https://clinicaltrials.gov/search?term=BPC-157", "https://www.elitefitness.com/forum/threads/best-ways-to-mix-and-dose-bpc-157.1514654/" ] }, "peptide:tb-500": { "id": "peptide:tb-500", "path": "/peptides/tb-500.html", "title": "TB-500 / Thymosin Beta-4", "summary": "A naturally occurring wound-response peptide released by platelets, used for muscle, tendon and neurological healing, often stacked with BPC-157.", "aliases": [ "TB-500", "TB4", "Thymosin β4", "Frag 17-23" ], "kind": "peptide", "categories": [ "recovery-healing" ], "legacy": { "name": "TB-500 / Thymosin Beta-4", "full_name": "Thymosin Beta-4 (full sequence) — products sold as 'TB-500' may contain either the full 43-amino-acid Tβ4 or just its Frag 17-23 fragment", "aliases": [ "TB-500", "TB4", "Thymosin β4", "Frag 17-23" ], "categories": [ "recovery-healing" ], "tagline": "A naturally occurring wound-response peptide released by platelets, used for muscle, tendon and neurological healing, often stacked with BPC-157.", "status": "Research chemical for the self-administered market. The active molecule (Tβ4) has gone through legitimate pharmaceutical development under RegeneRx as RGN-259 (eye drops, completed Phase III), RGN-352 (systemic injection, completed Phase I) and RGN-137 (topical gel, Phase II) — but none of these are approved, marketed drugs.", "origin": "Thymosin Beta-4 is a 43-amino-acid peptide present in nearly all human cells, especially platelets and white blood cells, released at wound sites as part of the natural clotting and repair cascade. 'TB-500' is a commercial name that's ambiguous: some vendors sell the full Tβ4 sequence, others sell only its Frag 17-23 region (LKKTETQ), the piece responsible for actin-binding and cell-migration effects. Check what a specific product actually contains before assuming.", "mechanism": "Different regions of the Tβ4 sequence do different jobs: amino acids 1-4 are anti-inflammatory and anti-fibrotic; 1-15 is anti-apoptotic/cytoprotective; 17-23 drives actin binding, cell migration, angiogenesis and dermal wound healing (and triggers mast-cell degranulation); 40-43 supports cardiac cell migration after ischemic injury. TB4 binds free actin monomers (G-actin) rather than a conventional receptor, effectively expanding the pool of building blocks cells use to rebuild cytoskeletal structure during repair.", "research_summary": "A 2015 meta-analysis found broad applicability across tissue regeneration, post-heart-attack cardiac repair, stroke and neurological recovery, kidney/liver repair, and bone/ligament/spinal cord injury in animal models. Human data is more substantial than for most research peptides: RGN-259 eye drops completed Phase III trials for dry eye and neurotrophic keratitis with statistically significant symptom improvement and no adverse events. RGN-352 systemic IV dosing was tested up to single doses of 1260 mg and repeated daily dosing for 14 days (cumulative ~18.9 g in one subject) with no dose-limiting toxicity, no cardiovascular/respiratory signal, and no cancers at 6-month follow-up; headache was the only adverse event, occurring equally in placebo. Pharmacokinetics show a short half-life (under 1-2 hours even at high doses) and dose-independent clearance, so TB4 doesn't meaningfully accumulate with daily dosing at the doses studied.", "reported_benefits": [ "Faster recovery from muscle strains and tears", "Reduced muscle spasticity / tightness (notably reported by people with hypermobility disorders)", "Support for tendon and ligament healing, often paired with BPC-157", "Reported improvements in flexibility, which some users find beneficial and others find undesirable (increased joint laxity)" ], "dosing_protocols": [ { "route": "Subcutaneous injection — loading protocol", "protocol": "A widely circulated protocol: 5 mg twice weekly (e.g. Monday/Thursday) for 5 weeks, then 5 mg once weekly for 2 more weeks (total ~35 mg over 7 weeks)." }, { "route": "Subcutaneous injection — daily lower-dose protocol", "protocol": "Alternative protocols use smaller daily doses: roughly 450-750 mcg per day for 20-30 days. Because Tβ4's half-life is short and it doesn't accumulate systemically, both large-infrequent and small-frequent dosing schemes appear in the literature with good animal results; there's no head-to-head human comparison." }, { "route": "Post-injury / acute dosing", "protocol": "Some practitioners use a short course of higher daily dosing (e.g. ~1.5 mg/day for about a week) immediately after an acute injury or surgery, on the theory of mimicking the natural post-injury Tβ4 spike, then tapering to a lower maintenance dose." } ], "side_effects": [ "Injection site irritation", "Possible mast-cell activation from the Frag 17-23 region — a concern for people with MCAS", "Theoretical proliferative/metastasis-promoting risk, since Tβ4 overexpression is associated with several cancer types at the cellular level (no data yet on whether exogenous dosing carries this risk in humans) — TB4 is generally considered contraindicated for anyone with active or recent cancer" ], "safety_notes": "Human injection safety data (RGN-352 Phase I) is reassuring at doses far higher than self-experimenters typically use: no dose-limiting toxicity, no cancer signal at 6-month follow-up. But that was a short trial in healthy volunteers, not a long-term study, and the theoretical cancer-proliferation concern from cell-biology data means anyone with a personal or strong family history of cancer should weigh that risk carefully and ideally talk to a physician.", "community_notes": "Frequently stacked with BPC-157: BPC for connective tissue and gut, TB4 for muscle, systemic inflammation and flexibility. People with Ehlers-Danlos/hypermobility spectrum disorders report mixed results on flexibility; most find reduced muscle spasticity helpful, a minority report an unwanted increase in joint hypermobility during use. Community also disputes what's actually being sold as 'TB-500': cheaper vials are more likely the smaller Frag 17-23 fragment rather than full Tβ4. That's not necessarily a scam (Frag 17-23 delivers more molecules per mg and covers the muscle/actin-binding effects), but buyers should know which one they're getting if they want Tβ4's broader immune and cardiac-repair activity too. Separately, some in the EDS/HSD community flag that TB-500's active sequence includes a region known to activate mast cells, and suggest starting low for anyone with Mast Cell Activation Syndrome (MCAS) or a history of mast-cell reactivity.", "related": [ "bpc-157", "ghk-cu", "kpv" ], "variant_note": "Sometimes sold as 'TB-500 Frag' or 'Thymosin Beta-4 Fragment' — a shorter fragment of the same parent protein, marketed as a cheaper alternative. It is not established as pharmacologically equivalent to full TB-500/Tβ4, and independent evidence for the fragment specifically is essentially absent; treat fragment products as a distinct, far less characterized compound rather than an interchangeable substitute.", "citations": [ { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study", "authors_year": "Biçer et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "authors_year": "Tewari et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing", "authors_year": "Nguyen et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41235866/" }, { "title": "Thymosin β4 and Actin: Binding Modes, Biological Functions and Clinical Applications", "authors_year": "Ying et al. 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36464872/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "ipamorelin", "ll-37", "mt-1", "mt-2", "pinealon", "selank", "semax", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [], "related": [ "library:peptide-tb-500", "peptide:bpc-157", "peptide:ghk-cu", "peptide:kpv" ], "conflicts": [ { "status": "identity-uncertain", "origins": [ "peptides.json#/tb-500/full_name", "audit/catalogue-authored.json#catalog:peptide:tb-500" ], "text": "This legacy article covers products sold under an ambiguous TB-500 name. The separate imported fragment entry is narrower. Full thymosin beta-4 trial results and its reported PK must not be assumed to apply to that fragment." } ], "sourceRefs": [ "pmid:42542926", "pmid:42578445", "pmid:41235866", "pmid:36464872" ] }, "peptide:kpv": { "id": "peptide:kpv", "path": "/peptides/kpv.html", "title": "KPV", "summary": "A tiny 3-amino-acid fragment of alpha-MSH studied mainly for gut and skin inflammation, popular among self-experimenters with IBD-type symptoms.", "aliases": [ "KPV tripeptide", "α-MSH(11-13)" ], "kind": "peptide", "categories": [ "recovery-healing" ], "legacy": { "name": "KPV", "full_name": "Lysine-Proline-Valine (C-terminal tripeptide fragment of alpha-MSH)", "aliases": [ "KPV tripeptide", "α-MSH(11-13)" ], "categories": [ "recovery-healing" ], "tagline": "A tiny 3-amino-acid fragment of alpha-MSH studied mainly for gut and skin inflammation, popular among self-experimenters with IBD-type symptoms.", "status": "Research chemical, no clinical approval. Preclinical (rodent, cell-culture) evidence only for the isolated tripeptide.", "origin": "KPV is the C-terminal three amino acids of alpha-melanocyte-stimulating hormone (alpha-MSH), a peptide with well-established anti-inflammatory and immune-modulating effects. KPV retains alpha-MSH's anti-inflammatory activity without the pigmentation (skin-darkening) effects that come from alpha-MSH's action on melanocortin receptors.", "mechanism": "KPV works partly independent of the classical melanocortin receptors, directly inhibiting NF-kB signaling, a central pathway driving inflammatory cytokine production. This gives it broad anti-inflammatory activity in gut epithelium and skin without the receptor-mediated side effects (tanning, appetite/libido changes) seen with full alpha-MSH analogs like Melanotan II.", "research_summary": "Rodent studies show KPV reduces colonic inflammation in colitis models, improves epithelial barrier integrity, and has topical anti-inflammatory and antimicrobial effects on skin, including activity against Staph aureus in some in-vitro work. No human clinical trials exist for KPV as an isolated compound; it's an academic compound of interest for IBD and dermatology, still firmly preclinical.", "reported_benefits": [ "Reduced GI inflammation and bloating reported by users with IBD-type or leaky-gut symptoms", "Topical use reported for inflammatory skin conditions (acne, eczema-type flares)", "Often used alongside BPC-157 for combined gut-healing protocols" ], "dosing_protocols": [ { "route": "Oral capsules/drops", "protocol": "Commonly reported range in self-experimentation communities is 200-500 mcg, once or twice daily, often cycled in blocks of a few weeks." }, { "route": "Subcutaneous injection", "protocol": "Less commonly injected than BPC-157/TB-500; when used, doses in the low hundreds of mcg per day are typical among self-experimenters, frequently combined with BPC-157 in the same syringe." }, { "route": "Topical", "protocol": "Compounded topical creams (skin conditions) are the other common route; no standardized concentration exists outside individual compounding pharmacy formulations." } ], "side_effects": [ "Limited human safety data — most reported issues are generic to peptide self-injection (site irritation)", "No known pigmentation or libido effects (unlike full-length alpha-MSH analogs)" ], "safety_notes": "There's essentially no human trial data for isolated KPV, so dosing and long-term safety rest entirely on extrapolation from animal work and community reporting. One of the least-studied compounds in this wiki.", "community_notes": "Popular in gut-health and autoimmune-adjacent corners of the peptide community as a companion to BPC-157, particularly for people who feel oral BPC-157 alone isn't enough for inflammatory GI symptoms. Reports are generally positive but sparse compared to BPC-157/TB-500, and much of the online protocol information traces back to a small number of vendor blog posts rather than independent user reporting.", "related": [ "bpc-157", "ara-290" ], "citations": [ { "title": "Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis", "authors_year": "Xiao et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28143741/" }, { "title": "Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases", "authors_year": "Brzoska et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18612139/" }, { "title": "Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model", "authors_year": "Viennois et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/27458604/" }, { "title": "Self-Cross-Linked Hydrogel of Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV for Alleviating TNBS-Induced Ulcerative Colitis in Rats", "authors_year": "Sun et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/34547895/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "ghk-cu" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:kpv", "title": "KPV", "summary": "Alpha-MSH tripeptide fragment studied for anti-inflammatory effects, largely in gut models.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "KPV is the final three amino acids of alpha-MSH. The owner's wiki lists it as a research chemical with preclinical evidence only. Rodent studies show less colonic inflammation in colitis models and better gut barrier integrity, and some in-vitro work reports anti-inflammatory and antimicrobial activity on skin. No human clinical trials exist for KPV as an isolated compound.", "verdict": { "benefits": [ "Only shown in rodents and cells: less colonic inflammation and better gut barrier integrity.", "In one mouse model tumour number, size and burden fell." ], "risks": [ "No human clinical trials exist for KPV as an isolated compound.", "Listed as a research chemical with preclinical evidence only.", "Protection vanished in mice lacking the PepT1 transporter, so it depends on one pathway." ], "bottomLine": "KPV is a research chemical with rodent and cell evidence in gut inflammation and no human trials at all." }, "originalLinks": [ { "title": "PubMed: KPV peptide", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=KPV+peptide" } ], "links": [ { "title": "Peptide Wiki: KPV", "url": "https://vespassassina.github.io/peptide-wiki/peptides/kpv.html" }, { "title": "Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis (Xiao et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28143741/" }, { "title": "Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases (Brzoska et al. 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18612139/" }, { "title": "Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model (Viennois et al. 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27458604/" }, { "title": "Self-Cross-Linked Hydrogel of Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV for Alleviating TNBS-Induced Ulcerative Colitis in Rats (Sun et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34547895/" } ], "protocols": [ { "population": "male FVB mice with DSS-induced colitis, 5 per group", "regimen": "16 microg/kg of KPV a day in hyaluronic-acid-functionalised nanoparticles inside a chitosan/alginate hydrogel, given by oral gavage twice daily", "duration": "5 days, on top of 8 days of 3% DSS drinking water", "outcome": "Treated mice lost the least weight, had TNF-alpha comparable to healthy controls, and colon tissue close to normal in epithelium and inflammatory infiltrate.", "source": { "title": "Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis (Xiao et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28143741/" }, "origins": [ "evidence.json#/catalog:peptide:kpv/protocols/0" ] }, { "population": "wild-type and PepT1-knockout mice in the AOM/DSS colitis-associated cancer model", "regimen": "KPV at 100 micromol/L in the drinking water during the DSS cycles", "duration": "the two DSS cycles following the azoxymethane injection", "outcome": "Tumour number, size and burden fell in wild-type mice; PepT1-knockout mice got no protection from KPV.", "source": { "title": "Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model (Viennois et al. 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27458604/" }, "origins": [ "evidence.json#/catalog:peptide:kpv/protocols/1" ] } ], "community": [ { "description": "A community protocol guide describes 0.5 to 1 milligram subcutaneously once or twice daily for 4 to 8 weeks when targeting systemic anti-inflammatory effects.", "source": { "title": "KPV Peptide Dosage: Protocol, Dose Per Day & Evidence", "url": "https://formblends.com/articles/peptide-hub/peptides-kpv-dosage" }, "origins": [ "evidence.json#/catalog:peptide:kpv/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:kpv/community/0", "url": "https://formblends.com/articles/peptide-hub/peptides-kpv-dosage", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [ "peptide:ara-290", "peptide:bpc-157" ], "conflicts": [], "sourceRefs": [ "pmid:28143741", "pmid:18612139", "pmid:27458604", "pmid:34547895", "https://vespassassina.github.io/peptide-wiki/peptides/kpv.html", "https://pubmed.ncbi.nlm.nih.gov/?term=KPV+peptide", "https://formblends.com/articles/peptide-hub/peptides-kpv-dosage" ] }, "peptide:ara-290": { "id": "peptide:ara-290", "path": "/peptides/ara-290.html", "title": "ARA-290", "summary": "A non-hematopoietic EPO fragment developed for neuropathic pain and small-fiber nerve repair, without EPO's blood-thickening effects.", "aliases": [ "ARA-290", "Cibinetide", "PH-BSP" ], "kind": "peptide", "categories": [ "recovery-healing" ], "legacy": { "name": "ARA-290", "full_name": "Cibinetide", "aliases": [ "ARA-290", "Cibinetide", "PH-BSP" ], "categories": [ "recovery-healing" ], "tagline": "A non-hematopoietic EPO fragment developed for neuropathic pain and small-fiber nerve repair, without EPO's blood-thickening effects.", "status": "Clinical-stage investigational drug (further along than most peptides in this wiki) — tested in several placebo-controlled human trials for small fiber neuropathy and diabetic neuropathy, but not yet an approved medication.", "origin": "Derived from erythropoietin (EPO), the hormone that drives red blood cell production. EPO's neuroprotective, anti-inflammatory, and nerve-repair effects run through a separate receptor complex (the innate repair receptor) from the one that stimulates red blood cells. ARA-290 was engineered to hit only the repair pathway, giving EPO-like tissue protection without raising red blood cell count or blood viscosity.", "mechanism": "Binds the innate repair receptor, distinct from the classical EPO receptor, triggering anti-inflammatory and cytoprotective signaling in nerve and vascular tissue. Trials have shown it increases corneal small-nerve-fiber density, a direct, measurable marker of nerve regeneration.", "research_summary": "Multiple placebo-controlled human trials exist. A double-blind trial in sarcoidosis patients with small fiber neuropathy (4 mg subcutaneous daily for 28 days) showed symptom improvement and increased corneal nerve fiber density versus placebo. Separate trials in type 2 diabetes patients with neuropathic symptoms showed improved metabolic control and symptom scores, with dose-ranging work across 1 mg, 4 mg, and 8 mg groups. It's one of the better-studied compounds in peptide communities, with real dose-response human data, a rarity here.", "reported_benefits": [ "Reduced neuropathic pain (burning, tingling, numbness from small fiber neuropathy)", "Reported benefit for some autonomic nervous system symptoms (dysautonomia) in community anecdotes, though this indication is not clinically validated", "Interest from the EDS/HSD community for small-fiber neuropathy that often accompanies connective tissue disorders" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Clinical trial dosing used 4 mg once daily for 28 days as the primary studied protocol; other trial arms used 1 mg and 8 mg daily. There is no established chronic/maintenance dosing outside trial contexts, and self-experimenters generally try to mirror the 4 mg daily trial protocol for a similar duration." } ], "side_effects": [ "Generally well tolerated in trials with no major red flags reported", "Does not raise red blood cell count or blood pressure the way EPO itself can — this was the whole design goal and trial data supports it" ], "safety_notes": "One of the more reassuring safety profiles here, backed by real placebo-controlled human dosing data. But trials ran only 28 days in specific patient populations (sarcoidosis, diabetic neuropathy); long-term use in healthy people or off-label indications like dysautonomia hasn't been studied.", "community_notes": "Less mainstream than BPC-157/TB-500, but draws strong interest from people with small fiber neuropathy, POTS/dysautonomia, and EDS/HSD, where standard treatment is mostly symptom management rather than repair. Cost and sourcing difficulty temper enthusiasm, and anecdotal reports of benefit are sparser than for the popular healing peptides.", "related": [ "bpc-157", "kpv" ], "citations": [ { "title": "Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain", "authors_year": "Culver et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28475703/" }, { "title": "ARA 290 for treatment of small fiber neuropathy in sarcoidosis", "authors_year": "van Velzen et al. 2014", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/24555851/" }, { "title": "The erythropoietin-derived peptide ARA290 reverses mechanical allodynia in the neuritis model", "authors_year": "Pulman et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23262243/" }, { "title": "Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy", "authors_year": "Brines et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29549285/" } ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "humanin", "igf-1-lr3", "ipamorelin", "kisspeptin", "kpv", "ll-37", "mgf", "mots-c", "mt-1", "mt-2", "nad", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ] } }, "research": [], "related": [ "peptide:bpc-157", "peptide:kpv" ], "conflicts": [], "sourceRefs": [ "pmid:28475703", "pmid:24555851", "pmid:23262243", "pmid:29549285" ] }, "peptide:ghk-cu": { "id": "peptide:ghk-cu", "path": "/peptides/ghk-cu.html", "title": "GHK-Cu", "summary": "A naturally occurring copper-binding tripeptide found in human plasma. The best-studied skin peptide, also investigated for wound healing, hair and connective tissue.", "aliases": [ "Copper peptide", "GHK-Copper", "Copper tripeptide-1" ], "kind": "peptide", "categories": [ "anti-aging", "recovery-healing" ], "legacy": { "name": "GHK-Cu", "full_name": "Glycyl-L-Histidyl-L-Lysine — Copper Complex", "aliases": [ "Copper peptide", "GHK-Copper", "Copper tripeptide-1" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "A naturally occurring copper-binding tripeptide found in human plasma. The best-studied skin peptide, also investigated for wound healing, hair and connective tissue.", "status": "Widely used as a cosmetic ingredient (topical, well-studied and legal essentially everywhere) and separately used off-label as an injectable/subcutaneous compound in the self-experimentation community, which is far less studied.", "origin": "First isolated from human blood plasma. Naturally circulating GHK declines substantially with age, from around 200 ng/mL at age 20 to about 80 ng/mL by age 60, part of why it's of interest for anti-aging use. Also found in saliva and urine.", "mechanism": "GHK-Cu regulates a large number of genes involved in tissue remodeling, collagen and elastin synthesis, antioxidant enzyme production, and anti-inflammatory signaling. It promotes fibroblast and keratinocyte activity, stimulates angiogenesis, and scavenges free radicals directly. In hair follicle studies it enlarges follicle size and increases blood vessel formation around follicles.", "research_summary": "Topically, GHK-Cu has a genuinely deep evidence base: decades of dermatology and wound-healing literature support improved skin firmness, reduced fine lines, faster wound healing and reduced hyperpigmentation. Gene-expression studies from Pickart and colleagues show GHK-Cu resets expression of over 4,000 genes toward a more youthful pattern in some analyses, an early-stage systems-biology finding, not a validated anti-aging therapy. Systemic/injectable use is far less studied in humans; most injectable dosing information circulating online is extrapolated from topical/animal data, not dedicated injection trials.", "reported_benefits": [ "Topical: improved skin firmness, texture and fine lines; faster healing of cuts, post-procedure skin; reduced hyperpigmentation", "Injectable (anecdotal): reported support for connective tissue repair alongside BPC-157/TB-500 stacks; reported hair density improvements when combined with topical minoxidil-style protocols", "Interest in immune modulation and antioxidant support from systemic research" ], "dosing_protocols": [ { "route": "Topical (cosmetic)", "protocol": "Commercial skincare products typically use 1-5% GHK-Cu-containing formulations or specific copper-peptide serums; this is the best-supported route." }, { "route": "Subcutaneous injection (self-experimentation, not clinically established)", "protocol": "Community-reported doses vary widely, roughly 1-2 mg per day in longer runs, or shorter 'cycles' around 20 mg total spread over 1-2 weeks. Because true injection dose-response data doesn't exist in humans, treat any specific number as a community convention, not a validated dose." } ], "side_effects": [ "Topical: generally very well tolerated; can transiently increase skin sun-sensitivity due to increased cell turnover — sunscreen use recommended during treatment", "Injectable: local injection-site reactions reported; systemic safety data at self-experimentation doses is essentially absent" ], "safety_notes": "Topical GHK-Cu is one of the safest and best-studied compounds in this wiki. Injectable/systemic use is different: popular in self-experimentation stacks, but without the same evidence backing as the topical form, and dosing is folk convention.", "community_notes": "Frequently added in small doses to BPC-157/TB-500 healing stacks and to hair-loss protocols alongside minoxidil/finasteride. Also popular as a standalone topical anti-aging ingredient outside the injectable-peptide community, showing up in mainstream skincare marketing. Community sentiment on injectable use is generally positive but far less confident and detailed than for BPC-157 or TB-500: people describe it as a nice addition, not a primary driver of results. Reported personal dosing patterns vary widely, from roughly 1 mg/day as a baseline addition to a stack, up to occasional higher-dose cycles around 20 mg — none of it standardized, and mostly folded into other peptides' protocols rather than run alone.", "related": [ "bpc-157", "tb-500", "epithalon" ], "variant_note": "Sometimes sold as plain 'GHK' (without copper already bound) rather than the copper-complexed GHK-Cu described on this page. GHK requires copper binding in vivo to exert its characteristic effects, so uncomplexed GHK is a meaningfully different product with a thinner evidence base than the copper complex.", "citations": [ { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "authors_year": "Tewari et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration", "authors_year": "Pickart et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26236730/" }, { "title": "The human tri-peptide GHK and tissue remodeling", "authors_year": "Pickart 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18644225/" }, { "title": "Augmented Skin Beneficial Effects of Thermus Thermophilus and Bacillus Subtilis Mixed-Culture Ferment Extract by Tripeptide GHK-Cu", "authors_year": "Wang et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42573538/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "kpv", "tb-500", "thymalin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:ghk-cu", "title": "GHK-Cu", "summary": "Copper tripeptide studied for skin remodelling and wound repair. Frequently used topically.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "GHK-Cu is a copper-binding tripeptide found naturally in human plasma. Decades of dermatology and wound-healing work support topical use for skin firmness, fine lines, healing and pigmentation, and it is a common cosmetic ingredient. Gene-expression studies from Pickart and colleagues describe broad effects on tissue remodelling, an early-stage finding rather than a proven anti-ageing therapy. Injectable or systemic use is far less studied in humans, with no dedicated injection trials. The owner's wiki rates topical GHK-Cu as one of its best-studied and safest entries.", "verdict": { "benefits": [ "Decades of dermatology and wound-healing work support topical use for firmness, lines and healing.", "A common cosmetic ingredient, rated in the owner's wiki among its best-studied, safest entries." ], "risks": [ "Gene-expression work on tissue remodelling is early-stage, not a proven anti-ageing therapy.", "Injected or systemic use is far less studied in humans, with no dedicated injection trials." ], "bottomLine": "GHK-Cu has long topical evidence for skin and wound healing; injected use has no dedicated human trials." }, "originalLinks": [ { "title": "PubMed: GHK-Cu", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=GHK-Cu" } ], "links": [ { "title": "Peptide Wiki: Glycyl-L-Histidyl-L-Lysine — Copper Complex", "url": "https://vespassassina.github.io/peptide-wiki/peptides/ghk-cu.html" }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine (Tewari et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration (Pickart et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26236730/" }, { "title": "The human tri-peptide GHK and tissue remodeling (Pickart 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18644225/" }, { "title": "Augmented Skin Beneficial Effects of Thermus Thermophilus and Bacillus Subtilis Mixed-Culture Ferment Extract by Tripeptide GHK-Cu (Wang et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42573538/" } ], "protocols": [], "community": [ { "description": "Community research protocols describe 1.0-1.5 mg administered subcutaneously daily over 4-6 week cycles, with a standard reconstitution of 50 mg in 2.0 mL bacteriostatic water yielding 25 mg/mL concentration.", "source": { "title": "GHK-Cu Peptide Dosing Guide", "url": "https://www.peptidedosingprotocols.com/protocol/ghk-cu" }, "origins": [ "evidence.json#/catalog:peptide:ghk-cu/community/0" ] }, { "description": "Topical community formulations document GHK-Cu at 1-3% concentration applied once or twice daily over 8-12 weeks for skin anti-aging purposes.", "source": { "title": "GHK-Cu Dosage Guide: Copper Peptide for Skin, Healing, and Longevity", "url": "https://peptiq.io/blog/ghk-cu-dosing-guide" }, "origins": [ "evidence.json#/catalog:peptide:ghk-cu/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:ghk-cu/community/0", "url": "https://www.peptidedosingprotocols.com/protocol/ghk-cu", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:ghk-cu/community/1", "url": "https://peptiq.io/blog/ghk-cu-dosing-guide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [ "peptide:bpc-157", "peptide:epithalon", "peptide:tb-500" ], "conflicts": [], "sourceRefs": [ "pmid:42578445", "pmid:26236730", "pmid:18644225", "pmid:42573538", "https://vespassassina.github.io/peptide-wiki/peptides/ghk-cu.html", "https://pubmed.ncbi.nlm.nih.gov/?term=GHK-Cu", "https://www.peptidedosingprotocols.com/protocol/ghk-cu", "https://peptiq.io/blog/ghk-cu-dosing-guide" ] }, "peptide:epithalon": { "id": "peptide:epithalon", "path": "/peptides/epithalon.html", "title": "Epithalon", "summary": "A synthetic tetrapeptide based on a natural pineal-gland extract, studied by Russian researchers for telomerase activation, sleep and immune aging.", "aliases": [ "Epitalon", "Epithalone", "AEDG peptide", "Epitalon" ], "kind": "peptide", "categories": [ "anti-aging", "longevity", "bioregulators" ], "legacy": { "name": "Epithalon", "full_name": "Epithalon / Epitalon (Ala-Glu-Asp-Gly)", "aliases": [ "Epitalon", "Epithalone", "AEDG peptide" ], "categories": [ "anti-aging", "longevity", "bioregulators" ], "tagline": "A synthetic tetrapeptide based on a natural pineal-gland extract, studied by Russian researchers for telomerase activation, sleep and immune aging.", "status": "Research chemical, no clinical approval anywhere. Human data comes mostly from a small body of Russian-language research (limited peer review by Western standards) plus animal studies.", "origin": "Synthetic analog of Epithalamin, a peptide complex extracted from calf pineal glands. Developed by Vladimir Khavinson's group in St. Petersburg starting in the 1980s as part of a broader program on peptide bioregulators.", "mechanism": "Proposed to activate telomerase in some cell types (extending telomere length in vitro in several Khavinson studies), regulate melatonin secretion via the pineal gland, and modulate the hypothalamic-pituitary axis. Also proposed to increase lymphocyte interferon-gamma production, relevant because declining interferon-gamma is linked to immune aging.", "research_summary": "The core human evidence comes from decades of Khavinson's work, including reports of extended lifespan in elderly cohorts given pineal/thymus peptide bioregulator courses and improved markers of biological aging. The research has real limitations by current standards: small cohorts, limited blinding detail, mostly published in Russian-language journals, and no independent replication in large Western randomized trials. Animal telomerase-activation data is stronger than the human longevity claims. Treat Epithalon as an interesting, under-replicated hypothesis, not an established longevity intervention.", "reported_benefits": [ "Reported improvement in sleep quality and depth", "Anecdotal reports of improved skin appearance and energy over multi-week cycles", "Interest as part of broader 'peptide bioregulator' anti-aging stacks" ], "dosing_protocols": [ { "route": "Subcutaneous injection — classic 'course' protocol", "protocol": "The traditional Khavinson-derived protocol is 5-10 mg per day for 10-20 days, done as a single annual or biannual course rather than continuous daily use — the theory being pulsed exposure rather than constant dosing." }, { "route": "Subcutaneous injection — lower dose variant", "protocol": "Some self-experimenters use lower daily doses (around 1 mg/day) for a similar 10-20 day course." } ], "side_effects": [ "Generally reported as well tolerated with few acute side effects", "Long-term human safety data at self-administered doses does not exist" ], "safety_notes": "The gap between Epithalon's marketing as a telomere/longevity peptide and the underlying human evidence is large. Treat the anti-aging framing skeptically: what's actually been shown is telomerase activity in some cell-culture and animal work, plus older, methodologically limited human cohort research from a single group.", "community_notes": "A staple of longevity stacks, usually run as an annual or twice-yearly short course rather than continuously. Sleep improvement is the most consistently reported subjective effect. Skepticism about how much of Khavinson's telomere/lifespan story translates to modern self-administered use is common even within the community.", "related": [ "thymosin-alpha-1", "mots-c", "ghk-cu", "nad", "dsip" ], "variant_note": "Sometimes sold as 'N-Acetyl Epitalon Amidate' rather than plain Epithalon (Epitalon/Epithalone). The acetylated, amidated form is marketed as more stable in solution; it has not been independently studied to the same degree as the parent tetrapeptide, and community reports of equivalence are anecdotal.", "citations": [ { "title": "Morphofunctional and molecular bases of pineal gland aging", "authors_year": "Khavinson and Lin'kova 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22567846/" }, { "title": "Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people", "authors_year": "Korkushko et al. 2007", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/17969590/" }, { "title": "The influence of melatonin and epithalon on blood leukocyte count and leukocyte alkaline phosphatase in rats under different lighting conditions during ontogenesis", "authors_year": "Uzenbaeva et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19432172/" }, { "title": "Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats", "authors_year": "Djeridane et al. 2003", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12809170/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "ghk-cu", "ghrp-2", "ghrp-6", "ipamorelin", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:epitalon", "title": "Epitalon", "summary": "Synthetic tetrapeptide studied in Russian literature for telomerase and pineal function. Evidence is limited.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Epithalon is a synthetic tetrapeptide and a research chemical with no approval anywhere. Most work comes from Khavinson's group in Russia, covering telomerase activation in cell culture and animals and the ageing pineal gland. One linked human study reports a normalising effect on the daily melatonin rhythm in elderly people and old monkeys; two others are rat studies. The human evidence is small, thinly described and not independently replicated in large trials. The animal telomerase data is stronger than the human longevity claims.", "verdict": { "benefits": [ "One small human study reported a normalised 24-hour melatonin rhythm in elderly people and old monkeys." ], "risks": [ "A research chemical with no approval anywhere.", "One linked rat study found no effect on melatonin secretion at either age.", "Most work comes from one research group, thinly described and not replicated in large trials." ], "bottomLine": "Epithalon is an unapproved research chemical; its human evidence is one small unreplicated study." }, "originalLinks": [ { "title": "PubMed: epitalon", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=epitalon" } ], "links": [ { "title": "Peptide Wiki: Epithalon / Epitalon (Ala-Glu-Asp-Gly)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/epithalon.html" }, { "title": "Morphofunctional and molecular bases of pineal gland aging (Khavinson 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22567846/" }, { "title": "Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people (Korkushko et al. 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17969590/" }, { "title": "The influence of melatonin and epithalon on blood leukocyte count and leukocyte alkaline phosphatase in rats under different lighting conditions during ontogenesis (Uzenbaeva et al. 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/19432172/" }, { "title": "Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats (Djeridane et al. 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12809170/" } ], "protocols": [ { "population": "Perifused pineal glands from young (9 weeks) and old (27 months) male Wistar rats", "regimen": "Synthetic tetrapeptide Ala-Glu-Asp-Gly at 10^-4 to 10^-6 M in a perifusion device", "duration": "Single in vitro perifusion", "outcome": "The tetrapeptide had no significant effect on melatonin secretion at either age, and did not change the melatonin rise produced by isoproterenol.", "source": { "title": "Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats (Djeridane et al. 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12809170/" }, "origins": [ "evidence.json#/catalog:peptide:epitalon/protocols/0" ] } ], "community": [ { "description": "Perfect B documents 10 mg (20 units) administered subcutaneously nightly for 10 consecutive days before bed in a fasted state (at least 2 hours after last meal), followed by a mandatory 4-month rest period, with a maximum of 3 cycles per year.", "source": { "title": "Epithalon Dosage Protocol: The 10-Day Cycle, Reconstitution Guide, and the Exact Schedule We Use", "url": "https://www.perfectb.com/epithalon-dosage-protocol/" }, "origins": [ "evidence.json#/catalog:peptide:epitalon/community/0" ] }, { "description": "Epitalon dosing guides document an alternative protocol of 5 mg per day by subcutaneous injection for 20 consecutive days, or 10 mg per day for 10 days, with cycles repeated 2–3 times per year.", "source": { "title": "Epitalon Dosage Chart: 2mg/Day for 20 Days, 3x/Year", "url": "https://thepeptidecatalog.com/articles/epitalon-dosing-guide" }, "origins": [ "evidence.json#/catalog:peptide:epitalon/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "Syringe units in the imported account depend on that source's preparation and concentration; they are not a transferable mass dose or calculator default." ], "community": [ { "origin": "evidence.json#/catalog:peptide:epitalon/community/0", "url": "https://www.perfectb.com/epithalon-dosage-protocol/", "claimMatch": "Syringe units in the imported account depend on that source's preparation and concentration; they are not a transferable mass dose or calculator default. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:epitalon/community/1", "url": "https://thepeptidecatalog.com/articles/epitalon-dosing-guide", "claimMatch": "Syringe units in the imported account depend on that source's preparation and concentration; they are not a transferable mass dose or calculator default. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.5, "source": "Short tetrapeptide" } } ], "related": [ "peptide:dsip", "peptide:ghk-cu", "peptide:mots-c", "peptide:nad", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:22567846", "pmid:17969590", "pmid:19432172", "pmid:12809170", "https://vespassassina.github.io/peptide-wiki/peptides/epithalon.html", "https://pubmed.ncbi.nlm.nih.gov/?term=epitalon", "https://www.perfectb.com/epithalon-dosage-protocol/", "https://thepeptidecatalog.com/articles/epitalon-dosing-guide" ] }, "peptide:thymosin-alpha-1": { "id": "peptide:thymosin-alpha-1", "path": "/peptides/thymosin-alpha-1.html", "title": "Thymosin Alpha-1", "summary": "A naturally occurring immune-regulating peptide, approved as a prescription drug (Zadaxin) in dozens of countries for chronic hepatitis B/C and as an immune adjuvant, one of the few peptides here with real regulatory approval somewhere in the world.", "aliases": [ "TA-1", "Tα1", "Zadaxin (brand name)", "Thymosin alpha-1" ], "kind": "peptide", "categories": [ "anti-aging", "longevity", "bioregulators" ], "legacy": { "name": "Thymosin Alpha-1", "full_name": "Thymosin α1 (Tα1)", "aliases": [ "TA-1", "Tα1", "Zadaxin (brand name)" ], "categories": [ "anti-aging", "longevity", "bioregulators" ], "tagline": "A naturally occurring immune-regulating peptide, approved as a prescription drug (Zadaxin) in dozens of countries for chronic hepatitis B/C and as an immune adjuvant, one of the few peptides here with real regulatory approval somewhere in the world.", "status": "Approved prescription drug (as Zadaxin) in roughly 35 countries for chronic hepatitis B/C, certain cancers as adjunct therapy, and immune support, though not FDA-approved in the United States. Widely used off-label/self-administered for general immune modulation.", "origin": "First isolated from the thymus gland in 1972, a naturally occurring 28-amino-acid peptide fragment involved in T-cell maturation and immune regulation.", "mechanism": "Modulates the immune system in both directions: it can boost an underactive response (helpful in chronic infection) while dampening an overactive one (of interest in some autoimmune contexts), largely through effects on dendritic cell maturation, T-cell differentiation and cytokine signalling, including toll-like receptor pathways.", "research_summary": "Genuinely well studied relative to most peptides in this wiki, including real RCTs: shown to improve outcomes in chronic hepatitis B and C (part of why it holds drug approval in multiple countries), studied as an adjuvant in several cancer types and for improving vaccine response in immunocompromised populations, and investigated for cystic fibrosis and various chronic/recurrent infections, including some COVID-19-era research for severe cases. One of the more legitimately evidence-backed compounds discussed in self-experimentation circles, even though it isn't FDA-approved domestically.", "reported_benefits": [ "Reduced frequency/severity of recurrent infections reported by long-term users", "Used by some with autoimmune conditions seeking immune 'rebalancing' rather than pure suppression or pure stimulation", "General immune support during illness or high-stress/high-training periods" ], "dosing_protocols": [ { "route": "Subcutaneous injection — standard protocol", "protocol": "The approved Zadaxin dosing (in countries where it's licensed) is 1.6 mg subcutaneously, twice weekly. Self-experimenters largely mirror this." }, { "route": "Acute illness / short-term immune support", "protocol": "Some users increase frequency to 2-3x per week during an active infection or high-risk exposure period, then return to twice-weekly maintenance." } ], "side_effects": [ "Generally well tolerated in the clinical literature backing its drug approval abroad", "Mild injection-site reactions reported", "As an immune modulator, caution is warranted for people on immunosuppressant therapy or with autoimmune conditions — effects on an already-dysregulated immune system are harder to predict" ], "safety_notes": "One of the better safety profiles in this wiki given genuine drug-approval-grade trial data, though most of that data comes from specific patient populations (chronic hepatitis, cancer adjuvant use) rather than healthy people using it prophylactically.", "community_notes": "Popular among people who get frequent colds/infections, and within the EDS/HSD and chronic-illness communities as a general immune-support peptide. Regarded as one of the 'more legitimate' peptides because of its overseas drug approval, a common talking point when comparing evidence quality across peptides.", "related": [ "epithalon", "ara-290", "kpv" ], "citations": [ { "title": "Safety and efficacy of Thymosin α1 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial", "authors_year": "Chen et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35616850/" }, { "title": "Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study", "authors_year": "Wu et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/30063860/" }, { "title": "A multicenter, randomized, observation-controlled clinical trial to evaluate the efficacy and safety of thymalfasin adjuvant therapy in patients with HBV-related HCC after curative resection - first announcement of the protocol", "authors_year": "Qiu et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26094695/" }, { "title": "Thymosin alpha 1 - Reimagine its broader applications in the immuno-oncology era", "authors_year": "Mao 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36871535/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "ll-37", "mgf", "pinealon", "selank", "semax", "tb-500", "thymalin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:thymosin-alpha-1", "title": "Thymosin alpha-1", "summary": "Immunomodulating peptide approved in some countries for hepatitis B and as a vaccine adjuvant.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Thymosin alpha-1 is a peptide that helps T cells mature. The owner's wiki records it as an approved prescription drug (Zadaxin) in roughly 35 countries for chronic hepatitis B and C and as an adjunct in some cancers, but not approved in the United States. A randomised trial in 120 patients with hepatitis B related acute-on-chronic liver failure reported higher 90-day transplant-free survival and fewer new infections, while a 690-patient trial adding it to entecavir in compensated cirrhosis found no difference in decompensation, liver cancer or death. Other links are a trial protocol and a review of possible cancer uses. The evidence comes from specific patient groups, not healthy people.", "verdict": { "benefits": [ "An approved prescription drug in roughly 35 countries for chronic hepatitis B and C.", "A randomised trial in hepatitis B liver failure found higher 90-day survival and fewer new infections." ], "risks": [ "Not approved in the United States.", "A 690-patient cirrhosis trial found no difference in decompensation, liver cancer or death.", "The evidence comes from specific patient groups, not from healthy people." ], "bottomLine": "Thymosin alpha-1 is approved abroad for hepatitis and helped in liver failure, but showed no benefit in cirrhosis.", "approvalStatus": "Approved in roughly 35 countries, not the United States." }, "originalLinks": [ { "title": "PubMed: thymosin alpha 1", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=thymosin+alpha+1" } ], "links": [ { "title": "Peptide Wiki: Thymosin α1 (Tα1)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/thymosin-alpha-1.html" }, { "title": "Safety and efficacy of Thymosin α1 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial (Chen et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35616850/" }, { "title": "Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study (Wu et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30063860/" }, { "title": "A multicenter, randomized, observation-controlled clinical trial to evaluate the efficacy and safety of thymalfasin adjuvant therapy in patients with HBV-related HCC after curative resection - first announcement of the protocol (Qiu et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26094695/" }, { "title": "Thymosin alpha 1 - Reimagine its broader applications in the immuno-oncology era (Mao 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36871535/" } ], "protocols": [ { "population": "120 patients with hepatitis B virus-related acute-on-chronic liver failure", "regimen": "1.6 mg thymosin alpha-1 subcutaneously once a day for the first week, then twice a week from week 2, on top of standard medical therapy", "duration": "12 weeks of treatment, outcomes assessed at 90 days", "outcome": "90-day transplant-free survival was 75.0% versus 53.4% with standard therapy alone, with fewer new infections and less hepatic encephalopathy.", "source": { "title": "Safety and efficacy of Thymosin α1 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial (Chen et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35616850/" }, "origins": [ "evidence.json#/catalog:peptide:thymosin-alpha-1/protocols/0" ] }, { "population": "690 patients with HBV-related compensated cirrhosis", "regimen": "thymosin alpha-1 added to entecavir, or entecavir alone, started after 26 weeks of entecavir", "duration": "52 weeks of combination, then continued entecavir; median follow-up 38.2 months", "outcome": "Liver decompensation, hepatocellular carcinoma and death were no different between the groups, and virologic and biochemical responses matched at week 104.", "source": { "title": "Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study (Wu et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30063860/" }, "origins": [ "evidence.json#/catalog:peptide:thymosin-alpha-1/protocols/1" ] } ], "community": [ { "description": "Phoenix Rising ME/CFS forum members report an anti-viral protocol of 500 mcg daily or alternatively 1.5 mg administered every 3 days via subcutaneous injection.", "source": { "title": "Thymosin Alpha-1", "url": "https://forums.phoenixrising.me/threads/thymosin-alpha-1.61531/" }, "origins": [ "evidence.json#/catalog:peptide:thymosin-alpha-1/community/0" ] }, { "description": "Peptide dosing protocols guide documents a standard clinical protocol of 1.6 mg administered subcutaneously twice weekly (typically Monday and Thursday, spaced 3–4 days apart), with typical durations of 6–12 months reported in hepatitis and immune support applications.", "source": { "title": "Thymosin Alpha-1 (TA1) Peptide Guide: Dosage, Reconstitution & Side Effects", "url": "https://www.peptidedosingprotocols.com/protocol/thymosin-alpha-1" }, "origins": [ "evidence.json#/catalog:peptide:thymosin-alpha-1/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:thymosin-alpha-1/community/0", "url": "https://forums.phoenixrising.me/threads/thymosin-alpha-1.61531/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:thymosin-alpha-1/community/1", "url": "https://www.peptidedosingprotocols.com/protocol/thymosin-alpha-1", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 2, "source": "Zadaxin product information" } } ], "related": [ "peptide:ara-290", "peptide:epithalon", "peptide:kpv" ], "conflicts": [], "sourceRefs": [ "pmid:35616850", "pmid:30063860", "pmid:26094695", "pmid:36871535", "https://vespassassina.github.io/peptide-wiki/peptides/thymosin-alpha-1.html", "https://pubmed.ncbi.nlm.nih.gov/?term=thymosin+alpha+1", "https://forums.phoenixrising.me/threads/thymosin-alpha-1.61531/", "https://www.peptidedosingprotocols.com/protocol/thymosin-alpha-1" ] }, "peptide:nad": { "id": "peptide:nad", "path": "/peptides/nad.html", "title": "NAD+", "summary": "Cellular coenzyme central to energy metabolism and DNA repair. Not actually a peptide, but a fixture of longevity peptide clinics and stacks.", "aliases": [ "NAD+", "NAD", "often discussed alongside precursors NMN and NR", "NAD+ (Nicotinamide Adenine Dinucleotide)" ], "kind": "supplement", "categories": [ "longevity" ], "legacy": { "name": "NAD+", "full_name": "Nicotinamide Adenine Dinucleotide (technically a coenzyme/dinucleotide, not a peptide)", "aliases": [ "NAD+", "NAD", "often discussed alongside precursors NMN and NR" ], "categories": [ "longevity" ], "tagline": "Cellular coenzyme central to energy metabolism and DNA repair. Not actually a peptide, but a fixture of longevity peptide clinics and stacks.", "status": "NAD+ itself is used clinically (IV infusion clinics) and sold as an injectable/subcutaneous product in the wellness/longevity space; its precursors NMN and NR are sold as oral supplements. Not FDA-approved as a therapeutic for any anti-aging indication.", "origin": "NAD+ is a coenzyme in every living cell, essential for redox reactions in energy metabolism (glycolysis, the citric acid cycle, oxidative phosphorylation) and as a substrate for DNA-repair enzymes (PARPs) and signaling enzymes (sirtuins, central to several longevity theories).", "mechanism": "Cellular NAD+ declines measurably with age, linked to reduced mitochondrial function, impaired DNA repair, and reduced sirtuin activity. Restoring it, directly or via precursors NMN/NR that the body converts to NAD+, is theorized to support mitochondrial and metabolic health. Whether raising NAD+ alone meaningfully changes the human aging trajectory is unresolved.", "research_summary": "Mouse studies show NMN or NR supplementation can improve metabolic health markers, mitochondrial function, and in some studies lifespan. Human trials of NMN and NR are more numerous than for most compounds in this wiki: NAD+ levels reliably rise with supplementation, and some metabolic markers (insulin sensitivity, blood pressure, physical performance) improve modestly in some but not all trials. Results are mixed, effect sizes small. Direct IV or subcutaneous NAD+ has far less rigorous human data than the oral precursor route; most 'NAD+ IV therapy' clinic use isn't backed by controlled trials, and self-reported effects (energy, mental clarity, less hangover-like fatigue) are the main evidence.", "reported_benefits": [ "Reported increase in energy and mental clarity, especially with IV/injectable administration", "Interest for supporting recovery from alcohol use, chronic fatigue, and long-COVID-type fatigue in wellness-clinic marketing (not clinically validated for these uses)", "Long-term interest as part of general metabolic-health/longevity stacks alongside exercise and caloric-restriction-mimetic strategies" ], "dosing_protocols": [ { "route": "IV infusion (clinic setting)", "protocol": "Typical clinic protocols range from 250 mg to 1000+ mg per infusion, sometimes over several hours due to infusion-rate-related side effects (flushing, chest tightness at faster rates); frequency varies from weekly to monthly." }, { "route": "Subcutaneous injection (self-administered)", "protocol": "Community-reported doses are much lower than IV, commonly in the 50-100 mg range per injection, a few times per week, partly because subcutaneous NAD+ injection is reported to be quite uncomfortable/stinging at higher concentrations." }, { "route": "Oral precursors (NMN/NR)", "protocol": "Typical studied oral doses are 250-1000 mg/day for NMN and 300-1000 mg/day for NR — these are the routes with the most actual human trial data." } ], "side_effects": [ "IV/injection: flushing, chest or throat tightness (especially with fast IV infusion rates), nausea", "Subcutaneous injection is frequently reported as painful/stinging", "Oral NMN/NR: generally very well tolerated, mild GI upset in some" ], "safety_notes": "Direct NAD+ injection causes more acute discomfort (flushing, chest tightness) than the oral precursor route, and has thinner human safety data despite heavy marketing in longevity clinics. For raising NAD+ with the best evidence-to-risk ratio, the oral precursor route (NMN/NR) is the better-supported option; IV/injectable NAD+ is more about acute subjective effects than proven long-term benefit.", "community_notes": "A fixture of longevity clinics and stacks, often bundled with anti-aging peptides like Epithalon. Community opinion splits between people reporting strong subjective energy benefits from IV/injectable NAD+ and a growing skeptical contingent pointing to the thin controlled-trial evidence for the injectable route, favoring oral NMN/NR as the better-studied way to raise NAD+.", "related": [ "epithalon", "mots-c", "humanin" ], "citations": [ { "title": "Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men", "authors_year": "Yamaguchi et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38191197/" }, { "title": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "authors_year": "Katayoshi et al. 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36797393/" }, { "title": "Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin", "authors_year": "Vreones et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36515353/" }, { "title": "Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men", "authors_year": "Dollerup et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31710095/" } ], "mixing_notes": { "clinic_combos": [ "humanin", "mots-c" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "igf-1-lr3", "ipamorelin", "kisspeptin", "kpv", "ll-37", "mgf", "mt-1", "mt-2", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ] } }, "research": [ { "id": "catalog:supplement:nad-plus", "title": "NAD+ (Nicotinamide Adenine Dinucleotide)", "summary": "A cellular cofactor with levels that decline with age; supplemental precursors and intravenous forms studied for aging-related benefits.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "NAD+ (nicotinamide adenine dinucleotide) is a cofactor for NAD+-dependent enzymes that regulate DNA repair, cellular metabolism, and immune function. Levels decline with age or disease and rise with exercise. Supplemental NAD+ and its precursors (NMN, NR) show beneficial effects on health in rodent models. Commercial clinical and wellness settings increasingly provide intravenous NAD+ and nicotinamide riboside (NR), with one study involving several consecutive days of intravenous administration and a 30-day follow-up. Dietary supplementation with NMN and NAD+ precursors has demonstrated ability to increase circulating NAD+ levels in middle-aged and older individuals. However, human studies on long-term efficacy and safety of injected NAD+ remain limited.", "verdict": { "benefits": [ "Supplemental precursors (NMN, NR) elevate circulating NAD+ levels", "Animal models show benefits on age-related disease", "Oral precursors may be more efficient than direct NAD+ administration" ], "risks": [ "Human studies on intravenous NAD+ are limited and mostly small pilot studies", "Long-term safety and efficacy of chronic intravenous administration unknown", "Mechanism of NAD+ precursor delivery and efficacy in humans not fully understood" ], "bottomLine": "NAD+ precursors show ability to elevate circulating NAD+ levels, with potential benefits in animal models, but human clinical evidence for intravenous NAD+ administration is limited." }, "originalLinks": [ { "title": "Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907335/" }, { "title": "Towards personalized nicotinamide mononucleotide (NMN) supplementation: nicotinamide adenine dinucleotide (NAD) concentration", "url": "https://www.medrxiv.org/content/10.1101/2024.02.19.24303025.full.pdf" }, { "title": "Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158788/" } ], "links": [ { "title": "Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907335/" }, { "title": "Towards personalized nicotinamide mononucleotide (NMN) supplementation: nicotinamide adenine dinucleotide (NAD) concentration", "url": "https://www.medrxiv.org/content/10.1101/2024.02.19.24303025.full.pdf" }, { "title": "Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158788/" } ], "protocols": [ { "population": "Healthy middle-aged and older adults in supplementation studies", "regimen": "Oral NMN or NR precursor supplementation", "duration": "Varies by study; some studies 12+ weeks", "outcome": "Elevated circulating NAD+ levels; effects on muscle function and metabolism observed", "source": { "title": "Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158788/" }, "origins": [ "evidence.json#/catalog:supplement:nad-plus/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.gethealthspan.com/research/article/nad-injections-benefits", "outcome": "no-practice-description", "reason": "The inspected clinic page promotes treatment products and benefit claims, with prescriptive selection and administration advice. No protocol was imported." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [ "peptide:epithalon", "peptide:humanin", "peptide:mots-c" ], "conflicts": [], "sourceRefs": [ "pmid:38191197", "pmid:36797393", "pmid:36515353", "pmid:31710095", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907335/", "https://www.medrxiv.org/content/10.1101/2024.02.19.24303025.full.pdf", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158788/" ] }, "peptide:mots-c": { "id": "peptide:mots-c", "path": "/peptides/mots-c.html", "title": "MOTS-c", "summary": "Mitochondrial-derived peptide encoded in mitochondrial DNA, studied for metabolic regulation and exercise-mimetic effects.", "aliases": [ "MOTS-c" ], "kind": "peptide", "categories": [ "longevity", "fitness-muscle" ], "legacy": { "name": "MOTS-c", "full_name": "Mitochondrial Open Reading Frame of the 12S rRNA-c", "aliases": [ "MOTS-c" ], "categories": [ "longevity", "fitness-muscle" ], "tagline": "Mitochondrial-derived peptide encoded in mitochondrial DNA, studied for metabolic regulation and exercise-mimetic effects.", "status": "Research chemical, no clinical approval. Human evidence is essentially nonexistent; almost all data is from rodent studies.", "origin": "Discovered in 2015. Unusual among peptides here: it's encoded not by nuclear DNA but within the mitochondrial genome, in the 12S ribosomal RNA region, and appears to signal mitochondrial status to the rest of the cell and body.", "mechanism": "In animal studies, MOTS-c activates AMPK, the energy-sensing pathway also triggered by exercise and caloric restriction, and moves to the nucleus under metabolic stress to regulate genes for glucose metabolism and antioxidant response. This exercise-mimetic mechanism drives interest in it for metabolic health and longevity.", "research_summary": "Mouse studies show MOTS-c can prevent age-dependent and diet-induced insulin resistance, improve exercise capacity, and in some studies extend healthspan markers in older mice. Circulating MOTS-c in humans declines with age and rises with exercise, the correlational basis for its 'exercise-in-a-vial' reputation. No published human interventional trials of injected MOTS-c exist. Early-stage, more hypothesis than validated therapy.", "reported_benefits": [ "Reported by users as supporting exercise capacity and recovery", "Interest for metabolic health/insulin sensitivity support", "Often stacked with other longevity peptides (Epithalon, NAD+) despite having a distinct, muscle/metabolism-focused mechanism" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Common community-reported protocol is roughly 5-10 mg per week, split across 2-3 injections, often cycled in blocks of several weeks with breaks. No human dose-finding trial exists, so treat any specific number as convention, not evidence-based dosing." } ], "side_effects": [ "Injection-site reactions reported", "No systematic human safety data exists at any dose" ], "safety_notes": "One of the least human-validated compounds in this wiki. The mouse mechanism is genuinely interesting to metabolic-disease researchers, but there's a large gap between promising mouse data and a known-safe, known-effective human compound.", "community_notes": "Popular in longevity stacks alongside Epithalon and NAD+, usually framed around metabolic health and exercise capacity rather than tissue repair. Discussion skews speculative and mechanism-focused rather than experience-report-focused, unlike BPC-157, reflecting how new and understudied it is.", "related": [ "nad", "epithalon", "humanin" ], "citations": [ { "title": "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance", "authors_year": "Lee et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/25738459/" }, { "title": "The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity", "authors_year": "Kim et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31293078/" }, { "title": "Mitochondrial-derived peptides and exercise", "authors_year": "Woodhead and Merry 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/34520826/" }, { "title": "Exercise-Induced Muscle-Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging", "authors_year": "Tero-Vescan et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40872612/" } ], "mixing_notes": { "clinic_combos": [ "humanin", "nad" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "bpc-157", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "igf-1-lr3", "ipamorelin", "kisspeptin", "kpv", "ll-37", "mgf", "mt-1", "mt-2", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ] } }, "research": [ { "id": "catalog:peptide:mots-c", "title": "MOTS-c", "summary": "Mitochondrial-derived peptide studied preclinically for metabolic regulation.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "MOTS-c is a peptide encoded inside mitochondrial DNA and is a research chemical with no clinical approval. Mouse studies show it prevents age-related and diet-induced insulin resistance, reduces obesity, and improves plasma markers of metabolic dysfunction. It activates AMPK, the same energy-sensing pathway triggered by exercise and calorie restriction, which is why it is called an exercise mimetic. Levels in human blood fall with age and rise after exercise, but no human interventional trial of injected MOTS-c has been published. The gap between mouse data and known-safe human use is large.", "verdict": { "benefits": [ "In mice it prevented age-related and diet-induced insulin resistance and reduced obesity", "It activates AMPK, the energy pathway exercise and calorie restriction also trigger" ], "risks": [ "A research chemical with no clinical approval", "No human interventional trial of the injected peptide has been published", "The gap between mouse results and known-safe human use is large" ], "bottomLine": "A mitochondrial peptide with striking mouse metabolic results and no published human trial of injecting it." }, "originalLinks": [ { "title": "PubMed: MOTS-c", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=MOTS-c" } ], "links": [ { "title": "Peptide Wiki: Mitochondrial Open Reading Frame of the 12S rRNA-c", "url": "https://vespassassina.github.io/peptide-wiki/peptides/mots-c.html" }, { "title": "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (Lee et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25738459/" }, { "title": "The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity (Kim et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31293078/" }, { "title": "Mitochondrial-derived peptides and exercise (Woodhead 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34520826/" }, { "title": "Exercise-Induced Muscle-Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (Tero-Vescan et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40872612/" } ], "protocols": [ { "population": "CD-1 mice fed a 60% high-fat diet", "regimen": "MOTS-c 0.5 mg/kg/day by intraperitoneal injection", "duration": "8 weeks", "outcome": "MOTS-c prevented diet-induced obesity and insulin resistance; in other mice it prevented age-dependent insulin resistance, acting through folate-cycle inhibition and AMPK activation.", "source": { "title": "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (Lee et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25738459/" }, "origins": [ "evidence.json#/catalog:peptide:mots-c/protocols/0" ] }, { "population": "high-fat-diet-induced obese mice", "regimen": "MOTS-c 2.5 mg/kg by intraperitoneal injection, twice a day", "duration": "3 consecutive days", "outcome": "Blood glucose was lower than controls and three plasma pathways tied to insulin resistance fell; body weight and food intake did not change.", "source": { "title": "The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity (Kim et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31293078/" }, "origins": [ "evidence.json#/catalog:peptide:mots-c/protocols/1" ] } ], "community": [ { "description": "Perfect B documents a protocol of 5 mg (25 units) administered subcutaneously once every 5 days for 4 total injections over a 20-day cycle, with morning fasted administration, followed by a 4-month minimum rest period.", "source": { "title": "MOTS-c Dosage Protocol: The 4-Injection Cycle, Reconstitution Guide, and the Exact Schedule We Use", "url": "https://www.perfectb.com/mots-c-dosage-protocol/" }, "origins": [ "evidence.json#/catalog:peptide:mots-c/community/0" ] }, { "description": "Peptide dosing protocols guide describes a standard protocol of 5 mg subcutaneously 3 times per week (e.g., Monday/Wednesday/Friday), with 4–6 week cycles followed by equal-length off periods, positioned as the most common research-planning anchor.", "source": { "title": "MOTS-c Peptide Dosing Guide: Protocol, Reconstitution & Metabolism", "url": "https://www.peptidedosingprotocols.com/protocol/mots-c" }, "origins": [ "evidence.json#/catalog:peptide:mots-c/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "Syringe units in the imported account depend on that source's preparation and concentration; they are not a transferable mass dose or calculator default." ], "community": [ { "origin": "evidence.json#/catalog:peptide:mots-c/community/0", "url": "https://www.perfectb.com/mots-c-dosage-protocol/", "claimMatch": "Syringe units in the imported account depend on that source's preparation and concentration; they are not a transferable mass dose or calculator default. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:mots-c/community/1", "url": "https://www.peptidedosingprotocols.com/protocol/mots-c", "claimMatch": "Syringe units in the imported account depend on that source's preparation and concentration; they are not a transferable mass dose or calculator default. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 2, "lowerHours": 1, "source": "Mitochondrial peptide; limited human PK", "upperHours": 3 } } ], "related": [ "peptide:epithalon", "peptide:humanin", "peptide:nad" ], "conflicts": [], "sourceRefs": [ "pmid:25738459", "pmid:31293078", "pmid:34520826", "pmid:40872612", "https://vespassassina.github.io/peptide-wiki/peptides/mots-c.html", "https://pubmed.ncbi.nlm.nih.gov/?term=MOTS-c", "https://www.perfectb.com/mots-c-dosage-protocol/", "https://www.peptidedosingprotocols.com/protocol/mots-c" ] }, "peptide:humanin": { "id": "peptide:humanin", "path": "/peptides/humanin.html", "title": "Humanin", "summary": "A mitochondrial-derived peptide originally discovered for neuroprotection against Alzheimer's-related cell death, now explored in metabolic and longevity research.", "aliases": [ "HN", "HNG (Humanin analog S14G)" ], "kind": "peptide", "categories": [ "longevity" ], "legacy": { "name": "Humanin", "full_name": "Humanin (HN)", "aliases": [ "HN", "HNG (Humanin analog S14G)" ], "categories": [ "longevity" ], "tagline": "A mitochondrial-derived peptide originally discovered for neuroprotection against Alzheimer's-related cell death, now explored in metabolic and longevity research.", "status": "Research chemical, no clinical approval. Human interventional data is essentially absent; most evidence is cell-culture and rodent-based.", "origin": "Discovered in 2001 in surviving neurons from Alzheimer's disease patients, encoded (like MOTS-c) within mitochondrial DNA. Circulating Humanin levels, like MOTS-c, tend to decline with age.", "mechanism": "In preclinical work, Humanin protects cells against a range of stressors by inhibiting apoptotic pathways, and shows insulin-sensitizing and anti-inflammatory effects. It signals partly through a receptor complex shared with other cytoprotective pathways.", "research_summary": "The evidence is mostly preclinical: cell-culture protection against amyloid-beta toxicity (the original Alzheimer's finding), rodent studies showing improved insulin sensitivity and reduced oxidative stress markers, and correlational human data linking higher circulating Humanin to healthier metabolic profiles and, in some cohort studies, to longevity in centenarian populations. No published human interventional trials exist for exogenous Humanin or its more potent synthetic analog HNG.", "reported_benefits": [ "Interest for cognitive/neuroprotective support, though this is extrapolated from cell and animal data rather than demonstrated in humans", "Included in some metabolic-health-focused longevity stacks", "Correlational human data linking naturally higher levels to healthier aging is a talking point, though this doesn't establish that raising levels artificially replicates the benefit" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Not a well-established self-experimentation compound compared to MOTS-c or Epithalon; where it is used, community-reported doses are in the low single-digit mg per week range for the synthetic HNG analog, split across a few injections. Evidence behind any specific number is essentially absent." } ], "side_effects": [ "No systematic human safety or side-effect data exists" ], "safety_notes": "One of the least practically useful entries here for anyone looking for dosing guidance grounded in real human data. It's included because it comes up often in longevity-peptide discussions, not because a mature protocol exists.", "community_notes": "Discussed far less often than MOTS-c in self-experimentation forums, usually mentioned alongside other mitochondrial-derived peptides in longevity-stack theorizing rather than carrying its own body of user reports.", "related": [ "mots-c", "nad", "epithalon" ], "citations": [ { "title": "Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults", "authors_year": "Hashimoto et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11717357/" }, { "title": "Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish mutant amyloid precursor protein", "authors_year": "Hashimoto et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11327724/" }, { "title": "Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives", "authors_year": "Karachaliou and Livaniou 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38132360/" }, { "title": "The Molecular Structure and Role of Humanin in Neural and Skeletal Diseases, and in Tissue Regeneration", "authors_year": "Zhu et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35372353/" } ], "mixing_notes": { "clinic_combos": [ "mots-c", "nad" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290" ] } }, "research": [ { "id": "catalog:peptide:humanin", "title": "Humanin", "summary": "A mitochondrial peptide associated with longevity in centenarians, studied only in cell and animal models.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "Humanin is a 21 or 24 amino acid mitochondrial-derived peptide discovered in 2001 during a screen for factors protective against amyloid-beta-induced neuronal death. In preclinical models, humanin demonstrates cytoprotective effects against oxidative stress, apoptosis, and amyloid toxicity. Circulating humanin levels decline with age in both mice and humans, and centenarians show higher levels than age-matched controls. Humanin analog HNG improved motor coordination and memory in mouse models of cognitive dysfunction. Despite 20 years of research suggesting therapeutic potential for Alzheimer's disease, humanin has never been tested for safety or efficacy in human clinical trials.", "verdict": { "benefits": [ "Protective effects against apoptosis and oxidative stress in cell and animal models", "Associated with exceptional longevity in centenarians" ], "risks": [ "No human efficacy or safety trials have been conducted", "Only preclinical (animal and cell culture) evidence exists", "Long-term safety in humans is completely unknown" ], "bottomLine": "Humanin shows cytoprotective effects in preclinical research and is associated with human longevity, but has never been tested in human clinical trials and is not an approved therapeutic." }, "originalLinks": [ { "title": "Humanin and Its Pathophysiological Roles in Aging: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135985/" }, { "title": "IGF-I regulates the age-dependent signaling peptide humanin", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172517/" }, { "title": "Humanin and Humanin Analogs", "url": "https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Humanin-and-humanin-analogs.pdf" } ], "links": [ { "title": "Humanin and Its Pathophysiological Roles in Aging: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135985/" }, { "title": "IGF-I regulates the age-dependent signaling peptide humanin", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172517/" }, { "title": "Humanin and Humanin Analogs", "url": "https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Humanin-and-humanin-analogs.pdf" } ], "protocols": [], "community": [ { "description": "A protocol documented on PeptidesExplorer describes 1-5 mg per day administered subcutaneously for cycles lasting 4-8 weeks as community-reported practice.", "source": { "title": "Humanin Peptide: Benefits, Dosing, Safety", "url": "https://peptidesexplorer.com/blog/humanin-peptide" }, "origins": [ "evidence.json#/catalog:peptide:humanin/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:humanin/community/0", "url": "https://peptidesexplorer.com/blog/humanin-peptide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [ "peptide:epithalon", "peptide:mots-c", "peptide:nad" ], "conflicts": [], "sourceRefs": [ "pmid:11717357", "pmid:11327724", "pmid:38132360", "pmid:35372353", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135985/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172517/", "https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Humanin-and-humanin-analogs.pdf", "https://peptidesexplorer.com/blog/humanin-peptide" ] }, "peptide:semaglutide": { "id": "peptide:semaglutide", "path": "/peptides/semaglutide.html", "title": "Semaglutide", "summary": "Long-acting GLP-1 receptor agonist that kicked off the modern GLP-1 weight-loss era. FDA-approved for type 2 diabetes and chronic weight management.", "aliases": [ "Ozempic (diabetes brand)", "Wegovy (weight-loss brand)", "Rybelsus (oral brand)" ], "kind": "peptide", "categories": [ "fat-loss" ], "legacy": { "name": "Semaglutide", "full_name": "Semaglutide (GLP-1 receptor agonist)", "aliases": [ "Ozempic (diabetes brand)", "Wegovy (weight-loss brand)", "Rybelsus (oral brand)" ], "categories": [ "fat-loss" ], "tagline": "Long-acting GLP-1 receptor agonist that kicked off the modern GLP-1 weight-loss era. FDA-approved for type 2 diabetes and chronic weight management.", "status": "FDA-approved prescription medication (Ozempic for type 2 diabetes, Wegovy for chronic weight management, Rybelsus as an oral tablet). Widely available by prescription; also present in the grey/compounded market, which carries additional quality-control risk.", "origin": "A synthetic analog of human GLP-1, modified with a fatty-acid side chain that binds albumin, extending its half-life from the native hormone's few minutes to about a week and allowing once-weekly injection.", "mechanism": "Activates GLP-1 receptors in the pancreas (glucose-dependent insulin secretion, glucagon suppression), the brain (appetite suppression via hypothalamic and brainstem centers, reduced food reward), and the gut (delayed gastric emptying, longer satiety after meals).", "research_summary": "One of the most rigorously studied drugs in this wiki: large RCTs (STEP for weight loss, SUSTAIN for diabetes) enrolling thousands of patients. STEP trials showed average weight loss around 15% of body weight over 68 weeks in non-diabetic participants at the 2.4 mg/week dose, versus roughly 2-3% with placebo. The SELECT cardiovascular outcomes trial showed fewer major adverse cardiovascular events in overweight/obese patients with existing cardiovascular disease. Long-term data beyond a few years is still accumulating, and weight regain after stopping is well documented: most trial participants regained a substantial portion of lost weight within a year of stopping.", "reported_benefits": [ "Substantial, well-documented weight loss in clinical trial populations", "Improved glycemic control in type 2 diabetes", "Reduced cardiovascular event risk in at-risk patients (per SELECT trial)", "Reported reduction in 'food noise' / compulsive eating thoughts, widely discussed in user communities" ], "dosing_protocols": [ { "route": "Subcutaneous injection, once weekly (standard prescribed titration)", "protocol": "Standard titration starts at 0.25 mg/week for 4 weeks, then increases roughly every 4 weeks (0.5 mg → 1 mg → 1.7 mg → 2.4 mg for Wegovy) to reduce GI side effects; maintenance dose depends on indication and tolerability." } ], "side_effects": [ "Nausea, vomiting, diarrhea or constipation, especially during dose escalation — the most common reason people stop", "Rare but serious: pancreatitis, gallbladder disease, risk of thyroid C-cell tumors (boxed warning based on rodent data; human relevance unconfirmed but the warning stands)", "Loss of lean muscle mass alongside fat mass is a well-documented concern, making resistance training and adequate protein intake important during treatment", "Not recommended in personal/family history of medullary thyroid carcinoma or MEN 2 syndrome" ], "safety_notes": "A real, extensively trialed prescription drug with a comparatively well-characterized safety profile versus the research-chemical peptides elsewhere in this wiki. Main practical risks for most users are GI side effects during titration and muscle loss if not paired with resistance training and enough protein. Compounded (non-brand) semaglutide sold outside the regulated pharmacy supply chain carries real quality and dosing-accuracy risk and has drawn FDA warnings.", "community_notes": "The most widely discussed weight-loss peptide by a wide margin. Community reporting consistently points to 'food noise' reduction as the most distinctive subjective effect, more than simply feeling less hungry. Slow dose titration to manage nausea, plus strength training and protein intake to preserve muscle during the cut, come up constantly. Weight regain after stopping is a recurring topic; many long-term users treat it as ongoing maintenance rather than a finite course.", "related": [ "tirzepatide", "retatrutide", "tesamorelin" ], "citations": [ { "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity", "authors_year": "Wilding et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33567185/" }, { "title": "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension", "authors_year": "Wilding et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35441470/" }, { "title": "Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program", "authors_year": "Perreault et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35724304/" }, { "title": "Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5", "authors_year": "Kushner et al. 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/32441473/" } ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board — not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "research": [ { "id": "catalog:peptide:semaglutide", "title": "Semaglutide", "summary": "GLP-1 receptor agonist. Approved products follow a stepped titration over months rather than starting at maintenance dose.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "regulatory", "evidenceSummary": "Semaglutide is a GLP-1 receptor agonist. The owner's wiki records it as FDA-approved for type 2 diabetes and for chronic weight management. It is among the most rigorously studied compounds in that wiki, with large randomised trials (the STEP and SUSTAIN programmes) enrolling thousands of people. STEP trials showed average weight loss of about 15% of body weight over 68 weeks, against roughly 2-3% with placebo. A trial extension showed most participants regained much of that weight after stopping.", "verdict": { "benefits": [ "Type 2 diabetes and for chronic weight management.", "Large randomised trials showed average weight loss near 15% against 2-3% on placebo", "More people with prediabetes returned to normal blood sugar than on placebo" ], "risks": [ "A trial extension showed most of the weight came back after stopping", "Cardiometabolic gains reverted towards baseline once treatment ended" ], "bottomLine": "An approved GLP-1 medicine with large trial evidence for weight loss that largely reverses on stopping.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "EMA: Ozempic", "url": "https://www.ema.europa.eu/en/medicines/human/EPAR/ozempic" }, { "title": "EMA: Wegovy", "url": "https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy" } ], "links": [ { "title": "Wegovy / Ozempic (semaglutide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b" }, { "title": "Peptide Wiki: Semaglutide", "url": "https://vespassassina.github.io/peptide-wiki/peptides/semaglutide.html" }, { "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity (Wilding et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33567185/" }, { "title": "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (Wilding et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35441470/" }, { "title": "Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program (Perreault et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35724304/" }, { "title": "Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5 (Kushner et al. 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32441473/" } ], "protocols": [ { "population": "adults, and children 12 and over, with obesity or overweight plus a weight-related condition, per the US Wegovy label", "regimen": "0.25 mg subcutaneously once weekly, escalating every 4 weeks through 0.5 mg, 1 mg and 1.7 mg to a 1.7-2.4 mg weekly maintenance dose", "duration": "ongoing, per the label", "outcome": "The label carries this schedule for weight reduction and for reducing cardiovascular events in adults with established cardiovascular disease.", "source": { "title": "Wegovy / Ozempic (semaglutide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b" }, "origins": [ "evidence.json#/catalog:peptide:semaglutide/protocols/0" ] }, { "population": "1,961 adults with BMI 30 or above, or 27 with a weight-related condition, without diabetes", "regimen": "semaglutide 2.4 mg subcutaneously once weekly or placebo, both with a lifestyle intervention", "duration": "68 weeks", "outcome": "Body weight fell 14.9% with semaglutide against 2.4% with placebo; 50.5% lost at least 15% of body weight versus 4.9% on placebo.", "source": { "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity (Wilding et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33567185/" }, "origins": [ "evidence.json#/catalog:peptide:semaglutide/protocols/1" ] }, { "population": "327 STEP 1 participants who completed 68 weeks of treatment and then stopped", "regimen": "semaglutide 2.4 mg once weekly or placebo for 68 weeks, then all treatment and lifestyle intervention withdrawn", "duration": "68 weeks on treatment, then one year off treatment (to week 120)", "outcome": "Semaglutide participants regained 11.6 of the 17.3 percentage points of weight lost, and cardiometabolic gains reverted towards baseline.", "source": { "title": "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (Wilding et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35441470/" }, "origins": [ "evidence.json#/catalog:peptide:semaglutide/protocols/2" ] }, { "population": "3,375 adults with overweight or obesity in STEP 1, 3 and 4, of whom 1,536 had prediabetes at baseline", "regimen": "semaglutide 2.4 mg subcutaneously once weekly plus lifestyle intervention versus placebo", "duration": "68 weeks", "outcome": "More participants with prediabetes reached normoglycaemia on semaglutide (84.1% vs 47.8% in STEP 1), with greater falls in HbA1c, fasting glucose and HOMA-IR.", "source": { "title": "Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program (Perreault et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35724304/" }, "origins": [ "evidence.json#/catalog:peptide:semaglutide/protocols/3" ] } ], "community": [ { "description": "EliteFitness bodybuilding forum users report starting semaglutide at 0.25 mg weekly and titrating upward every 4 weeks, with experienced users recommending not to exceed 1-2 mg weekly.", "source": { "title": "How should I use Semaglutide to cut down?", "url": "https://www.elitefitness.com/forum/threads/how-should-i-use-semaglutide-to-cut-down.1516722/" }, "origins": [ "evidence.json#/catalog:peptide:semaglutide/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:semaglutide/community/0", "url": "https://www.elitefitness.com/forum/threads/how-should-i-use-semaglutide-to-cut-down.1516722/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 168, "source": "EMA/FDA product information" } } ], "related": [ "peptide:retatrutide", "peptide:tesamorelin", "peptide:tirzepatide" ], "conflicts": [], "sourceRefs": [ "pmid:33567185", "pmid:35441470", "pmid:35724304", "pmid:32441473", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b", "https://vespassassina.github.io/peptide-wiki/peptides/semaglutide.html", "https://www.ema.europa.eu/en/medicines/human/EPAR/ozempic", "https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy", "https://www.elitefitness.com/forum/threads/how-should-i-use-semaglutide-to-cut-down.1516722/" ] }, "peptide:tirzepatide": { "id": "peptide:tirzepatide", "path": "/peptides/tirzepatide.html", "title": "Tirzepatide", "summary": "A dual GIP/GLP-1 receptor agonist that generally outperforms semaglutide for weight loss in head-to-head trials. FDA-approved for type 2 diabetes and chronic weight management.", "aliases": [ "Mounjaro (diabetes brand)", "Zepbound (weight-loss brand)" ], "kind": "peptide", "categories": [ "fat-loss" ], "legacy": { "name": "Tirzepatide", "full_name": "Tirzepatide (dual GIP/GLP-1 receptor agonist)", "aliases": [ "Mounjaro (diabetes brand)", "Zepbound (weight-loss brand)" ], "categories": [ "fat-loss" ], "tagline": "A dual GIP/GLP-1 receptor agonist that generally outperforms semaglutide for weight loss in head-to-head trials. FDA-approved for type 2 diabetes and chronic weight management.", "status": "FDA-approved prescription medication (Mounjaro for type 2 diabetes, Zepbound for chronic weight management).", "origin": "A single synthetic peptide engineered to activate both the GIP and GLP-1 receptors, combining two incretin hormone pathways in one molecule, with a fatty-acid modification giving it a once-weekly half-life similar to semaglutide.", "mechanism": "GLP-1 receptor activation provides the same appetite-suppression, gastric-emptying-delay and glucose-control effects as semaglutide. Added GIP receptor activation appears to enhance insulin sensitivity and may directly affect fat cell metabolism, thought to explain tirzepatide's larger average weight-loss effect in trials.", "research_summary": "The SURMOUNT trial program showed average weight loss around 20-22% of body weight at the highest studied dose (15 mg/week) over 72 weeks in non-diabetic participants, meaningfully larger than semaglutide's ~15% in comparable trial designs. A head-to-head trial (SURMOUNT-5) found tirzepatide produced significantly more weight loss than semaglutide directly. Visceral fat reduction, measured via DXA scan substudies, showed roughly 40% reduction in visceral fat mass over the ~72-week SURMOUNT trial period.", "reported_benefits": [ "Larger average weight loss than semaglutide in head-to-head and cross-trial comparison", "Strong visceral fat reduction specifically (measured via imaging in trial substudies)", "Improved glycemic control in type 2 diabetes, generally considered at least as effective as semaglutide for this indication" ], "dosing_protocols": [ { "route": "Subcutaneous injection, once weekly (standard prescribed titration)", "protocol": "Starting dose 2.5 mg/week for 4 weeks, then increasing in 2.5 mg increments roughly every 4 weeks as tolerated, up to a maximum studied/approved dose of 15 mg/week." } ], "side_effects": [ "Similar GI side-effect profile to semaglutide: nausea, diarrhea, vomiting, constipation, most pronounced during dose escalation", "Same boxed warning regarding thyroid C-cell tumor risk based on rodent data", "Lean mass loss alongside fat loss, same caveat as semaglutide regarding resistance training and protein intake", "Not recommended with personal/family history of medullary thyroid carcinoma or MEN 2" ], "safety_notes": "Like semaglutide, this is a properly trialed, FDA-approved medication with a comparatively well-characterized safety profile versus most entries in this wiki. Requires sustained treatment (72+ weeks in trials) to reach full visceral-fat-reduction effect; the compounded/grey-market version carries the same quality-control caveats as compounded semaglutide.", "community_notes": "Generally reported as more potent than semaglutide for both appetite suppression and weight loss, sometimes at the cost of more pronounced GI side effects during titration. A frequent discussion point is trading off tirzepatide's stronger effect against semaglutide's gentler side-effect profile for people sensitive to GI symptoms.", "related": [ "semaglutide", "retatrutide" ], "citations": [ { "title": "Tirzepatide Once Weekly for the Treatment of Obesity", "authors_year": "Jastreboff et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35658024/" }, { "title": "Tirzepatide for Obesity Treatment and Diabetes Prevention", "authors_year": "Jastreboff et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39536238/" } ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board — not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "research": [ { "id": "catalog:peptide:tirzepatide", "title": "Tirzepatide", "summary": "Dual GIP and GLP-1 receptor agonist. Like semaglutide, follows a stepped titration.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "regulatory", "evidenceSummary": "Tirzepatide activates both the GIP and GLP-1 receptors. The owner's wiki records it as an approved prescription medicine for type 2 diabetes and for chronic weight management. In SURMOUNT-1, a phase 3 double-blind trial in 2539 adults with obesity, mean body weight fell by about 15% to 21% depending on the amount given, against about 3% with placebo over 72 weeks. A follow-on analysis of participants with obesity and prediabetes found the weight loss largely held at 176 weeks and progression to type 2 diabetes was delayed.", "verdict": { "benefits": [ "Prescribed for type 2 diabetes and for chronic weight management.", "In a phase 3 trial of 2539 adults, mean weight fell about 15-21% against about 3% on placebo", "In longer follow-up the loss largely held and far fewer developed diabetes, 1.3% against 13.3%" ], "risks": [ "Gastrointestinal adverse events were the most common side effects in the trial", "The label also covers cardiovascular risk reduction, which is a separate approved use", "The material here covers weight and blood sugar outcomes, not safety beyond those trials" ], "bottomLine": "Tirzepatide is an approved medicine with large, replicated weight loss in phase 3 trials and common gut side effects.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "EMA: Mounjaro", "url": "https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro" } ], "links": [ { "title": "Mounjaro (tirzepatide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0" }, { "title": "Peptide Wiki: Tirzepatide", "url": "https://vespassassina.github.io/peptide-wiki/peptides/tirzepatide.html" }, { "title": "Tirzepatide Once Weekly for the Treatment of Obesity (Jastreboff et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35658024/" }, { "title": "Tirzepatide for Obesity Treatment and Diabetes Prevention (Jastreboff et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39536238/" } ], "protocols": [ { "population": "adults and children 10 years and older with type 2 diabetes, per the US label", "regimen": "2.5 mg subcutaneously once weekly to start, raised in 2.5 mg steps after at least 4 weeks, to at most 15 mg weekly in adults and 10 mg in children", "duration": "ongoing, per the label", "outcome": "The label approves this dosing as an adjunct to diet and exercise for glycaemic control, and to cut major adverse cardiovascular events in adults at high risk.", "source": { "title": "Mounjaro (tirzepatide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0" }, "origins": [ "evidence.json#/catalog:peptide:tirzepatide/protocols/0" ] }, { "population": "2539 adults with obesity, or BMI 27 or more with a weight-related complication, excluding diabetes", "regimen": "tirzepatide 5 mg, 10 mg or 15 mg subcutaneously once weekly, or placebo, after a 20-week dose-escalation period", "duration": "72 weeks", "outcome": "Mean weight change was -15.0%, -19.5% and -20.9% on 5, 10 and 15 mg against -3.1% on placebo; gastrointestinal adverse events were the most common.", "source": { "title": "Tirzepatide Once Weekly for the Treatment of Obesity (Jastreboff et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35658024/" }, "origins": [ "evidence.json#/catalog:peptide:tirzepatide/protocols/1" ] }, { "population": "1032 SURMOUNT-1 participants with both obesity and prediabetes", "regimen": "tirzepatide 5 mg, 10 mg or 15 mg subcutaneously once weekly, or placebo, then 17 weeks off treatment", "duration": "176 weeks on treatment plus 17 weeks off", "outcome": "Mean weight change at 176 weeks was -12.3%, -18.7% and -19.7% against -1.3% on placebo, and 1.3% versus 13.3% were diagnosed with type 2 diabetes.", "source": { "title": "Tirzepatide for Obesity Treatment and Diabetes Prevention (Jastreboff et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39536238/" }, "origins": [ "evidence.json#/catalog:peptide:tirzepatide/protocols/2" ] } ], "community": [ { "description": "An article on tirzepatide for weight loss describes the standard titration protocol: starting at 2.5 mg weekly, increasing to 5 mg after 4 weeks, then increasing by 2.5 mg increments every 4 weeks as tolerated.", "source": { "title": "Zepbound/Mounjaro (Tirzepatide) for Weight Loss - Part 1", "url": "https://weightandhealthcare.substack.com/p/zepbound-tirzepatide-for-weight-loss" }, "origins": [ "evidence.json#/catalog:peptide:tirzepatide/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:tirzepatide/community/0", "url": "https://weightandhealthcare.substack.com/p/zepbound-tirzepatide-for-weight-loss", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 120, "source": "FDA label, Mounjaro" } } ], "related": [ "peptide:retatrutide", "peptide:semaglutide" ], "conflicts": [], "sourceRefs": [ "pmid:35658024", "pmid:39536238", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0", "https://vespassassina.github.io/peptide-wiki/peptides/tirzepatide.html", "https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro", "https://weightandhealthcare.substack.com/p/zepbound-tirzepatide-for-weight-loss" ] }, "peptide:retatrutide": { "id": "peptide:retatrutide", "path": "/peptides/retatrutide.html", "title": "Retatrutide", "summary": "Investigational triple-hormone-receptor agonist with the largest weight-loss effect of any GLP-1-class compound tested so far. Not FDA-approved.", "aliases": [ "LY3437943", "Triple-G agonist" ], "kind": "peptide", "categories": [ "fat-loss" ], "legacy": { "name": "Retatrutide", "full_name": "Retatrutide (triple GIP/GLP-1/glucagon receptor agonist)", "aliases": [ "LY3437943", "Triple-G agonist" ], "categories": [ "fat-loss" ], "tagline": "Investigational triple-hormone-receptor agonist with the largest weight-loss effect of any GLP-1-class compound tested so far. Not FDA-approved.", "status": "Investigational — in Phase 3 clinical trials as of this writing, not yet FDA-approved for any indication. Available through research-chemical/grey-market channels despite lacking approval, which carries significant additional risk versus using a regulated, approved drug.", "origin": "Developed by Eli Lilly. A single synthetic peptide engineered to hit three receptors at once: GLP-1, GIP, and glucagon. The first 'triple agonist' in this class to reach late-stage trials.", "mechanism": "Combines GLP-1 and GIP receptor activity (as in tirzepatide) with glucagon receptor agonism, which raises energy expenditure and drives lipolysis in the liver. That stacks a metabolic-rate effect on top of the appetite suppression the other GLP-1-class drugs already provide.", "research_summary": "A Phase 2 trial in the New England Journal of Medicine reported average weight loss around 24% of body weight at the highest dose (12 mg/week) at 48 weeks, the largest effect size reported for this class at time of publication. Weight loss was still trending down, not plateaued, at trial's end, suggesting more loss with continued treatment. Phase 3 trials are underway to confirm long-term efficacy and safety at scale; longer-term glucagon-receptor effects are still being worked out.", "reported_benefits": [ "Largest average weight-loss effect reported for any GLP-1-class compound in trials to date", "Added metabolic-rate/energy-expenditure component beyond pure appetite suppression, due to glucagon receptor activity", "Trial data suggests effect had not plateaued by 48 weeks, unlike some comparator trials" ], "dosing_protocols": [ { "route": "Subcutaneous injection, once weekly (as studied in trials)", "protocol": "Phase 2 trial dosing escalated up to 12 mg/week; because this drug is not yet approved, there is no standardized prescribing protocol, and self-sourced dosing is based on extrapolating from trial data rather than an established, regulated titration schedule." } ], "side_effects": [ "GI side effects similar to but potentially more pronounced than semaglutide/tirzepatide given the added glucagon receptor activity, including nausea, diarrhea and reduced appetite", "Increased heart rate has been observed in trials, thought related to glucagon receptor activation — a distinguishing safety signal versus the dual/single agonists", "Long-term safety data does not yet exist at the scale available for semaglutide or tirzepatide" ], "safety_notes": "This is an investigational drug, not an approved medication. Anyone using it outside a trial is taking a compound with an unestablished long-term human safety profile, sourced through channels with zero regulatory quality control. Take the heart-rate signal seen in trials seriously: it's mechanistically distinct from the other GLP-1-class drugs.", "community_notes": "Big buzz in weight-loss and longevity circles as the 'next generation' GLP-1 drug on the strength of its trial results. But access is entirely grey-market research-chemical sourcing since it isn't FDA-approved, a meaningfully different risk than prescribed semaglutide or tirzepatide. Weigh that against just waiting for approval or using what's already approved.", "related": [ "tirzepatide", "semaglutide" ], "citations": [ { "title": "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial", "authors_year": "Jastreboff et al. 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/37366315/" }, { "title": "The power of three: Retatrutide's role in modern obesity and diabetes therapy", "authors_year": "Abdul-Rahman et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39515565/" } ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board — not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "research": [ { "id": "catalog:peptide:retatrutide", "title": "Retatrutide", "summary": "Triple GIP, GLP-1 and glucagon receptor agonist in clinical trials. Not approved.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Retatrutide is an investigational triple receptor agonist (GLP-1, GIP and glucagon) and is not approved by any regulator. A phase 2 randomised placebo-controlled trial in 338 adults with obesity reported average weight loss of about 24% at the highest dose after 48 weeks, against about 2% with placebo, and weight was still falling at the end. Phase 3 trials are under way. Reported side effects include nausea and diarrhoea, and a rise in heart rate has been seen in trials, which sets it apart from other drugs in this class.", "verdict": { "benefits": [ "A phase 2 randomised trial in obesity found average weight loss near a quarter of body weight.", "Placebo lost about 2%, and weight was still falling when the trial ended." ], "risks": [ "Investigational and not approved by any regulator; phase 3 trials are still running.", "Nausea and diarrhoea were reported, and heart rate rose, unlike others in this class.", "Evidence rests on one phase 2 trial, so long-term safety is unknown." ], "bottomLine": "Retatrutide produced large weight loss in a phase 2 trial but remains unapproved, with raised heart rate reported." }, "originalLinks": [ { "title": "ClinicalTrials.gov: retatrutide", "url": "https://clinicaltrials.gov/search?term=retatrutide" } ], "links": [ { "title": "Peptide Wiki: Retatrutide (triple GIP/GLP-1/glucagon receptor agonist)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/retatrutide.html" }, { "title": "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial (Jastreboff et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37366315/" }, { "title": "The power of three: Retatrutide's role in modern obesity and diabetes therapy (Abdul-Rahman et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39515565/" } ], "protocols": [ { "population": "338 adults with a BMI of 30 or more, or 27-30 plus a weight-related condition", "regimen": "subcutaneous retatrutide 1, 4, 8 or 12 mg once weekly, or placebo, some arms starting at a lower dose", "duration": "48 weeks", "outcome": "Body weight fell 8.7% on 1 mg, 17.1% on 4 mg, 22.8% on 8 mg and 24.2% on 12 mg against 2.1% on placebo; gastrointestinal events and heart-rate rises were dose-related.", "source": { "title": "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial (Jastreboff et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37366315/" }, "origins": [ "evidence.json#/catalog:peptide:retatrutide/protocols/0" ] } ], "community": [ { "description": "EliteFitness forum users report a retatrutide protocol of 1.5 mg weekly for the first 6 weeks, increasing to 2.5 mg weekly for weeks 7-10, then reducing to 1 mg weekly for maintenance.", "source": { "title": "retatrutide protocol and tips", "url": "https://www.elitefitness.com/forum/threads/retatrutide-protocol-and-tips.1514576/" }, "origins": [ "evidence.json#/catalog:peptide:retatrutide/community/0" ] }, { "description": "Another EliteFitness discussion describes starting retatrutide at 0.5 mg administered four times per week, with alternative approaches of 1 mg weekly increased by 0.2-0.4 mg increments weekly.", "source": { "title": "proper use of retatrutide", "url": "https://www.elitefitness.com/forum/threads/proper-use-of-retatrutide.1513961/" }, "origins": [ "evidence.json#/catalog:peptide:retatrutide/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:retatrutide/community/0", "url": "https://www.elitefitness.com/forum/threads/retatrutide-protocol-and-tips.1514576/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:retatrutide/community/1", "url": "https://www.elitefitness.com/forum/threads/proper-use-of-retatrutide.1513961/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 144, "source": "Phase 2 PK, supports weekly dosing" } } ], "related": [ "peptide:semaglutide", "peptide:tirzepatide" ], "conflicts": [], "sourceRefs": [ "pmid:37366315", "pmid:39515565", "https://vespassassina.github.io/peptide-wiki/peptides/retatrutide.html", "https://clinicaltrials.gov/search?term=retatrutide", "https://www.elitefitness.com/forum/threads/retatrutide-protocol-and-tips.1514576/", "https://www.elitefitness.com/forum/threads/proper-use-of-retatrutide.1513961/" ] }, "peptide:aod-9604": { "id": "peptide:aod-9604", "path": "/peptides/aod-9604.html", "title": "AOD-9604", "summary": "A growth hormone fragment engineered to isolate the fat-burning effect and drop HGH's blood sugar and tissue growth effects. Trialed for obesity, never reached market.", "aliases": [ "AOD-9604", "hGH Fragment 176-191" ], "kind": "peptide", "categories": [ "fat-loss" ], "legacy": { "name": "AOD-9604", "full_name": "Anti-Obesity Drug 9604 (a modified fragment of human growth hormone, amino acids 176-191)", "aliases": [ "AOD-9604", "hGH Fragment 176-191" ], "categories": [ "fat-loss" ], "tagline": "A growth hormone fragment engineered to isolate the fat-burning effect and drop HGH's blood sugar and tissue growth effects. Trialed for obesity, never reached market.", "status": "Failed to reach approval as an obesity drug after Phase IIb trials showed insufficient efficacy versus placebo; sold today only as a research chemical, with no clinical approval anywhere.", "origin": "Australian biotech Metabolic Pharmaceuticals isolated the C-terminal fragment of human growth hormone (amino acids 176-191), the piece responsible for GH's lipolytic activity, and dropped the rest of the molecule that drives growth and blood-sugar effects.", "mechanism": "Meant to stimulate lipolysis and block lipogenesis in adipose tissue, mimicking one piece of GH's action without touching IGF-1, bone/tissue growth, or insulin resistance.", "research_summary": "Early studies, including some human work, suggested a modest fat-metabolism effect, enough to advance it to Phase IIb obesity trials. Those trials, the most rigorous human data that exists for this compound, found no statistically significant weight-loss benefit over placebo, and development for obesity was dropped. It hasn't been meaningfully re-investigated since.", "reported_benefits": [ "Marketed by research-chemical vendors as supporting fat loss, but this is not supported by the compound's own Phase IIb trial results", "Some anecdotal reports of mild fat-loss support when stacked with a caloric deficit and other compounds, difficult to disentangle from those other interventions" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community-reported doses commonly range 250-500 mcg/day; there is no validated effective human dose because the compound failed its efficacy trials at the doses tested." } ], "side_effects": [ "Reported as generally well tolerated in trials (this was not the reason development stopped — lack of efficacy was)", "Limited independent safety data outside the original manufacturer's trials" ], "safety_notes": "This compound went through real Phase IIb human obesity trials and didn't beat placebo. That's a worse evidence situation than most research peptides, which simply haven't been tested rigorously at all. Read continued marketing for fat loss in that light.", "community_notes": "Still sold and discussed occasionally, but enthusiasm has cooled as the failed trial results became more widely known. Overshadowed now by tesamorelin, which has real approved-drug evidence for visceral fat, and by the GLP-1 drugs, which have far stronger trial results.", "related": [ "tesamorelin", "semaglutide" ], "citations": [ { "title": "The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice", "authors_year": "Heffernan et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11713213/" }, { "title": "Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment", "authors_year": "Heffernan et al. 2001", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11673763/" }, { "title": "Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone", "authors_year": "Ng et al. 2000", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/11146367/" } ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [], "reported_avoid": [ "ara-290", "cjc-1295", "cjc-1295-dac", "dsip", "epithalon", "ghk-cu", "ghrp-2", "ghrp-6", "hcg", "hexarelin", "hgh-somatropin", "humanin", "igf-1-lr3", "kisspeptin", "kpv", "ll-37", "mgf", "mots-c", "mt-1", "mt-2", "nad", "p21", "pe-22-28", "pinealon", "pt-141", "selank", "semax", "tb-500", "thymalin", "thymosin-alpha-1" ] } }, "research": [ { "id": "catalog:peptide:aod-9604", "title": "AOD-9604", "summary": "Modified fragment of hGH studied for fat metabolism without the growth-promoting effects of full hGH.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "The linked studies are all in animals: obese mice and Zucker rats lost weight and oxidised more fat with this growth hormone fragment, without the blood sugar effects of full growth hormone. The wiki records that the compound went on to phase 2b human obesity trials and failed to beat placebo, after which development was dropped. That makes its evidence position worse than peptides that were simply never tested. Marketing for fat loss is not supported by the compound's own trial results, and it has no clinical approval anywhere.", "verdict": { "benefits": [ "Only shown in rodents: less weight gain and more fat oxidation, without growth hormone's sugar effects" ], "risks": [ "Human phase 2b obesity trials failed to beat placebo and development was dropped", "Not approved anywhere, and fat-loss marketing is contradicted by its own trial results", "Its evidence position is worse than compounds simply never tested in people" ], "bottomLine": "AOD-9604 worked in rodents but failed against placebo in human obesity trials, and it is approved nowhere." }, "originalLinks": [ { "title": "PubMed: AOD9604", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=AOD9604" } ], "links": [ { "title": "Peptide Wiki: Anti-Obesity Drug 9604 (a modified fragment of human growth hormone, amino acids 176-191)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/aod-9604.html" }, { "title": "The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice (Heffernan et al. 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11713213/" }, { "title": "Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment (Heffernan et al. 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11673763/" }, { "title": "Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone (Ng et al. 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/11146367/" } ], "protocols": [ { "population": "Obese (ob/ob) mice and beta3-adrenergic receptor knock-out mice", "regimen": "Human growth hormone or AOD9604 by chronic intraperitoneal administration", "duration": "14 days", "outcome": "Both cut body weight and body fat and raised beta3-receptor RNA in obese mice; in knock-out mice neither changed body weight or lipolysis.", "source": { "title": "The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice (Heffernan et al. 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11713213/" }, "origins": [ "evidence.json#/catalog:peptide:aod-9604/protocols/0" ] }, { "population": "Obese (ob/ob) and lean C57BL/6J mice", "regimen": "Human growth hormone, AOD9604 or saline delivered continuously by mini-osmotic pump", "duration": "14 days", "outcome": "Both cut body weight gain and raised fat oxidation and plasma glycerol; unlike hGH, AOD9604 caused no hyperglycaemia and did not bind the hGH receptor.", "source": { "title": "Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment (Heffernan et al. 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11673763/" }, "origins": [ "evidence.json#/catalog:peptide:aod-9604/protocols/1" ] }, { "population": "Obese Zucker rats", "regimen": "AOD9604 by mouth, 500 micrograms per kg body weight daily", "duration": "19 days", "outcome": "Body weight gain fell by over 50% (15.8 g versus 35.6 g) and adipose lipolysis rose, with no adverse effect on insulin sensitivity on euglycaemic clamp.", "source": { "title": "Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone (Ng et al. 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/11146367/" }, "origins": [ "evidence.json#/catalog:peptide:aod-9604/protocols/2" ] } ], "community": [ { "description": "A protocol referenced on community peptide forums describes 300 mcg administered subcutaneously once daily over a 12-week cycle, typically injected in a fasted state with cardio within 30 minutes.", "source": { "title": "AOD-9604 Dosage Chart & Reconstitution Guide (2026)", "url": "https://www.peptidedosingprotocols.com/protocol/aod-9604" }, "origins": [ "evidence.json#/catalog:peptide:aod-9604/community/0" ] }, { "description": "A dosing guide on peptide community sites describes a phased protocol: weeks 1-4 at 300 mcg daily, weeks 5-12 at 500 mcg daily, administered subcutaneously.", "source": { "title": "AOD-9604 Community Research Protocols", "url": "https://www.bhrcenter.com/aod-9604-dosage-guide-complete-protocol-for-safe-administration/" }, "origins": [ "evidence.json#/catalog:peptide:aod-9604/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:aod-9604/community/0", "url": "https://www.peptidedosingprotocols.com/protocol/aod-9604", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:aod-9604/community/1", "url": "https://www.bhrcenter.com/aod-9604-dosage-guide-complete-protocol-for-safe-administration/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.75, "lowerHours": 0.5, "source": "hGH fragment 176-191", "upperHours": 1 } } ], "related": [ "peptide:semaglutide", "peptide:tesamorelin" ], "conflicts": [], "sourceRefs": [ "pmid:11713213", "pmid:11673763", "pmid:11146367", "https://vespassassina.github.io/peptide-wiki/peptides/aod-9604.html", "https://pubmed.ncbi.nlm.nih.gov/?term=AOD9604", "https://www.peptidedosingprotocols.com/protocol/aod-9604", "https://www.bhrcenter.com/aod-9604-dosage-guide-complete-protocol-for-safe-administration/" ] }, "peptide:tesamorelin": { "id": "peptide:tesamorelin", "path": "/peptides/tesamorelin.html", "title": "Tesamorelin", "summary": "FDA-approved GHRH analog specifically approved for reducing visceral fat in HIV-associated lipodystrophy, used off-label more broadly for visceral fat reduction and as a growth-hormone secretagogue.", "aliases": [ "Egrifta" ], "kind": "peptide", "categories": [ "fat-loss", "fitness-muscle" ], "legacy": { "name": "Tesamorelin", "full_name": "Tesamorelin (a growth hormone releasing hormone / GHRH analog)", "aliases": [ "Egrifta" ], "categories": [ "fat-loss", "fitness-muscle" ], "tagline": "FDA-approved GHRH analog specifically approved for reducing visceral fat in HIV-associated lipodystrophy, used off-label more broadly for visceral fat reduction and as a growth-hormone secretagogue.", "status": "FDA-approved prescription drug (Egrifta) for reduction of excess visceral fat in HIV-associated lipodystrophy. Used off-label for general visceral fat reduction and GH-axis support.", "origin": "A synthetic analog of GHRH, stabilized against enzymatic breakdown to extend its action compared to native GHRH.", "mechanism": "Stimulates the pituitary to release the body's own growth hormone in a pulsatile, physiological pattern rather than injecting synthetic HGH directly. That raises IGF-1 and has been shown to reduce visceral adipose tissue, the metabolically dangerous fat around internal organs, more than subcutaneous fat.", "research_summary": "The pivotal trials supporting FDA approval were conducted in HIV-associated lipodystrophy patients and showed a statistically significant reduction in visceral adipose tissue (measured by CT scan) versus placebo, along with improved triglycerides. Since the mechanism (raising endogenous GH/IGF-1) isn't HIV-specific, tesamorelin is used off-label in the general population for visceral fat reduction, and by some in longevity/performance medicine as a 'cleaner' GH-axis stimulator than exogenous HGH, since it preserves the pituitary's natural pulsatile release and negative feedback control.", "reported_benefits": [ "Clinically demonstrated visceral fat reduction (in its approved indication population)", "Reported improvements in sleep quality and body composition among off-label users", "Considered by some GH-axis-focused practitioners to be gentler/more physiological than direct HGH injection because it preserves the body's own feedback regulation" ], "dosing_protocols": [ { "route": "Subcutaneous injection, daily", "protocol": "The FDA-approved dose is 2 mg once daily, injected subcutaneously in the abdomen, typically at bedtime; this is also the dose most commonly used off-label." } ], "side_effects": [ "Injection-site reactions", "Joint pain, swelling or fluid retention (edema) — a known class effect of raising GH/IGF-1", "Increased blood glucose has been observed in trials — caution advised for people with insulin resistance or diabetes", "Contraindicated in active malignancy given IGF-1's growth-promoting effects" ], "safety_notes": "A real, FDA-approved drug with a genuine efficacy trial behind its specific indication, firmer ground than most 'GH secretagogue' research peptides. Watch for the known GH-axis side effects (fluid retention, joint discomfort, blood sugar effects), particularly if you have pre-diabetes or diabetes.", "community_notes": "Popular in longevity and physique-focused communities specifically for visceral fat reduction, often discussed as a more evidence-backed alternative to peptide-only GH secretagogue stacks (CJC-1295/Ipamorelin) because it has actual placebo-controlled human trial data behind it, even though that data comes from a specific patient population rather than healthy adults.", "related": [ "semaglutide", "cjc-1295", "ipamorelin" ], "citations": [ { "title": "Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data", "authors_year": "Falutz et al. 2010", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20554713/" }, { "title": "Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation", "authors_year": "Falutz et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18690162/" }, { "title": "Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin", "authors_year": "Stanley et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22495074/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin" ], "anecdotal_combos": [], "reported_avoid": [ "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:tesamorelin", "title": "Tesamorelin", "summary": "GHRH analogue approved for HIV-associated lipodystrophy. Studied for visceral fat reduction.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "regulatory", "evidenceSummary": "Tesamorelin is a GHRH analogue. The owner's wiki records it as FDA-approved, as Egrifta, for reducing excess visceral fat in HIV-associated lipodystrophy. Placebo-controlled phase 3 trials in that population showed a significant fall in visceral fat on CT and improved triglycerides. It prompts the pituitary to release the body's own growth hormone, so natural feedback is preserved, unlike injected HGH. Known side effects include fluid retention, joint pain and raised blood glucose, and it is contraindicated in active cancer.", "verdict": { "benefits": [ "Egrifta for excess visceral fat in HIV-associated lipodystrophy.", "Phase 3 trials showed visceral fat fell on CT scan against placebo, with better triglycerides.", "It prompts the pituitary to release the body's own growth hormone, preserving feedback." ], "risks": [ "Visceral fat returned after stopping, and HDL fell slightly in longer follow-up.", "Known side effects include fluid retention, joint pain and raised blood glucose.", "Contraindicated in active cancer; trial evidence comes from one patient population." ], "bottomLine": "Tesamorelin is FDA-approved for visceral fat in HIV lipodystrophy; the fat returns once treatment stops.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: tesamorelin", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=tesamorelin" } ], "links": [ { "title": "Egrifta SV (tesamorelin) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224" }, { "title": "Peptide Wiki: Tesamorelin (a growth hormone releasing hormone / GHRH analog)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/tesamorelin.html" }, { "title": "Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data (Falutz et al. 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20554713/" }, { "title": "Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation (Falutz et al. 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18690162/" }, { "title": "Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin (Stanley et al. 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22495074/" } ], "protocols": [ { "population": "HIV-infected adult patients with lipodystrophy, per the US Egrifta SV label", "regimen": "1.4 mg tesamorelin (0.35 mL of reconstituted solution) injected subcutaneously into the abdomen once daily, rotating sites", "duration": "ongoing, per the label; no fixed treatment duration is given", "outcome": "The label reports about 14-18% mean reduction in visceral adipose tissue over 26 weeks against 0-2% on placebo, with visceral fat returning after discontinuation.", "source": { "title": "Egrifta SV (tesamorelin) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224" }, "origins": [ "evidence.json#/catalog:peptide:tesamorelin/protocols/0" ] }, { "population": "806 HIV patients on antiretroviral therapy with excess abdominal fat, pooled from two phase 3 trials", "regimen": "tesamorelin 2 mg or matching placebo subcutaneously once daily, randomised 2:1, with re-randomisation at week 26", "duration": "26 weeks, with a 26-week extension to 52 weeks", "outcome": "Visceral fat fell 24 cm2 against a 2 cm2 gain on placebo (-15.4% treatment effect); triglycerides fell; subcutaneous fat and glucose parameters did not change.", "source": { "title": "Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data (Falutz et al. 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20554713/" }, "origins": [ "evidence.json#/catalog:peptide:tesamorelin/protocols/1" ] }, { "population": "410 HIV patients with central fat accumulation on antiretroviral therapy", "regimen": "tesamorelin 2 mg or placebo subcutaneously once daily, with re-randomisation at week 26 to continue, stop or switch", "duration": "26 weeks plus a 26-week extension, 52 weeks in total", "outcome": "Visceral fat stayed 18% below baseline and triglycerides 51 mg/dL lower over 52 weeks; HDL fell slightly and visceral fat reaccumulated after stopping.", "source": { "title": "Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation (Falutz et al. 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18690162/" }, "origins": [ "evidence.json#/catalog:peptide:tesamorelin/protocols/2" ] }, { "population": "402 men and women with HIV-associated abdominal fat accumulation randomised to tesamorelin in two phase 3 trials", "regimen": "tesamorelin or placebo subcutaneously daily, 2:1 randomisation, with those on tesamorelin re-randomised at week 26", "duration": "26 weeks, then 26 more weeks", "outcome": "Patients whose visceral fat fell 8% or more had larger triglyceride and adiponectin improvements and preserved glucose control against non-responders.", "source": { "title": "Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin (Stanley et al. 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22495074/" }, "origins": [ "evidence.json#/catalog:peptide:tesamorelin/protocols/3" ] } ], "community": [ { "description": "An EliteFitness forum discussion documents starting tesamorelin at 1 mg daily, then increasing by 0.5 mg each week until reaching 5 mg daily, with administration before bed on an empty stomach.", "source": { "title": "tesamorelin proper dosage for fat dude", "url": "https://www.elitefitness.com/forum/threads/tesamorelin-proper-dosage-for-fat-dude.1512747/" }, "origins": [ "evidence.json#/catalog:peptide:tesamorelin/community/0" ] }, { "description": "Forum moderators recommend tesamorelin dosing of 2 mg once daily administered before bedtime while fasted, at least 90 minutes after eating.", "source": { "title": "tesamorelin proper dosage for fat dude", "url": "https://www.elitefitness.com/forum/threads/tesamorelin-proper-dosage-for-fat-dude.1512747/" }, "origins": [ "evidence.json#/catalog:peptide:tesamorelin/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The two imported community accounts report different dose-escalation and fixed-dose approaches. They are not regulatory instructions or an agreed safe regimen." ], "community": [ { "origin": "evidence.json#/catalog:peptide:tesamorelin/community/0", "url": "https://www.elitefitness.com/forum/threads/tesamorelin-proper-dosage-for-fat-dude.1512747/", "claimMatch": "The two imported community accounts report different dose-escalation and fixed-dose approaches. They are not regulatory instructions or an agreed safe regimen. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:tesamorelin/community/1", "url": "https://www.elitefitness.com/forum/threads/tesamorelin-proper-dosage-for-fat-dude.1512747/", "claimMatch": "The two imported community accounts report different dose-escalation and fixed-dose approaches. They are not regulatory instructions or an agreed safe regimen. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.6333333333333333, "source": "FDA label, Egrifta" } } ], "related": [ "peptide:cjc-1295", "peptide:ipamorelin", "peptide:semaglutide" ], "conflicts": [], "sourceRefs": [ "pmid:20554713", "pmid:18690162", "pmid:22495074", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "https://vespassassina.github.io/peptide-wiki/peptides/tesamorelin.html", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=tesamorelin", "https://www.elitefitness.com/forum/threads/tesamorelin-proper-dosage-for-fat-dude.1512747/" ] }, "peptide:cjc-1295": { "id": "peptide:cjc-1295", "path": "/peptides/cjc-1295.html", "title": "CJC-1295 / Mod-GRF (1-29)", "summary": "A modified GHRH analog for boosting growth hormone release, almost always stacked with a GHRP like Ipamorelin. The 'without DAC' version (Mod-GRF) sees far more use than the long-acting DAC version.", "aliases": [ "Mod-GRF (1-29)", "CJC-1295 without DAC", "CJC-1295 with DAC", "CJC-1295 (no DAC)" ], "kind": "peptide", "categories": [ "fitness-muscle" ], "legacy": { "name": "CJC-1295 / Mod-GRF (1-29)", "full_name": "Modified Growth Hormone Releasing Factor (1-29), with or without Drug Affinity Complex (DAC)", "aliases": [ "Mod-GRF (1-29)", "CJC-1295 without DAC", "CJC-1295 with DAC" ], "categories": [ "fitness-muscle" ], "tagline": "A modified GHRH analog for boosting growth hormone release, almost always stacked with a GHRP like Ipamorelin. The 'without DAC' version (Mod-GRF) sees far more use than the long-acting DAC version.", "status": "Research chemical, not FDA-approved for any indication. GHRH analogs as a class have approved relatives (e.g. tesamorelin) but CJC-1295/Mod-GRF specifically has not gone through human drug trials.", "origin": "A synthetically modified fragment of growth hormone releasing hormone (GHRH). The DAC version has a Drug Affinity Complex attached that binds serum albumin, extending half-life from minutes to roughly a week. The far more commonly used version without DAC, technically Mod-GRF 1-29, behaves like a short-acting GHRH lasting about 30 minutes, which better suits the pulsatile dosing pattern users are trying to replicate.", "mechanism": "GHRH analogs increase the number and sensitivity of pituitary cells that respond to a co-administered GHRP like Ipamorelin, amplifying the GH pulse those compounds produce. The two classes are meant to be used together, not alone, since they act on complementary parts of the GH release pathway.", "research_summary": "Human data is limited mostly to older, small pharmacokinetic and pharmacodynamic studies of the underlying GHRH(1-29) sequence, not dedicated trials of the modified compounds sold today. The DAC-bearing long-acting version has drawn more safety concern in self-experimentation circles: prolonged, less-controllable elevation of GH/IGF-1 and a higher rate of reported adverse reactions than the short-acting Mod-GRF version. Most experienced users and harm-reduction guides now favor Mod-GRF over CJC-1295 with DAC.", "reported_benefits": [ "Improved sleep quality (commonly reported, consistent with GH's normal role in sleep architecture)", "Modest reported improvements in recovery and body composition when combined with a GHRP and resistance training", "Considered a cost-effective way to amplify the GH pulse from a GHRP like Ipamorelin rather than a strong standalone compound" ], "dosing_protocols": [ { "route": "Subcutaneous injection (Mod-GRF, without DAC) — the generally preferred version", "protocol": "Commonly cited compounding-pharmacy protocol: 200 mcg once daily, 5x/week, paired with a GHRP. Many experienced self-experimenters use notably lower doses — around 100 mcg or less — arguing that higher doses increase GH only marginally further while adding cost and side-effect risk. Nobody in harm-reduction-focused communities recommends exceeding 100 mcg per injection." }, { "route": "Timing", "protocol": "Standard advice is to inject in a fasted state (2-3 hours after eating, avoiding food for 30 minutes after), commonly before bed and/or immediately on waking, to align with the body's natural pulsatile GH release windows and avoid insulin blunting the GH pulse." } ], "side_effects": [ "Flushing, hot skin, itchiness reported especially at higher doses — treated by cautious users as an early warning sign to reduce dose, not a benign sign of 'working'", "Heart palpitations reported at higher doses — a stop-and-reassess signal", "Water retention / mild edema, joint discomfort — general GH-axis class effects", "The DAC (long-acting) version specifically has more reports of allergic-type reactions in self-experimentation communities than Mod-GRF" ], "safety_notes": "Since no dedicated human trials of these modified compounds exist, dosing is community convention, not established pharmacology. The harm-reduction-minded corner of the community has shifted toward lower doses and the shorter-acting Mod-GRF version, based on accumulated adverse-reaction reports at higher doses and with the DAC version.", "community_notes": "Almost always discussed and used paired with Ipamorelin or another GHRP, rather than alone. Widely seen as one of the 'gateway' GH-secretagogue combos, and a frequent subject of debate over optimal (generally lower-than-marketed) dosing.", "related": [ "ipamorelin", "sermorelin", "mk-677", "tesamorelin" ], "variant_note": "Not to be confused with 'CJC-1295 with DAC' (see the separate page for that long-acting, albumin-binding variant) — the two are pharmacokinetically distinct compounds with different half-lives and dosing frequency, despite the similar name.", "citations": [ { "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults", "authors_year": "Teichman et al. 2006", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/16352683/" }, { "title": "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog", "authors_year": "Ionescu and Frohman 2006", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/17018654/" }, { "title": "A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review", "authors_year": "Coutinho et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41880199/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "epithalon", "ghk-cu", "ghrp-6", "hexarelin", "ipamorelin", "mgf", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "igf-1-lr3" ], "reported_avoid": [ "aod-9604", "ara-290", "hgh-somatropin", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:cjc-1295", "title": "CJC-1295 (no DAC)", "summary": "GHRH analogue studied for amplifying GH pulses. The no-DAC form is short acting and dosed daily.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "CJC-1295 without DAC (Mod-GRF 1-29) is a modified GHRH fragment, sold as a research chemical and not approved for any use. Human data is mostly older, small studies of the underlying GHRH sequence rather than the compounds sold today. Two linked studies in healthy adults showed the long-acting DAC version raised growth hormone and IGF-1 while pulsatile release continued. The wiki notes the DAC version draws more safety concern in self-experimentation circles than the short-acting form. A critical review covers peptide use in sport and bodybuilding.", "verdict": { "benefits": [ "In healthy adults the long-acting DAC version raised growth hormone and IGF-1, with pulsing preserved.", "No serious adverse reactions were reported in those small studies." ], "risks": [ "Not approved for any use and sold as a research chemical.", "Human data is older and small, and covers the DAC version, not the compound sold today.", "The wiki notes the DAC version draws more safety concern in self-experimentation circles." ], "bottomLine": "CJC-1295 is an unapproved research chemical whose hormone data comes from small studies of another version." }, "originalLinks": [ { "title": "PubMed: CJC-1295", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=CJC-1295" } ], "links": [ { "title": "Peptide Wiki: CJC-1295 (no DAC)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/cjc-1295.html" }, { "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults (Teichman et al. 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/" }, { "title": "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog (Ionescu 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/17018654/" }, { "title": "A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review (Coutinho et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41880199/" } ], "protocols": [ { "population": "healthy adults aged 21-61 in two randomised, placebo-controlled, double-blind ascending-dose trials", "regimen": "CJC-1295 subcutaneously: four ascending single doses in the first trial, then two or three weekly or biweekly doses in the second; 30 or 60 microg/kg best tolerated", "duration": "28 days and 49 days", "outcome": "Mean plasma GH rose 2- to 10-fold for 6 days or more and IGF-1 1.5- to 3-fold for 9-11 days; no serious adverse reactions were reported.", "source": { "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults (Teichman et al. 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-1295/protocols/0" ] }, { "population": "healthy men aged 20-40", "regimen": "one injection of CJC-1295 at 60 or 90 microg/kg, with 20-minute blood sampling over 12 overnight hours before and one week after", "duration": "single dose", "outcome": "Trough GH rose 7.5-fold, mean GH 46% and IGF-1 45%, with pulse frequency and magnitude unchanged; the two doses did not differ significantly.", "source": { "title": "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog (Ionescu 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/17018654/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-1295/protocols/1" ] } ], "community": [ { "description": "An EliteFitness forum discussion on CJC and ipamorelin stacking protocols documents users reporting 100 mcg of CJC-1295 (no DAC) administered twice daily, with forum members recommending increases to 150-200 mcg per injection, and recommendations for meal timing coordination.", "source": { "title": "CJC and ipamorelin stack for lean gains", "url": "https://www.elitefitness.com/forum/threads/cjc-and-ipamorelin-stack-for-lean-gains.1517933/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-1295/community/0" ] }, { "description": "An EliteFitness forum thread on ipamorelin and CJC-1295 combinations documents one experienced user reporting 100 mcg of each peptide administered in the morning and before sleep, with later adjustments to 150 mcg CJC and 200 mcg ipamorelin post-workout, and an alternative protocol citing 1000 mcg CJC-1295 (no DAC) on Tuesday, Thursday, and Saturday combined with 100 mcg ipamorelin three times daily.", "source": { "title": "Ipamorelin and CJC 1295", "url": "https://www.elitefitness.com/forum/threads/ipamorelin-and-cjc-1295.739383/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-1295/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:cjc-1295/community/0", "url": "https://www.elitefitness.com/forum/threads/cjc-and-ipamorelin-stack-for-lean-gains.1517933/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:cjc-1295/community/1", "url": "https://www.elitefitness.com/forum/threads/ipamorelin-and-cjc-1295.739383/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.5, "source": "Mod GRF 1-29, no DAC" } } ], "related": [ "peptide:ipamorelin", "peptide:mk-677", "peptide:sermorelin", "peptide:tesamorelin" ], "conflicts": [ { "status": "unresolved", "origins": [ "peptides.json#/cjc-1295/full_name", "peptides.json#/cjc-1295/variant_note", "audit/catalogue-authored.json#catalog:peptide:cjc-1295" ], "text": "The legacy full name/aliases mention both DAC and no-DAC, while its variant note and imported catalogue identity identify no-DAC. The no-DAC research is attached here; the long-acting DAC variant keeps its separate page. Original wording is preserved, not treated as equivalence." } ], "sourceRefs": [ "pmid:16352683", "pmid:17018654", "pmid:41880199", "https://vespassassina.github.io/peptide-wiki/peptides/cjc-1295.html", "https://pubmed.ncbi.nlm.nih.gov/?term=CJC-1295", "https://www.elitefitness.com/forum/threads/cjc-and-ipamorelin-stack-for-lean-gains.1517933/", "https://www.elitefitness.com/forum/threads/ipamorelin-and-cjc-1295.739383/" ] }, "peptide:ipamorelin": { "id": "peptide:ipamorelin", "path": "/peptides/ipamorelin.html", "title": "Ipamorelin", "summary": "One of the most selective growth hormone secretagogues available. It stimulates GH release without the cortisol, prolactin or appetite spikes of older GHRPs, and is almost always paired with a GHRH analog like CJC-1295/Mod-GRF.", "aliases": [ "NNC 26-0161" ], "kind": "peptide", "categories": [ "fitness-muscle" ], "legacy": { "name": "Ipamorelin", "full_name": "Ipamorelin (a Growth Hormone Releasing Peptide / GHRP)", "aliases": [ "NNC 26-0161" ], "categories": [ "fitness-muscle" ], "tagline": "One of the most selective growth hormone secretagogues available. It stimulates GH release without the cortisol, prolactin or appetite spikes of older GHRPs, and is almost always paired with a GHRH analog like CJC-1295/Mod-GRF.", "status": "Research chemical, not FDA-approved for any indication.", "origin": "A pentapeptide developed in the 1990s specifically to be a more selective ghrelin-receptor agonist than earlier growth hormone releasing peptides like GHRP-6 or Hexarelin.", "mechanism": "Binds the ghrelin/growth hormone secretagogue receptor in the pituitary, triggering release of stored growth hormone. Its selectivity means it does this without meaningfully raising ACTH, cortisol, prolactin, or other pituitary hormones that earlier-generation GHRPs also stimulate, the main reason it largely replaced GHRP-6 and GHRP-2 in self-experimentation use.", "research_summary": "Preclinical and early pharmacology studies established its GH-releasing selectivity and potency relative to older GHRPs, but like CJC-1295, no large-scale modern human efficacy trial exists for the doses and chronic use patterns common in self-experimentation. The broader GH-axis literature (physiological GH pulses, collagen synthesis, body composition) is used to infer likely effects, but this is extrapolation, not direct trial evidence for Ipamorelin at self-administered doses.", "reported_benefits": [ "Improved sleep depth/quality, widely reported and consistent with GH's normal physiological role in sleep", "Improved recovery from training", "Modest reported improvements in body composition (more fat loss, better muscle retention) over months of consistent use combined with training", "Considered gentler / fewer side effects than older GHRPs like GHRP-6, notably without the strong hunger-stimulating effect GHRP-6 is known for" ], "dosing_protocols": [ { "route": "Subcutaneous injection, paired with a GHRH analog", "protocol": "A commonly cited compounding-pharmacy protocol is 200 mcg once daily, 5x/week, paired with Mod-GRF/CJC-1295. Some self-experimenters use up to 200-300 mcg, up to 3x/day spaced 4+ hours apart. A more conservative, cost-effective approach favored by parts of the harm-reduction community caps doses around 100-125 mcg, arguing that higher doses increase GH release only marginally further." }, { "route": "Timing", "protocol": "Same fasted-state, pre-bed and/or on-waking timing logic as CJC-1295/Mod-GRF — insulin can blunt the GH pulse, so injecting away from meals is standard advice." } ], "side_effects": [ "Allergic-type reactions have been anecdotally reported, though generally considered rare and more associated with high doses or with the co-administered GHRH", "Mild injection-site reactions", "Water retention / mild joint discomfort possible as part of the general GH-axis effect", "Users are advised to start at a low dose specifically to screen for individual reaction sensitivity before committing to a regular protocol" ], "safety_notes": "Considered one of the gentler GH secretagogues by the self-experimentation community, but gentler than GHRP-6 is a relative, community-derived judgment, not a conclusion from controlled human trials. As with CJC-1295, start low and watch for flushing, itching or palpitations as a signal to reduce dose.", "community_notes": "The default GHRP choice in most modern GH-secretagogue stacks, almost always paired with CJC-1295/Mod-GRF. Sleep quality improvement is the most consistently and confidently reported effect, more so than body-composition change, which users describe as modest and cumulative over months.", "related": [ "cjc-1295", "sermorelin", "mk-677", "bpc-157" ], "citations": [ { "title": "Ipamorelin, the first selective growth hormone secretagogue", "authors_year": "Raun et al. 1998", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" }, { "title": "Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus", "authors_year": "Venkova et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19289567/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:ipamorelin", "title": "Ipamorelin", "summary": "Growth hormone secretagogue studied for GH release. Selective, with little effect on cortisol or prolactin.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "Ipamorelin is a research chemical, not approved anywhere. The linked evidence is preclinical: the 1998 pharmacology paper showed selective growth hormone release in rat pituitary cells, anaesthetised rats and pigs without raising cortisol or prolactin, and a later study tested it in a rodent model of postoperative ileus. No modern human efficacy trial exists for the patterns of use common in self-experimentation. Claims about body composition or recovery are extrapolated from the wider growth hormone literature, not measured for this compound.", "verdict": { "benefits": [ "Only shown in animals: selective growth hormone release without raising cortisol or prolactin" ], "risks": [ "A research chemical, approved nowhere, with no modern human efficacy trial", "Body composition and recovery claims come from the wider growth hormone literature, not from this compound", "No human evidence of benefit in the sources here" ], "bottomLine": "Ipamorelin's evidence is preclinical; no human trial supports the uses it is sold for, and it is approved nowhere." }, "originalLinks": [ { "title": "PubMed: ipamorelin", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=ipamorelin" } ], "links": [ { "title": "Peptide Wiki: Ipamorelin", "url": "https://vespassassina.github.io/peptide-wiki/peptides/ipamorelin.html" }, { "title": "Ipamorelin, the first selective growth hormone secretagogue (Raun et al. 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" }, { "title": "Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus (Venkova et al. 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19289567/" } ], "protocols": [ { "population": "Primary rat pituitary cells, pentobarbital-anaesthetised rats and conscious swine", "regimen": "Single doses of ipamorelin; ED50 80 nmol/kg in anaesthetised rats and 2.3 nmol/kg in swine, against GHRP-6 and GHRP-2", "duration": "Single dose", "outcome": "Released growth hormone as potently as GHRP-6 without raising ACTH, cortisol, FSH, LH, prolactin or TSH, even 200-fold above the ED50.", "source": { "title": "Ipamorelin, the first selective growth hormone secretagogue (Raun et al. 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" }, "origins": [ "evidence.json#/catalog:peptide:ipamorelin/protocols/0" ] }, { "population": "Fasted male rats after laparotomy and intestinal manipulation, a model of postoperative ileus", "regimen": "Intravenous ipamorelin 0.01-1 mg/kg, either a single bolus or four doses a day at 3-hour intervals", "duration": "2 days of repeat dosing, monitored for 48 hours", "outcome": "A single 1 mg/kg dose shortened time to first bowel movement but did not change faecal output, food intake or weight; repeat dosing raised all three.", "source": { "title": "Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus (Venkova et al. 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19289567/" }, "origins": [ "evidence.json#/catalog:peptide:ipamorelin/protocols/1" ] } ], "community": [ { "description": "Swolverine's ipamorelin dosage guide documents beginner protocols at 100-150 mcg once daily before sleep, standard protocols at 200-300 mcg per day split into morning and evening injections 6-8 hours apart, and advanced protocols up to 400 mcg per day divided into two doses, with recommended cycle lengths of 8-16 weeks.", "source": { "title": "Ipamorelin Dosage Guide: Optimal Protocols for Recovery and Muscle Growth", "url": "https://swolverine.com/blogs/blog/ipamorelin-dosage-guide-optimal-protocols-for-recovery-and-muscle-growth" }, "origins": [ "evidence.json#/catalog:peptide:ipamorelin/community/0" ] }, { "description": "An EliteFitness forum thread on CJC and ipamorelin stacking documents a user protocol of 100 mcg of each peptide administered both morning and before sleep, adjusted to 150 mcg CJC with 200 mcg ipamorelin post-workout, with multiple forum members confirming effectiveness at 150-200 mcg of each per day.", "source": { "title": "CJC and ipamorelin stack for lean gains", "url": "https://www.elitefitness.com/forum/threads/cjc-and-ipamorelin-stack-for-lean-gains.1517933/" }, "origins": [ "evidence.json#/catalog:peptide:ipamorelin/community/1" ] }, { "description": "An EliteFitness forum discussion on ipamorelin and CJC-1295 combinations documents a user starting with 100 mcg of each peptide in morning and before-bed injections, with adjustments to 150 mcg CJC and 200 mcg ipamorelin post-workout, and an alternative protocol of 1000 mcg CJC three times weekly (Tuesday, Thursday, Saturday) combined with 100 mcg ipamorelin three times daily.", "source": { "title": "Ipamorelin and CJC 1295", "url": "https://www.elitefitness.com/forum/threads/ipamorelin-and-cjc-1295.739383/" }, "origins": [ "evidence.json#/catalog:peptide:ipamorelin/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:ipamorelin/community/0", "url": "https://swolverine.com/blogs/blog/ipamorelin-dosage-guide-optimal-protocols-for-recovery-and-muscle-growth", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:ipamorelin/community/1", "url": "https://www.elitefitness.com/forum/threads/cjc-and-ipamorelin-stack-for-lean-gains.1517933/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:ipamorelin/community/2", "url": "https://www.elitefitness.com/forum/threads/ipamorelin-and-cjc-1295.739383/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 2, "source": "Ghrelin receptor agonist PK" } } ], "related": [ "peptide:bpc-157", "peptide:cjc-1295", "peptide:mk-677", "peptide:sermorelin" ], "conflicts": [], "sourceRefs": [ "pmid:9849822", "pmid:19289567", "https://vespassassina.github.io/peptide-wiki/peptides/ipamorelin.html", "https://pubmed.ncbi.nlm.nih.gov/?term=ipamorelin", "https://swolverine.com/blogs/blog/ipamorelin-dosage-guide-optimal-protocols-for-recovery-and-muscle-growth", "https://www.elitefitness.com/forum/threads/cjc-and-ipamorelin-stack-for-lean-gains.1517933/", "https://www.elitefitness.com/forum/threads/ipamorelin-and-cjc-1295.739383/" ] }, "peptide:sermorelin": { "id": "peptide:sermorelin", "path": "/peptides/sermorelin.html", "title": "Sermorelin", "summary": "The original, FDA-approved GHRH analog (its approved brand was later discontinued), the natural-sequence precursor that CJC-1295/Mod-GRF are modified versions of.", "aliases": [ "GRF 1-29", "Geref (discontinued brand)" ], "kind": "peptide", "categories": [ "fitness-muscle" ], "legacy": { "name": "Sermorelin", "full_name": "Sermorelin (GHRH 1-29, the natural-sequence growth hormone releasing hormone fragment)", "aliases": [ "GRF 1-29", "Geref (discontinued brand)" ], "categories": [ "fitness-muscle" ], "tagline": "The original, FDA-approved GHRH analog (its approved brand was later discontinued), the natural-sequence precursor that CJC-1295/Mod-GRF are modified versions of.", "status": "Was FDA-approved (as Geref) for diagnostic testing of growth hormone deficiency and as a treatment for GH deficiency in children; the branded product was discontinued for commercial reasons, not safety. Now mainly available through compounding pharmacies (often prescribed off-label by anti-aging/hormone clinics) or research-chemical vendors.", "origin": "The first 29 amino acids of the naturally occurring 44-amino-acid GHRH molecule, the shortest fragment found to retain full GH-releasing activity.", "mechanism": "Same mechanism as the modified GHRH analogs: binds GHRH receptors in the pituitary, stimulating release of stored growth hormone in a pulsatile, physiological pattern. Preserves the body's natural negative-feedback regulation, unlike direct HGH injection.", "research_summary": "Because it held actual FDA approval, sermorelin has more legitimate human clinical trial history behind it than most GH secretagogues discussed in self-experimentation circles, including diagnostic pharmacokinetic data and pediatric GH-deficiency treatment trials. Its short half-life, a few minutes, versus modified analogs like CJC-1295 with DAC, is generally seen as an advantage for preserving physiological pulsatility, not a downside.", "reported_benefits": [ "Improved sleep quality", "Used in anti-aging/hormone-optimization clinics specifically for adults with low-normal IGF-1 as a 'gentler' alternative to direct HGH therapy", "Considered by some clinicians a reasonable starting point for GH-axis support given its approval history, even though current off-label use for aging/body composition isn't itself trial-validated" ], "dosing_protocols": [ { "route": "Subcutaneous injection, nightly", "protocol": "A commonly used clinical/off-label dose is 200-300 mcg injected subcutaneously at bedtime, daily, aiming to align with the largest natural nighttime GH pulse." } ], "side_effects": [ "Injection-site reactions", "Flushing, headache reported in some users, generally at higher doses", "Same general GH-axis caveats as other secretagogues: fluid retention, joint discomfort possible with sustained elevated GH/IGF-1" ], "safety_notes": "Among the more reassuring GH secretagogues given its genuine (if now discontinued as a branded product) FDA approval history. Current off-label adult use for body composition/anti-aging isn't the indication that approval was based on.", "community_notes": "Often recommended by hormone-optimization clinics as a first step before GHRP combinations. Some in self-experimentation communities view it as 'safer by reputation' than compounds that never went through any approval process, even though day-to-day self-administered use isn't itself clinically validated.", "related": [ "cjc-1295", "ipamorelin", "mk-677" ], "citations": [ { "title": "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency", "authors_year": "Prakash and Goa 1999", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18031173/" }, { "title": "Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration", "authors_year": "Wilton et al. 1993", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/8329825/" }, { "title": "The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals", "authors_year": "Achermann et al. 1999", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/10594518/" } ] }, "research": [ { "id": "catalog:peptide:sermorelin", "title": "Sermorelin", "summary": "GHRH analogue studied for stimulating endogenous growth hormone release.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Sermorelin is a fragment of natural growth hormone releasing hormone. The owner's wiki records that it once held FDA approval as Geref for diagnosing and treating growth hormone deficiency in children, and that the branded product was withdrawn for commercial reasons rather than safety; it is now mainly compounded. A review describes it as a rapid and fairly specific test for growth hormone deficiency, with limited data supporting treatment of children with idiopathic deficiency. A study in 30 healthy men showed it released growth hormone by both intravenous and intranasal routes, with low nasal absorption. No linked trial covers adult body composition or anti-ageing use.", "verdict": { "benefits": [ "Once FDA-approved as Geref for diagnosing and treating growth hormone deficiency in children.", "A review calls it a rapid, fairly specific test, with fewer false positives than other tests.", "In healthy men it released growth hormone by both intravenous and intranasal routes." ], "risks": [ "The branded product was withdrawn for commercial reasons; it is now mainly compounded.", "Growth gains in children were smaller than with somatropin, and treatment data are limited.", "No linked trial covers adult body composition or anti-ageing use." ], "bottomLine": "Sermorelin has evidence as a growth hormone deficiency test in children and none for adult anti-ageing use." }, "originalLinks": [ { "title": "PubMed: sermorelin", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=sermorelin" } ], "links": [ { "title": "Peptide Wiki: Sermorelin (GHRH 1-29, the natural-sequence growth hormone releasing hormone fragment)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/sermorelin.html" }, { "title": "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency (Prakash 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/18031173/" }, { "title": "Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration (Wilton et al. 1993)", "url": "https://pubmed.ncbi.nlm.nih.gov/8329825/" }, { "title": "The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals (Achermann et al. 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10594518/" } ], "protocols": [ { "population": "children assessed for growth hormone deficiency, per the review", "regimen": "sermorelin 1 µg/kg bodyweight intravenously as a provocative test, alongside conventional tests", "duration": "single dose", "outcome": "The review reports it as a rapid, relatively specific test with fewer false positives than other provocative tests, but a normal response cannot exclude a hypothalamic deficit.", "source": { "title": "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency (Prakash 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/18031173/" }, "origins": [ "evidence.json#/catalog:peptide:sermorelin/protocols/0" ] }, { "population": "prepubertal children with idiopathic growth hormone deficiency, per the review", "regimen": "sermorelin 30 µg/kg bodyweight subcutaneously once daily at bedtime", "duration": "12 months, with data in a few children out to 36 months", "outcome": "Height velocity rose and most children showed catch-up growth, but gains were smaller than with once-daily somatropin at the same microgram dose.", "source": { "title": "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency (Prakash 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/18031173/" }, "origins": [ "evidence.json#/catalog:peptide:sermorelin/protocols/1" ] }, { "population": "30 healthy men aged 19-43", "regimen": "GHRH(1-29)-NH2 given intravenously at 0.25 to 2 µg/kg, or intranasally at up to about 50 µg/kg including three doses in one day", "duration": "single doses, with one repeated-dosing day", "outcome": "Maximal growth hormone release came from 1-2 µg/kg intravenously; nasal bioavailability was only 3-5% and overnight secretion was not suppressed.", "source": { "title": "Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration (Wilton et al. 1993)", "url": "https://pubmed.ncbi.nlm.nih.gov/8329825/" }, "origins": [ "evidence.json#/catalog:peptide:sermorelin/protocols/2" ] }, { "population": "12 adult male long-term survivors of childhood brain tumours and 9 matched control volunteers", "regimen": "continuous subcutaneous GHRH(1-29)NH2 at 60 ng/kg/min for 24 h, with intermittent intravenous somatostatin(1-14) at 20 µg/m²/h, 3 h on and 1 h off", "duration": "24-hour infusion plus 8-12 hour clamp cycles", "outcome": "In controls GHRH raised peak GH from 21.1 to 62.0 mU/l; in irradiated survivors GH release stayed far below control levels.", "source": { "title": "The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals (Achermann et al. 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10594518/" }, "origins": [ "evidence.json#/catalog:peptide:sermorelin/protocols/3" ] } ], "community": [ { "description": "Sermorelin dosing guides and healthcare resources consistently document a protocol of 0.2-0.3 mg (200-300 mcg) administered once nightly by subcutaneous injection, approximately 30-60 minutes before bedtime.", "source": { "title": "CJC-1295 & Sermorelin: Complete Dosing, Administration & Safety Guide", "url": "https://cjc-1295.com/article/cjc-1295-sermorelin-dosing-administration-safety" }, "origins": [ "evidence.json#/catalog:peptide:sermorelin/community/0" ] }, { "description": "Sermorelin dosing protocols for anti-aging and general growth hormone support describe 0.2-0.3 mg administered daily, typically 30 minutes before bedtime on an empty stomach.", "source": { "title": "Sermorelin Dosing Guide: Nightly GHRH Protocol (2026)", "url": "https://www.peptidedosingprotocols.com/protocol/sermorelin" }, "origins": [ "evidence.json#/catalog:peptide:sermorelin/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:sermorelin/community/0", "url": "https://cjc-1295.com/article/cjc-1295-sermorelin-dosing-administration-safety", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:sermorelin/community/1", "url": "https://www.peptidedosingprotocols.com/protocol/sermorelin", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.2, "source": "GHRH 1-29 PK" } } ], "related": [ "peptide:cjc-1295", "peptide:ipamorelin", "peptide:mk-677" ], "conflicts": [], "sourceRefs": [ "pmid:18031173", "pmid:8329825", "pmid:10594518", "https://vespassassina.github.io/peptide-wiki/peptides/sermorelin.html", "https://pubmed.ncbi.nlm.nih.gov/?term=sermorelin", "https://cjc-1295.com/article/cjc-1295-sermorelin-dosing-administration-safety", "https://www.peptidedosingprotocols.com/protocol/sermorelin" ] }, "peptide:mk-677": { "id": "peptide:mk-677", "path": "/peptides/mk-677.html", "title": "MK-677 (Ibutamoren)", "summary": "Orally active ghrelin mimetic that raises growth hormone and IGF-1 without injections. Not actually a peptide, but a fixture of GH-secretagogue discussions.", "aliases": [ "Ibutamoren", "Ibutamoren Mesylate", "Nutrobal" ], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "legacy": { "name": "MK-677 (Ibutamoren)", "full_name": "Ibutamoren (not a peptide — an orally active small-molecule ghrelin receptor agonist, included here because it's routinely grouped with GH-secretagogue peptides)", "aliases": [ "Ibutamoren", "Ibutamoren Mesylate", "Nutrobal" ], "categories": [ "fitness-muscle" ], "tagline": "Orally active ghrelin mimetic that raises growth hormone and IGF-1 without injections. Not actually a peptide, but a fixture of GH-secretagogue discussions.", "status": "Was investigated by pharmaceutical companies (Merck and others) for GH deficiency, sarcopenia and hip fracture recovery in the elderly, but never received FDA approval for any indication and development was discontinued. Sold today only as a research chemical/grey-market product.", "origin": "A small synthetic molecule, not a peptide, developed as an orally bioavailable ghrelin receptor agonist. The appeal: a daily pill instead of daily injections for GH-axis stimulation.", "mechanism": "Activates the same ghrelin/GH secretagogue receptor as injectable GHRPs like Ipamorelin, but produces a sustained GH/IGF-1 elevation over roughly 12-24 hours per dose instead of the sharper, shorter pulse from injectables. Because it mimics ghrelin, the hunger hormone, it reliably increases appetite — a plus for some users, a problem for others.", "research_summary": "Human trial data is more substantial than for most research peptides. Studies in the elderly showed increased lean body mass and improved some muscle function markers, with the clearest benefit in people who actually had low GH to begin with — a caveat for younger, GH-replete users expecting the same results. A hip fracture trial was stopped early over safety concerns: increased congestive heart failure and edema in the treatment group. That trial is a big part of why it never reached approval.", "reported_benefits": [ "Increased appetite (often deliberately used for this reason during muscle-gain phases)", "Improved sleep quality, commonly and consistently reported", "Reported improvements in skin, hair and nail quality with extended use, attributed to sustained IGF-1 elevation", "Reported strength/recovery benefits, more consistently in older or lower-baseline-GH individuals per the available trial data" ], "dosing_protocols": [ { "route": "Oral, once daily", "protocol": "Commonly cited doses range from 10-25 mg once daily, typically taken at night given its sedating/sleep-promoting effect and to align with nighttime GH release; many self-experimenters start at the lower end (10 mg) to assess tolerance, particularly for blood-sugar and water-retention effects before increasing." } ], "side_effects": [ "Increased appetite/hunger — often significant and sometimes unwanted", "Water retention, mild edema, especially in the hands/feet/face — a known dose-related effect", "Elevated blood glucose / reduced insulin sensitivity reported with sustained use — worth monitoring, especially for anyone with pre-diabetes", "The hip-fracture trial safety signal (increased heart failure/edema rates) is a genuine red flag, particularly for anyone with existing cardiovascular disease", "Lethargy or grogginess reported by some users the morning after dosing" ], "safety_notes": "MK-677 has real human efficacy data, unusual for this class, but the same trial history includes a safety signal serious enough to halt a study: increased heart failure and edema in hip fracture patients. That's one of the most clearly documented risk signals in this wiki, especially relevant for anyone with existing cardiovascular risk factors.", "community_notes": "Popular because it's oral, no injections, and reliably improves sleep and appetite, which appeals to people trying to gain muscle. Water retention and blood sugar effects get discussed often. The community generally knows about the cardiovascular signal from the discontinued hip-fracture trial, though not everyone treats it with real caution.", "related": [ "ipamorelin", "cjc-1295", "igf-1-lr3" ], "citations": [ { "title": "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial", "authors_year": "Nass et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18981485/" }, { "title": "Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects", "authors_year": "Chapman et al. 1996", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/8954023/" }, { "title": "Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure", "authors_year": "Svensson et al. 1998", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/9467542/" } ] }, "research": [ { "id": "catalog:hormone:mk-677", "title": "MK-677 (Ibutamoren)", "summary": "A growth hormone secretagogue that was investigated for various conditions but never received FDA approval.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "MK-677 (Ibutamoren) is a non-peptidic, orally active growth hormone secretagogue developed at Merck. It mimics ghrelin action, stimulating growth hormone and IGF-1 secretion. Originally developed for growth hormone deficiency and muscle-wasting conditions. A trial showed MK-677 was ineffective in slowing Alzheimer disease progression despite target engagement as shown by IGF-1 increases.", "verdict": { "benefits": [ "Stimulates GH and IGF-1 secretion", "Reverses diet-induced catabolism in short-term studies" ], "risks": [ "Failed to slow Alzheimer disease progression", "Potential metabolic side effects from chronic GH elevation", "Long-term safety data limited" ], "bottomLine": "Preclinical and early-stage research only; not FDA-approved despite development for multiple conditions.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "MK-677 Metabolism in Human Urine - Journal of Analytical Chemistry", "url": "https://link.springer.com/article/10.1134/S1061934824020072" }, { "title": "MK-677 in Alzheimer Disease - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/19015485/" }, { "title": "Effects of Oral GH Secretagogue on Body Composition - ClinicalTrials.gov", "url": "https://clinicaltrials.gov/study/NCT00474279" } ], "links": [ { "title": "MK-677 Metabolism in Human Urine - Journal of Analytical Chemistry", "url": "https://link.springer.com/article/10.1134/S1061934824020072" }, { "title": "MK-677 in Alzheimer Disease - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/19015485/" }, { "title": "Effects of Oral GH Secretagogue on Body Composition - ClinicalTrials.gov", "url": "https://clinicaltrials.gov/study/NCT00474279" } ], "protocols": [ { "population": "Older adults with age-related muscle weakness", "regimen": "Oral ghrelin receptor agonist", "duration": "Trials varied", "outcome": "Reversal of diet-induced nitrogen wasting; studies on body composition and functional ability in older adults conducted", "source": { "title": "Effects of Oral GH Secretagogue on Body Composition - ClinicalTrials.gov", "url": "https://clinicaltrials.gov/study/NCT00474279" }, "origins": [ "evidence.json#/catalog:hormone:mk-677/protocols/0" ] } ], "community": [ { "description": "A standard protocol from Path To Peptides reports 25 mg taken before bed once daily for 8-12+ weeks as a commonly discussed dosing pattern.", "source": { "title": "MK-677 Protocol Guide", "url": "https://www.pathtopeptides.com/mk-677-protocol.html" }, "origins": [ "evidence.json#/catalog:hormone:mk-677/community/0" ] }, { "description": "A conservative approach documented on Path To Peptides describes 10-15 mg daily taken before bed for 1-8 weeks.", "source": { "title": "MK-677 Protocol Guide", "url": "https://www.pathtopeptides.com/mk-677-protocol.html" }, "origins": [ "evidence.json#/catalog:hormone:mk-677/community/1" ] }, { "description": "A lower-dose extended protocol from Path To Peptides involves 10 mg daily taken before bed for up to 24 weeks.", "source": { "title": "MK-677 Protocol Guide", "url": "https://www.pathtopeptides.com/mk-677-protocol.html" }, "origins": [ "evidence.json#/catalog:hormone:mk-677/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:mk-677/community/0", "url": "https://www.pathtopeptides.com/mk-677-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:mk-677/community/1", "url": "https://www.pathtopeptides.com/mk-677-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:mk-677/community/2", "url": "https://www.pathtopeptides.com/mk-677-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 5, "lowerHours": 4, "source": "Chapman et al. 1996, J Clin Endocrinol Metab 81(12):4249-4257, PMID 8954023; Copinschi et al. 1996, J Clin Endocrinol Metab 81(8):2776-2782, PMID 8768828 — human clinical PK trials", "upperHours": 6 } } ], "related": [ "peptide:cjc-1295", "peptide:igf-1-lr3", "peptide:ipamorelin" ], "conflicts": [], "sourceRefs": [ "pmid:18981485", "pmid:8954023", "pmid:9467542", "https://link.springer.com/article/10.1134/S1061934824020072", "pmid:19015485", "https://clinicaltrials.gov/study/NCT00474279", "https://www.pathtopeptides.com/mk-677-protocol.html" ] }, "peptide:igf-1-lr3": { "id": "peptide:igf-1-lr3", "path": "/peptides/igf-1-lr3.html", "title": "IGF-1 LR3", "summary": "A modified, long-acting version of IGF-1, the growth factor downstream of growth hormone that directly drives muscle cell proliferation. Used in bodybuilding circles for localized and systemic muscle growth.", "aliases": [ "IGF-1 LR3", "Long R3 IGF-1" ], "kind": "peptide", "categories": [ "fitness-muscle" ], "legacy": { "name": "IGF-1 LR3", "full_name": "Long R3 Insulin-like Growth Factor 1 (a modified, longer-acting analog of IGF-1)", "aliases": [ "IGF-1 LR3", "Long R3 IGF-1" ], "categories": [ "fitness-muscle" ], "tagline": "A modified, long-acting version of IGF-1, the growth factor downstream of growth hormone that directly drives muscle cell proliferation. Used in bodybuilding circles for localized and systemic muscle growth.", "status": "Research chemical, not FDA-approved for any indication. Native IGF-1 (mecasermin) is an approved drug for a rare pediatric growth-failure condition, but the modified LR3 analog discussed here has no approval of its own.", "origin": "Native IGF-1 mediates most of growth hormone's downstream tissue-building effects, but has a very short half-life (minutes) because it's rapidly bound and cleared by IGF-binding proteins. LR3 carries an amino acid substitution and an added 13-amino-acid extension that dramatically reduces binding to those clearance proteins, extending the functional half-life to many hours.", "mechanism": "Binds the IGF-1 receptor, directly stimulating satellite cell proliferation and differentiation, the process by which muscle fibers gain new nuclei and grow. Unlike GH secretagogues, which work upstream by increasing the body's own hormone release, IGF-1 LR3 works downstream, delivering the growth signal directly. Some bodybuilders inject it locally near a specific muscle group aiming for localized hypertrophy, though whether meaningful localization occurs versus rapid systemic distribution is disputed.", "research_summary": "Native IGF-1's biology is extremely well studied in growth hormone deficiency and general physiology, but the modified LR3 analog has essentially no dedicated human clinical trial data. It exists almost entirely as a bodybuilding/self-experimentation compound, not a researched pharmaceutical candidate. Unlike tesamorelin, where the underlying biology and the product in use are both studied, here the biology (IGF-1's role in muscle growth) is established but the specific product and dosing patterns are not tested in controlled human trials.", "reported_benefits": [ "Reported increases in muscle fullness/pump during use, sometimes described as more pronounced and immediate than GH secretagogues", "Interest for localized muscle growth via site-specific injection, though this specific claim is more folklore than established pharmacology", "Sometimes used short-term around intense training blocks rather than continuously" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection", "protocol": "Community-reported doses are typically very low — commonly 20-50 mcg per day — reflecting IGF-1's high potency; doses are often kept short-term (a few weeks) rather than continuous, partly due to concerns about hypoglycemia and receptor downregulation with longer use." } ], "side_effects": [ "Hypoglycemia (low blood sugar) is a well-documented risk given IGF-1's insulin-like receptor cross-activity — this is one of the more acutely dangerous side effects discussed in this wiki and requires blood glucose awareness, especially combined with fasting or low-carb dieting", "Injection site reactions, and with intramuscular use, more significant local soreness", "Theoretical organ growth (organomegaly) concern with prolonged high-dose use, extrapolated from IGF-1's known growth-promoting physiology", "Theoretical cancer-growth-promotion concern given IGF-1's role in cell proliferation signalling — a reason it's generally considered contraindicated for anyone with active or recent cancer" ], "safety_notes": "The hypoglycemia risk is real and distinct from most other compounds here: IGF-1 cross-reacts with the insulin receptor at high enough local concentrations, and self-experimenters have reported acute low-blood-sugar episodes. This is a genuinely different, more acute risk profile than the GH secretagogues it's often grouped with.", "community_notes": "Popular in bodybuilding-adjacent corners of the peptide community for its rapid, visible pump and fullness effect, generally used in short cycles rather than continuously. Discussion centers on hypoglycemia risk management, keeping fast-acting carbohydrate on hand, avoiding fasted use, more than for most other compounds here, reflecting real awareness of this specific danger.", "related": [ "mk-677", "cjc-1295", "ipamorelin" ], "citations": [ { "title": "Revolutionary decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration", "authors_year": "Yavuz et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41015370/" }, { "title": "Provisional Treatment of Volumetric Muscle Loss With Insulin-like Growth Factor 1 Releasing Muscle Void Fillers", "authors_year": "Clark et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41418663/" }, { "title": "Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs", "authors_year": "Dunshea et al. 2002", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12067429/" } ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "bpc-157", "cjc-1295" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:igf-1-lr3", "title": "IGF-1 LR3", "summary": "Long-acting IGF-1 analogue. Research chemical with no human indication; systemic growth signalling carries real risk.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "IGF-1 LR3 is a modified, longer-acting version of IGF-1. The owner's wiki records it as a research chemical with no approval of its own and essentially no dedicated human trial data; native IGF-1 is a separate approved drug for a rare paediatric condition. The linked studies are animal work: a rat nerve-repair conduit releasing IGF-1 LR3, a rat muscle-loss study where the higher amount raised muscle weight but did not improve force, and infusions in neonatal pigs that did not increase growth overall. It is used mainly in bodybuilding self-experimentation.", "verdict": { "benefits": [ "Only shown in rats: a conduit releasing IGF-1 LR3 improved nerve regeneration without systemic toxicity." ], "risks": [ "No approval of its own and essentially no dedicated human trial data.", "In rat muscle-loss work, muscle weight rose but force, fibre size and fibrosis were unchanged.", "Infusions in neonatal pigs did not raise growth overall; use is mainly self-experimentation." ], "bottomLine": "IGF-1 LR3 is an unapproved research chemical whose only evidence here is mixed animal work, with no human trials." }, "originalLinks": [ { "title": "PubMed: IGF-1 LR3", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=IGF-1+LR3" } ], "links": [ { "title": "Peptide Wiki: IGF-1 LR3", "url": "https://vespassassina.github.io/peptide-wiki/peptides/igf-1-lr3.html" }, { "title": "Revolutionary decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration (Yavuz et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41015370/" }, { "title": "Provisional Treatment of Volumetric Muscle Loss With Insulin-like Growth Factor 1 Releasing Muscle Void Fillers (Clark et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41418663/" }, { "title": "Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs (Dunshea et al. 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12067429/" } ], "protocols": [ { "population": "30 rats with a 1 cm sciatic nerve defect, in six groups of five", "regimen": "decellularized Alstroemeria stem nerve conduit with GelMA and controlled IGF-1 LR3 release, implanted at the defect, against autologous grafts and commercial conduits", "duration": "not stated", "outcome": "The IGF-1 LR3-releasing conduit improved axonal regeneration to a level comparable with autologous nerve grafts, without systemic toxicity.", "source": { "title": "Revolutionary decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration (Yavuz et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41015370/" }, "origins": [ "evidence.json#/catalog:peptide:igf-1-lr3/protocols/0" ] }, { "population": "adult male Lewis rats after volumetric muscle loss surgery", "regimen": "polyethylene glycol-acrylate muscle void filler carrying soluble or PLGA-encapsulated IGF1-LR3 at 28 µg (low) or 280 µg (high), or no IGF1-LR3", "duration": "28 days", "outcome": "High-dose encapsulated IGF1-LR3 raised muscle weight, but specific and maximum torque, fibre size, fibre count and fibrosis were unchanged.", "source": { "title": "Provisional Treatment of Volumetric Muscle Loss With Insulin-like Growth Factor 1 Releasing Muscle Void Fillers (Clark et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41418663/" }, "origins": [ "evidence.json#/catalog:peptide:igf-1-lr3/protocols/1" ] }, { "population": "42 artificially-reared neonatal pigs of about 2 kg, limit-fed milk replacer (experiment 1)", "regimen": "continuous infusion of IGF-I or LR3IGF-I at 2, 4 or 8 µg/h, against control infusion", "duration": "8 days", "outcome": "No overall effect on daily weight gain or slaughter weight; milk intake was higher with the growth factors (909 vs 867 g/d).", "source": { "title": "Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs (Dunshea et al. 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12067429/" }, "origins": [ "evidence.json#/catalog:peptide:igf-1-lr3/protocols/2" ] }, { "population": "18 artificially-reared neonatal pigs of about 2 kg, fed cows' milk ad libitum (experiment 2)", "regimen": "continuous infusion of IGF-I or LR3IGF-I at 8 µg/h for 9 days, then 16 µg/h for a further 9 days, against saline", "duration": "18 days", "outcome": "No effect in the first 9 days; over the second 9 days weight gain rose with LR3IGF-I (457 vs 386 g/d) but not with IGF-I.", "source": { "title": "Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs (Dunshea et al. 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12067429/" }, "origins": [ "evidence.json#/catalog:peptide:igf-1-lr3/protocols/3" ] } ], "community": [ { "description": "Community protocols describe starting at 20 micrograms daily via subcutaneous injection for initial tolerance assessment, with progression to 40-80 micrograms daily over subsequent cycles, using 4-6 week on periods with equal off time.", "source": { "title": "IGF-1 LR3 Peptide Dosage Guide", "url": "https://www.peptidedosingprotocols.com/protocol/igf-1-lr3" }, "origins": [ "evidence.json#/catalog:peptide:igf-1-lr3/community/0" ] }, { "description": "A community protocol guide describes typical dosing at 20-100 micrograms once daily via subcutaneous injection, with administration either post-workout with carbohydrates or with a morning meal, cycling 4-6 weeks on with minimum 4 weeks recovery.", "source": { "title": "IGF-1 LR3 Dosing and Cycle Protocol", "url": "https://peptideinitiative.com/peptides/protocols/igf-1-lr3-protocol" }, "origins": [ "evidence.json#/catalog:peptide:igf-1-lr3/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The initial live check did not establish the full staged escalation/cycling claims. Relevant terms alone do not verify a protocol. Community accounts and animal research do not establish a validated human regimen." ], "community": [ { "origin": "evidence.json#/catalog:peptide:igf-1-lr3/community/0", "url": "https://www.peptidedosingprotocols.com/protocol/igf-1-lr3", "claimMatch": "The initial live check did not establish the full staged escalation/cycling claims. Relevant terms alone do not verify a protocol. Community accounts and animal research do not establish a validated human regimen. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "partial-match-unverified" }, { "origin": "evidence.json#/catalog:peptide:igf-1-lr3/community/1", "url": "https://peptideinitiative.com/peptides/protocols/igf-1-lr3-protocol", "claimMatch": "The initial live check did not establish the full staged escalation/cycling claims. Relevant terms alone do not verify a protocol. Community accounts and animal research do not establish a validated human regimen. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "partial-match-unverified" } ] }, "pk": { "hours": 20, "source": "Reduced IGFBP binding extends clearance; preclinical" } } ], "related": [ "peptide:cjc-1295", "peptide:ipamorelin", "peptide:mk-677" ], "conflicts": [], "sourceRefs": [ "pmid:41015370", "pmid:41418663", "pmid:12067429", "https://vespassassina.github.io/peptide-wiki/peptides/igf-1-lr3.html", "https://pubmed.ncbi.nlm.nih.gov/?term=IGF-1+LR3", "https://www.peptidedosingprotocols.com/protocol/igf-1-lr3", "https://peptideinitiative.com/peptides/protocols/igf-1-lr3-protocol" ] }, "peptide:pt-141": { "id": "peptide:pt-141", "path": "/peptides/pt-141.html", "title": "PT-141 (Bremelanotide)", "summary": "A melanocortin-receptor agonist that acts on the brain's sexual-arousal pathways rather than on blood flow directly — FDA-approved as Vyleesi for hypoactive sexual desire disorder in premenopausal women, used off-label by men for erectile/libido support.", "aliases": [ "PT-141", "Vyleesi (FDA-approved brand, for women)", "PT-141 (bremelanotide)" ], "kind": "peptide", "categories": [ "sexual-health" ], "legacy": { "name": "PT-141 (Bremelanotide)", "full_name": "Bremelanotide", "aliases": [ "PT-141", "Vyleesi (FDA-approved brand, for women)" ], "categories": [ "sexual-health" ], "tagline": "A melanocortin-receptor agonist that acts on the brain's sexual-arousal pathways rather than on blood flow directly — FDA-approved as Vyleesi for hypoactive sexual desire disorder in premenopausal women, used off-label by men for erectile/libido support.", "status": "FDA-approved prescription drug (Vyleesi) for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Used off-label, including by men, and also available through the grey/research-chemical market outside a prescription.", "origin": "A synthetic analog of alpha-MSH engineered specifically for activity at melanocortin 4 receptors (MC4R) in the brain, which govern sexual arousal, distinct from the pigmentation-related MC1R pathway.", "mechanism": "Unlike PDE5 inhibitors (sildenafil, tadalafil), which work locally by increasing blood flow to genital tissue, bremelanotide acts centrally on melanocortin receptors in the neural arousal pathway. That's why it's framed as addressing 'desire' rather than mechanical erectile function, and why it treats a condition, HSDD, that PDE5 inhibitors don't touch.", "research_summary": "The RECONNECT trials that supported Vyleesi's FDA approval were conducted in premenopausal women with HSDD and showed statistically significant improvement in desire and reduction in distress versus placebo, though the effect size was modest and placebo response was meaningful too, typical for this trial category. Male sexual-function research on bremelanotide is smaller in scale, mostly from earlier-stage development, including erectile dysfunction trials before development pivoted to the female HSDD indication. It showed improved erectile response, but that's not the compound's approved use in men.", "reported_benefits": [ "Increased subjective sexual desire/arousal, the primary effect in its approved female indication", "Reported improved erectile response in men (off-label use), sometimes combined with PDE5 inhibitors for complementary mechanisms", "Effect is described by users as psychological/arousal-focused rather than purely mechanical" ], "dosing_protocols": [ { "route": "Subcutaneous injection (approved autoinjector dose)", "protocol": "The approved Vyleesi dose is 1.75 mg, self-injected at least 45 minutes before anticipated sexual activity, with a maximum of one dose per 24 hours and no more than 8 doses per month." }, { "route": "Off-label / self-sourced use (commonly lower doses than the approved autoinjector)", "protocol": "Community-reported doses are often lower than the approved 1.75 mg autoinjector dose, commonly in the 0.5-1.5 mg range, adjusted based on side-effect tolerance (particularly nausea), taken roughly an hour before activity." } ], "side_effects": [ "Nausea is the most common and often dose-limiting side effect — frequently reported and can be significant", "Flushing, headache", "Transient increase in blood pressure and decrease in heart rate observed in trials — worth caution for anyone with cardiovascular disease", "Skin/gum darkening has been reported with frequent, prolonged use, related to melanocortin receptor activity on pigmentation pathways" ], "safety_notes": "Nausea is common enough that many users experiment with the lowest effective dose instead of the full approved autoinjector amount. Blood pressure and heart rate effects warrant caution for anyone with cardiovascular conditions, and should be discussed with a physician even for off-label male use.", "community_notes": "Widely discussed as an alternative or complement to PDE5 inhibitors, specifically because it works on desire and arousal rather than blood flow. Some men report using both together for a more complete effect. Nausea management, via lower doses or timing around meals, is the most common practical topic in user communities.", "related": [ "oxytocin", "kisspeptin" ], "variant_note": "Occasionally discussed alongside PSK/other melanocortin-pathway variants sold under adjacent names; PT-141 (bremelanotide) itself is the only form with FDA approval (as Vyleesi, for HSDD in women) and the only form with real human trial data.", "citations": [ { "title": "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials", "authors_year": "Kingsberg et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31599840/" }, { "title": "Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder", "authors_year": "Simon et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31599847/" }, { "title": "Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide", "authors_year": "Althof et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31277966/" } ], "mixing_notes": { "clinic_combos": [ "ghrp-2", "kisspeptin", "pinealon", "semax" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:pt-141", "title": "PT-141 (bremelanotide)", "summary": "Melanocortin receptor agonist approved for hypoactive sexual desire disorder in premenopausal women.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "regulatory", "evidenceSummary": "Bremelanotide (PT-141) is recorded in the owner's wiki as FDA-approved, as Vyleesi, for acquired generalised hypoactive sexual desire disorder in premenopausal women. Two randomised phase 3 trials (RECONNECT) showed statistically significant improvement in desire and less distress versus placebo, with modest effect sizes and a meaningful placebo response. It acts on melanocortin receptors in brain arousal pathways, unlike PDE5 inhibitors, which act on blood flow. Nausea is the most common side effect, and trials recorded a transient rise in blood pressure with a fall in heart rate. Use in men is off-label and much less studied.", "verdict": { "benefits": [ "Vyleesi for acquired, generalised low sexual desire in premenopausal women.", "Two randomised phase 3 trials showed more desire and less distress than placebo.", "It acts on melanocortin receptors in brain arousal pathways, unlike PDE5 inhibitors." ], "risks": [ "Effect sizes were modest and the placebo response meaningful.", "Nausea, flushing and headache each affected at least one in ten; blood pressure rose transiently.", "The label excludes postmenopausal women and men; use in men is off-label and little studied." ], "bottomLine": "Bremelanotide is FDA-approved for low sexual desire in premenopausal women; benefit is modest, nausea common.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: bremelanotide", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=bremelanotide" } ], "links": [ { "title": "Vyleesi (bremelanotide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf" }, { "title": "Peptide Wiki: Bremelanotide", "url": "https://vespassassina.github.io/peptide-wiki/peptides/pt-141.html" }, { "title": "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials (Kingsberg et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31599840/" }, { "title": "Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder (Simon et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31599847/" }, { "title": "Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide (Althof et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31277966/" } ], "protocols": [ { "population": "Premenopausal women with acquired, generalised hypoactive sexual desire disorder, per the US label", "regimen": "1.75 mg subcutaneously into the abdomen or thigh at least 45 minutes before anticipated sexual activity; at most one dose in 24 hours and 8 a month", "duration": "The label says to stop after 8 weeks if symptoms have not improved", "outcome": "Approved for acquired, generalised HSDD in premenopausal women; the label states it is not for postmenopausal women, men, or improving sexual performance.", "source": { "title": "Vyleesi (bremelanotide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf" }, "origins": [ "evidence.json#/catalog:peptide:pt-141/protocols/0" ] }, { "population": "1,267 premenopausal women with hypoactive sexual desire disorder in two phase 3 trials", "regimen": "Bremelanotide 1.75 mg subcutaneously as needed, or placebo, randomised 1:1", "duration": "24 weeks", "outcome": "Desire score rose 0.30 and 0.42 over placebo and distress fell 0.37 and 0.29; nausea, flushing and headache each affected 10% or more in both studies.", "source": { "title": "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials (Kingsberg et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31599840/" }, "origins": [ "evidence.json#/catalog:peptide:pt-141/protocols/1" ] }, { "population": "684 premenopausal women continuing from the RECONNECT core phase", "regimen": "Open-label bremelanotide 1.75 mg subcutaneously as needed", "duration": "52 weeks", "outcome": "No new safety signals; nausea 40.4%, flushing 20.6%, headache 12.0%; 272 of 684 completed, and improvements in desire and distress held.", "source": { "title": "Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder (Simon et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31599847/" }, "origins": [ "evidence.json#/catalog:peptide:pt-141/protocols/2" ] }, { "population": "Premenopausal women with hypoactive sexual desire disorder, female sexual arousal disorder or both", "regimen": "Bremelanotide 1.75 mg subcutaneously against placebo, in a phase 2b dose-ranging study", "duration": "Not stated", "outcome": "Responder rates at 1.75 mg beat placebo on all seven patient-reported endpoints (p <= 0.03).", "source": { "title": "Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide (Althof et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31277966/" }, "origins": [ "evidence.json#/catalog:peptide:pt-141/protocols/3" ] } ], "community": [ { "description": "Community research protocols reference 1-2 mg (1000-2000 mcg) administered subcutaneously, typically 45-60 minutes before anticipated sexual activity.", "source": { "title": "PT-141 (bremelanotide) Dosage Guide", "url": "https://www.peptidedosingprotocols.com/protocol/bremelanotide-pt-141" }, "origins": [ "evidence.json#/catalog:peptide:pt-141/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:pt-141/community/0", "url": "https://www.peptidedosingprotocols.com/protocol/bremelanotide-pt-141", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 2.5, "lowerHours": 2, "source": "FDA label, Vyleesi", "upperHours": 3 } } ], "related": [ "peptide:kisspeptin", "peptide:oxytocin" ], "conflicts": [], "sourceRefs": [ "pmid:31599840", "pmid:31599847", "pmid:31277966", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf", "https://vespassassina.github.io/peptide-wiki/peptides/pt-141.html", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=bremelanotide", "https://www.peptidedosingprotocols.com/protocol/bremelanotide-pt-141" ] }, "peptide:oxytocin": { "id": "peptide:oxytocin", "path": "/peptides/oxytocin.html", "title": "Oxytocin", "summary": "The 'bonding hormone' — an FDA-approved drug for labor induction and postpartum hemorrhage, explored off-label for social bonding, sexual intimacy and anxiety.", "aliases": [ "Pitocin/Syntocinon (FDA-approved brands for labor/postpartum indications)" ], "kind": "medication-hormone", "categories": [ "sexual-health" ], "legacy": { "name": "Oxytocin", "full_name": "Oxytocin (a naturally occurring neuropeptide hormone)", "aliases": [ "Pitocin/Syntocinon (FDA-approved brands for labor/postpartum indications)" ], "categories": [ "sexual-health" ], "tagline": "The 'bonding hormone' — an FDA-approved drug for labor induction and postpartum hemorrhage, explored off-label for social bonding, sexual intimacy and anxiety.", "status": "FDA-approved prescription drug (as Pitocin/Syntocinon) for labor induction/augmentation and postpartum hemorrhage control. Off-label and research-chemical use for social/sexual/anxiety purposes is not an approved indication.", "origin": "A naturally occurring neuropeptide hormone produced in the hypothalamus and released by the posterior pituitary. Classically known for childbirth (uterine contractions) and lactation (milk let-down), more recently studied for social bonding, trust, and attachment.", "mechanism": "Acts on oxytocin receptors throughout the brain, especially regions involved in social cognition and reward, and peripherally on uterine smooth muscle. The 'bonding hormone' label comes from behavioral neuroscience research showing oxytocin administration increases trust, in-group bonding, eye contact, and emotional empathy in experimental settings, alongside its role in orgasm and post-intimacy bonding physiology.", "research_summary": "Intranasal oxytocin has a large academic literature on social cognition, trust, autism-spectrum social behavior, and anxiety. The field has also faced a real replication crisis: several high-profile early findings, increased trust especially, failed to replicate cleanly in larger, more rigorous follow-up studies. Honest read: real biological effects on social/bonding behavior exist, but the magnitude and reliability in typical adults is weaker than early 2000s-2010s media coverage suggested.", "reported_benefits": [ "Reported increased feelings of closeness/bonding with a partner, especially around intimacy", "Some report anxiolytic (anxiety-reducing) and socially 'softening' effects", "Explored (with mixed trial results) for social difficulties in autism spectrum contexts, though this remains an active and unsettled research area, not an established treatment" ], "dosing_protocols": [ { "route": "Intranasal spray (most common self-administered route)", "protocol": "Community and research-context doses commonly range from 10-40 IU, taken 15-45 minutes before an intended social or intimate context; research studies most commonly use 24 IU or 40 IU intranasal doses." } ], "side_effects": [ "Generally well tolerated at studied doses", "Nasal irritation with intranasal use", "Theoretical concern about blunting rather than enhancing some social responses in certain contexts/doses per some of the more nuanced recent research — the effect isn't simply 'more is better' in all social situations" ], "safety_notes": "Oxytocin's approved uses are obstetric (labor, postpartum bleeding), at doses and routes very different from intranasal self-administration for social or sexual purposes. Off-label users are relying on the separate, more mixed academic literature on intranasal effects, not the approval that put it on the market.", "community_notes": "Popular as a couples' intimacy aid, sometimes used alongside PT-141. Reports of a subjective 'warmth' or closeness effect are common, but consistent with the replication concerns, some users report no noticeable effect at all. Response varies a lot between individuals and contexts.", "related": [ "pt-141", "kisspeptin" ], "citations": [ { "title": "Does intranasal oxytocin reduce symptoms of mental disorders? A meta-analysis of clinical trials", "authors_year": "Bonnieux et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42134427/" }, { "title": "A key gene modulating oxytocin efficacy in autism: genome-wide discovery and verification in randomized controlled trials datasets", "authors_year": "Kuwabara et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41904269/" }, { "title": "The role of the oxytocinergic system in oral microbiome composition in children with autism: evidence from a randomized controlled trial of intranasal oxytocin", "authors_year": "Evenepoel et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41876480/" }, { "title": "Biological modulators of treatment outcome during psychiatric care: The interplay between inflammation and oxytocin", "authors_year": "Sedoff et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42156189/" } ] }, "research": [ { "id": "catalog:medication:oxytocin", "title": "Oxytocin", "summary": "An endogenous neuropeptide available as intranasal spray, studied in clinical trials for psychiatric and behavioral conditions with mixed results.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "clinical-study", "evidenceSummary": "Oxytocin is an endogenous neuropeptide available as intranasal spray that has been studied in multiple randomized controlled trials for various neuropsychiatric and behavioral conditions. Published trials investigated oxytocin nasal spray in early psychosis, autism spectrum disorder, frontotemporal dementia, and chronic pain, with 24 to 48 International Units tested in various regimens. Results have been mixed, with some trials showing no significant benefit over placebo. A meta-analysis of 38 randomized controlled trials (1990-2010) identified side effects including mild effects on mood and calmness, lightheadedness, and nasal irritation.", "verdict": { "benefits": [ "Multiple randomized trials completed in autism, psychosis, dementia, and pain conditions", "Mild, non-serious side effects observed in clinical trials" ], "risks": [ "Several randomized trials failed to find significant benefit over placebo", "Bioavailability of intranasal administration to central nervous system is uncertain", "Efficacy evidence remains inconsistent across different indications" ], "bottomLine": "Intranasal oxytocin has been extensively studied in human trials for psychiatric and neurological conditions, but evidence of benefit over placebo is inconsistent." }, "originalLinks": [ { "title": "A Double-Blind Randomized Controlled Trial of Oxytocin Nasal Spray and Social Cognition Training for Young People With Early Psychosis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4332939/" }, { "title": "The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial", "url": "https://www.nature.com/articles/s41380-022-01845-8" }, { "title": "Intranasal oxytocin", "url": "https://www.alzforum.org/therapeutics/intranasal-oxytocin" } ], "links": [ { "title": "A Double-Blind Randomized Controlled Trial of Oxytocin Nasal Spray and Social Cognition Training for Young People With Early Psychosis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4332939/" }, { "title": "The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial", "url": "https://www.nature.com/articles/s41380-022-01845-8" }, { "title": "Intranasal oxytocin", "url": "https://www.alzforum.org/therapeutics/intranasal-oxytocin" } ], "protocols": [ { "population": "52 individuals aged 16-35 with early psychosis schizophrenia-spectrum illness", "regimen": "Oxytocin nasal spray (24 International Units) or placebo twice-daily", "duration": "6 weeks", "outcome": "No significant benefit of oxytocin over placebo on primary clinical measures", "source": { "title": "A Double-Blind Randomized Controlled Trial of Oxytocin Nasal Spray and Social Cognition Training for Young People With Early Psychosis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4332939/" }, "origins": [ "evidence.json#/catalog:medication:oxytocin/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7815514/", "outcome": "trial-only", "reason": "The inspected review concerns experimental intranasal administration and research methods; it does not establish a non-study community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [ "peptide:kisspeptin", "peptide:pt-141" ], "conflicts": [], "sourceRefs": [ "pmid:42134427", "pmid:41904269", "pmid:41876480", "pmid:42156189", "https://pmc.ncbi.nlm.nih.gov/articles/PMC4332939/", "https://www.nature.com/articles/s41380-022-01845-8", "https://www.alzforum.org/therapeutics/intranasal-oxytocin" ] }, "peptide:kisspeptin": { "id": "peptide:kisspeptin", "path": "/peptides/kisspeptin.html", "title": "Kisspeptin", "summary": "The master upstream regulator of the reproductive hormone axis, more recently studied for direct effects on sexual and emotional brain processing, not just downstream hormone levels.", "aliases": [ "KP-10", "Metastin (older name)" ], "kind": "peptide", "categories": [ "sexual-health" ], "legacy": { "name": "Kisspeptin", "full_name": "Kisspeptin (KP-10 and related fragments, encoded by the KISS1 gene)", "aliases": [ "KP-10", "Metastin (older name)" ], "categories": [ "sexual-health" ], "tagline": "The master upstream regulator of the reproductive hormone axis, more recently studied for direct effects on sexual and emotional brain processing, not just downstream hormone levels.", "status": "Research/investigational compound. Not FDA-approved for any indication, though it has been used in legitimate clinical research settings (including UK academic trials on sexual response and reproductive hormone stimulation) more than most 'research chemical' peptides.", "origin": "The peptide product of the KISS1 gene, discovered originally in cancer-metastasis-suppression research (hence its older name metastin) before its essential role triggering puberty and regulating the reproductive hormone axis was identified.", "mechanism": "Kisspeptin neurons in the hypothalamus sit directly upstream of GnRH neurons: kisspeptin release triggers GnRH release, which drives LH/FSH release from the pituitary and ultimately testosterone/estrogen production. Beyond this classic reproductive-axis role, functional brain imaging studies from Imperial College London show kisspeptin administration modulates activity in brain regions tied to sexual and romantic processing directly, effects beyond downstream hormone stimulation.", "research_summary": "One of the more legitimately academically researched compounds in the sexual-health category, with published human trials, including controlled fMRI studies, showing kisspeptin administration increases sexual and romantic brain activity in men, and separately increases LH pulsatility in reproductive-axis research. Also studied as a potential fertility-treatment adjunct for triggering ovulation in IVF protocols. None of this has translated into an approved, marketed drug; it remains a research and early clinical-trial compound.", "reported_benefits": [ "Research-documented increase in reproductive hormone axis activity (LH, and downstream testosterone/estrogen)", "Academic research (not yet self-experimentation-community-level evidence) suggesting direct effects on sexual/romantic brain processing", "Interest in fertility contexts (IVF ovulation triggering) is a genuine, ongoing area of clinical research" ], "dosing_protocols": [ { "route": "Subcutaneous injection (self-experimentation, extrapolated from research protocols)", "protocol": "Research studies commonly use kisspeptin doses in the range of a few hundred nanomoles to low micrograms-per-kg, given as single doses or short infusions in controlled research settings — very different from the community-sourced 'daily dosing' patterns common for other peptides, since kisspeptin's research use has mostly been in acute, single-administration study designs rather than chronic self-dosing protocols." } ], "side_effects": [ "Generally well tolerated in the research trials conducted to date", "Because it sits at the top of the reproductive hormone cascade, theoretical concern about disrupting normal hormonal feedback loops with chronic/frequent dosing outside a controlled research context — this hasn't been well studied" ], "safety_notes": "Kisspeptin's research pedigree is unusually strong for a peptide discussed in self-experimentation spaces, but nearly all of it used acute, single-dose or short-infusion protocols in controlled clinical settings, not the ongoing, self-directed daily/weekly dosing typical of self-experimentation. That mismatch between how it's been studied and how it's actually used off-label matters.", "community_notes": "Less mainstream than PT-141 in self-experimentation communities. Interest tends to come from people who've read the Imperial College London fMRI research rather than from a large base of self-reported user experience, the opposite pattern from something like BPC-157: the academic research is ahead of the community-use track record.", "related": [ "pt-141", "oxytocin" ], "citations": [ { "title": "Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy", "authors_year": "Abbara et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26192876/" }, { "title": "A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial", "authors_year": "Abbara et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28854728/" }, { "title": "The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function", "authors_year": "Owens et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29206944/" } ], "mixing_notes": { "clinic_combos": [ "pinealon", "pt-141" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [], "related": [ "library:peptide-kisspeptin-10", "peptide:oxytocin", "peptide:pt-141" ], "conflicts": [], "sourceRefs": [ "pmid:26192876", "pmid:28854728", "pmid:29206944" ] }, "peptide:semax": { "id": "peptide:semax", "path": "/peptides/semax.html", "title": "Semax", "summary": "Russian-developed nootropic peptide, approved as a prescription drug in Russia for stroke recovery and cognitive/attention support. Widely used off-label elsewhere as a nasal-spray nootropic.", "aliases": [ "Semax", "N-Acetyl Semax Amidate" ], "kind": "peptide", "categories": [ "nootropics-cognitive" ], "legacy": { "name": "Semax", "full_name": "Semax (a synthetic ACTH(4-10) analog)", "aliases": [ "Semax", "N-Acetyl Semax Amidate" ], "categories": [ "nootropics-cognitive" ], "tagline": "Russian-developed nootropic peptide, approved as a prescription drug in Russia for stroke recovery and cognitive/attention support. Widely used off-label elsewhere as a nasal-spray nootropic.", "status": "Approved prescription drug in Russia (for ischemic stroke, optic nerve atrophy, and ADHD-type attention difficulties). Not approved in the US, EU, or most other countries; used there as a research chemical/off-label nasal spray.", "origin": "Developed by Russian researchers at the Institute of Molecular Genetics, Russian Academy of Sciences, in the 1980s. Derived from a fragment of ACTH but modified to remove ACTH's hormonal (adrenal-stimulating) activity while keeping its CNS effects.", "mechanism": "Increases brain-derived neurotrophic factor (BDNF) expression in animal studies, modulates dopaminergic and serotonergic signalling, and shows neuroprotective and antioxidant effects in stroke and hypoxia models. It doesn't act like a stimulant; effects are described as neuroplasticity and neuroprotection support rather than acute energizing.", "research_summary": "Russian clinical trials, the basis for its drug approval, studied it in ischemic stroke patients, showing improved neurological outcome scores in some trials versus standard care, and in children with attention difficulties. This evidence, like Epithalon's, comes largely from a research tradition with less rigorous international peer review and independent replication than Western regulatory standards require, so weight it accordingly even with genuine drug approval in its country of origin.", "reported_benefits": [ "Reported improvements in focus, mental clarity and motivation, commonly described by users as smoother/less jittery than stimulants", "Reported mood-lifting effect by some users", "Interest for post-concussion or general cognitive-recovery support, extrapolating from its stroke-recovery research" ], "dosing_protocols": [ { "route": "Intranasal spray", "protocol": "Commonly reported doses are 200-600 mcg per dose (a few sprays), once to a few times per day; because tolerance/desensitization is reported by some users with continuous daily use, many self-experimenters cycle it (e.g. several days on, then a break) rather than dosing continuously long-term." } ], "side_effects": [ "Generally reported as well tolerated at typical nasal-spray doses", "Nasal irritation from the spray itself", "Some users report reduced subjective effect with continuous daily use, prompting cycling protocols", "Long-term safety data at self-administered doses outside Russian clinical trial contexts is limited" ], "safety_notes": "The Russian drug-approval status is a genuine point in its favor relative to purely speculative research peptides, but comes from a regulatory tradition with less overlap with FDA/EMA-style trial and review standards, worth more independent scrutiny from Western readers.", "community_notes": "One of the more popular 'Russian peptide' nootropics, often discussed alongside Selank as a complementary pair: Semax for focus/motivation, Selank for anxiolytic/calming. Reports of diminishing effect with continuous use are common enough that cycling is standard practice, not a niche precaution.", "related": [ "selank", "dsip" ], "variant_note": "Sometimes sold as 'NA-Semax amidate' (N-acetyl, amidated form) rather than the original Semax sequence. The amidate modification is intended to improve stability, and community reports treat it as roughly interchangeable in effect, but it has not been independently studied to the same extent as the parent compound.", "citations": [ { "title": "[The efficacy of semax in the treatment of patients at different stages of ischemic stroke]", "authors_year": "Gusev et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29798983/" }, { "title": "[The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia]", "authors_year": "Stavchanskiĭ et al. 2011", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22295573/" }, { "title": "Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action", "authors_year": "Shadrina et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19662538/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghrp-2", "ghrp-6", "hexarelin", "ipamorelin", "ll-37", "mgf", "pt-141", "tb-500", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "dsip", "p21" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:semax", "title": "Semax", "summary": "ACTH(4-10) analogue developed in Russia as a nootropic. Approved there; not elsewhere.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Semax is an approved prescription drug in Russia for ischaemic stroke and attention problems, and is not approved in the US, EU or most other countries. The linked human study followed 110 patients after ischaemic stroke and reported higher BDNF levels and faster functional recovery alongside rehabilitation. The other two linked studies are rat experiments on neurotrophin gene expression. This evidence comes largely from a research tradition with less independent replication than Western regulators require, so it carries less weight than the drug approval alone suggests.", "verdict": { "benefits": [ "An approved prescription drug in Russia for ischaemic stroke and attention problems.", "A study of 110 stroke patients reported higher BDNF and faster functional recovery." ], "risks": [ "Not approved in the US, EU or most other countries.", "The supporting research tradition has little independent replication.", "The other linked studies are rat experiments on gene expression, not human outcomes." ], "bottomLine": "Semax is approved for stroke in Russia only, on human evidence that is limited and unreplicated elsewhere.", "approvalStatus": "Approved in Russia only (not FDA or EMA)." }, "originalLinks": [ { "title": "PubMed: Semax", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=Semax" } ], "links": [ { "title": "Peptide Wiki: Semax", "url": "https://vespassassina.github.io/peptide-wiki/peptides/semax.html" }, { "title": "[The efficacy of semax in the tretament of patients at different stages of ischemic stroke] (Gusev et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29798983/" }, { "title": "[The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia] (Stavchanskiĭ et al. 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/22295573/" }, { "title": "Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action (Shadrina et al. 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/19662538/" } ], "protocols": [ { "population": "110 patients after ischaemic stroke (43 men, 67 women, mean age 58) in early or late rehabilitation", "regimen": "two courses of semax at 6000 micrograms per day for 10 days, separated by a 20-day interval, alongside rehabilitation", "duration": "two 10-day courses over about 40 days", "outcome": "Plasma BDNF rose and stayed high, and Barthel index improvement and final outcome were faster and better than without semax.", "source": { "title": "[The efficacy of semax in the tretament of patients at different stages of ischemic stroke] (Gusev et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29798983/" }, "origins": [ "evidence.json#/catalog:peptide:semax/protocols/0" ] } ], "community": [ { "description": "A dosing guide reports intranasal administration of 200-600 mcg once to three times daily for cognitive and attention research, with morning dosing preferred and 2 weeks on / 2 weeks off cycling common.", "source": { "title": "Semax Dosage Guide: Nasal and Injection Administration, Reconstitution, and Dosing Protocol", "url": "https://knowyourpeptide.com/blog/semax-dosage-guide-nasal-injection-reconstitution-protocol" }, "origins": [ "evidence.json#/catalog:peptide:semax/community/0" ] }, { "description": "Klearmind Clinics documents intranasal Semax (0.1% spray) at 100-600 mcg daily in 1-2 daily doses with 10-20 day cycles followed by 1-2 week breaks, noting that morning administration is recommended for focus while evening use is typically avoided.", "source": { "title": "Semax Dosage Guide: Dosage, Safety & Side Effects", "url": "https://www.klearmindclinics.com/blog/semax-dosing-guide" }, "origins": [ "evidence.json#/catalog:peptide:semax/community/1" ] }, { "description": "Beverly Hills Rejuvenation Center's stacking guide reports Semax intranasal administration of 200-600 mcg per day split between morning and early afternoon, noting effects appear within 15-30 minutes, with subcutaneous injection dosing documented as 250-600 mcg per dose.", "source": { "title": "Semax & Selank: Dosage, Stacking Protocol & Nootropic Effects", "url": "https://www.bhrcenter.com/semax-selank-dosage-stacking-guide/" }, "origins": [ "evidence.json#/catalog:peptide:semax/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:semax/community/0", "url": "https://knowyourpeptide.com/blog/semax-dosage-guide-nasal-injection-reconstitution-protocol", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:semax/community/1", "url": "https://www.klearmindclinics.com/blog/semax-dosing-guide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:semax/community/2", "url": "https://www.bhrcenter.com/semax-selank-dosage-stacking-guide/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.4, "lowerHours": 0.3, "source": "Rapid clearance; intranasal route studied", "upperHours": 0.5 } } ], "related": [ "peptide:dsip", "peptide:selank" ], "conflicts": [], "sourceRefs": [ "pmid:29798983", "pmid:22295573", "pmid:19662538", "https://vespassassina.github.io/peptide-wiki/peptides/semax.html", "https://pubmed.ncbi.nlm.nih.gov/?term=Semax", "https://knowyourpeptide.com/blog/semax-dosage-guide-nasal-injection-reconstitution-protocol", "https://www.klearmindclinics.com/blog/semax-dosing-guide", "https://www.bhrcenter.com/semax-selank-dosage-stacking-guide/" ] }, "peptide:selank": { "id": "peptide:selank", "path": "/peptides/selank.html", "title": "Selank", "summary": "Russian-developed anxiolytic peptide, approved as a prescription drug in Russia for anxiety and mixed anxiety-depressive disorders. Used off-label elsewhere as a calming nasal-spray nootropic.", "aliases": [ "Selank" ], "kind": "peptide", "categories": [ "nootropics-cognitive" ], "legacy": { "name": "Selank", "full_name": "Selank (a synthetic analog of the endogenous immunomodulatory peptide tuftsin)", "aliases": [ "Selank" ], "categories": [ "nootropics-cognitive" ], "tagline": "Russian-developed anxiolytic peptide, approved as a prescription drug in Russia for anxiety and mixed anxiety-depressive disorders. Used off-label elsewhere as a calming nasal-spray nootropic.", "status": "Approved prescription drug in Russia for generalized anxiety disorder and mixed anxiety-depressive states. Not approved in the US, EU, or most other countries.", "origin": "Comes from the same Russian research tradition as Semax. Selank is a synthetic peptide based on tuftsin, a naturally occurring immunomodulatory peptide, modified for stability and CNS activity.", "mechanism": "Modulates GABAergic and serotonergic signalling, which drives its anxiolytic effect, without the sedation or dependence risk of benzodiazepines. Like Semax, it's been shown in animal studies to influence BDNF expression and carries mild immunomodulatory effects, a holdover from its tuftsin origin.", "research_summary": "The Russian trials behind its drug approval studied generalized anxiety disorder and mixed anxiety-depression, generally reporting anxiolytic effects comparable to reference anxiolytics but with a better side-effect and dependence profile. As with Semax, this evidence comes from a research and regulatory tradition with less independent international replication than Western-standard trials.", "reported_benefits": [ "Reported reduction in anxiety and stress reactivity without the sedation typically associated with benzodiazepines", "Reported improved focus under stress (calm-but-alert effect, distinct from a sedative)", "Often used situationally (before a stressful event) rather than as a continuous daily regimen" ], "dosing_protocols": [ { "route": "Intranasal spray", "protocol": "Commonly reported doses are 250-750 mcg per dose, taken as needed for acute anxiety/stress, or once to twice daily for ongoing use; similar to Semax, some users cycle it rather than using continuously, though reported tolerance/desensitization concerns are generally described as less pronounced than with Semax." } ], "side_effects": [ "Generally reported as well tolerated", "Nasal irritation from the spray formulation", "Limited independent (non-Russian-trial) human safety data" ], "safety_notes": "Genuine drug-approval status in Russia counts for something, but the trial base behind it has less international independent replication than Western regulatory review typically demands. Treat it as more evidence-backed than a typical research chemical, less so than an FDA/EMA-approved medication.", "community_notes": "Often paired with Semax: Selank for calm/anxiety, Semax for focus/motivation. Popular as a non-sedating alternative to benzodiazepines for situational anxiety, like before public speaking or other high-stress events.", "related": [ "semax", "dsip" ], "variant_note": "Sometimes sold as 'Selank amidate' rather than the original Selank sequence. As with Semax's amidate variant, this is a stability-oriented modification with a thinner independent evidence base than the parent peptide, though community reports treat it as similar in effect.", "citations": [ { "title": "[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia]", "authors_year": "Zozulia et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18454096/" } ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "ll-37", "pinealon", "tb-500", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "dsip", "p21" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:selank", "title": "Selank", "summary": "Tuftsin analogue studied for anxiolytic effect. Approved in Russia; not elsewhere.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Selank is a synthetic peptide based on tuftsin. The owner's wiki records it as an approved prescription drug in Russia for generalised anxiety and mixed anxiety-depressive states, and not approved in the US, EU or most other countries. The linked Russian trial reports anxiolytic effects comparable to reference anxiolytics, with a better side-effect and dependence profile. This evidence comes from one research and regulatory tradition with little independent international replication.", "verdict": { "benefits": [ "An approved prescription anxiolytic in Russia for generalised anxiety and anxiety-depressive states", "A Russian trial reports effects comparable to reference anxiolytics with fewer side effects" ], "risks": [ "Not approved in the US, the EU or most other countries", "Evidence comes from one research and regulatory tradition, with little independent replication" ], "bottomLine": "Selank is a prescription anxiolytic in Russia only, resting on trials no one outside that tradition has replicated.", "approvalStatus": "Approved in Russia only (not FDA or EMA)." }, "originalLinks": [ { "title": "PubMed: Selank", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=Selank" } ], "links": [ { "title": "Peptide Wiki: Selank", "url": "https://vespassassina.github.io/peptide-wiki/peptides/selank.html" }, { "title": "[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia] (Zozulia et al. 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18454096/" } ], "protocols": [], "community": [ { "description": "The Peptide Protocol Wiki community section documents a standard intranasal protocol of 200-300 mcg given 2-3 times daily for 4-6 weeks, with most users cycling 1 month on and 1 month off, and subcutaneous injection dosing reported as 250-500 mcg once daily with 5 days on / 2 days off cycling.", "source": { "title": "Selank Community Protocols & Anecdotal Reports", "url": "https://www.peptideprotocolwiki.com/peptides/selank/community" }, "origins": [ "evidence.json#/catalog:peptide:selank/community/0" ] }, { "description": "Peptide Dosing Protocols documents a subcutaneous injection approach starting with 250-300 mcg for weeks 1-2, escalating to 400-500 mcg for weeks 3-4, then cycling off for weeks 5-8, with intranasal spray protocols ranging from 600-2,700 mcg per day split into 2-3 administrations.", "source": { "title": "Selank Dosage Guide & Chart: Injection, SubQ & Nasal (2026)", "url": "https://www.peptidedosingprotocols.com/protocol/selank" }, "origins": [ "evidence.json#/catalog:peptide:selank/community/1" ] }, { "description": "Beverly Hills Rejuvenation Center's guide reports Selank intranasal spray (0.15% standard form) at 250-500 mcg per day for routine use, noted as flexible for timing and stress-responsive dosing, with subcutaneous injection at 250-500 mcg per dose, and higher divided ranges up to approximately 900 mcg per day for higher stress conditions.", "source": { "title": "Semax & Selank: Dosage, Stacking Protocol & Nootropic Effects", "url": "https://www.bhrcenter.com/semax-selank-dosage-stacking-guide/" }, "origins": [ "evidence.json#/catalog:peptide:selank/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:selank/community/0", "url": "https://www.peptideprotocolwiki.com/peptides/selank/community", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:selank/community/1", "url": "https://www.peptidedosingprotocols.com/protocol/selank", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:selank/community/2", "url": "https://www.bhrcenter.com/semax-selank-dosage-stacking-guide/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.35, "lowerHours": 0.2, "source": "Rapid clearance; intranasal route studied", "upperHours": 0.5 } } ], "related": [ "peptide:dsip", "peptide:semax" ], "conflicts": [], "sourceRefs": [ "pmid:18454096", "https://vespassassina.github.io/peptide-wiki/peptides/selank.html", "https://pubmed.ncbi.nlm.nih.gov/?term=Selank", "https://www.peptideprotocolwiki.com/peptides/selank/community", "https://www.peptidedosingprotocols.com/protocol/selank", "https://www.bhrcenter.com/semax-selank-dosage-stacking-guide/" ] }, "peptide:dsip": { "id": "peptide:dsip", "path": "/peptides/dsip.html", "title": "DSIP", "summary": "A short peptide first isolated from the brains of sleeping rabbits, explored for sleep, stress and pain modulation. Human evidence for an actual sleep-inducing effect is thin, despite the name.", "aliases": [ "DSIP", "DSIP (delta sleep-inducing peptide)" ], "kind": "peptide", "categories": [ "nootropics-cognitive" ], "legacy": { "name": "DSIP", "full_name": "Delta Sleep-Inducing Peptide", "aliases": [ "DSIP" ], "categories": [ "nootropics-cognitive" ], "tagline": "A short peptide first isolated from the brains of sleeping rabbits, explored for sleep, stress and pain modulation. Human evidence for an actual sleep-inducing effect is thin, despite the name.", "status": "Research chemical, no clinical approval anywhere. Human trial data is sparse and dated.", "origin": "First isolated in 1977 from rabbit blood during electrically induced slow-wave (delta) sleep, hence the name. Later research found DSIP has a wider range of physiologic and endocrine roles than sleep induction alone.", "mechanism": "Proposed to modulate ACTH levels, inhibit somatostatin secretion (relevant to GH-release timing, since somatostatin blocks GH release), normalize blood pressure, and alter pain perception, alongside its namesake but weakly proven role in delta-wave sleep.", "research_summary": "The human evidence that DSIP reliably induces or deepens delta-wave sleep is older and weaker than most people assume. Studies from the 1970s-80s produced mixed results, and no rigorous, modern, large-scale human sleep trial has followed. Most claims in wellness/peptide marketing trace back to this limited older literature.", "reported_benefits": [ "Reported improvement in sleep onset or depth by some users, though response is described as inconsistent between individuals", "Reported reduction in stress reactivity", "Sometimes included in stacks with Epithalon for a broader 'sleep and recovery' framing" ], "dosing_protocols": [ { "route": "Subcutaneous injection, before bed", "protocol": "Commonly reported doses are 100-300 mcg, injected 30-60 minutes before intended sleep; given inconsistent reported response, many users treat it as worth a short trial period rather than an assumed-effective compound." } ], "side_effects": [ "Generally reported as well tolerated at typical self-administered doses", "Limited modern human safety data" ], "safety_notes": "The name promises more than the evidence supports. User reports are more mixed and inconsistent than Ipamorelin's sleep effect, which has a more consistent reporting pattern in the GH-secretagogue community.", "community_notes": "A lower-confidence addition to sleep/recovery stacks. Discussed less often and with more mixed reviews than the GH secretagogues or Epithalon.", "related": [ "epithalon", "semax", "selank" ], "citations": [ { "title": "Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke", "authors_year": "Tukhovskaya et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/34500605/" }, { "title": "DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion", "authors_year": "Tukhovskaya et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33918965/" }, { "title": "Secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models", "authors_year": "Mu et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39444618/" }, { "title": "Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude", "authors_year": "Roy et al. 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/30107169/" } ], "mixing_notes": { "clinic_combos": [ "epithalon" ], "anecdotal_combos": [ "selank", "semax" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:dsip", "title": "DSIP (delta sleep-inducing peptide)", "summary": "Nonapeptide investigated for sleep architecture. Human evidence is old and thin; no approved indication.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "DSIP is a short peptide first isolated in 1977 during slow-wave sleep research. The owner's wiki lists it as a research chemical with no approval anywhere and calls the human sleep evidence old and weak. Studies from the 1970s and 1980s gave mixed results, and no large modern human sleep trial has followed. The other linked studies are animal work: rat stroke and heart-attack models, a mouse insomnia model, and a rat memory study at altitude.", "verdict": { "benefits": [ "Animal work reports smaller heart and brain infarcts, more sleep and better maze memory in rodents" ], "risks": [ "A research chemical with no approval anywhere", "Human sleep evidence is old, weak and mixed, with no large modern trial since the 1980s", "In one rat experiment, giving the peptides during artery occlusion killed all the animals" ], "bottomLine": "An unapproved sleep peptide whose human evidence is decades old and mixed, with the rest done in rodents." }, "originalLinks": [ { "title": "PubMed: delta sleep-inducing peptide", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=delta+sleep+inducing+peptide" } ], "links": [ { "title": "Peptide Wiki: DSIP (delta sleep-inducing peptide)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/dsip.html" }, { "title": "Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke (Tukhovskaya et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34500605/" }, { "title": "DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion (Tukhovskaya et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33918965/" }, { "title": "Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models (Mu et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39444618/" }, { "title": "Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude (Roy et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30107169/" } ], "protocols": [ { "population": "Sprague-Dawley rats with focal stroke induced by middle cerebral artery occlusion", "regimen": "DSIP 120 µg/kg intranasally, about 60 minutes before occlusion and daily for 7 days after reperfusion", "duration": "8 days", "outcome": "Brain infarction was smaller but not significantly so; rotarod motor performance recovered significantly versus vehicle.", "source": { "title": "Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke (Tukhovskaya et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34500605/" }, "origins": [ "evidence.json#/catalog:peptide:dsip/protocols/0" ] }, { "population": "SD rats with acute myocardial infarction and C57Bl/6 mice with acute focal stroke", "regimen": "DSIP-like KND peptide injected in the first minute of reperfusion, intranasally in the stroke model", "duration": "single dose at reperfusion", "outcome": "Myocardial infarct area was 19.1% versus 42.1% and brain infarct volume 7.4% versus 12.2%; a pilot giving the peptides during occlusion killed all animals.", "source": { "title": "DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion (Tukhovskaya et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33918965/" }, "origins": [ "evidence.json#/catalog:peptide:dsip/protocols/1" ] }, { "population": "Morris water maze-trained Sprague-Dawley rats exposed to simulated high altitude of 7,620 m", "regimen": "phosphorylated DSIP 10 µg/kg bodyweight intraperitoneally, once daily at 18:30 during hypobaric hypoxia exposure", "duration": "not stated", "outcome": "Non-REM and REM sleep increased, maze performance improved and hippocampal CREB phosphorylation rose; naloxone reversed the memory effect.", "source": { "title": "Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude (Roy et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30107169/" }, "origins": [ "evidence.json#/catalog:peptide:dsip/protocols/2" ] } ], "community": [ { "description": "A community protocol guide describes 200 micrograms subcutaneously administered 30-60 minutes before bedtime, with 3-4 week cycles followed by 2 week breaks.", "source": { "title": "DSIP (Delta Sleep-Inducing Peptide) Dosing", "url": "https://peptideinitiative.com/peptides/dsip" }, "origins": [ "evidence.json#/catalog:peptide:dsip/community/0" ] }, { "description": "Community protocols report beginner use at 100 micrograms nightly, standard use at 200 micrograms, and enhanced protocols at 300 micrograms subcutaneously before sleep, with varying cycle structures of 2-4 weeks on.", "source": { "title": "DSIP Peptide Dosage: Sleep Protocols", "url": "https://peptidesexplorer.com/blog/dsip-peptide-dosage" }, "origins": [ "evidence.json#/catalog:peptide:dsip/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:dsip/community/0", "url": "https://peptideinitiative.com/peptides/dsip", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:dsip/community/1", "url": "https://peptidesexplorer.com/blog/dsip-peptide-dosage", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.2, "lowerHours": 0.1, "source": "Rapid plasma clearance; preclinical", "upperHours": 0.3 } } ], "related": [ "peptide:epithalon", "peptide:selank", "peptide:semax" ], "conflicts": [], "sourceRefs": [ "pmid:34500605", "pmid:33918965", "pmid:39444618", "pmid:30107169", "https://vespassassina.github.io/peptide-wiki/peptides/dsip.html", "https://pubmed.ncbi.nlm.nih.gov/?term=delta+sleep+inducing+peptide", "https://peptideinitiative.com/peptides/dsip", "https://peptidesexplorer.com/blog/dsip-peptide-dosage" ] }, "peptide:cagrilintide": { "id": "peptide:cagrilintide", "path": "/peptides/cagrilintide.html", "title": "Cagrilintide", "summary": "Long-acting amylin agonist that adds synergistic weight loss on top of GLP-1 drugs.", "aliases": [ "long-acting amylin analog", "amylin agonist" ], "kind": "medication-hormone", "categories": [ "fat-loss", "fitness-muscle" ], "legacy": { "name": "Cagrilintide", "full_name": "NN2640 (long-acting amylin receptor agonist)", "aliases": [ "long-acting amylin analog", "amylin agonist" ], "categories": [ "fat-loss", "fitness-muscle" ], "tagline": "Long-acting amylin agonist that adds synergistic weight loss on top of GLP-1 drugs.", "status": "Investigational (Phase 3) | Pending FDA approval", "origin": "Novo Nordisk built cagrilintide as a long-acting amylin receptor agonist derived from human amylin, the pancreatic hormone co-secreted with insulin. Lipidation technology extends its half-life for once-weekly dosing, unlike first-generation amylin analogs that needed daily injections. Development accelerated after Phase 2/3 data showed enhanced efficacy combined with semaglutide in the fixed-dose CagriSema.", "mechanism": "Activates amylin receptors (AMYR) and calcitonin receptors (CTR) in the hindbrain and hypothalamus, suppressing appetite, slowing gastric emptying, and driving satiation through neural circuits distinct from GLP-1 agonism. Combined with a GLP-1 agonist, activation in complementary brain regions produces additive satiety.", "research_summary": "Meta-analyses of Phase 2/3 trials show cagrilintide monotherapy produces about 6% body weight reduction; the CagriSema combination adds 7-10% weight loss beyond semaglutide alone. Adverse events are mostly gastrointestinal and dose-related, with no unexpected safety signals so far. Trials run 12-52 weeks; there's no data on safety or durability beyond 1-2 years.", "citations": [ { "title": "Maximizing weight loss with cagrisema: a systematic review and GRADE-assessed meta-analysis of randomized controlled trials", "authors_year": "Khan et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42608559/" }, { "title": "Co-agonism of GLP-1R and CTR/AMYR in the lateral dorsal tegmental nucleus produces additive effects on homeostatic and motivated feeding", "authors_year": "Sanchez-Navarro et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42603595/" } ], "reported_benefits": [ "weight loss (6-10% body weight reduction)", "reduced waist circumference", "improved glycemic control in diabetic subsets", "reduced hunger and food motivation" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Once-weekly: escalation from 0.25 mg to target maintenance doses of 2.0-2.4 mg (monotherapy) or 2.4 mg when combined with semaglutide (CagriSema)." } ], "side_effects": [ "nausea (dose-dependent)", "vomiting", "diarrhea", "gastric reflux", "injection site reactions", "fatigue" ], "safety_notes": "GI adverse events are the limiting factor: grade 3 nausea/vomiting hits 5-20% of users at higher doses. Caution advised for anyone with a pancreatitis history. No major cardiac, renal, or hepatic signals so far, but safety beyond 2 years isn't established.", "community_notes": "Anecdotal reports describe it as a potent satiety agent, more nausea-inducing than GLP-1 monotherapy alone. It's not available outside trials, and black-market sourcing brings potency variance and purity concerns.", "related": [ "semaglutide", "tirzepatide", "mazdutide", "survodutide" ] }, "research": [ { "id": "catalog:medication:cagrilintide", "title": "Cagrilintide", "summary": "An amylin analog combined with GLP-1 agonist showing substantial weight loss in Phase III trials, pending approval.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "clinical-study", "evidenceSummary": "Cagrilintide is an amylin analog used in combination with semaglutide (a GLP-1 receptor agonist) in the fixed-dose combination CagriSema for weight management. In the REDEFINE 1 Phase III trial, once-weekly CagriSema achieved mean weight reductions of 20.4-22.7% at 68 weeks compared to 2.3-3.0% with placebo, with 60% of participants achieving at least 20% weight loss and 23% losing 30% or more. The combination also significantly improved systolic blood pressure, waist circumference, lipid levels, and glycemic control, with 88% of prediabetic participants returning to normoglycemia. Safety profile was consistent with GLP-1 receptor agonists, primarily featuring transient mild-to-moderate gastrointestinal adverse events (nausea 55%), with low discontinuation rates (6-8.4%). Cagrilintide's mechanism enhances satiety and delays gastric emptying via brainstem pathways.", "verdict": { "benefits": [ "Phase III trial demonstrates substantial weight loss (20-23% mean reduction)", "Improvements in blood pressure, lipids, waist circumference, and glycemic control", "88% of prediabetic participants returned to normoglycemia" ], "risks": [ "Not yet approved; awaiting regulatory decisions", "Gastrointestinal side effects common (nausea in 55%)", "Long-term safety beyond 68 weeks not established" ], "bottomLine": "Cagrilintide in combination with semaglutide has shown substantial weight loss and cardiometabolic benefits in Phase III trials, pending regulatory approval.", "approvalStatus": "Not yet approved anywhere; awaiting regulatory decisions." }, "originalLinks": [ { "title": "REDEFINE 1 Trial Finds Cagrilintide–Semaglutide Combo Delivers Over 20% Weight Loss in Majority of Patients", "url": "https://www.appliedclinicaltrialsonline.com/view/cagrilintide-semaglutide-weight-loss" }, { "title": "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial", "url": "https://www.sciencedirect.com/science/article/abs/pii/S0140673621017517" }, { "title": "Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270663/" } ], "links": [ { "title": "REDEFINE 1 Trial Finds Cagrilintide–Semaglutide Combo Delivers Over 20% Weight Loss in Majority of Patients", "url": "https://www.appliedclinicaltrialsonline.com/view/cagrilintide-semaglutide-weight-loss" }, { "title": "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial", "url": "https://www.sciencedirect.com/science/article/abs/pii/S0140673621017517" }, { "title": "Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270663/" } ], "protocols": [ { "population": "Participants in REDEFINE 1 Phase III trial for obesity", "regimen": "Once-weekly CagriSema (cagrilintide plus semaglutide) or placebo injection", "duration": "68 weeks", "outcome": "Mean weight loss 20.4-22.7% vs. 2.3-3.0% placebo; 60% achieved ≥20% weight loss, 23% lost ≥30%", "source": { "title": "REDEFINE 1 Trial Finds Cagrilintide–Semaglutide Combo Delivers Over 20% Weight Loss in Majority of Patients", "url": "https://www.appliedclinicaltrialsonline.com/view/cagrilintide-semaglutide-weight-loss" }, "origins": [ "evidence.json#/catalog:medication:cagrilintide/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.biospace.com/press-releases/novos-cagrisema-delivers-superior-weight-loss-and-cardiometabolic-benefits-compared-to-semaglutide-in-head-to-head-phase-3b-trial", "outcome": "not-found", "reason": "Independent direct retrieval returned HTTP 404. No description was verified at this attempted address." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 177, "lowerHours": 159, "source": "Enebo et al. 2021, Lancet, PMID 33894838 — phase 1b trial, co-administered with semaglutide 2.4 mg", "upperHours": 195 } } ], "related": [ "peptide:mazdutide", "peptide:semaglutide", "peptide:survodutide", "peptide:tirzepatide" ], "conflicts": [], "sourceRefs": [ "pmid:42608559", "pmid:42603595", "https://www.appliedclinicaltrialsonline.com/view/cagrilintide-semaglutide-weight-loss", "https://www.sciencedirect.com/science/article/abs/pii/S0140673621017517", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270663/" ] }, "peptide:mazdutide": { "id": "peptide:mazdutide", "path": "/peptides/mazdutide.html", "title": "Mazdutide", "summary": "Dual GLP-1/glucagon agonist in Phase 3 trials showing 15-20% weight loss with metabolic benefits beyond weight reduction.", "aliases": [ "LY3305677", "GCG/GLP-1 dual agonist" ], "kind": "medication-hormone", "categories": [ "fat-loss", "longevity" ], "legacy": { "name": "Mazdutide", "full_name": "LY3305677 (dual glucagon and GLP-1 receptor agonist)", "aliases": [ "LY3305677", "GCG/GLP-1 dual agonist" ], "categories": [ "fat-loss", "longevity" ], "tagline": "Dual GLP-1/glucagon agonist in Phase 3 trials showing 15-20% weight loss with metabolic benefits beyond weight reduction.", "status": "Investigational (Phase 3) | Positive Phase 2 data", "origin": "Developed by Eli Lilly and Innovent Biologics as a once-weekly subcutaneous GLP-1/glucagon dual agonist. Moved from Phase 1 through Phase 2 US trials to Phase 3 in Chinese populations, with 15-20% weight loss.", "mechanism": "Near-equipotent agonist at GLP-1 and glucagon receptors (GCGR). GLP-1R activation suppresses appetite; GCGR activation raises hepatic and peripheral lipid oxidation and energy expenditure. The glucagon component may preferentially mobilize visceral and hepatic fat.", "research_summary": "Phase 2 US trial: 10-16 mg produced 15.6-18.1% weight loss at week 32 vs -0.9% for placebo. Phase 3 China data show up to 20.1% weight loss. GI adverse events are dose-limiting, worst at 16 mg (20% discontinuation). Cardiovascular safety is still being evaluated in ongoing outcomes trials.", "citations": [ { "title": "Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial", "authors_year": "Hsia et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42628555/" } ], "reported_benefits": [ "weight loss (15-20% body weight reduction)", "reduced waist circumference", "improved glycemic control", "preferential visceral/hepatic fat loss", "potential kidney protection" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Once-weekly: dose escalation from 3 mg to maintenance of 10 mg or 16 mg depending on tolerability." } ], "side_effects": [ "nausea", "vomiting", "diarrhea", "constipation", "abdominal pain", "increased heart rate", "fatigue" ], "safety_notes": "GI toxicity is dose-limiting at 16 mg. Heart rate rises at all doses. Cardiovascular outcomes trial ongoing. No teratogenicity data; not studied in pregnancy.", "community_notes": "Access for self-experimenters is limited since it's still a Phase 3 drug. Trial participants report more weight loss and stronger appetite suppression than semaglutide alone.", "related": [ "semaglutide", "tirzepatide", "survodutide", "retatrutide" ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board — not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "research": [ { "id": "catalog:medication:mazdutide", "title": "Mazdutide", "summary": "A dual GLP-1/glucagon agonist approved in China for obesity and type 2 diabetes, showing over 20% weight loss in trials.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "clinical-study", "evidenceSummary": "Mazdutide (IBI362) is a dual GLP-1/glucagon receptor agonist developed through a partnership between Innovent Biologics and Eli Lilly. It received regulatory approval from China's National Medical Products Administration (NMPA) in April 2026 for chronic weight management in adults with elevated BMI, with or without weight-related comorbidities, and for glycemic control in type 2 diabetes as monotherapy or combination therapy. Mazdutide is the first dual-target GLP-1R/GCGR agonist to complete Phase III trials. The company unveiled Phase III data in adults with type 2 diabetes, and separately reported substantial weight loss at the highest studied dose in obese adults without type 2 diabetes after a year of treatment with a stepped titration. Phase III results from GLORY-1 (weight management) were published in The New England Journal of Medicine, and DREAMS-1 and DREAMS-2 (type 2 diabetes) were published in Nature.", "verdict": { "benefits": [ "Approved in China for weight management and type 2 diabetes (April 2026)", "Phase III trials demonstrate over 20% weight loss with single dose regimen", "Dual-agonist mechanism provides metabolic benefits for both weight and glucose control" ], "risks": [ "Approved only in China as of April 2026; status in other major markets pending", "Gastrointestinal adverse events expected with GLP-1 agonist mechanism", "Long-term safety data accumulating" ], "bottomLine": "Mazdutide is the first dual GLP-1/glucagon agonist approved in China, showing substantial weight loss in Phase III trials; availability in other markets pending regulatory decisions.", "approvalStatus": "Approved in China only (April 2026); not yet FDA-approved." }, "originalLinks": [ { "title": "With China approval, Lilly and Innovent's mazdutide breaks into new class for GLP-1 obesity drugs", "url": "https://www.fiercepharma.com/pharma/china-approval-lilly-and-innovents-mazdutide-breaks-new-class-glp-1-obesity-drugs" }, { "title": "A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719339/" }, { "title": "Innovent Announces Mazdutide, First Dual GCG/GLP-1 Receptor Agonist, Received Approval from China's NMPA for Chronic Weight Management", "url": "https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html" } ], "links": [ { "title": "With China approval, Lilly and Innovent's mazdutide breaks into new class for GLP-1 obesity drugs", "url": "https://www.fiercepharma.com/pharma/china-approval-lilly-and-innovents-mazdutide-breaks-new-class-glp-1-obesity-drugs" }, { "title": "A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719339/" }, { "title": "Innovent Announces Mazdutide, First Dual GCG/GLP-1 Receptor Agonist, Received Approval from China's NMPA for Chronic Weight Management", "url": "https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html" } ], "protocols": [ { "population": "731 adults with type 2 diabetes and obesity", "regimen": "Mazdutide subcutaneous injection with 2-step dose titration", "duration": "52 weeks (Phase III DREAMS-1/2)", "outcome": "Mazdutide 9 mg achieved over 20% weight loss; improved glycemic control", "source": { "title": "With China approval, Lilly and Innovent's mazdutide breaks into new class for GLP-1 obesity drugs", "url": "https://www.fiercepharma.com/pharma/china-approval-lilly-and-innovents-mazdutide-breaks-new-class-glp-1-obesity-drugs" }, "origins": [ "evidence.json#/catalog:medication:mazdutide/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-received-approval-from-chinas-national-medical-products-administration-nmpa-for-the-treatment-of-chronic-weight-management-302561434.html", "outcome": "not-found", "reason": "Independent direct retrieval returned HTTP 404. No description was verified at this attempted address." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 277.2, "lowerHours": 150.9, "source": "Ji et al. 2021, EClinicalMedicine, PMID 34430840 — phase 1b ascending-dose study, Chinese adults, range reflects the 3.0/4.5/6.0 mg dose cohorts", "upperHours": 403.5 } } ], "related": [ "peptide:retatrutide", "peptide:semaglutide", "peptide:survodutide", "peptide:tirzepatide" ], "conflicts": [], "sourceRefs": [ "pmid:42628555", "https://www.fiercepharma.com/pharma/china-approval-lilly-and-innovents-mazdutide-breaks-new-class-glp-1-obesity-drugs", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719339/", "https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html" ] }, "peptide:survodutide": { "id": "peptide:survodutide", "path": "/peptides/survodutide.html", "title": "Survodutide", "summary": "Boehringer Ingelheim's GLP-1/glucagon dual agonist in Phase 3, showing 17-22% weight loss with a cardiovascular outcomes trial underway.", "aliases": [ "BI 456906", "GLP-1/GCGR dual agonist" ], "kind": "medication-hormone", "categories": [ "fat-loss", "longevity" ], "legacy": { "name": "Survodutide", "full_name": "BI 456906 (dual glucagon and GLP-1 receptor agonist)", "aliases": [ "BI 456906", "GLP-1/GCGR dual agonist" ], "categories": [ "fat-loss", "longevity" ], "tagline": "Boehringer Ingelheim's GLP-1/glucagon dual agonist in Phase 3, showing 17-22% weight loss with a cardiovascular outcomes trial underway.", "status": "Investigational (Phase 3) | Cardiovascular outcomes trial ongoing", "origin": "Developed by Boehringer Ingelheim as a once-weekly subcutaneous GLP-1/glucagon receptor dual agonist. In Phase 3 following positive Phase 2 dose-finding trials in obesity, with multiple regional Phase 3 trials active including a dedicated cardiovascular outcomes trial.", "mechanism": "Selective dual agonist of GLP-1R and GCGR with balanced activity at both, combining appetite suppression with hepatic lipogenesis inhibition and higher energy expenditure. Preclinical and early clinical data suggest it preferentially reduces visceral and hepatic adiposity.", "research_summary": "Phase 2/3 data show survodutide 3.6-4.8 mg produces 17-22% body weight reductions over 52 weeks, with reported liver-fat reductions of 60-80% in some cohorts. Heart-rate elevation is observed and under formal cardiovascular evaluation. GI adverse events are dose-limiting but typically mild-to-moderate. Evidence is limited to 52-76 weeks of exposure.", "citations": [ { "title": "Survodutide for Obesity in Chinese Adults: Phase 3 Randomized Trial Design and Baseline Characteristics (SYNCHRONIZE-CN)", "authors_year": "Ji et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42599381/" } ], "reported_benefits": [ "weight loss (17-22% body weight reduction)", "improved glycemic control", "preferential visceral and liver-fat reduction", "potential cardioprotection (under investigation)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Once-weekly: gradual escalation to maintenance at 3.6 or 4.8 mg over 4-8 weeks." } ], "side_effects": [ "nausea", "vomiting", "diarrhea", "constipation", "fatigue", "increased heart rate", "potential QTc prolongation (under investigation)" ], "safety_notes": "GI tolerability improves with slower dose escalation. Heart-rate elevation is consistent across dual agonists and under formal evaluation. Cardiovascular outcomes and safety remain the key open Phase 3 question.", "community_notes": "Biohacker access is limited since it's a Phase 3 drug. Scattered anecdotal trial-participant reports suggest efficacy similar to or better than mazdutide with slightly better liver-fat reduction.", "related": [ "mazdutide", "semaglutide", "tirzepatide", "retatrutide" ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board — not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "research": [ { "id": "catalog:medication:survodutide", "title": "Survodutide", "summary": "A dual glucagon and GLP-1 receptor agonist showing 16.6% weight loss in Phase III trials, pending regulatory approval.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "clinical-study", "evidenceSummary": "Survodutide is a dual agonist of glucagon receptor and GLP-1 receptor being developed for obesity and weight-related conditions. In Phase II trials, survodutide elicited significant weight loss in individuals with obesity without type 2 diabetes. Two Phase III trials are currently underway: SYNCHRONIZE-1 enrolled 725 participants without type 2 diabetes, showing baseline BMI of 37.9 kg/m² and diverse comorbidities including hypertension (40%), dyslipidemia (33.7%), and sleep apnea (18.3%). SYNCHRONIZE-2 is evaluating survodutide in people with type 2 diabetes. Boehringer Ingelheim announced positive topline results from SYNCHRONIZE-1 showing mean weight loss of 16.6% at 76 weeks versus 3.2% with placebo. Additional Phase III trials (LIVERAGE, LIVERAGE-Cirrhosis) are investigating efficacy in metabolic dysfunction-associated steatohepatitis (MASH) with varying fibrosis stages.", "verdict": { "benefits": [ "Phase III trials demonstrate substantial weight loss (16.6% at 76 weeks)", "Dual-agonist mechanism targets multiple metabolic pathways", "Ongoing trials in type 2 diabetes and MASH indicate broader therapeutic potential" ], "risks": [ "Not yet approved; Phase III trials ongoing through 2026", "Gastrointestinal adverse events expected given GLP-1 agonist mechanism", "Long-term safety data not yet available" ], "bottomLine": "Survodutide is a dual GLP-1/glucagon agonist showing substantial weight loss in Phase III trials, with results expected to inform regulatory decisions in 2026." }, "originalLinks": [ { "title": "Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12673442/" }, { "title": "Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial", "url": "https://pubmed.ncbi.nlm.nih.gov/38330987/" }, { "title": "Survodutide Once Weekly for the Treatment of Adults with Obesity", "url": "https://www.nejm.org/doi/abs/10.1056/NEJMoa2600751" } ], "links": [ { "title": "Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12673442/" }, { "title": "Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial", "url": "https://pubmed.ncbi.nlm.nih.gov/38330987/" }, { "title": "Survodutide Once Weekly for the Treatment of Adults with Obesity", "url": "https://www.nejm.org/doi/abs/10.1056/NEJMoa2600751" } ], "protocols": [ { "population": "725 adults with obesity without type 2 diabetes (SYNCHRONIZE-1 baseline)", "regimen": "Once-weekly survodutide injection or placebo", "duration": "76 weeks (SYNCHRONIZE-1 phase III)", "outcome": "Mean weight loss 16.6% with survodutide vs. 3.2% with placebo at 76 weeks", "source": { "title": "Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12673442/" }, "origins": [ "evidence.json#/catalog:medication:survodutide/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://markets.businessinsider.com/news/stocks/zealand-pharma-announces-survodutide-phase-3-synchronize-2-trial", "outcome": "not-found", "reason": "Independent direct retrieval returned HTTP 404. No description was verified at this attempted address." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [ "peptide:mazdutide", "peptide:retatrutide", "peptide:semaglutide", "peptide:tirzepatide" ], "conflicts": [], "sourceRefs": [ "pmid:42599381", "https://pmc.ncbi.nlm.nih.gov/articles/PMC12673442/", "pmid:38330987", "https://www.nejm.org/doi/abs/10.1056/NEJMoa2600751" ] }, "peptide:liraglutide": { "id": "peptide:liraglutide", "path": "/peptides/liraglutide.html", "title": "Liraglutide", "summary": "First-generation GLP-1 receptor agonist, FDA-approved for weight loss (Saxenda) and diabetes (Victoza) with well-established safety and efficacy.", "aliases": [ "Saxenda", "Victoza", "NN2211" ], "kind": "medication-hormone", "categories": [ "fat-loss", "longevity" ], "legacy": { "name": "Liraglutide", "full_name": "GLP-1 receptor agonist (Saxenda for weight loss, Victoza for diabetes)", "aliases": [ "Saxenda", "Victoza", "NN2211" ], "categories": [ "fat-loss", "longevity" ], "tagline": "First-generation GLP-1 receptor agonist, FDA-approved for weight loss (Saxenda) and diabetes (Victoza) with well-established safety and efficacy.", "status": "FDA-approved (2014 for diabetes, 2016 for weight loss)", "origin": "Developed by Novo Nordisk as a once-daily subcutaneous GLP-1 receptor agonist, derived from human GLP-1 with a single amino-acid substitution and lipid modification for extended pharmacokinetics. Approved as Victoza (2010, diabetes) and Saxenda (2014, chronic weight management). The longest-marketed GLP-1 agonist.", "mechanism": "Activates GLP-1 receptors distributed through the brain, pancreatic islets, and GI tract. Central GLP-1R activation suppresses appetite; peripheral activation stimulates glucose-dependent insulin secretion and suppresses glucagon. Slows gastric emptying. Glucose-dependent signaling minimizes hypoglycemia risk.", "research_summary": "Evaluated in thousands of published studies. Pivotal SCALE obesity trials demonstrated 4.5-6% body weight reduction vs placebo at 56 weeks. The LEADER cardiovascular outcomes trial showed reduced major adverse cardiovascular events and mortality in type 2 diabetes. Long-term safety data span 15+ years; the most common adverse events are gastrointestinal and generally diminish with time.", "citations": [ { "title": "Assessing the Association Between GLP-1 Receptor Agonists and Diabetic Foot Complications Using Real-World Pharmacovigilance Database and Mendelian Randomization", "authors_year": "Zhang et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42726083/" } ], "reported_benefits": [ "weight loss (4.5-6% body weight reduction vs placebo)", "improved glycemic control", "reduced cardiovascular events and mortality", "improved lipid profiles" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Saxenda: 0.6 mg once-daily, escalating weekly to 3.0 mg maintenance. Victoza: 0.6 mg once-daily, escalating to 1.2-1.8 mg maintenance." } ], "side_effects": [ "nausea (30-40% mild)", "vomiting", "diarrhea", "constipation", "headache", "decreased appetite" ], "safety_notes": "GI adverse events typically resolve within 2-4 weeks. Pancreatitis risk is uncommon; causality debated. Rodent-only medullary thyroid carcinoma signal; contraindicated with personal/family MTC or MEN2A/2B history. Pregnancy category C.", "community_notes": "The most widely used GLP-1 agonist for self-experimentation; forums report modest but reliable 4-6% weight loss with pronounced early nausea that improves, and better tolerability than tirzepatide at lower doses.", "related": [ "semaglutide", "tirzepatide" ], "mixing_caution": "This chart's source flags GLP-1/GIP/glucagon-receptor drugs as broadly avoided in combination with other research peptides across the board — not a peptide-specific interaction, more a general caution against stacking incretin drugs with anything else. Treat any combination here as unverified." }, "research": [ { "id": "catalog:medication:liraglutide", "title": "Liraglutide", "summary": "An FDA-approved GLP-1 receptor agonist for weight management in adults and adolescents, administered by once-daily injection.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Liraglutide (Saxenda) is a GLP-1 receptor agonist approved by the FDA for chronic weight management in adults with a BMI of 30 kg/m² or higher or BMI of 27 kg/m² or greater with at least one weight-related condition, and in adolescents (ages 12-17) with obesity. FDA approval occurred on December 23, 2014, with the adolescent indication added in December 2020. Liraglutide is dosed as a once-daily injection and is used as an adjunct to reduced-calorie diet and increased physical activity. Clinical trials showed 62% of patients on liraglutide achieved at least 5% weight loss compared to 34% on placebo. The prescribing label contains a boxed warning regarding the risk of thyroid c-cell tumors. Generic liraglutide was approved in 2025, marking the first generic GLP-1 receptor agonist indicated specifically for weight management in the US.", "verdict": { "benefits": [ "Chronic weight management in adults and adolescents.", "Clinical trials demonstrate meaningful weight loss in majority of patients" ], "risks": [ "Boxed warning regarding thyroid c-cell tumor risk (preclinical finding in rodents)", "Contraindicated with other liraglutide-containing or GLP-1 receptor agonist products", "Long-term safety data extend to years in trials but long-term use effects continue to accrue" ], "bottomLine": "Liraglutide (Saxenda) is an FDA-approved GLP-1 receptor agonist for chronic weight management with demonstrated efficacy and established safety profile.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "Label: VICTOZA (liraglutide) - DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9ef4ea-c76a-4d34-a604-27c5b505f5a4" }, { "title": "FDA approves weight management drug for patients aged 12 and older", "url": "https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-weight-management-drug-patients-aged-12-and-older" }, { "title": "Saxenda (liraglutide) FDA Approval History", "url": "https://www.drugs.com/history/saxenda.html" }, { "title": "Liraglutide for Type 2 diabetes and obesity: a 2015 update", "url": "https://pubmed.ncbi.nlm.nih.gov/26106933/" } ], "links": [ { "title": "Label: VICTOZA (liraglutide) - DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9ef4ea-c76a-4d34-a604-27c5b505f5a4" }, { "title": "FDA approves weight management drug for patients aged 12 and older", "url": "https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-weight-management-drug-patients-aged-12-and-older" }, { "title": "Saxenda (liraglutide) FDA Approval History", "url": "https://www.drugs.com/history/saxenda.html" }, { "title": "Liraglutide for Type 2 diabetes and obesity: a 2015 update", "url": "https://pubmed.ncbi.nlm.nih.gov/26106933/" } ], "protocols": [ { "population": "Adults with obesity or overweight with weight-related conditions", "regimen": "Liraglutide once-daily injection as adjunct to diet and physical activity", "duration": "Chronic ongoing therapy", "outcome": "62% achieved at least 5% weight loss vs. 34% with placebo", "source": { "title": "FDA approves weight management drug for patients aged 12 and older", "url": "https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-weight-management-drug-patients-aged-12-and-older" }, "origins": [ "evidence.json#/catalog:medication:liraglutide/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The quoted brand and indication identity does not establish community practice; the proposed injection-schedule wording goes beyond that excerpt.", "checks": [ { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5358074/", "outcome": "no-practice-description", "reason": "The quoted brand and indication identity does not establish community practice; the proposed injection-schedule wording goes beyond that excerpt." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 13, "source": "FDA label, Victoza: elimination half-life approximately 13 hours" } } ], "related": [ "peptide:semaglutide", "peptide:tirzepatide" ], "conflicts": [], "sourceRefs": [ "pmid:42726083", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9ef4ea-c76a-4d34-a604-27c5b505f5a4", "https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-weight-management-drug-patients-aged-12-and-older", "https://www.drugs.com/history/saxenda.html", "pmid:26106933" ] }, "peptide:adipotide": { "id": "peptide:adipotide", "path": "/peptides/adipotide.html", "title": "Adipotide", "summary": "Proapoptotic peptide that kills off adipose-tissue blood vessels; pulled from development after it damaged kidneys in human trials.", "aliases": [ "FTPP", "peptide CKGGRAKDC-KLAKLAK-2", "Adipotide (FTPP)" ], "kind": "peptide", "categories": [ "fat-loss" ], "legacy": { "name": "Adipotide", "full_name": "CKGGRAKDC-GG-D-KLAKLAK-2 (proapoptotic peptide targeting adipose vasculature)", "aliases": [ "FTPP", "peptide CKGGRAKDC-KLAKLAK-2" ], "categories": [ "fat-loss" ], "tagline": "Proapoptotic peptide that kills off adipose-tissue blood vessels; pulled from development after it damaged kidneys in human trials.", "status": "Discontinued (Phase 1 nephrotoxicity) | Research chemical only", "origin": "Arrowhead Research built it as a targeted anti-angiogenesis strategy for obesity: an RGD homing motif binds integrin-expressing endothelial cells in white adipose tissue, fused to a proapoptotic KLAKLAK-2 domain. Efficacy in obese primates led to Phase 1 human trials in 2012, discontinued in 2019 for dose-limiting nephrotoxicity.", "mechanism": "The RGD sequence binds integrin-expressing endothelial cells in adipose vasculature; the KLAKLAK domain then permeabilizes the membrane and triggers apoptosis. Killing the vessels starves adipocytes of oxygen and shrinks fat tissue directly, with no appetite or glucose pathway involved.", "research_summary": "In obese rhesus monkeys, 0.43 mg/kg/day for 28 days produced about 11% body weight loss and improved insulin sensitivity. Phase 1 human trials hit dose-limiting renal toxicity: elevated creatinine and BUN, acute tubular injury. Development was abandoned, and no human efficacy data beyond preliminary reports was ever published.", "citations": [ { "title": "Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium", "authors_year": "Kim et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22733798/" } ], "reported_benefits": [ "weight loss in preclinical primate models (11% over 28 days)", "weight-independent metabolic improvements in animal models" ], "dosing_protocols": [ { "route": "Intravenous or subcutaneous injection", "protocol": "Preclinical primate studies used 0.43 mg/kg/day; no validated human dose exists." } ], "side_effects": [ "acute kidney injury", "elevated serum creatinine", "elevated BUN", "acute tubular necrosis", "fatigue" ], "safety_notes": "Caused dose-limiting renal toxicity in humans and was discontinued in 2019. There's no antidote or reversal strategy. Self-experimentation risks acute renal failure.", "community_notes": "Cited in biohacker circles as a cautionary tale, not a protocol. Black-market 'adipotide' is often misidentified or contaminated. Not recommended.", "related": [] }, "research": [ { "id": "catalog:peptide:adipotide", "title": "Adipotide (FTPP)", "summary": "A targeted peptide that showed weight loss in animal models but development was halted due to kidney toxicity in human trials.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "Adipotide (FTPP, Fat-Targeted Proapoptotic Peptide) is a synthetic peptidomimetic designed to induce apoptosis selectively in the vasculature of white adipose tissue. Developed at MD Anderson Cancer Center, adipotide showed promising preclinical results: up to 30% weight loss in obese mice and 11% reduction in body weight in obese rhesus monkeys. A Phase I clinical trial in prostate cancer patients with obesity was initiated around 2012 but was terminated due to nephrotoxicity (kidney injury). Clinical development was discontinued in 2019. As of April 2026, no completed peer-reviewed human efficacy or safety trial has been published.", "verdict": { "benefits": [ "Showed significant weight loss in preclinical animal models (30% in mice, 11% in primates)" ], "risks": [ "Phase I human trial was terminated due to nephrotoxicity (kidney damage)", "No completed human efficacy or safety trials have been published", "Clinical development was discontinued in 2019", "Use outside clinical trials is not supported by evidence and carries significant safety risks" ], "bottomLine": "Adipotide showed promise in animal models but human development was halted due to kidney toxicity; it is not approved for human use." }, "originalLinks": [ { "title": "Adipotide (FTPP): Research, Safety, and Status — Superpower", "url": "https://superpower.com/guides/peptides/adipotide" }, { "title": "Prohibitin-targeting peptide 1", "url": "https://en.wikipedia.org/wiki/Prohibitin-targeting_peptide_1" }, { "title": "Phase 1 trial of ADI-PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729058/" } ], "links": [ { "title": "Adipotide (FTPP): Research, Safety, and Status — Superpower", "url": "https://superpower.com/guides/peptides/adipotide" }, { "title": "Prohibitin-targeting peptide 1", "url": "https://en.wikipedia.org/wiki/Prohibitin-targeting_peptide_1" }, { "title": "Phase 1 trial of ADI-PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729058/" } ], "protocols": [], "community": [ { "description": "A peptide information source documents a protocol of 500 mcg administered subcutaneously daily in the abdomen or thigh over a four-week course.", "source": { "title": "Adipotide Peptide Dosage Guide - Peptide Mind", "url": "https://peptidemind.com/peptides/adipotide" }, "origins": [ "evidence.json#/catalog:peptide:adipotide/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:adipotide/community/0", "url": "https://peptidemind.com/peptides/adipotide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:22733798", "https://superpower.com/guides/peptides/adipotide", "https://en.wikipedia.org/wiki/Prohibitin-targeting_peptide_1", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729058/", "https://peptidemind.com/peptides/adipotide" ] }, "peptide:aicar": { "id": "peptide:aicar", "path": "/peptides/aicar.html", "title": "AICAR", "summary": "AMPK activator marketed as 'exercise in a pill.' WADA-banned in sport, not FDA-approved for anything.", "aliases": [ "AICA ribonucleoside", "AMP-mimetic" ], "kind": "supplement", "categories": [ "fitness-muscle", "fat-loss", "anti-aging" ], "legacy": { "name": "AICAR", "full_name": "5-aminoimidazole-4-carboxamide ribonucleoside (AMPK activator, small molecule nucleoside)", "aliases": [ "AICA ribonucleoside", "AMP-mimetic" ], "categories": [ "fitness-muscle", "fat-loss", "anti-aging" ], "tagline": "AMPK activator marketed as 'exercise in a pill.' WADA-banned in sport, not FDA-approved for anything.", "status": "Research chemical | WADA-banned | Not FDA-approved", "origin": "A nucleoside derivative first used as a research tool for studying AMPK signaling. A 2008 mouse study showing improved exercise endurance without any actual training turned it into an 'exercise mimetic.' Not FDA-approved; WADA banned it from competition in 2009.", "mechanism": "Mimics AMP to directly activate AMPK, the cell's energy sensor. That triggers fatty-acid oxidation and mitochondrial biogenesis via PGC-1-alpha, reproducing some of the metabolic adaptations of aerobic exercise.", "research_summary": "Rodent studies show improved glucose tolerance, reduced hepatic steatosis, and better endurance without exercise. Human trial data is sparse, no large registered trials have been completed, and oral bioavailability is poor (under 5%). No long-term human safety data exists.", "citations": [], "reported_benefits": [ "improved glucose tolerance and insulin sensitivity (animal/cell studies)", "enhanced mitochondrial biogenesis (theoretical)", "improved endurance in mice" ], "dosing_protocols": [ { "route": "Intraperitoneal, intravenous (no validated human route)", "protocol": "Animal studies use 500 mg/kg IP or IV; community biohacker protocols report 50-100 mg/day oral or 0.5-1 mg/kg subcutaneous, unvalidated." } ], "side_effects": [ "nausea (anecdotal)", "gastrointestinal upset", "potential gout exacerbation (elevated uric acid)", "fatigue or malaise" ], "safety_notes": "No human toxicology data exists and it's not FDA-approved. It elevates uric acid and can trigger gout or acute kidney injury in predisposed people. Black-market purity is unverifiable.", "community_notes": "Discussed as an exercise mimetic in longevity forums. Reports range from modest weight loss and better endurance to nothing noticeable. Even fans admit the preclinical data is strong and the human data is nonexistent.", "related": [] }, "research": [ { "id": "catalog:supplement:aicar", "title": "AICAR", "summary": "A naturally produced AMPK activator with limited clinical use due to poor oral bioavailability and requirement for intravenous administration.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is produced naturally in the body and activates AMP-activated protein kinase (AMPK). In limited human studies, systemic AICAR administration reduced hepatic glucose output and increased glucose uptake in skeletal muscle. AICAR has been used clinically in select settings for myocardial protection in cardiac bypass surgery and cardiac ischemia. However, AICAR has poor oral bioavailability and the only viable clinical route is continuous intravenous infusion, which severely limits its use for chronic treatment. Importantly, many effects previously attributed to AMPK activation by AICAR are now known to be AMPK-independent.", "verdict": { "benefits": [ "Reduces hepatic glucose output and increases muscle glucose uptake in clinical use", "Has been used clinically for myocardial protection in cardiac surgery" ], "risks": [ "Very poor oral bioavailability; requires intravenous infusion for clinical effect", "Intravenous route is unsuitable for chronic treatment of metabolic disorders", "Many AICAR effects are AMPK-independent, complicating understanding of mechanism", "Long-term safety in chronic systemic use is not established" ], "bottomLine": "AICAR has shown metabolic effects in limited human studies but poor oral bioavailability and requirement for intravenous administration have prevented its development as a chronic therapeutic." }, "originalLinks": [ { "title": "What Athletes Should Know About AICAR and Others", "url": "https://www.usada.org/spirit-of-sport/aicar-and-other-prohibited-amp-activated-protein-kinase-activators/" }, { "title": "AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147799/" }, { "title": "AICAR inhibits NFκB DNA binding independently of AMPK to attenuate LPS-triggered inflammatory responses in human macrophages", "url": "https://www.nature.com/articles/s41598-018-26102-3" } ], "links": [ { "title": "What Athletes Should Know About AICAR and Others", "url": "https://www.usada.org/spirit-of-sport/aicar-and-other-prohibited-amp-activated-protein-kinase-activators/" }, { "title": "AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147799/" }, { "title": "AICAR inhibits NFκB DNA binding independently of AMPK to attenuate LPS-triggered inflammatory responses in human macrophages", "url": "https://www.nature.com/articles/s41598-018-26102-3" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.usada.org/spirit-of-sport/aicar-and-other-prohibited-amp-activated-protein-kinase-activators/", "outcome": "no-practice-description", "reason": "The inspected anti-doping article discusses prohibited-substance use, safety warnings and research mechanisms. No usage protocol was imported from it." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.usada.org/spirit-of-sport/aicar-and-other-prohibited-amp-activated-protein-kinase-activators/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147799/", "https://www.nature.com/articles/s41598-018-26102-3" ] }, "peptide:5-amino-1mq": { "id": "peptide:5-amino-1mq", "path": "/peptides/5-amino-1mq.html", "title": "5-Amino-1MQ", "summary": "NNMT inhibitor that redirects nicotinamide into NAD+ synthesis. Popular in biohacker circles, backed by zero human trials.", "aliases": [ "5-A1MQ", "NNMT inhibitor" ], "kind": "supplement", "categories": [ "fat-loss", "longevity", "anti-aging" ], "legacy": { "name": "5-Amino-1MQ", "full_name": "5-amino-1-methylquinolinium (NNMT inhibitor, small molecule)", "aliases": [ "5-A1MQ", "NNMT inhibitor" ], "categories": [ "fat-loss", "longevity", "anti-aging" ], "tagline": "NNMT inhibitor that redirects nicotinamide into NAD+ synthesis. Popular in biohacker circles, backed by zero human trials.", "status": "Research chemical | Not FDA-approved", "origin": "Inhibits nicotinamide N-methyltransferase (NNMT), the enzyme that diverts nicotinamide away from NAD+ synthesis. Mouse studies from 2015-2020 showed NNMT inhibition improves metabolic markers, and the compound moved into biohacker circles around 2021. No regulatory approval anywhere.", "mechanism": "Blocking NNMT redirects nicotinamide into the NAD+ salvage pathway. More NAD+ drives sirtuin and PARP activity, which preclinical work ties to mitochondrial biogenesis, metabolic flexibility, reduced fibrosis, and immune modulation.", "research_summary": "Mouse models show improved insulin sensitivity, higher energy expenditure, and less hepatic steatosis. No published human trials exist, and human pharmacokinetics and dose-response are unknown.", "citations": [ { "title": "A Bisubstrate Inhibitor of NNMT Suppresses Myofibroblast Reprogramming to Mitigate Skin Fibrosis", "authors_year": "Saba et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42716212/" } ], "reported_benefits": [ "potential weight loss via increased energy expenditure (animal models)", "improved insulin sensitivity (preclinical)", "increased NAD+ bioavailability (theoretical)" ], "dosing_protocols": [ { "route": "Oral capsule or powder; subcutaneous (anecdotal)", "protocol": "No human-validated dose. Community protocols (unvalidated) range 50-250 mg once or twice daily orally." } ], "side_effects": [ "potential gastrointestinal upset (anecdotal)", "potential nausea (anecdotal)", "unknown long-term effects" ], "safety_notes": "No human trials or toxicology data exist; safety in people is unknown. NNMT has other jobs in the cell, so chronic inhibition could impair methylation capacity. Sourced product purity is unverified.", "community_notes": "Discussed as a NAD+ restoration tool alongside NMN, NR, and metformin. Users report more energy and better body composition, but it's all unblinded and self-reported.", "related": [ "nad" ] }, "research": [ { "id": "catalog:supplement:5-amino-1mq", "title": "5-Amino-1MQ", "summary": "An experimental NNMT inhibitor showing weight loss effects in mice, with no completed human trials.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "preclinical", "evidenceSummary": "5-Amino-1MQ is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that depletes S-adenosylmethionine in adipose tissue. In preclinical animal studies, 5-Amino-1MQ reversed diet-induced obesity and improved glucose tolerance in mice, with effects on fat oxidation and energy expenditure. As of June 2026, no human clinical trials have been completed or published in peer-reviewed journals, and no trials appear on ClinicalTrials.gov. It has not been evaluated by any regulatory body (FDA, EMA, MHRA) and is not a licensed medicine in any jurisdiction.", "verdict": { "benefits": [ "Animal studies show reversal of diet-induced obesity and improved glucose tolerance" ], "risks": [ "No human clinical trials have been completed or published", "Safety and efficacy in humans are completely unknown", "Not regulated or approved by any regulatory agency", "Effects shown in mice may not translate to humans" ], "bottomLine": "5-Amino-1MQ is an experimental research compound with only preclinical evidence; no human trials have been conducted and it is not approved for human use." }, "originalLinks": [ { "title": "5-Amino-1MQ: NNMT Inhibitor Research — Superpower", "url": "https://superpower.com/guides/peptides/5-amino-1mq" }, { "title": "Quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof", "url": "https://image-ppubs.julius.com/dirsearch-public/print/downloadPdf/12071409" }, { "title": "5-Amino-1MQ Human Clinical Trial: What the Evidence Actually Shows", "url": "https://formblends.com/articles/peptide-hub/directory-5-amino-1mq-human-clinical-trial" } ], "links": [ { "title": "5-Amino-1MQ: NNMT Inhibitor Research — Superpower", "url": "https://superpower.com/guides/peptides/5-amino-1mq" }, { "title": "Quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof", "url": "https://image-ppubs.julius.com/dirsearch-public/print/downloadPdf/12071409" }, { "title": "5-Amino-1MQ Human Clinical Trial: What the Evidence Actually Shows", "url": "https://formblends.com/articles/peptide-hub/directory-5-amino-1mq-human-clinical-trial" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://peptidemind.com/where-to-buy-5-amino-1mq", "outcome": "no-practice-description", "reason": "The inspected page promotes research-chemical vendors and product purchasing. It was not accepted as a trustworthy practice source." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [ "peptide:nad" ], "conflicts": [], "sourceRefs": [ "pmid:42716212", "https://superpower.com/guides/peptides/5-amino-1mq", "https://image-ppubs.julius.com/dirsearch-public/print/downloadPdf/12071409", "https://formblends.com/articles/peptide-hub/directory-5-amino-1mq-human-clinical-trial" ] }, "peptide:hgh-somatropin": { "id": "peptide:hgh-somatropin", "path": "/peptides/hgh-somatropin.html", "title": "Somatropin", "summary": "FDA-approved recombinant growth hormone for deficiency, widely used off-label for performance and body composition.", "aliases": [ "rHGH", "rhGH", "synthetic human growth hormone", "HGH 191AA", "Growth hormone (somatropin)" ], "kind": "medication-hormone", "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "legacy": { "name": "Somatropin", "full_name": "Recombinant human growth hormone, 191-amino acid", "aliases": [ "rHGH", "rhGH", "synthetic human growth hormone", "HGH 191AA" ], "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "tagline": "FDA-approved recombinant growth hormone for deficiency, widely used off-label for performance and body composition.", "status": "FDA-approved (GHD treatment) | Off-label use widespread", "origin": "Recombinant human growth hormone produced via genetic engineering starting in the 1980s, replacing cadaver-derived pituitary extracts. Now available in daily and long-acting pegylated/fusion formulations.", "mechanism": "Binds growth hormone receptor (GHR) on target tissues, promoting IGF-1 production in the liver (endocrine) and peripheral tissues (autocrine/paracrine). Stimulates lipolysis, amino acid uptake, protein synthesis in muscle, and bone mineral density.", "research_summary": "Long-acting GH formulations show non-inferiority to daily GH in height velocity and similar safety. Approved for childhood and adult GHD. Off-label performance use is common but carries risks including hyperglycemia, insulin resistance, and carpal tunnel syndrome; long-term safety data in off-label populations is limited.", "citations": [ { "title": "Treatment of growth hormone deficiency with long-acting growth hormones in children, adolescents and adults: Clinical evidence and practical considerations", "authors_year": "Linglart et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42727727/" } ], "reported_benefits": [ "increased lean muscle mass", "improved body composition", "enhanced recovery", "increased bone mineral density" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "FDA: 0.04-0.1 mg/kg/day (adult GHD). Off-label athletic use: typically 2-6 IU daily or 4-8 IU every other day." } ], "side_effects": [ "hyperglycemia", "insulin resistance", "carpal tunnel syndrome", "gynecomastia", "fluid retention", "joint pain" ], "safety_notes": "FDA-approved only for documented GHD. Off-label supraphysiological use carries undefined long-term risk. Contraindicated in active cancer. Requires monitoring of glucose, IGF-1, bone density.", "community_notes": "Widely sourced from underground labs and diverted pharmaceutical supply. Common protocols 2-10 IU daily, often stacked with secretagogues. Users report muscle/recovery gains alongside water retention and joint pain.", "related": [ "cjc-1295-dac", "ipamorelin", "sermorelin", "hexarelin" ], "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "cjc-1295", "cjc-1295-dac", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:hormone:hgh", "title": "Growth hormone (somatropin)", "summary": "Recombinant human growth hormone. Dosed in IU or mg depending on the product, which is a common source of error.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Somatropin is recombinant human growth hormone. The linked FDA label (Norditropin) approves it for children with growth failure from growth hormone deficiency, Noonan syndrome, Turner syndrome, and small size for gestational age without catch-up growth, and for adults with growth hormone deficiency. Other somatropin products carry their own approved uses, which this label does not cover. The label also warns about raised blood glucose and intracranial hypertension.", "verdict": { "benefits": [ "Several causes of growth failure in children and for adult growth hormone deficiency." ], "risks": [ "The label warns about raised blood glucose and raised pressure inside the skull", "Approval covers named deficiency conditions only; other somatropin products have their own approved uses", "This is regulator-approved labelling, not evidence for use outside those conditions" ], "bottomLine": "Somatropin is approved for specific growth hormone deficiency conditions and carries glucose and brain-pressure warnings.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "EMA: somatropin", "url": "https://www.ema.europa.eu/en/medicines/human/referrals/somatropin" } ], "links": [ { "title": "Norditropin (somatropin) injection FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021148s049lbl.pdf" } ], "protocols": [ { "population": "children with growth failure from growth hormone deficiency, per the US label", "regimen": "0.024 to 0.034 mg/kg/day subcutaneously, 6 to 7 times a week", "duration": "ongoing, per the label", "outcome": "The label approves this dosing for the treatment of children with growth failure due to growth hormone deficiency.", "source": { "title": "Norditropin (somatropin) injection FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021148s049lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:hgh/protocols/0" ] }, { "population": "adults with adult-onset or childhood-onset growth hormone deficiency, per the US label", "regimen": "0.004 mg/kg/day subcutaneously, raised as tolerated to no more than 0.016 mg/kg/day after about 6 weeks; or about 0.2 mg/day (range 0.15-0.30)", "duration": "ongoing, per the label", "outcome": "The label approves this dosing for the treatment of adults with growth hormone deficiency.", "source": { "title": "Norditropin (somatropin) injection FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021148s049lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:hgh/protocols/1" ] }, { "population": "children with short stature associated with Turner syndrome, per the US label", "regimen": "up to 0.067 mg/kg/day subcutaneously", "duration": "ongoing, per the label", "outcome": "The label approves this dosing for short stature associated with Turner syndrome.", "source": { "title": "Norditropin (somatropin) injection FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021148s049lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:hgh/protocols/2" ] }, { "population": "children with short stature associated with Noonan syndrome, per the US label", "regimen": "up to 0.066 mg/kg/day subcutaneously", "duration": "ongoing, per the label", "outcome": "The label approves this dosing for short stature associated with Noonan syndrome.", "source": { "title": "Norditropin (somatropin) injection FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021148s049lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:hgh/protocols/3" ] } ], "community": [ { "description": "Community-reported protocols range from 1–2 IU subcutaneously daily for anti-aging and wellness purposes to 2–4 IU per day split between morning and evening doses for body recomposition, with titration guided by IGF-1 levels.", "source": { "title": "HGH (Somatropin) Protocol Guide — Dosing & Administration", "url": "https://www.pathtopeptides.com/hgh-somatropin-protocol.html" }, "origins": [ "evidence.json#/catalog:hormone:hgh/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:hgh/community/0", "url": "https://www.pathtopeptides.com/hgh-somatropin-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 3, "source": "FDA label, Genotropin: SC half-life 3.0 h in GHD adults (vs 0.4 h IV — slow SC absorption dominates)" } } ], "related": [ "peptide:cjc-1295-dac", "peptide:hexarelin", "peptide:ipamorelin", "peptide:sermorelin" ], "conflicts": [], "sourceRefs": [ "pmid:42727727", "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021148s049lbl.pdf", "https://www.ema.europa.eu/en/medicines/human/referrals/somatropin", "https://www.pathtopeptides.com/hgh-somatropin-protocol.html" ] }, "peptide:ghrp-2": { "id": "peptide:ghrp-2", "path": "/peptides/ghrp-2.html", "title": "GHRP-2", "summary": "Potent synthetic growth hormone secretagogue with strong GH stimulation and emerging research support for tissue repair.", "aliases": [ "pralmorelin", "GPA-748" ], "kind": "peptide", "categories": [ "fitness-muscle", "recovery-healing" ], "legacy": { "name": "GHRP-2", "full_name": "Growth hormone releasing peptide-2 (pralmorelin)", "aliases": [ "pralmorelin", "GPA-748" ], "categories": [ "fitness-muscle", "recovery-healing" ], "tagline": "Potent synthetic growth hormone secretagogue with strong GH stimulation and emerging research support for tissue repair.", "status": "Research compound | Used experimentally in clinical settings", "origin": "Synthetic hexapeptide GH secretagogue mimicking ghrelin, INN pralmorelin. Originally developed for diagnostic testing of pituitary GH reserve.", "mechanism": "Potent agonist of GHSR1a on anterior pituitary somatotrophs, stimulating rapid GH release via Gq/11 signaling. Recent research suggests immune-modulation and tissue-repair effects independent of GH.", "research_summary": "Produces robust GH responses (peak >80 ng/mL) in diagnostic use. Animal studies show improved tendon-bone healing in rotator cuff models through macrophage modulation. Clinical applications remain limited to diagnostic testing; long-term data in non-clinical populations is sparse.", "citations": [ { "title": "Robust growth hormone responses to GH-releasing peptide 2 in adolescents", "authors_year": "Onuki et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38958228/" } ], "reported_benefits": [ "growth hormone stimulation", "tendon/ligament healing", "reduced inflammation (animal models)", "muscle recovery" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg once or twice daily; often stacked with other GHRPs or CJC-1295." } ], "side_effects": [ "appetite stimulation (mild)", "cortisol elevation with repeated doses", "prolactin elevation", "numbness/tingling" ], "safety_notes": "Not approved for human use outside clinical research. Repeated dosing may raise prolactin/cortisol. Limited long-term safety data.", "community_notes": "Used with CJC-1295 or ipamorelin as a peptide stack. Anecdotal reports of improved recovery and faster minor-injury healing.", "related": [ "ghrp-6", "hexarelin", "cjc-1295-dac", "ipamorelin" ], "mixing_notes": { "clinic_combos": [ "epithalon", "pt-141", "semax" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:ghrp-2", "title": "GHRP-2", "summary": "Growth hormone releasing peptide studied for GH secretion. Raises appetite via ghrelin signalling.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "GHRP-2 (pralmorelin) is a synthetic growth hormone secretagogue. The owner's wiki records it as a research compound used experimentally in clinical settings, mainly for testing pituitary GH reserve. A linked human study in adolescents reports strong growth hormone responses. Animal work suggests tendon-bone healing through macrophage modulation, separate from GH itself. Long-term human safety data outside clinical research is sparse.", "verdict": { "benefits": [ "A human study in adolescents reports strong growth hormone responses", "Used experimentally to test how much growth hormone the pituitary can release" ], "risks": [ "A research compound, not an approved medicine outside clinical research settings", "The tendon-bone healing evidence is from animals only", "Long-term human safety data outside clinical research is sparse" ], "bottomLine": "GHRP-2 reliably provokes growth hormone release in testing, but remains a research compound with sparse safety data." }, "originalLinks": [ { "title": "PubMed: GHRP-2", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=GHRP-2" } ], "links": [ { "title": "Peptide Wiki: Growth hormone releasing peptide-2 (pralmorelin)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/ghrp-2.html" }, { "title": "Robust growth hormone responses to GH-releasing peptide 2 in adolescents (Onuki et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38958228/" } ], "protocols": [], "community": [ { "description": "EliteFitness forum moderator states a protocol of 125–250 mcg once to twice daily, noting this range represents the consensus recommendation across community discussions.", "source": { "title": "GHRP-2 Proper Dosing", "url": "https://www.elitefitness.com/forum/threads/ghrp-2-proper-dosing.1516518/" }, "origins": [ "evidence.json#/catalog:peptide:ghrp-2/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:ghrp-2/community/0", "url": "https://www.elitefitness.com/forum/threads/ghrp-2-proper-dosing.1516518/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 1, "source": "Published PK" } } ], "related": [ "peptide:cjc-1295-dac", "peptide:ghrp-6", "peptide:hexarelin", "peptide:ipamorelin" ], "conflicts": [], "sourceRefs": [ "pmid:38958228", "https://vespassassina.github.io/peptide-wiki/peptides/ghrp-2.html", "https://pubmed.ncbi.nlm.nih.gov/?term=GHRP-2", "https://www.elitefitness.com/forum/threads/ghrp-2-proper-dosing.1516518/" ] }, "peptide:ghrp-6": { "id": "peptide:ghrp-6", "path": "/peptides/ghrp-6.html", "title": "GHRP-6", "summary": "Potent GH secretagogue with distinctive strong appetite stimulation via ghrelin receptor mimicry.", "aliases": [ "growth hormone releasing peptide-6" ], "kind": "peptide", "categories": [ "fitness-muscle", "recovery-healing" ], "legacy": { "name": "GHRP-6", "full_name": "Growth hormone releasing hexapeptide", "aliases": [ "growth hormone releasing peptide-6" ], "categories": [ "fitness-muscle", "recovery-healing" ], "tagline": "Potent GH secretagogue with distinctive strong appetite stimulation via ghrelin receptor mimicry.", "status": "Research compound | Used experimentally", "origin": "Synthetic hexapeptide developed in the 1990s as a ghrelin receptor agonist, one of the earliest synthetic GH secretagogues. Used experimentally in GI motility research.", "mechanism": "Selective GHSR1a agonist that stimulates rapid GH secretion. Distinctively produces strong appetite stimulation via central ghrelin-like signaling in the arcuate nucleus and lateral hypothalamus.", "research_summary": "Stimulates GH release and robustly stimulates appetite in rodent and human studies. Accelerates GI transit in post-operative ileus models. Primary clinical research application has been GI motility disorders; evidence for muscle-building effects is limited to animal models and anecdote.", "citations": [ { "title": "The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic", "authors_year": "Hewson et al. 2002", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12453894/" } ], "reported_benefits": [ "growth hormone stimulation", "appetite stimulation", "gastrointestinal motility", "muscle recovery" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg 1-3x daily; some use 50-100 mcg pre-meal to enhance appetite." } ], "side_effects": [ "strong appetite stimulation (pronounced)", "increased cortisol", "prolactin elevation", "water retention", "potential blood pressure elevation" ], "safety_notes": "Not approved outside research. Continuous ghrelin agonism can elevate cortisol and may cause salt-sensitive hypertension. Limited long-term human safety data.", "community_notes": "Popular for bulking phases due to the intense hunger effect. Often stacked with other GHRPs to smooth appetite effects.", "related": [ "ghrp-2", "hexarelin", "cjc-1295-dac", "ipamorelin" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "hexarelin", "mgf", "semax", "thymalin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:ghrp-6", "title": "GHRP-6", "summary": "Growth hormone releasing peptide with a pronounced appetite-stimulating effect.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "GHRP-6 is a growth hormone secretagogue that acts on the ghrelin receptor. The owner's wiki records it as a research compound, not approved for human use, that raises growth hormone and strongly raises appetite, with gastrointestinal motility the main clinical research use. The wiki states that evidence for muscle-building effects is limited to animal models and anecdote. The only study linked here is rat work showing that leptin and insulin blunt the brain's response to a ghrelin mimetic.", "verdict": { "benefits": [ "Raises growth hormone and strongly raises appetite; gut motility is its main clinical research use" ], "risks": [ "A research compound, not approved for human use", "Muscle-building effects rest on animal models and anecdote only", "The single linked study is rat brain work, not a human trial" ], "bottomLine": "An unapproved secretagogue that raises appetite, with muscle claims resting on animals and anecdote." }, "originalLinks": [ { "title": "PubMed: GHRP-6", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=GHRP-6" } ], "links": [ { "title": "Peptide Wiki: Growth hormone releasing hexapeptide", "url": "https://vespassassina.github.io/peptide-wiki/peptides/ghrp-6.html" }, { "title": "The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic (Hewson et al. 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12453894/" } ], "protocols": [ { "population": "rats, both fed and 48-hour fasted Wistar rats and obese Zucker rats", "regimen": "a single intravenous injection of a maximally effective dose of GHRP-6, with chronic central infusion of insulin or leptin during the fast", "duration": "single injection after a 48-hour fast, with the central infusion running through the fast", "outcome": "Fasting tripled the arcuate Fos response to GHRP-6; central insulin or leptin suppressed that rise, and obese Zucker rats responded twice as strongly as lean controls.", "source": { "title": "The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic (Hewson et al. 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12453894/" }, "origins": [ "evidence.json#/catalog:peptide:ghrp-6/protocols/0" ] } ], "community": [ { "description": "SeekPeptides community guide documents 100 mcg per injection administered 2–3 times daily (upon waking fasted, immediately post-workout, and 30 minutes before bed), with 8–12 week cycle lengths commonly reported.", "source": { "title": "GHRP-6 Peptide: Complete Guide to Benefits, Dosage, and Protocols", "url": "https://www.seekpeptides.com/blog/articles/ghrp-6-peptide-complete-guide" }, "origins": [ "evidence.json#/catalog:peptide:ghrp-6/community/0" ] }, { "description": "The same source documents an advanced protocol of 100–200 mcg per injection, 3 times daily, when combined with Mod GRF 1-29, for 12–16 week cycles.", "source": { "title": "GHRP-6 Peptide: Complete Guide to Benefits, Dosage, and Protocols", "url": "https://www.seekpeptides.com/blog/articles/ghrp-6-peptide-complete-guide" }, "origins": [ "evidence.json#/catalog:peptide:ghrp-6/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:ghrp-6/community/0", "url": "https://www.seekpeptides.com/blog/articles/ghrp-6-peptide-complete-guide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:ghrp-6/community/1", "url": "https://www.seekpeptides.com/blog/articles/ghrp-6-peptide-complete-guide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 0.9166666666666666, "source": "Published PK" } } ], "related": [ "peptide:cjc-1295-dac", "peptide:ghrp-2", "peptide:hexarelin", "peptide:ipamorelin" ], "conflicts": [], "sourceRefs": [ "pmid:12453894", "https://vespassassina.github.io/peptide-wiki/peptides/ghrp-6.html", "https://pubmed.ncbi.nlm.nih.gov/?term=GHRP-6", "https://www.seekpeptides.com/blog/articles/ghrp-6-peptide-complete-guide" ] }, "peptide:hexarelin": { "id": "peptide:hexarelin", "path": "/peptides/hexarelin.html", "title": "Hexarelin", "summary": "Potent dual-receptor GH secretagogue with cardioprotective properties, limited by rapid receptor desensitization.", "aliases": [ "Rix-002" ], "kind": "peptide", "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "legacy": { "name": "Hexarelin", "full_name": "Growth hormone secretagogue hexarelin", "aliases": [ "Rix-002" ], "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "tagline": "Potent dual-receptor GH secretagogue with cardioprotective properties, limited by rapid receptor desensitization.", "status": "Research compound | Experimental cardiovascular use", "origin": "Synthetic hexapeptide GH secretagogue that also binds CD36 receptors on cardiac and endothelial cells, unlike GHRP-2/6 which target GHSR1a primarily. More chemically stable than natural ghrelin.", "mechanism": "GHSR1a agonism drives pituitary GH release; CD36 binding on cardiomyocytes triggers cardioprotective signaling via IL-1Ra upregulation and reduced myocardial oxidative stress during ischemia-reperfusion.", "research_summary": "Protects rat cardiomyocytes from ischemia-reperfusion injury via IL-1 signaling. Multiple rodent studies document cardioprotection. Major limitation: rapid tachyphylaxis, meaning GH response and possibly cardioprotection diminish sharply with repeated dosing. Clinical translation is limited.", "citations": [ { "title": "The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway", "authors_year": "Huang et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28321024/" } ], "reported_benefits": [ "growth hormone stimulation", "cardioprotection (animal evidence)", "anti-inflammatory effects (theoretical)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg 1-3x daily; cycling protocols (e.g. 5 days on/2 off) used to manage tachyphylaxis." } ], "side_effects": [ "appetite stimulation (mild-moderate)", "cortisol elevation", "prolactin elevation", "rapid tolerance development (tachyphylaxis)" ], "safety_notes": "Not FDA-approved. Primary concern is rapid receptor desensitization limiting utility. Cardioprotective effects are documented only in acute animal models; no human long-term outcome data.", "community_notes": "Adoption limited by tachyphylaxis. Some cycle or pulse-dose to maintain responsiveness; theoretical cardioprotective appeal in longevity circles.", "related": [ "ghrp-2", "ghrp-6", "cjc-1295-dac" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "ghrp-6", "mgf", "semax" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:hexarelin", "title": "Hexarelin", "summary": "Growth hormone secretagogue. More potent than ipamorelin but with greater cortisol and prolactin effect.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "Hexarelin is a research compound, not approved anywhere. The linked study is in rats: hexarelin treatment after induced heart ischaemia and reperfusion improved heart function and cardiomyocyte survival through interleukin-1 signalling. It stimulates growth hormone through the ghrelin receptor and also binds CD36 on heart cells, which is what sets it apart from GHRP-2 and GHRP-6. The main limitation recorded in the wiki is rapid tolerance, so the growth hormone response fades with repeated use. There is no human long-term outcome data.", "verdict": { "benefits": [ "Only shown in rats: better heart function and more surviving heart cells after induced ischaemia.", "It stimulates growth hormone through the ghrelin receptor and also binds CD36 on heart cells." ], "risks": [ "Not approved anywhere, and there is no human long-term outcome data here.", "Rapid tolerance is recorded, so the growth hormone response fades with repeated use." ], "bottomLine": "Hexarelin is an unapproved research compound: heart findings are from rats, and tolerance blunts its effect." }, "originalLinks": [ { "title": "PubMed: hexarelin", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=hexarelin" } ], "links": [ { "title": "Peptide Wiki: Growth hormone secretagogue hexarelin", "url": "https://vespassassina.github.io/peptide-wiki/peptides/hexarelin.html" }, { "title": "The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway (Huang et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28321024/" } ], "protocols": [ { "population": "male Sprague-Dawley rats after 30 minutes of coronary artery ligation followed by reperfusion", "regimen": "hexarelin 100 micrograms per kg per day subcutaneously, twice daily, against ghrelin 400 micrograms per kg per day or saline", "duration": "7 days", "outcome": "Hexarelin improved cardiac systolic function, lowered malondialdehyde and increased surviving cardiomyocytes, slightly more than equimolar ghrelin.", "source": { "title": "The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway (Huang et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28321024/" }, "origins": [ "evidence.json#/catalog:peptide:hexarelin/protocols/0" ] } ], "community": [ { "description": "A community protocol documented on Swolverine discusses 100–200 mcg administered 1–2 times per day via subcutaneous injection, with typical cycles running 8–12 weeks on followed by 4 weeks off.", "source": { "title": "Hexarelin For Beginners: Dosage, Benefits, and Peptide Stacking Guide", "url": "https://swolverine.com/blogs/blog/hexarelin-for-beginners-dosage-benefits-and-peptide-stacking-guide" }, "origins": [ "evidence.json#/catalog:peptide:hexarelin/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:hexarelin/community/0", "url": "https://swolverine.com/blogs/blog/hexarelin-for-beginners-dosage-benefits-and-peptide-stacking-guide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 1.1666666666666667, "source": "Published PK" } } ], "related": [ "peptide:cjc-1295-dac", "peptide:ghrp-2", "peptide:ghrp-6" ], "conflicts": [], "sourceRefs": [ "pmid:28321024", "https://vespassassina.github.io/peptide-wiki/peptides/hexarelin.html", "https://pubmed.ncbi.nlm.nih.gov/?term=hexarelin", "https://swolverine.com/blogs/blog/hexarelin-for-beginners-dosage-benefits-and-peptide-stacking-guide" ] }, "peptide:cjc-1295-dac": { "id": "peptide:cjc-1295-dac", "path": "/peptides/cjc-1295-dac.html", "title": "CJC-1295 with DAC", "summary": "Long-acting GHRH analog with week-long half-life via albumin binding; distinct from daily-dosing CJC-1295.", "aliases": [ "CJC-1295 DAC", "CJC-1295/DAC" ], "kind": "peptide", "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "legacy": { "name": "CJC-1295 with DAC", "full_name": "CJC-1295 drug affinity complex (GHRH analog with albumin-binding modification)", "aliases": [ "CJC-1295 DAC", "CJC-1295/DAC" ], "categories": [ "fitness-muscle", "anti-aging", "recovery-healing" ], "tagline": "Long-acting GHRH analog with week-long half-life via albumin binding; distinct from daily-dosing CJC-1295.", "status": "Research compound | Used in compounding pharmacies", "origin": "A synthetic 30-amino-acid GHRH analog. The DAC (drug affinity complex) variant adds four lysine residues that bind serum albumin, stretching half-life from about 10 minutes to 7-10 days, unlike plain CJC-1295 (Mod GRF 1-29), which needs multiple daily doses.", "mechanism": "A selective GHRH receptor agonist on somatotrophs, stimulating pulsatile GH release via Gs/cAMP signaling. Albumin binding blocks rapid renal clearance, which is what makes it long-acting.", "research_summary": "GHRH analogs are potent GH stimulators used diagnostically and preclinically. CJC-1295 with DAC hasn't been extensively studied in published human trials; most evidence comes from compounding-pharmacy literature and community protocols. Its advantage over plain CJC-1295 is fewer injections, at the cost of less precise titration.", "citations": [], "reported_benefits": [ "growth hormone stimulation", "reduced injection frequency (weekly vs daily)", "improved muscle mass", "enhanced recovery" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "100-200 mcg to 2mg SC weekly; often stacked with GHRP-2 or GHRP-6." } ], "side_effects": [ "mild water retention", "joint aches (rare)", "carpal tunnel-like symptoms (rare)", "cortisol elevation at high doses" ], "safety_notes": "Not FDA-approved. The key distinction from plain CJC-1295: DAC produces steady-state albumin-bound hormone instead of pulsatile dosing. Long-term human safety data is limited.", "community_notes": "Widely used for convenient weekly dosing, frequently stacked with GHRP-2/6. It differs fundamentally from CJC-1295 without DAC (short half-life, about 30 minutes, requiring 2-3x daily dosing); the two get confused constantly despite being pharmacokinetically distinct compounds.", "related": [ "ghrp-2", "ghrp-6", "hexarelin", "ipamorelin", "sermorelin", "cjc-1295" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "epithalon", "ghk-cu", "ghrp-6", "hexarelin", "ipamorelin", "mgf", "pe-22-28", "pinealon", "selank", "semax", "tb-500", "tesamorelin", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "hgh-somatropin", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:cjc-1295-dac", "title": "CJC-1295 with DAC", "summary": "Long-acting GHRH analogue. The drug affinity complex extends half-life to around a week.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "reference", "evidenceSummary": "CJC-1295 with DAC is a GHRH analogue modified to bind albumin, which makes it long-acting. The owner's wiki records it as a research compound used in compounding pharmacies, not an approved medicine. The wiki states it has not been extensively studied in published human trials and lists no peer-reviewed citations for it, so the evidence here is a single reference page. Claims about muscle or recovery come from community reports, not trials.", "verdict": { "benefits": [ "No published human evidence of benefit in the sources here." ], "risks": [ "Not an approved medicine: recorded as a research compound used by compounding pharmacies.", "The single source is a reference wiki page with no peer-reviewed citations.", "Muscle and recovery claims come from community reports, not from trials." ], "bottomLine": "CJC-1295 with DAC is an unapproved research compound with no published human trials in the sources here." }, "originalLinks": [ { "title": "PubMed: CJC-1295 DAC", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=CJC-1295+DAC" } ], "links": [ { "title": "Peptide Wiki: CJC-1295 with DAC", "url": "https://vespassassina.github.io/peptide-wiki/peptides/cjc-1295-dac.html" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 168, "source": "DAC albumin binding extends half-life" } } ], "related": [ "peptide:cjc-1295", "peptide:ghrp-2", "peptide:ghrp-6", "peptide:hexarelin", "peptide:ipamorelin", "peptide:sermorelin" ], "conflicts": [], "sourceRefs": [ "https://vespassassina.github.io/peptide-wiki/peptides/cjc-1295-dac.html", "https://pubmed.ncbi.nlm.nih.gov/?term=CJC-1295+DAC" ] }, "peptide:mgf": { "id": "peptide:mgf", "path": "/peptides/mgf.html", "title": "MGF", "summary": "Muscle-specific IGF-1 isoform generated by mechanical stress; promotes local muscle repair and satellite cell activation.", "aliases": [ "mechano growth factor", "IGF-1Ec" ], "kind": "peptide", "categories": [ "fitness-muscle", "recovery-healing" ], "legacy": { "name": "MGF", "full_name": "Mechano Growth Factor (IGF-1Ec splice variant)", "aliases": [ "mechano growth factor", "IGF-1Ec" ], "categories": [ "fitness-muscle", "recovery-healing" ], "tagline": "Muscle-specific IGF-1 isoform generated by mechanical stress; promotes local muscle repair and satellite cell activation.", "status": "Research compound | Experimental use", "origin": "IGF-1 splice variant produced locally in muscle after mechanical loading or injury, first described by Goldspink in the 1990s. Unlike systemic hepatic IGF-1, it acts autocrine/paracrine, right where it's made.", "mechanism": "Binds IGF-1 receptor on satellite cells, driving proliferation, differentiation, and fusion into myofibers via PI3K-Akt and MAPK-ERK signaling. First responder to muscle damage.", "research_summary": "Mechanistic work is mostly preclinical, animal and cell culture. Human trials of exogenous MGF are close to nonexistent. Compounding pharmacies sell it for experimental use, but human efficacy and safety are poorly characterized.", "citations": [], "reported_benefits": [ "local muscle hypertrophy", "muscle repair and recovery", "satellite cell activation" ], "dosing_protocols": [ { "route": "Local subcutaneous/intramuscular injection", "protocol": "100-200 mcg injected near target muscle post-workout, 2-3x weekly." } ], "side_effects": [ "local inflammation at injection site", "bruising", "potential systemic hypoglycemia if absorbed systemically" ], "safety_notes": "Not FDA-approved, minimal human trial data. Theoretical concern: exogenous IGF-1 pathway activity could feed occult malignancy growth, though this is speculative.", "community_notes": "Used post-workout for recovery. The local-MGF vs systemic PEG-MGF distinction matters for timing and use case.", "related": [ "ace-031", "hgh-somatropin", "ipamorelin" ], "variant_note": "PEG-MGF is a pegylated variant with extended half-life (minutes to hours) enabling more systemic distribution beyond the injection site, versus native MGF's local/periosteal action. Dosed similarly but with enhanced systemic bioavailability.", "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "ghrp-6", "hexarelin", "semax", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [], "related": [ "peptide:ace-031", "peptide:hgh-somatropin", "peptide:ipamorelin" ], "conflicts": [], "sourceRefs": [] }, "peptide:ace-031": { "id": "peptide:ace-031", "path": "/peptides/ace-031.html", "title": "ACE-031", "summary": "Myostatin decoy receptor that showed early promise in muscular dystrophy trials, then got shut down over vascular side effects.", "aliases": [ "ramatercept", "ACVR2B-Fc" ], "kind": "peptide", "categories": [ "fitness-muscle" ], "legacy": { "name": "ACE-031", "full_name": "ACVR2B-Fc fusion protein (soluble activin receptor type IIB fused to human IgG1)", "aliases": [ "ramatercept", "ACVR2B-Fc" ], "categories": [ "fitness-muscle" ], "tagline": "Myostatin decoy receptor that showed early promise in muscular dystrophy trials, then got shut down over vascular side effects.", "status": "Investigational (halted clinical trials) | Safety concerns unresolved", "origin": "Acceleron Pharma fused the ACVR2B ectodomain to IgG1 to build a high-affinity decoy receptor for myostatin and activins, aimed at muscle-wasting diseases like Duchenne muscular dystrophy.", "mechanism": "Binds myostatin and activins as a soluble decoy receptor, removing their brake on myogenesis and letting muscle protein synthesis run unopposed.", "research_summary": "A randomized placebo-controlled DMD trial was stopped early after vascular safety signals, epistaxis and telangiectasias, appeared. Before that, it showed non-significant trends toward maintained 6-minute walk distance and increased lean mass.", "citations": [ { "title": "Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial", "authors_year": "Campbell et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/27462804/" } ], "reported_benefits": [ "increased lean muscle mass (preclinical/animal)", "muscle strength preservation (animal models)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Clinical trial dosing every 2-4 weeks, ascending; no community-standard dosing due to trial discontinuation." } ], "side_effects": [ "epistaxis (nosebleeds)", "telangiectasias (abnormal blood vessel proliferation)", "potential vascular complications" ], "safety_notes": "Trials were halted for vascular safety signals. Acceleron discontinued development entirely; no trials are ongoing. Using it outside a trial is experimental and not recommended.", "community_notes": "Some still chase it for myostatin inhibition, but manufacturing cost limits underground supply, and most informed users skip it given the safety signal.", "related": [ "hgh-somatropin", "mgf" ] }, "research": [], "related": [ "peptide:hgh-somatropin", "peptide:mgf" ], "conflicts": [], "sourceRefs": [ "pmid:27462804" ] }, "peptide:mt-2": { "id": "peptide:mt-2", "path": "/peptides/mt-2.html", "title": "Melanotan II", "summary": "Unregulated synthetic melanocortin agonist used illicitly for tanning and erectile function, with significant cardiovascular and melanoma safety concerns.", "aliases": [ "melanotan-2", "MT-II" ], "kind": "peptide", "categories": [ "sexual-health", "anti-aging" ], "legacy": { "name": "Melanotan II", "full_name": "alpha-Melanocyte-stimulating hormone (α-MSH) analog (synthetic)", "aliases": [ "melanotan-2", "MT-II" ], "categories": [ "sexual-health", "anti-aging" ], "tagline": "Unregulated synthetic melanocortin agonist used illicitly for tanning and erectile function, with significant cardiovascular and melanoma safety concerns.", "status": "Research chemical | Not approved for any medical indication | Significant safety signals", "origin": "Synthetic alpha-MSH analogue developed in the 1980s, unregulated globally, sold through uncontrolled internet suppliers and tanning networks. Known for UV-independent tanning and, coincidentally, libido-enhancing effects. It's the parent compound PT-141 was later developed from.", "mechanism": "Non-selective melanocortin agonist: activates MC1R on melanocytes for melanin production and tanning, and centrally MC3R/MC4R in the hypothalamus for pro-sexual behavior and erectile function via dopamine and nitric-oxide pathways. The non-selective binding also hits appetite and sympathetic tone.", "research_summary": "Human evidence is mostly anecdotal and case-report based. Dermatology literature documents rapid mole darkening, dysplastic nevi, and melanoma emergence during or after use, though causality isn't firmly established. Priapism, hypertension, and thrombotic concerns are reported. No large prospective trials exist; regulatory bodies have issued safety warnings.", "citations": [ { "title": "Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review.", "authors_year": "Habbema et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28266027/" }, { "title": "Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?", "authors_year": "Langan et al. 2010", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20545686/" } ], "reported_benefits": [ "skin darkening/tanning", "increased libido and sexual arousal (anecdotal)", "improved erectile function (anecdotal)" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Typical self-dosing: loading 0.25-1 mg every 1-2 days until desired tan, then 0.5-1 mg/week maintenance. Uncontrolled, forum-derived protocols." } ], "side_effects": [ "nausea", "facial flushing", "rapid darkening/proliferation of moles", "dysplastic nevi", "priapism", "hypertension", "possible increased melanoma risk (case reports)" ], "safety_notes": "Multiple case reports document melanomas emerging from existing or new moles during or after use. Causality is unproven but has prompted formal health-authority warnings. Priapism can require emergency intervention. Strongly contraindicated with a personal or family melanoma history.", "community_notes": "Popular for rapid tanning (5-14 days) and reported spontaneous erections and increased libido, though tolerance to the sexual effects often develops over weeks to months. Communities warn of priapism risk.", "related": [ "pt-141", "mt-1" ], "mixing_notes": { "clinic_combos": [ "tb-500" ], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:melanotan-2", "title": "Melanotan II", "summary": "Melanocortin agonist studied for pigmentation. Not approved; sold as a research chemical.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "reference", "evidenceSummary": "Melanotan II is an unapproved synthetic analogue of alpha-melanocyte stimulating hormone, sold as a research chemical. The owner's wiki and two dermatology reviews describe human evidence as case reports and anecdote, with no prospective trials. Reported problems include rapid darkening of moles, new dysplastic naevi, and four case reports of melanoma appearing during or shortly after use, though cause has not been established. The reviews also flag unknown purity, unsafe self-injection and needle sharing, and note that afamelanotide is the only regulated analogue in this family.", "verdict": { "benefits": [ "No controlled human evidence of benefit in the sources here, only case reports and anecdote" ], "risks": [ "Case reports describe rapid darkening of moles, new dysplastic naevi and melanoma during or after use", "Reviews flag unknown purity, unsafe self-injection and needle sharing" ], "bottomLine": "Melanotan II is unapproved, has no prospective trials, and carries case reports of mole changes and melanoma.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "PubMed: melanotan II", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=melanotan+II" } ], "links": [ { "title": "Peptide Wiki: alpha-Melanocyte-stimulating hormone (α-MSH) analog (synthetic)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/mt-2.html" }, { "title": "Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. (Habbema et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28266027/" }, { "title": "Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'? (Langan et al. 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20545686/" } ], "protocols": [], "community": [ { "description": "An EliteFitness forum thread describes a loading phase starting with 0.25 mg daily, escalating over two weeks to 1 mg daily, followed by maintenance dosing at 1 mg weekly.", "source": { "title": "melanotan II maintenance dose? | EliteFitness.com Bodybuilding Forums", "url": "https://www.elitefitness.com/forum/anabolic-steroids/melanotan-ii-maintenance-dose-753493.html" }, "origins": [ "evidence.json#/catalog:peptide:melanotan-2/community/0" ] }, { "description": "An EliteFitness forum thread documents a protocol with a two-week loading schedule: days 1-2 at 2.5 units, days 3-5 at 5 units, days 6-7 at 7.5 units, days 8-14 at 10 units (approximately 250-1000 mcg), followed by maintenance every 2-7 days.", "source": { "title": "melanotan II dosage? | EliteFitness.com Bodybuilding Forums", "url": "https://www.elitefitness.com/forum/threads/melanotan-ii-dosage.494208/" }, "origins": [ "evidence.json#/catalog:peptide:melanotan-2/community/1" ] }, { "description": "Community discussions on EliteFitness describe 0.5-1.0 mg (500-1000 mcg) maintenance dosing every 1-2 weeks after reaching desired pigmentation, with users noting effects continue darkening for up to 60 days after discontinuation.", "source": { "title": "Get my tan on | EliteFitness.com Bodybuilding Forums", "url": "https://www.elitefitness.com/forum/threads/get-my-tan-on.1005673/" }, "origins": [ "evidence.json#/catalog:peptide:melanotan-2/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The historical forum's syringe-unit examples depend on a particular preparation. Do not reuse their unit-to-mass assumptions for a different vial or concentration." ], "community": [ { "origin": "evidence.json#/catalog:peptide:melanotan-2/community/0", "url": "https://www.elitefitness.com/forum/anabolic-steroids/melanotan-ii-maintenance-dose-753493.html", "claimMatch": "The historical forum's syringe-unit examples depend on a particular preparation. Do not reuse their unit-to-mass assumptions for a different vial or concentration. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:melanotan-2/community/1", "url": "https://www.elitefitness.com/forum/threads/melanotan-ii-dosage.494208/", "claimMatch": "The historical forum's syringe-unit examples depend on a particular preparation. Do not reuse their unit-to-mass assumptions for a different vial or concentration. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:melanotan-2/community/2", "url": "https://www.elitefitness.com/forum/threads/get-my-tan-on.1005673/", "claimMatch": "The historical forum's syringe-unit examples depend on a particular preparation. Do not reuse their unit-to-mass assumptions for a different vial or concentration. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 33, "source": "Published PK" } } ], "related": [ "peptide:mt-1", "peptide:pt-141" ], "conflicts": [], "sourceRefs": [ "pmid:28266027", "pmid:20545686", "https://vespassassina.github.io/peptide-wiki/peptides/mt-2.html", "https://pubmed.ncbi.nlm.nih.gov/?term=melanotan+II", "https://www.elitefitness.com/forum/anabolic-steroids/melanotan-ii-maintenance-dose-753493.html", "https://www.elitefitness.com/forum/threads/melanotan-ii-dosage.494208/", "https://www.elitefitness.com/forum/threads/get-my-tan-on.1005673/" ] }, "peptide:mt-1": { "id": "peptide:mt-1", "path": "/peptides/mt-1.html", "title": "Melanotan I", "summary": "FDA- and EU-approved MC1R agonist for erythropoietic protoporphyria; regulated pharmaceutical with photoprotection benefits, distinct from unregulated MT-2.", "aliases": [ "afamelanotide", "Scenesse" ], "kind": "peptide", "categories": [ "anti-aging", "recovery-healing" ], "legacy": { "name": "Melanotan I", "full_name": "Afamelanotide (NDP-α-MSH)", "aliases": [ "afamelanotide", "Scenesse" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "FDA- and EU-approved MC1R agonist for erythropoietic protoporphyria; regulated pharmaceutical with photoprotection benefits, distinct from unregulated MT-2.", "status": "FDA approved (2019, USA) | EMA approved (2014, EU) | Indication: Erythropoietic Protoporphyria (EPP)", "origin": "Chemically modified, MC1R-selective α-MSH analogue developed by Clinuvel Pharmaceuticals for photosensitivity disorders, notably erythropoietic protoporphyria. The structural modifications give it receptor selectivity and better stability than the non-selective MT-2.", "mechanism": "Selectively activates MC1R on melanocytes, increasing eumelanin synthesis via cAMP signaling for UV-absorbing photoprotection. The MC1R selectivity minimizes the CNS and systemic off-target effects seen with MT-2.", "research_summary": "Phase III trials in EPP patients showed significant reduction in phototoxic reaction frequency and severity, combined with photoprotection measures. Safety is well-characterized: adverse events are mostly mild nausea and injection-site effects. The cardiovascular, melanoma, and priapism signals seen with MT-2 haven't shown up in controlled afamelanotide trials.", "citations": [ { "title": "Hormones and skin pigmentation: fundamentals and clinical relevance.", "authors_year": "Böhm et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41489668/" } ], "reported_benefits": [ "significant reduction in phototoxic reactions in EPP", "increased skin pigmentation/UV photoprotection", "improved quality of life in photosensitive patients" ], "dosing_protocols": [ { "route": "Subcutaneous implant", "protocol": "FDA-approved (EPP): 16 mg subcutaneous implant every 2 months, combined with strict photoprotection." } ], "side_effects": [ "injection-site erythema/induration", "nausea (5-10%, usually transient)", "headache (mild)", "hyperpigmentation" ], "safety_notes": "Strong safety profile in controlled trials, with none of MT-2's cardiovascular, melanoma, or priapism signals. Use is restricted to documented photoprotection deficiency, with specialist dermatological surveillance recommended.", "community_notes": "Off-label tanning or anti-aging use is uncommon due to regulatory restriction and cost. No solid evidence supports cosmetic tanning or general anti-aging use outside the approved EPP indication.", "related": [ "mt-2" ], "mixing_notes": { "clinic_combos": [ "tb-500" ], "anecdotal_combos": [ "hcg" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [], "related": [ "peptide:mt-2" ], "conflicts": [], "sourceRefs": [ "pmid:41489668" ] }, "peptide:gonadorelin": { "id": "peptide:gonadorelin", "path": "/peptides/gonadorelin.html", "title": "Gonadorelin acetate", "summary": "GnRH agonist peptide that stimulates endogenous LH and FSH to preserve testicular function and fertility during testosterone replacement therapy.", "aliases": [ "GnRH", "LHRH", "luliberin", "Gonadorelin" ], "kind": "peptide", "categories": [ "sexual-health" ], "legacy": { "name": "Gonadorelin acetate", "full_name": "Gonadotropin-releasing hormone (GnRH) decapeptide acetate", "aliases": [ "GnRH", "LHRH", "luliberin" ], "categories": [ "sexual-health" ], "tagline": "GnRH agonist peptide that stimulates endogenous LH and FSH to preserve testicular function and fertility during testosterone replacement therapy.", "status": "FDA approved | Off-label: HPG-axis preservation during TRT", "origin": "A synthetic decapeptide copy of endogenous GnRH, FDA-approved since 1981 for evaluating gonadotropin reserve and treating hypogonadotropic hypogonadism. Increasingly used off-label to prevent testicular suppression from exogenous testosterone.", "mechanism": "Agonizes GnRH receptors on pituitary gonadotrophs, stimulating LH and FSH release. Pulsatile dosing maintains HPG-axis output; continuous exposure paradoxically suppresses it, the basis of medical castration. In TRT-suppressed men, pulsatile/low-dose gonadorelin restimulates endogenous testosterone and spermatogenesis.", "research_summary": "A 2026 narrative review identified GnRH-based strategies as promising for TRT-induced reproductive suppression, though evidence for full spermatogenesis/fertility restoration remains limited. Small studies show combination therapy (TRT + low-dose gonadorelin + hCG) partially restores FSH/LH and reduces testicular atrophy, with variable success.", "citations": [ { "title": "Emerging peptide and neuroendocrine strategies for TRT-induced reproductive suppression and functional male hypogonadism: a narrative review.", "authors_year": "Cretu et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42666625/" } ], "reported_benefits": [ "preservation/restoration of endogenous testosterone in TRT users", "maintenance of spermatogenesis during TRT", "reduced testicular atrophy" ], "dosing_protocols": [ { "route": "Subcutaneous or intravenous injection", "protocol": "Off-label TRT protocol: ~150 mcg subcutaneous twice weekly, or pulsatile pump dosing; not well standardized." } ], "side_effects": [ "local injection-site reactions", "transient nausea and headache", "gynecomastia", "mood changes" ], "safety_notes": "Generally well-tolerated at low/pulsatile dosing. Continuous high-dose agonism causes prolonged suppression. Pulsatile administration is critical to avoid paradoxical effects. Caution with pituitary pathology.", "community_notes": "TRT users report using low-dose gonadorelin alongside testosterone to maintain the HPG axis and fertility, often combined with hCG and clomiphene. Reported outcomes are variable.", "related": [ "hcg", "pt-141" ] }, "research": [ { "id": "catalog:peptide:gonadorelin", "title": "Gonadorelin", "summary": "A GnRH peptide that was FDA-approved for diagnostic pituitary testing but is no longer commercially available.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "reference", "evidenceSummary": "Gonadorelin (GnRH) was approved by the FDA as Factrel for diagnostic evaluation of pituitary function, specifically to differentiate pituitary from hypothalamic causes of hypogonadotropic hypogonadism. A functional pituitary responds to IV GnRH with an LH surge; non-functional pituitary does not. Factrel was voluntarily discontinued for commercial reasons.", "verdict": { "benefits": [ "Diagnostic evaluation of pituitary function." ], "risks": [ "Approved product (Factrel) voluntarily discontinued from U.S. market" ], "bottomLine": "Regulatory approval for diagnostic use only; approved product discontinued, leaving no current FDA-approved gonadorelin available.", "approvalStatus": "FDA-approved for diagnostic use, but the approved product was discontinued." }, "originalLinks": [ { "title": "Gonadorelin: GnRH Peptide Overview - Superpower", "url": "https://superpower.com/guides/gonadorelin" }, { "title": "Gonadorelin Peptide - Peptides Institute", "url": "https://www.peptidesinstitute.org/peptides/gonadorelin" } ], "links": [ { "title": "Gonadorelin: GnRH Peptide Overview - Superpower", "url": "https://superpower.com/guides/gonadorelin" }, { "title": "Gonadorelin Peptide - Peptides Institute", "url": "https://www.peptidesinstitute.org/peptides/gonadorelin" } ], "protocols": [], "community": [ { "description": "A protocol documented on PeptideDosage describes 50-250 mcg per injection administered 2-3 times weekly, with weeks 1-2 at 50 mcg, weeks 3-4 at 100 mcg, and weeks 5-8 at 100-150 mcg maintenance via subcutaneous injection.", "source": { "title": "Gonadorelin Dosage Chart and Reconstitution Protocol", "url": "https://www.peptidedosage.org/peptides/gonadorelin/dosage" }, "origins": [ "evidence.json#/catalog:peptide:gonadorelin/community/0" ] }, { "description": "An alternative protocol shared on PeptideDosage describes a 7-day burst phase at 200 mcg daily, followed by a 7-day taper at 100 mcg daily, then maintenance dosing of 100 mcg 2-3 times weekly via subcutaneous injection.", "source": { "title": "Gonadorelin Dosage Chart and Reconstitution Protocol", "url": "https://www.peptidedosage.org/peptides/gonadorelin/dosage" }, "origins": [ "evidence.json#/catalog:peptide:gonadorelin/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:gonadorelin/community/0", "url": "https://www.peptidedosage.org/peptides/gonadorelin/dosage", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:gonadorelin/community/1", "url": "https://www.peptidedosage.org/peptides/gonadorelin/dosage", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [ "peptide:hcg", "peptide:pt-141" ], "conflicts": [], "sourceRefs": [ "pmid:42666625", "https://superpower.com/guides/gonadorelin", "https://www.peptidesinstitute.org/peptides/gonadorelin", "https://www.peptidedosage.org/peptides/gonadorelin/dosage" ] }, "peptide:hcg": { "id": "peptide:hcg", "path": "/peptides/hcg.html", "title": "Human Chorionic Gonadotropin", "summary": "Placental hormone that mimics LH to stimulate testicular testosterone production and sperm output. Used clinically for hypogonadism/fertility, off-label in TRT, and in doping.", "aliases": [ "hCG", "Pregnyl", "Novarel", "hCG (chorionic gonadotropin)" ], "kind": "medication-hormone", "categories": [ "sexual-health", "fitness-muscle" ], "legacy": { "name": "Human Chorionic Gonadotropin", "full_name": "Human chorionic gonadotropin (hCG), placental hormone", "aliases": [ "hCG", "Pregnyl", "Novarel" ], "categories": [ "sexual-health", "fitness-muscle" ], "tagline": "Placental hormone that mimics LH to stimulate testicular testosterone production and sperm output. Used clinically for hypogonadism/fertility, off-label in TRT, and in doping.", "status": "FDA approved | Off-label/illicit use: TRT adjunct, anabolic steroid doping", "origin": "A glycoprotein hormone produced by the placenta during pregnancy, purified from urine or produced recombinantly. Approved since the mid-20th century for male hypogonadotropic hypogonadism and female ovulation induction, and a ubiquitous TRT/AAS adjunct in the fitness community.", "mechanism": "Binds LH receptors on testicular Leydig cells, stimulating testosterone synthesis. Unlike exogenous testosterone, hCG stimulates endogenous production and helps maintain spermatogenesis and testicular size during TRT.", "research_summary": "hCG monotherapy restores testosterone and can induce spermatogenesis in ~70% of men with hypogonadotropic hypogonadism. Small studies support combined hCG + testosterone protocols for fertility preservation on TRT, with variable response; dosing strategies are empirically derived rather than from large RCTs.", "citations": [ { "title": "Human Chorionic Gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL.", "authors_year": "Madhusoodanan et al. 2019", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31408289/" }, { "title": "Systematic review of hormone replacement therapy in the infertile man.", "authors_year": "El Meliegy et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/29713545/" } ], "reported_benefits": [ "stimulation of endogenous testosterone production", "maintenance/recovery of spermatogenesis", "reduced testicular atrophy during TRT", "fertility preservation" ], "dosing_protocols": [ { "route": "Intramuscular or subcutaneous injection", "protocol": "Hypogonadotropic hypogonadism: 1,000-2,000 IU IM 2-3x weekly. TRT adjunct (off-label): 250-500 IU 3x weekly." } ], "side_effects": [ "gynecomastia", "acne", "testicular discomfort", "mood swings", "elevated hematocrit", "potential thrombotic complications at doping doses" ], "safety_notes": "Well-tolerated at therapeutic TRT-adjunct doses. High doping doses risk excessive testosterone, severe gynecomastia, and polycythemia. Requires periodic monitoring of testosterone, estradiol, hematocrit.", "community_notes": "Extremely common in TRT/PED communities; typical protocol 250-500 IU 2-3x weekly alongside testosterone. Higher doses (1,000-5,000 IU) used in AAS cycles to maintain testicular size.", "related": [ "gonadorelin" ], "variant_note": "HMG (human menopausal gonadotropin / menotropins) is a related fertility drug providing both FSH and LH (unlike hCG's LH-only activity), making it more effective for complete spermatogenesis recovery. Used clinically, often combined with hCG, but has a thinner off-label TRT following due to cost and complexity; not covered as a separate leaf page.", "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "bpc-157", "cjc-1295-dac", "hgh-somatropin", "mt-1", "mt-2" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:hormone:hcg", "title": "hCG (chorionic gonadotropin)", "summary": "Gonadotropin used to maintain testicular function during testosterone therapy, and in fertility protocols.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Chorionic gonadotropin for injection is approved by the US FDA for prepubertal cryptorchidism not caused by anatomical blockage, for selected cases of hypogonadotropic hypogonadism in males, and to induce ovulation in some infertile women. The label states plainly that hCG has not been shown to help in obesity and does not reduce hunger or change body fat distribution. It acts much like luteinising hormone, stimulating testicular or ovarian steroid production. The evidence is a regulator-approved label.", "verdict": { "benefits": [ "Prepubertal cryptorchidism that is not caused by anatomical blockage.", "Selected male hypogonadotropic hypogonadism and for ovulation induction.", "Acts much like luteinising hormone, stimulating testicular or ovarian steroid production." ], "risks": [ "The label states plainly that hCG has not been shown to help in obesity.", "It does not reduce hunger and does not change how body fat is distributed.", "For some approved uses the label reports no trial result alongside the regimen." ], "bottomLine": "hCG is FDA-approved for undescended testes, some male hypogonadism and ovulation induction, with no proven role in obesity.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: chorionic gonadotropin", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=chorionic+gonadotropin" } ], "links": [ { "title": "Novarel (Chorionic Gonadotropin for Injection) FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017016s156lbl.pdf" }, { "title": "The availability of gonadotropin therapy from FDA-approved pharmacies for men with hypogonadism and infertility", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10083688/" } ], "protocols": [ { "population": "prepubertal boys with cryptorchidism not caused by anatomical obstruction, per the US label", "regimen": "intramuscular injection; one labelled option is 4,000 USP Units three times weekly for three weeks", "duration": "three weeks, per that labelled option", "outcome": "The label lists this among several alternative regimens for prepubertal cryptorchidism and reports no trial result alongside it.", "source": { "title": "Novarel (Chorionic Gonadotropin for Injection) FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017016s156lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:hcg/protocols/0" ] }, { "population": "males with hypogonadotropic hypogonadism secondary to pituitary deficiency, per the US label", "regimen": "intramuscular injection; 500 to 1,000 USP Units three times a week for three weeks, then the same dose twice a week for three weeks", "duration": "six weeks, per that labelled option", "outcome": "The label also gives a longer alternative of 4,000 USP Units three times weekly for six to nine months, then 2,000 USP Units three times weekly.", "source": { "title": "Novarel (Chorionic Gonadotropin for Injection) FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017016s156lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:hcg/protocols/1" ] }, { "population": "anovulatory infertile women pre-treated with menotropins, per the US label", "regimen": "5,000 to 10,000 USP Units intramuscularly, one day after the last dose of menotropins", "duration": "single dose per cycle, per the label", "outcome": "The label describes this as inducing ovulation after adequate follicular development, and states hCG has no proven effect in obesity.", "source": { "title": "Novarel (Chorionic Gonadotropin for Injection) FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017016s156lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:hcg/protocols/2" ] } ], "community": [ { "description": "Community members on an anabolic forum report 500 IU of hCG per week divided into two injections during testosterone replacement therapy to maintain testicular function.", "source": { "title": "Experience with hcg? | Anabolic Steroids Discussion and Bodybuilding Forum", "url": "https://www.anasci.org/threads/experience-with-hcg.28857/" }, "origins": [ "evidence.json#/catalog:hormone:hcg/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:hcg/community/0", "url": "https://www.anasci.org/threads/experience-with-hcg.28857/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 30, "lowerHours": 24, "source": "Biphasic; terminal phase", "upperHours": 36 } } ], "related": [ "peptide:gonadorelin" ], "conflicts": [], "sourceRefs": [ "pmid:31408289", "pmid:29713545", "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017016s156lbl.pdf", "https://pmc.ncbi.nlm.nih.gov/articles/PMC10083688/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=chorionic+gonadotropin", "https://www.anasci.org/threads/experience-with-hcg.28857/" ] }, "peptide:ss-31": { "id": "peptide:ss-31", "path": "/peptides/ss-31.html", "title": "SS-31", "summary": "Mitochondria-targeted tetrapeptide that stabilizes cardiolipin and restores oxidative phosphorylation. FDA-approved for rare Barth syndrome, investigational in heart failure and aging-related conditions.", "aliases": [ "elamipretide", "Bendavia", "MTP-131", "SS-31 (elamipretide)" ], "kind": "peptide", "categories": [ "longevity", "fitness-muscle", "recovery-healing" ], "legacy": { "name": "SS-31", "full_name": "Elamipretide; Szeto-Schiller peptide 31", "aliases": [ "elamipretide", "Bendavia", "MTP-131" ], "categories": [ "longevity", "fitness-muscle", "recovery-healing" ], "tagline": "Mitochondria-targeted tetrapeptide that stabilizes cardiolipin and restores oxidative phosphorylation. FDA-approved for rare Barth syndrome, investigational in heart failure and aging-related conditions.", "status": "FDA Accelerated Approval (2025) for Barth Syndrome | Investigational in heart failure/HFpEF | Not approved for longevity use", "origin": "Designed by Hazel Szeto and Peter Schiller to cross the mitochondrial membrane and stabilize cardiolipin. Developed by Stealth BioTherapeutics/Reata, it received FDA Accelerated Approval in 2025 for Barth syndrome, a rare cardiolipin-remodeling genetic disorder, the first FDA-approved mitochondrial medicine.", "mechanism": "Accumulates in the inner mitochondrial membrane, binding and stabilizing cardiolipin, essential for respiratory chain complex assembly. Restoring cardiolipin integrity improves electron transport efficiency, raises ATP production, and cuts mitochondrial ROS.", "research_summary": "Preclinical/animal models show reduced oxidative stress and prevention of cardiomyocyte/skeletal muscle senescence. Phase 2 heart failure trials (HFrEF/HFpEF) show modest-to-moderate functional improvements. Barth syndrome trial data led to accelerated approval, but clinical benefit size is still being characterized. Human longevity/aging evidence is extremely limited.", "citations": [ { "title": "Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model.", "authors_year": "Vahle et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42290373/" } ], "reported_benefits": [ "improved mitochondrial respiratory capacity", "reduced oxidative stress (preclinical)", "prevention of cellular senescence (cell/animal models)", "FDA-approved benefit in Barth syndrome" ], "dosing_protocols": [ { "route": "Intravenous infusion", "protocol": "Investigational off-label protocols: ~0.05-0.1 mg/kg IV once daily or 2-3x weekly; no consensus dosing outside approved indication." } ], "side_effects": [ "generally well tolerated in Phase 2 trials", "headache/dizziness", "infusion-site reactions", "rare hypotension/syncope" ], "safety_notes": "Excellent tolerability in Phase 2 trials to date, no major organ toxicity reported. Long-term safety outside rare-disease populations isn't established.", "community_notes": "High interest in longevity forums based on the mitochondrial mechanism, but human access is limited to clinical trials or high-cost research sourcing. Enthusiasm exceeds current human evidence.", "related": [ "foxo4-dri", "mots-c" ] }, "research": [ { "id": "catalog:peptide:ss-31", "title": "SS-31 (elamipretide)", "summary": "Mitochondria-targeting peptide studied in trials for mitochondrial myopathy.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "regulatory", "evidenceSummary": "The linked study is in rats: elamipretide improved skeletal muscle force and cardiolipin measures in a model of heart failure with preserved ejection fraction. It works inside mitochondria, binding and stabilising cardiolipin so the respiratory chain works better and produces less oxidative stress. The wiki records US accelerated approval in 2025 for Barth syndrome, a rare genetic disorder, and phase 2 heart failure trials with modest functional gains; those trial reports are not among the links. Tolerability in phase 2 trials was good, and human evidence for ageing or longevity use is very limited.", "verdict": { "benefits": [ "US accelerated approval in 2025 for Barth syndrome, a rare genetic disorder", "In a rat heart failure model, muscle force rose and atrophy was prevented", "Phase 2 heart failure trials showed modest functional gains and good tolerability" ], "risks": [ "That approval rests on an intermediate endpoint, knee extensor strength, not a final outcome", "Human evidence for ageing or longevity use is very limited", "The phase 2 trial reports are not among the linked sources" ], "bottomLine": "Elamipretide has narrow approval for Barth syndrome; wider use rests on animal work and small phase 2 trials.", "approvalStatus": "US accelerated approval for Barth syndrome only." }, "originalLinks": [ { "title": "ClinicalTrials.gov: elamipretide", "url": "https://clinicaltrials.gov/search?term=elamipretide" } ], "links": [ { "title": "Forzinity (elamipretide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=146bf34c-76f2-48db-ac07-fb29cce2cd75" }, { "title": "Peptide Wiki: Elamipretide; Szeto-Schiller peptide 31", "url": "https://vespassassina.github.io/peptide-wiki/peptides/ss-31.html" }, { "title": "Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model. (Vahle et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42290373/" } ], "protocols": [ { "population": "Adults and children with Barth syndrome weighing at least 30 kg, per the US label", "regimen": "40 mg subcutaneously once daily at the same time each day, rotating between abdomen and outer thigh; 20 mg daily in severe renal impairment", "duration": "Ongoing, per the label", "outcome": "Given accelerated approval to improve muscle strength, based on knee extensor strength as an intermediate clinical endpoint.", "source": { "title": "Forzinity (elamipretide) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=146bf34c-76f2-48db-ac07-fb29cce2cd75" }, "origins": [ "evidence.json#/catalog:peptide:ss-31/protocols/0" ] }, { "population": "24 obese female ZSF1 rats modelling HFpEF, against 10 lean controls", "regimen": "Elamipretide or saline, started at 20 weeks of age", "duration": "12 weeks", "outcome": "Soleus force rose 8.2% and EDL force 10.9%, titin phosphorylation fell and atrophy was prevented; single-fibre gain in EDL was not significant.", "source": { "title": "Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model. (Vahle et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42290373/" }, "origins": [ "evidence.json#/catalog:peptide:ss-31/protocols/1" ] } ], "community": [ { "description": "Community protocol reports on peptide wiki document 1-5 mg administered subcutaneously once daily for 4-8 week cycles for mitochondrial support.", "source": { "title": "SS-31 Community Protocols & Anecdotal Reports", "url": "https://www.peptideprotocolwiki.com/peptides/ss-31/community" }, "origins": [ "evidence.json#/catalog:peptide:ss-31/community/0" ] }, { "description": "A dosing guide describes a low-dose maintenance protocol: 0.5-1 mg administered 3-5 times per week over 8-12 weeks with breaks for sustained mitochondrial support.", "source": { "title": "SS-31 (Elamipretide) Dosing Guide", "url": "https://peptideinitiative.com/peptides/protocols/ss-31" }, "origins": [ "evidence.json#/catalog:peptide:ss-31/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:ss-31/community/0", "url": "https://www.peptideprotocolwiki.com/peptides/ss-31/community", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:ss-31/community/1", "url": "https://peptideinitiative.com/peptides/protocols/ss-31", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 3, "source": "Elamipretide published PK" } } ], "related": [ "peptide:foxo4-dri", "peptide:mots-c" ], "conflicts": [], "sourceRefs": [ "pmid:42290373", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=146bf34c-76f2-48db-ac07-fb29cce2cd75", "https://vespassassina.github.io/peptide-wiki/peptides/ss-31.html", "https://clinicaltrials.gov/search?term=elamipretide", "https://www.peptideprotocolwiki.com/peptides/ss-31/community", "https://peptideinitiative.com/peptides/protocols/ss-31" ] }, "peptide:foxo4-dri": { "id": "peptide:foxo4-dri", "path": "/peptides/foxo4-dri.html", "title": "FOXO4-DRI", "summary": "Senolytic peptide that disrupts the FOXO4-p53 interaction to induce selective apoptosis of senescent cells. Highly promising in mouse models, with minimal human evidence.", "aliases": [ "FOXO4-DRI" ], "kind": "peptide", "categories": [ "longevity", "anti-aging" ], "legacy": { "name": "FOXO4-DRI", "full_name": "FOXO4 D-Retro-Inverso peptide (senolytic)", "aliases": [ "FOXO4-DRI" ], "categories": [ "longevity", "anti-aging" ], "tagline": "Senolytic peptide that disrupts the FOXO4-p53 interaction to induce selective apoptosis of senescent cells. Highly promising in mouse models, with minimal human evidence.", "status": "Research compound | Preclinical-stage (mostly mouse models) | Not FDA approved for any indication", "origin": "Developed at Utrecht University from the discovery that senescent cells depend on the FOXO4-p53 interaction for survival. A D-retro-inverso peptide (mirror-image, reversed-sequence variant) emerged around 2017 as senolytic therapy gained attention. Most published evidence is mouse-based.", "mechanism": "Binds FOXO4, disrupting the FOXO4-p53 complex that normally shields senescent cells from apoptosis. Restoring p53 pro-apoptotic signaling in cells with high FOXO4-p53 complexes triggers selective apoptosis in senescent cells while sparing normal ones.", "research_summary": "In aged mice, FOXO4-DRI reduces senescent cell burden across tissues and improves function/healthspan in some models, including Alzheimer's disease-model mice. A 2022 study found senolytic depletion (including FOXO4-DRI) paradoxically worsened pulmonary hypertension in mice, showing the effect is context-dependent. No published human trials exist as of 2026.", "citations": [ { "title": "The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.", "authors_year": "Bourgeois et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40593617/" }, { "title": "Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.", "authors_year": "Born et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36515093/" } ], "reported_benefits": [ "selective apoptosis of senescent cells (mouse models)", "reduced senescent cell burden across tissues (mouse studies)", "improved organ function in aged mice (specific models)" ], "dosing_protocols": [ { "route": "Intravenous or intraperitoneal injection", "protocol": "Mouse studies: 5-10 mg/kg IV/IP 2-3x weekly. No established human protocol; community dosing entirely speculative." } ], "side_effects": [ "minimal direct toxicity reported in mouse studies", "potential harmful effects in specific disease contexts (e.g. worsened pulmonary hypertension)", "human safety essentially unknown" ], "safety_notes": "Senolytic depletion is not universally beneficial: context-dependent harm has been shown in at least one disease model. No Phase 2/3 human trials exist. Access outside research is via unregulated suppliers with unverified purity.", "community_notes": "High enthusiasm in longevity communities based on mouse lifespan data, but real human experience is essentially nonexistent. The gap between mouse promise and human evidence is large.", "related": [ "ss-31" ] }, "research": [], "related": [ "peptide:ss-31" ], "conflicts": [], "sourceRefs": [ "pmid:40593617", "pmid:36515093" ] }, "peptide:ahk-cu": { "id": "peptide:ahk-cu", "path": "/peptides/ahk-cu.html", "title": "AHK-Cu", "summary": "Topical copper tripeptide marketed for hair follicle stimulation, distinct from (and less studied than) GHK-Cu.", "aliases": [ "copper tripeptide-3" ], "kind": "peptide", "categories": [ "anti-aging", "recovery-healing" ], "legacy": { "name": "AHK-Cu", "full_name": "Alanyl-Histidyl-Lysine Copper(II) Complex", "aliases": [ "copper tripeptide-3" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "Topical copper tripeptide marketed for hair follicle stimulation, distinct from (and less studied than) GHK-Cu.", "status": "Cosmetic ingredient (topical, unregulated as drug)", "origin": "A synthetic copper-peptide complex built as a hair-focused variant of the better-studied GHK-Cu, leaning on copper's role in collagen synthesis and wound healing, aimed at androgenetic alopecia and scalp health.", "mechanism": "Delivers bioavailable copper to dermal papilla cells, where it acts as an enzymatic cofactor. In-vitro data suggests it upregulates VEGF for follicle blood flow and extends the anagen (growth) phase, but this hasn't been validated on intact human scalp.", "research_summary": "Evidence is in-vitro and cosmetic-industry sourced. The foundational study showed tripeptide-copper complexes stimulate isolated human hair follicles in culture, but no human RCTs exist. Most efficacy claims lean on the GHK-Cu literature rather than AHK-Cu-specific data.", "citations": [ { "title": "The effect of tripeptide-copper complex on human hair growth in vitro", "authors_year": "2007", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/17703734/" } ], "reported_benefits": [ "stimulation of hair follicle anagen phase", "increased follicle blood flow (theoretical)", "improved hair density claims" ], "dosing_protocols": [ { "route": "Topical serum/solution", "protocol": "Applied to scalp 1-2x daily, sometimes with microneedling; concentrations 2-5% in cosmetic formulations, no standardized dose." } ], "side_effects": [ "local scalp irritation (rare)", "contact dermatitis in sensitive individuals" ], "safety_notes": "Systemic absorption through intact skin is low, but long-term human safety data doesn't exist. Avoid if you have copper sensitivity or Wilson disease.", "community_notes": "Used in scalp serums, often stacked with minoxidil or finasteride. Users report subjective improvement after 3-6 months, though expectations are probably inflated by confusing it with GHK-Cu's stronger evidence.", "related": [ "ghk-cu", "matrixyl", "ptd-dbm" ] }, "research": [], "related": [ "peptide:ghk-cu", "peptide:matrixyl", "peptide:ptd-dbm" ], "conflicts": [], "sourceRefs": [ "pmid:17703734" ] }, "peptide:snap-8": { "id": "peptide:snap-8", "path": "/peptides/snap-8.html", "title": "Snap-8", "summary": "Topical cosmetic peptide marketed as a non-invasive alternative to Botox for expression lines.", "aliases": [ "acetyl octapeptide-3" ], "kind": "peptide", "categories": [ "anti-aging" ], "legacy": { "name": "Snap-8", "full_name": "Acetyl Octapeptide-3", "aliases": [ "acetyl octapeptide-3" ], "categories": [ "anti-aging" ], "tagline": "Topical cosmetic peptide marketed as a non-invasive alternative to Botox for expression lines.", "status": "Cosmetic ingredient (topical, unregulated as drug)", "origin": "A derivative of Argireline (hexapeptide-3), synthesized in the 2000s as an anti-wrinkle cosmetic ingredient. Entirely topical; no injectable formulations or clinical trials exist.", "mechanism": "Theorized to interfere with the SNARE protein complex/SNAP-25 involved in acetylcholine release at the neuromuscular junction, potentially dampening repetitive facial-muscle contraction. Unproven in human skin; peptide skin penetration at cosmetic concentrations is poor.", "research_summary": "Minimal independent clinical evidence specific to Snap-8; most claims derive from older Argireline research. Cosmetic studies report modest, mixed results, mostly industry-sponsored and non-blinded. Skin hydration/smoothness improvements are more consistently documented than muscle-relaxation effects.", "citations": [], "reported_benefits": [ "reduced appearance of expression lines/crow's feet", "improved skin smoothness and hydration" ], "dosing_protocols": [ { "route": "Topical cosmetic serum/cream", "protocol": "Applied 1-2x daily; commercial concentrations 3-10%; results if any require 4-12 weeks of use." } ], "side_effects": [ "minimal; rare contact dermatitis/irritation" ], "safety_notes": "Strong safety record in cosmetic use given low systemic absorption. The real concern is overstated marketing claims, not safety.", "community_notes": "Mixed user reports of subtle softening of fine lines after 8-12 weeks. Community acknowledges the evidence gap versus Botox/retinoids.", "related": [ "matrixyl", "ghk-cu" ] }, "research": [], "related": [ "peptide:ghk-cu", "peptide:matrixyl" ], "conflicts": [], "sourceRefs": [] }, "peptide:matrixyl": { "id": "peptide:matrixyl", "path": "/peptides/matrixyl.html", "title": "Matrixyl", "summary": "Lipidated collagen-mimetic peptide (palmitoyl-KTTKS) that pushes fibroblasts to make more collagen and glycosaminoglycans.", "aliases": [ "palmitoyl pentapeptide-4", "KTTKS" ], "kind": "peptide", "categories": [ "anti-aging" ], "legacy": { "name": "Matrixyl", "full_name": "Palmitoyl Pentapeptide-4", "aliases": [ "palmitoyl pentapeptide-4", "KTTKS" ], "categories": [ "anti-aging" ], "tagline": "Lipidated collagen-mimetic peptide (palmitoyl-KTTKS) that pushes fibroblasts to make more collagen and glycosaminoglycans.", "status": "Cosmetic ingredient (topical, unregulated as drug)", "origin": "Developed in the early 2000s. KTTKS mimics a bioactive fragment of type I procollagen that fibroblasts recognize; a palmitoyl fatty-acid tail was added for skin penetration. Classic 'matrikine' cosmetic strategy.", "mechanism": "Triggers fibroblast matrikine signaling, activating TGF-β and boosting synthesis of collagen I/III, fibronectin, and glycosaminoglycans. Restores dermal support and reduces wrinkle depth.", "research_summary": "Better cosmetic data than Snap-8, still thin next to pharmaceutical standards. Trials show significant wrinkle-depth improvement over 12 weeks in photoaged skin, but cohorts are small (20-60 participants) and industry-funded. Effect size: 10-20% wrinkle-depth reduction, roughly matching mild retinoids.", "citations": [ { "title": "Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin", "authors_year": "Robinson et al. 2008", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18492182/" } ], "reported_benefits": [ "reduced wrinkle depth and fine lines", "improved skin elasticity/firmness", "increased dermal hydration" ], "dosing_protocols": [ { "route": "Topical serum/cream/moisturizer", "protocol": "2-5% palmitoyl pentapeptide-4 applied 1-2x daily; measurable improvement may take 8-12 weeks." } ], "side_effects": [ "minimal; rare local irritation/sensitization" ], "safety_notes": "Strong topical safety record. Peptide size and lipid modification keep systemic absorption negligible.", "community_notes": "Common in anti-aging serums, often paired with vitamin C and retinoids. Seen as better-evidenced than Snap-8 but weaker than prescription retinoids.", "related": [ "snap-8", "ghk-cu" ] }, "research": [], "related": [ "peptide:ghk-cu", "peptide:snap-8" ], "conflicts": [], "sourceRefs": [ "pmid:18492182" ] }, "peptide:ptd-dbm": { "id": "peptide:ptd-dbm", "path": "/peptides/ptd-dbm.html", "title": "PTD-DBM", "summary": "Preclinical peptide that blocks a Wnt-pathway inhibitor (CXXC5) in hair follicles, designed to restore hair regrowth through molecular disinhibition.", "aliases": [ "CXXC5 inhibitor", "DBM peptide" ], "kind": "peptide", "categories": [ "anti-aging", "recovery-healing" ], "legacy": { "name": "PTD-DBM", "full_name": "Protein Transduction Domain–Dishevelled Binding Motif", "aliases": [ "CXXC5 inhibitor", "DBM peptide" ], "categories": [ "anti-aging", "recovery-healing" ], "tagline": "Preclinical peptide that blocks a Wnt-pathway inhibitor (CXXC5) in hair follicles, designed to restore hair regrowth through molecular disinhibition.", "status": "Research chemical | Preclinical stage (no human trials)", "origin": "Developed after researchers found that DHT upregulates CXXC5 in balding-scalp dermal papilla cells, where CXXC5 normally suppresses the Wnt/beta-catenin signaling hair growth needs. PTD-DBM was designed to displace CXXC5 and restore that signaling, often paired experimentally with valproic acid.", "mechanism": "The PTD domain enables cell penetration; the DBM domain competes with CXXC5 for Dishevelled (Dvl) binding, displacing CXXC5 and freeing up Wnt/beta-catenin signaling, which upregulates downstream hair-growth genes.", "research_summary": "All evidence is preclinical. Mouse studies show stimulated hair regrowth and follicle neogenesis. As of 2026, no completed human clinical trials, Phase I safety data, or dosing studies exist.", "citations": [], "reported_benefits": [ "stimulation of hair follicle anagen phase (mouse models)", "follicle neogenesis in rodents", "reversal of DHT-mediated Wnt suppression (theoretical)" ], "dosing_protocols": [ { "route": "Topical application (preclinical only)", "protocol": "No human dosing protocols exist; unregulated vendors offer unvalidated topical formulations." } ], "side_effects": [ "unknown in humans; animal studies report no acute toxicity" ], "safety_notes": "No human safety data. Theoretical oncology concern: disinhibiting Wnt/beta-catenin, which is upregulated in several cancers, in genetically predisposed individuals. Contraindicated in pregnancy given the absence of reproductive toxicology data.", "community_notes": "Used by underground hair-loss self-experimenters, often stacked with minoxidil, finasteride, and valproic acid. Anecdotal, uncontrolled reports of regrowth over 3-6 months.", "related": [ "ahk-cu", "bpc-157" ] }, "research": [], "related": [ "peptide:ahk-cu", "peptide:bpc-157" ], "conflicts": [], "sourceRefs": [] }, "peptide:ll-37": { "id": "peptide:ll-37", "path": "/peptides/ll-37.html", "title": "LL-37", "summary": "Endogenous antimicrobial and immunomodulatory peptide with evidence for topical wound healing and emerging systemic applications.", "aliases": [ "cathelicidin LL-37", "hCAP18" ], "kind": "peptide", "categories": [ "recovery-healing", "anti-aging" ], "legacy": { "name": "LL-37", "full_name": "Human Cathelicidin Antimicrobial Peptide 37", "aliases": [ "cathelicidin LL-37", "hCAP18" ], "categories": [ "recovery-healing", "anti-aging" ], "tagline": "Endogenous antimicrobial and immunomodulatory peptide with evidence for topical wound healing and emerging systemic applications.", "status": "FDA Category 1 bulk drug (compounding-pharmacy use only) | Investigational for systemic use", "origin": "The sole cathelicidin antimicrobial peptide encoded by the human genome, produced by neutrophils and epithelial cells, cleaved from the hCAP18 precursor. Studied for three decades as a bridge between innate and adaptive immunity, now explored for wound healing and infection.", "mechanism": "Direct antimicrobial activity via amphipathic alpha-helical membrane disruption of bacteria, fungi, and enveloped viruses. Also signals through FPRL1 to recruit immune cells, and promotes keratinocyte migration/angiogenesis for tissue repair.", "research_summary": "The strongest human clinical evidence of this batch. A Phase IIb trial in venous ulcer patients found complete wound closure in 28.1% on LL-37 vs 8.1% placebo in large-wound subgroups. A diabetic foot ulcer trial showed greater granulation and faster closure. However, LL-37 complexes with self-DNA in psoriasis pathogenesis and drives rosacea inflammation, and pro-tumorigenic activity has been documented in several cancers; exogenous use may exacerbate both.", "citations": [ { "title": "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial", "authors_year": "2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/25041740/" }, { "title": "Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial", "authors_year": "2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/37480520/" } ], "reported_benefits": [ "enhanced venous/diabetic ulcer closure", "antimicrobial activity against bacteria/fungi/viruses", "promotion of angiogenesis and keratinocyte migration" ], "dosing_protocols": [ { "route": "Topical cream/gel (wound application)", "protocol": "Clinical trials used 0.5-1.6 mg/mL applied topically 2-3x weekly for 8-13 weeks." } ], "side_effects": [ "topical: local skin reactions (erythema, irritation)" ], "safety_notes": "Good topical safety in wound trials, but LL-37 is an established autoantigen in psoriasis and a driver of rosacea; systemic or high topical exposure may worsen these conditions. Pro-tumorigenic effects documented in cancer cell lines suggest caution in cancer patients.", "community_notes": "Used primarily in clinical/compounding-pharmacy wound-care contexts. Some functional-medicine practitioners theorize intranasal benefits, but this is speculative. Because LL-37 is itself part of the innate immune system's own antimicrobial-peptide arsenal, some caution that introducing it exogenously can trigger an inflammatory response — another reason people who do try it tend to start at low doses.", "related": [ "vip", "bpc-157" ], "mixing_notes": { "clinic_combos": [ "selank", "semax", "tb-500", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:ll-37", "title": "LL-37", "summary": "Human cathelicidin antimicrobial peptide studied for wound healing and immune modulation.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "LL-37 is the human cathelicidin antimicrobial peptide. The owner's wiki lists it as an FDA Category 1 bulk substance for compounding and investigational for systemic use, with the strongest human data of its batch. A first-in-man randomised placebo-controlled trial in 34 people with hard-to-heal venous leg ulcers found faster healing at the two lower concentrations and no safety concerns. A randomised double-blind trial of LL-37 cream in diabetic foot ulcers found better granulation over four weeks. The wiki also notes LL-37's role in psoriasis and rosacea inflammation and pro-tumour activity in some cancers.", "verdict": { "benefits": [ "A randomised placebo-controlled trial in hard-to-heal venous leg ulcers found faster healing.", "A randomised double-blind trial of LL-37 cream in diabetic foot ulcers found better granulation.", "Listed as an FDA Category 1 bulk substance for compounding." ], "risks": [ "The strongest concentration tested did no better than placebo, and the trials were small.", "Inflammation markers and bacterial colonisation did not differ from placebo in the foot-ulcer trial.", "LL-37 drives inflammation in psoriasis and rosacea and acts pro-tumour in some cancers." ], "bottomLine": "LL-37 sped wound healing in two small randomised trials; systemic use stays investigational and it can drive inflammation." }, "originalLinks": [ { "title": "PubMed: LL-37 cathelicidin", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=LL-37+cathelicidin" } ], "links": [ { "title": "Peptide Wiki: LL-37", "url": "https://vespassassina.github.io/peptide-wiki/peptides/ll-37.html" }, { "title": "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial (Grönberg et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/25041740/" }, { "title": "Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial (Miranda et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37480520/" } ], "protocols": [ { "population": "34 people with hard-to-heal venous leg ulcers", "regimen": "topical LL-37 at 0.5, 1.6 or 3.2 mg/mL or placebo, applied twice weekly, after a 3-week open-label placebo run-in", "duration": "4-week randomised treatment phase plus 4 weeks of follow-up", "outcome": "Healing rate constants were about sixfold higher at 0.5 mg/mL and threefold at 1.6 mg/mL than placebo; 3.2 mg/mL did not differ from placebo, with no safety concerns.", "source": { "title": "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial (Grönberg et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/25041740/" }, "origins": [ "evidence.json#/catalog:peptide:ll-37/protocols/0" ] }, { "population": "people with diabetic foot ulcer with mild infection", "regimen": "LL-37 cream or placebo cream applied twice a week, with wounds measured on days 7, 14, 21 and 28", "duration": "4 weeks", "outcome": "Granulation index rose more with LL-37 at every timepoint, but IL-1alpha, TNF-alpha and aerobic bacterial colonisation did not differ from placebo.", "source": { "title": "Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial (Miranda et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37480520/" }, "origins": [ "evidence.json#/catalog:peptide:ll-37/protocols/1" ] } ], "community": [ { "description": "A community protocol guide describes starting at 100-200 micrograms daily via subcutaneous injection, with some users progressing to 500 micrograms daily, administered once daily often 5 days per week for 2-4 week cycles.", "source": { "title": "LL-37 Peptide Protocol Guide", "url": "https://www.peptidedosingprotocols.com/protocol/ll-37" }, "origins": [ "evidence.json#/catalog:peptide:ll-37/community/0" ] }, { "description": "Reddit community members report 2 milligrams subcutaneous injection twice weekly (4 milligrams total weekly) as the most frequently discussed protocol, with other users describing daily protocols ranging from 1-3 milligrams.", "source": { "title": "LL-37 Reddit Reviews Community", "url": "https://www.realpeptides.co/ll-37-reddit-reviews-community-user-insights/" }, "origins": [ "evidence.json#/catalog:peptide:ll-37/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The imported accounts differ substantially in quantities and schedules. They are unvalidated community claims, not a combined range or evidence that any reported amount is safe." ], "community": [ { "origin": "evidence.json#/catalog:peptide:ll-37/community/0", "url": "https://www.peptidedosingprotocols.com/protocol/ll-37", "claimMatch": "The imported accounts differ substantially in quantities and schedules. They are unvalidated community claims, not a combined range or evidence that any reported amount is safe. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:ll-37/community/1", "url": "https://www.realpeptides.co/ll-37-reddit-reviews-community-user-insights/", "claimMatch": "The imported accounts differ substantially in quantities and schedules. They are unvalidated community claims, not a combined range or evidence that any reported amount is safe. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [ "peptide:bpc-157", "peptide:vip" ], "conflicts": [], "sourceRefs": [ "pmid:25041740", "pmid:37480520", "https://vespassassina.github.io/peptide-wiki/peptides/ll-37.html", "https://pubmed.ncbi.nlm.nih.gov/?term=LL-37+cathelicidin", "https://www.peptidedosingprotocols.com/protocol/ll-37", "https://www.realpeptides.co/ll-37-reddit-reviews-community-user-insights/" ] }, "peptide:vip": { "id": "peptide:vip", "path": "/peptides/vip.html", "title": "VIP", "summary": "Endogenous neuropeptide and vasodilator with immunomodulatory properties, used investigationally for mold-illness immune dysregulation and pulmonary hypertension.", "aliases": [ "vasoactive intestinal polypeptide", "Vasoactive Intestinal Peptide (VIP)" ], "kind": "peptide", "categories": [ "recovery-healing", "nootropics-cognitive" ], "legacy": { "name": "VIP", "full_name": "Vasoactive Intestinal Peptide", "aliases": [ "vasoactive intestinal polypeptide" ], "categories": [ "recovery-healing", "nootropics-cognitive" ], "tagline": "Endogenous neuropeptide and vasodilator with immunomodulatory properties, used investigationally for mold-illness immune dysregulation and pulmonary hypertension.", "status": "FDA investigational (synthetic aviptadil had Fast Track status for COVID-19, not approved) | Compounding-pharmacy use only", "origin": "A naturally occurring 28-amino-acid neuropeptide produced in the central/peripheral nervous system and gut. Its vasodilatory and anti-inflammatory properties drove cardiovascular/inflammatory-disorder research. The CIRS (chronic inflammatory response syndrome/mold illness) community adopted intranasal VIP off-label based on proposed immune mechanisms.", "mechanism": "Binds VPAC1/VPAC2/PAC1 GPCRs, elevating cAMP and suppressing NF-κB inflammatory signaling, reducing pro-inflammatory cytokines and expanding regulatory T cells. Also drives direct vasodilation via smooth-muscle relaxation.", "research_summary": "Strong mechanistic foundation. The synthetic analog aviptadil showed selective pulmonary vasodilation, reducing vascular resistance ~50% in trials. Human RCT evidence for compounded intranasal VIP specifically for CIRS is limited; small case series suggest symptom improvement but lack blinding/placebo control. FDA Fast Track for aviptadil in COVID-19 was granted but never led to approval.", "citations": [], "reported_benefits": [ "reduction in systemic inflammation markers", "pulmonary vasodilation and improved cardiac output (early data)", "immune dysregulation correction (CIRS community anecdote)" ], "dosing_protocols": [ { "route": "Intranasal spray (compounded)", "protocol": "Compounding-pharmacy formulations: 0.5-2 mg per dose, 1-3x daily; not FDA-standardized." } ], "side_effects": [ "transient nasal irritation/rhinitis", "flushing/mild headache", "symptomatic hypotension", "gastrointestinal effects" ], "safety_notes": "Low reported adverse-event frequency in small case series, but systemic hypotension is a real concern, particularly with baseline low blood pressure. Compounding-pharmacy quality/sterility varies.", "community_notes": "Enthusiastically adopted in the CIRS/mold-illness community based on theoretical mechanisms. Patient reports describe improved fatigue and cognition over weeks to months, but no blinded human data support CIRS-specific efficacy.", "related": [ "ll-37", "bpc-157" ] }, "research": [ { "id": "catalog:peptide:vip", "title": "Vasoactive Intestinal Peptide (VIP)", "summary": "An endogenous neuropeptide with vasodilatory and anti-inflammatory properties studied only in preclinical models.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "Vasoactive Intestinal Peptide (VIP) is an endogenous neuropeptide with potent vasodilatory, anti-inflammatory, and immunomodulatory properties throughout the cardiopulmonary system. In vitro and animal studies demonstrate effects including vascular and airway dilation, anti-inflammatory signaling, and modulation of immune responses. Despite decades of research into its therapeutic potential, VIP has not been advanced into human clinical efficacy trials due to poor metabolic stability, short plasma half-life, and difficulties with drug delivery to target tissues. Research continues on VIP analogues aimed at improving these properties.", "verdict": { "benefits": [ "Demonstrated vasodilatory and anti-inflammatory effects in preclinical models" ], "risks": [ "No human efficacy or safety trials have been completed", "Clinical translation has been prevented by poor metabolic stability and short plasma half-life", "Human safety and efficacy remain unknown" ], "bottomLine": "VIP shows promise in preclinical research for cardiopulmonary disorders, but has never been tested for safety or efficacy in humans and is not an approved therapeutic." }, "originalLinks": [ { "title": "Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090995/" }, { "title": "Therapeutic potential of vasoactive intestinal peptide and its receptors in neurological disorders", "url": "https://pubmed.ncbi.nlm.nih.gov/20632962/" }, { "title": "Structure-activity relationship of vasoactive intestinal peptide (VIP): potent agonists and potential clinical applications", "url": "https://pubmed.ncbi.nlm.nih.gov/18172612/" } ], "links": [ { "title": "Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090995/" }, { "title": "Therapeutic potential of vasoactive intestinal peptide and its receptors in neurological disorders", "url": "https://pubmed.ncbi.nlm.nih.gov/20632962/" }, { "title": "Structure-activity relationship of vasoactive intestinal peptide (VIP): potent agonists and potential clinical applications", "url": "https://pubmed.ncbi.nlm.nih.gov/18172612/" } ], "protocols": [], "community": [ { "description": "A protocol from peptidedosingprotocols.com describes community-reported subcutaneous dosing of 50 mcg administered once daily for 1-2 weeks as a conservative starting point.", "source": { "title": "VIP Peptide Dosing Guide", "url": "https://www.peptidedosingprotocols.com/protocol/vip" }, "origins": [ "evidence.json#/catalog:peptide:vip/community/0" ] }, { "description": "A standard research-level protocol documented on peptidedosingprotocols.com involves 100 mcg administered 1-2 times daily on an ongoing basis.", "source": { "title": "VIP Peptide Dosing Guide", "url": "https://www.peptidedosingprotocols.com/protocol/vip" }, "origins": [ "evidence.json#/catalog:peptide:vip/community/1" ] }, { "description": "A protocol from peptideinitiative.com describes 50 mcg administered twice daily via subcutaneous injection (morning and evening), or 50 mcg per inhalation taken four times daily.", "source": { "title": "VIP Injection Dosage & Protocol", "url": "https://peptideinitiative.com/peptides/protocols/vip-vasoactive-intestinal-peptide" }, "origins": [ "evidence.json#/catalog:peptide:vip/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:vip/community/0", "url": "https://www.peptidedosingprotocols.com/protocol/vip", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:vip/community/1", "url": "https://www.peptidedosingprotocols.com/protocol/vip", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:vip/community/2", "url": "https://peptideinitiative.com/peptides/protocols/vip-vasoactive-intestinal-peptide", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [ "peptide:bpc-157", "peptide:ll-37" ], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090995/", "pmid:20632962", "pmid:18172612", "https://www.peptidedosingprotocols.com/protocol/vip", "https://peptideinitiative.com/peptides/protocols/vip-vasoactive-intestinal-peptide" ] }, "peptide:teriparatide": { "id": "peptide:teriparatide", "path": "/peptides/teriparatide.html", "title": "Teriparatide", "summary": "FDA-approved PTH analog that stimulates bone formation. Used clinically for osteoporosis and investigationally for stress fractures and fracture healing.", "aliases": [ "Forteo" ], "kind": "medication-hormone", "categories": [ "recovery-healing", "anti-aging", "fitness-muscle" ], "legacy": { "name": "Teriparatide", "full_name": "Parathyroid Hormone 1-34 (PTH 1-34)", "aliases": [ "Forteo" ], "categories": [ "recovery-healing", "anti-aging", "fitness-muscle" ], "tagline": "FDA-approved PTH analog that stimulates bone formation. Used clinically for osteoporosis and investigationally for stress fractures and fracture healing.", "status": "FDA-approved for osteoporosis in post-menopausal women and men", "origin": "Recombinant human PTH 1-34, the N-terminal active fragment of parathyroid hormone. FDA-approved in 2002 as an anabolic bone agent, unlike antiresorptive bisphosphonates, with 20+ years of post-market surveillance.", "mechanism": "Binds PTH1 receptors on osteoblasts, activating Wnt/beta-catenin signaling and increasing osteoid production. Intermittent (daily) dosing favors bone anabolism over resorption, building cortical and trabecular bone mass.", "research_summary": "Large RCTs demonstrated a 65% reduction in vertebral fracture risk and a 53% reduction in non-vertebral fracture risk. Post-market surveillance of over 75,000 patients found zero attributable osteosarcoma cases despite a rat-toxicology signal at very high doses; the FDA removed the black-box osteosarcoma warning in 2023. Off-label use for stress fractures/delayed union is growing but less evidenced. PTH resistance caps therapy at 2 years maximum.", "citations": [ { "title": "The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years", "authors_year": "2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22991313/" }, { "title": "Teriparatide and Osteosarcoma Risk: History, Science, Elimination of Boxed Warning, and Other Label Updates", "authors_year": "2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36111201/" } ], "reported_benefits": [ "significant increase in bone mineral density", "65% reduction in vertebral fracture risk", "53% reduction in non-vertebral fracture risk", "off-label: potential acceleration of stress-fracture healing" ], "dosing_protocols": [ { "route": "Subcutaneous self-injection", "protocol": "FDA-approved: 20 mcg once daily via pen injector; maximum duration 2 years." } ], "side_effects": [ "dizziness (transient, first 4 hours post-dose)", "injection-site reactions", "mild hypercalcemia", "nausea", "leg cramps" ], "safety_notes": "Black-box osteosarcoma warning removed in 2023 following a large surveillance study. Contraindicated in active/history of bone metastases, skeletal malignancies, prior skeletal radiation, and Paget's disease. Requires periodic calcium/phosphate monitoring.", "community_notes": "Clinical osteoporosis use is well-established. Off-label athletic/orthopedic interest for stress-fracture healing is growing on mechanistic appeal, though RCT evidence for that use remains limited; competitive-sport use raises doping/ethical concerns.", "related": [ "ll-37", "bpc-157" ] }, "research": [ { "id": "catalog:medication:teriparatide", "title": "Teriparatide", "summary": "An FDA-approved recombinant parathyroid hormone used for osteoporosis to stimulate bone formation.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Teriparatide (recombinant human parathyroid hormone fragment rhPTH1-34) is an FDA-approved injectable medication for osteoporosis. It is approved for postmenopausal women with osteoporosis, men with primary or hypogonadal osteoporosis at high fracture risk, and glucocorticoid-induced osteoporosis in men and women. It operates by stimulating osteoblastic activity to promote bone formation. Clinical trials demonstrated increased bone mineral density and reduced fracture incidence. In November 2020, the FDA removed the 2-year lifetime treatment limit from the label and removed the boxed warning regarding potential osteosarcoma risk, based on post-marketing safety data.", "verdict": { "benefits": [ "FDA-approved with demonstrated bone density increases and fracture risk reduction", "Multiple osteoporosis indications including glucocorticoid-induced bone loss." ], "risks": [ "Post-marketing surveillance identified elevated blood calcium as the strongest adverse signal (PRR 50.73)", "Pain in extremities and muscle spasms reported in post-marketing data", "35 previously unreported adverse events identified in FDA database analysis through 2023" ], "bottomLine": "Teriparatide is an FDA-approved medication for osteoporosis with demonstrated efficacy in bone formation, but requires monitoring for hypercalcemia and other adverse effects in clinical use.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: teriparatide", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=teriparatide" }, { "title": "FDA approved new indication for teriparatide to treat osteoporosis", "url": "https://www.healio.com/news/endocrinology/20120331/fda-approved-new-indication-for-teriparatide-to-treat-osteoporosis" }, { "title": "Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS)", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335658/" }, { "title": "Teriparatide - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK559248/" } ], "links": [ { "title": "DailyMed: teriparatide", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=teriparatide" }, { "title": "FDA approved new indication for teriparatide to treat osteoporosis", "url": "https://www.healio.com/news/endocrinology/20120331/fda-approved-new-indication-for-teriparatide-to-treat-osteoporosis" }, { "title": "Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS)", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335658/" }, { "title": "Teriparatide - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK559248/" } ], "protocols": [ { "population": "Postmenopausal women with osteoporosis at high risk for fracture", "regimen": "Teriparatide injection for bone formation and fracture risk reduction", "duration": "Treatment duration varies; 2-year limitation was removed from label in 2020", "outcome": "Increased bone mineral density and reduced fracture incidence compared to control", "source": { "title": "FDA approved new indication for teriparatide to treat osteoporosis", "url": "https://www.healio.com/news/endocrinology/20120331/fda-approved-new-indication-for-teriparatide-to-treat-osteoporosis" }, "origins": [ "evidence.json#/catalog:medication:teriparatide/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://medlineplus.gov/druginfo/meds/a603018.html", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 1, "source": "FDA label, Forteo: serum half-life about 1 hour" } } ], "related": [ "peptide:bpc-157", "peptide:ll-37" ], "conflicts": [], "sourceRefs": [ "pmid:22991313", "pmid:36111201", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=teriparatide", "https://www.healio.com/news/endocrinology/20120331/fda-approved-new-indication-for-teriparatide-to-treat-osteoporosis", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335658/", "https://www.ncbi.nlm.nih.gov/books/NBK559248/" ] }, "peptide:cerebrolysin": { "id": "peptide:cerebrolysin", "path": "/peptides/cerebrolysin.html", "title": "Cerebrolysin", "summary": "Porcine neuropeptide preparation with clinical use for stroke and dementia in non-US countries.", "aliases": [ "cerebrolysine" ], "kind": "peptide", "categories": [ "nootropics-cognitive", "longevity", "recovery-healing" ], "legacy": { "name": "Cerebrolysin", "full_name": "Porcine brain-derived neuropeptide complex", "aliases": [ "cerebrolysine" ], "categories": [ "nootropics-cognitive", "longevity", "recovery-healing" ], "tagline": "Porcine neuropeptide preparation with clinical use for stroke and dementia in non-US countries.", "status": "Approved in 40+ countries (Austria, Russia, Eastern Europe, Asia); not FDA-approved in US", "origin": "A standardized complex of neuropeptides and free amino acids derived from porcine brain tissue, developed in Austria and used clinically in Europe and Asia since the 1970s-80s for stroke, dementia, and Alzheimer's disease.", "mechanism": "Modulates inflammatory cytokines, reducing IL-1β and IL-6 while boosting IL-10, enhances neurotrophic signaling, promotes neuroplasticity (dendritic spine density in hippocampus and cortex), and stabilizes the blood-brain barrier.", "research_summary": "Neuroprotective effects are documented in in-vitro stroke and TBI models, with improved memory and increased hippocampal spine density in animal models. Clinical trials in dementia and vascular cognitive impairment show modest cognitive benefits, particularly post-stroke, mostly from European and Eastern European institutions. No large US FDA-track trials have been completed.", "citations": [ { "title": "Cerebrolysin treatment improved short-term memory deficits while simultaneously increasing hippocampal spine density in hypertensive female rats", "authors_year": "Espinoza et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39826813/" } ], "reported_benefits": [ "cognitive support in dementia", "stroke recovery", "post-TBI neuroprotection", "neuroinflammation reduction" ], "dosing_protocols": [ { "route": "Intravenous or intramuscular injection", "protocol": "Typically 30 mL (1000-1500 mg) daily for 10-20 days in clinical trials; varies by indication." } ], "side_effects": [ "generally well tolerated", "rare local injection-site reactions", "rare mild allergic responses" ], "safety_notes": "Derived from animal tissue, carrying a theoretical prion-disease risk that hasn't shown up clinically. Decades of European clinical use report good tolerability. Not recommended in pregnancy.", "community_notes": "Nootropic users report modest subjective cognitive benefit. Legal and available by prescription or import in many non-US jurisdictions.", "related": [ "epithalon", "thymalin", "semax" ] }, "research": [ { "id": "catalog:peptide:cerebrolysin", "title": "Cerebrolysin", "summary": "A peptide extract from porcine brain studied for neurological recovery in stroke and Alzheimer's disease.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Cerebrolysin is a peptide extract derived from porcine brain that has been studied in multiple randomized controlled trials for acute ischemic stroke and Alzheimer's disease. Meta-analyses of nine to fourteen stroke trials involving over 1,800 patients showed statistically significant improvements in neurological recovery at 30 days compared to placebo, with a number-needed-to-treat of approximately 7. Efficacy in Alzheimer's disease has shown dose-dependent effects in moderate to moderately severe stages. Safety profile in trials was comparable to placebo.", "verdict": { "benefits": [ "Improved neurological recovery and motor function in acute ischemic stroke trials", "Dose-dependent cognitive effects in moderate to moderately severe Alzheimer's disease" ], "risks": [ "Safety profile in trials comparable to placebo, with adverse events mainly mild", "Off-label use outside clinical trial settings has not been formally evaluated in controlled studies" ], "bottomLine": "Cerebrolysin has shown statistically significant benefits in randomized trials of stroke recovery and Alzheimer's disease, with safety comparable to placebo, though approval status varies by country." }, "originalLinks": [ { "title": "Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials", "url": "https://pubmed.ncbi.nlm.nih.gov/29248999/" }, { "title": "Safety and Efficacy of Cerebrolysin for Neurorecovery After Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of 14 Randomized Controlled Trials", "url": "https://pubmed.ncbi.nlm.nih.gov/41018475/" }, { "title": "Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin", "url": "https://pubmed.ncbi.nlm.nih.gov/20500802/" } ], "links": [ { "title": "Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials", "url": "https://pubmed.ncbi.nlm.nih.gov/29248999/" }, { "title": "Safety and Efficacy of Cerebrolysin for Neurorecovery After Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of 14 Randomized Controlled Trials", "url": "https://pubmed.ncbi.nlm.nih.gov/41018475/" }, { "title": "Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin", "url": "https://pubmed.ncbi.nlm.nih.gov/20500802/" } ], "protocols": [], "community": [ { "description": "A weekly titration protocol on peptidedosingprotocols.com describes an escalating dosage pattern starting at 20 mg daily in week 1, increasing to 24 mg in week 2, 28 mg in week 3, and reaching 32 mg daily by week 4 and beyond.", "source": { "title": "Cerebrolysin Dosing Guide", "url": "https://www.peptidedosingprotocols.com/protocol/cerebrolysin" }, "origins": [ "evidence.json#/catalog:peptide:cerebrolysin/community/0" ] }, { "description": "A protocol documented on PeptIQ describes 5-10 mL of pharmaceutical ampoule solution daily (approximately 500-1000 mg protein hydrolysate) administered subcutaneously or intramuscularly using a 5-days-on, 2-days-off schedule for 4-8 weeks.", "source": { "title": "Cerebrolysin: Dosing, Reconstitution, and What to Expect", "url": "https://peptiq.io/blog/cerebrolysin-nootropic-peptide-guide" }, "origins": [ "evidence.json#/catalog:peptide:cerebrolysin/community/1" ] }, { "description": "A lower-dose pattern from PeptIQ involves 5 mL daily for anti-aging use, or 10 mL administered subcutaneously daily in 20-day cycles for research contexts.", "source": { "title": "Cerebrolysin: Dosing, Reconstitution, and What to Expect", "url": "https://peptiq.io/blog/cerebrolysin-nootropic-peptide-guide" }, "origins": [ "evidence.json#/catalog:peptide:cerebrolysin/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "Imported community accounts use different mass/volume quantities and routes. These are not interchangeable formulations or validated human administration instructions; no conversion or reconciliation has been inferred." ], "community": [ { "origin": "evidence.json#/catalog:peptide:cerebrolysin/community/0", "url": "https://www.peptidedosingprotocols.com/protocol/cerebrolysin", "claimMatch": "Imported community accounts use different mass/volume quantities and routes. These are not interchangeable formulations or validated human administration instructions; no conversion or reconciliation has been inferred. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "inconsistent-units-and-route" }, { "origin": "evidence.json#/catalog:peptide:cerebrolysin/community/1", "url": "https://peptiq.io/blog/cerebrolysin-nootropic-peptide-guide", "claimMatch": "Imported community accounts use different mass/volume quantities and routes. These are not interchangeable formulations or validated human administration instructions; no conversion or reconciliation has been inferred. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "inconsistent-units-and-route" }, { "origin": "evidence.json#/catalog:peptide:cerebrolysin/community/2", "url": "https://peptiq.io/blog/cerebrolysin-nootropic-peptide-guide", "claimMatch": "Imported community accounts use different mass/volume quantities and routes. These are not interchangeable formulations or validated human administration instructions; no conversion or reconciliation has been inferred. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "inconsistent-units-and-route" } ] } } ], "related": [ "peptide:epithalon", "peptide:semax", "peptide:thymalin" ], "conflicts": [], "sourceRefs": [ "pmid:39826813", "pmid:29248999", "pmid:41018475", "pmid:20500802", "https://www.peptidedosingprotocols.com/protocol/cerebrolysin", "https://peptiq.io/blog/cerebrolysin-nootropic-peptide-guide" ] }, "peptide:pe-22-28": { "id": "peptide:pe-22-28", "path": "/peptides/pe-22-28.html", "title": "PE 22-28", "summary": "Engineered spadin analog with improved TREK-1 channel inhibition and fast-acting antidepressant properties.", "aliases": [ "mini-spadin" ], "kind": "peptide", "categories": [ "nootropics-cognitive" ], "legacy": { "name": "PE 22-28", "full_name": "PE 22-28; shortened spadin analog", "aliases": [ "mini-spadin" ], "categories": [ "nootropics-cognitive" ], "tagline": "Engineered spadin analog with improved TREK-1 channel inhibition and fast-acting antidepressant properties.", "status": "Research chemical; investigational, not approved for human use", "origin": "A shortened 7-amino-acid analog of spadin, itself derived from sortilin/NTSR3 receptor maturation, engineered by French researchers (CNRS) to improve metabolic stability and TREK-1 potency over the parent molecule. First described in 2017.", "mechanism": "Blocks TREK-1, a two-pore-domain potassium channel implicated in depression. This increases serotonergic neuron firing in the dorsal raphe nucleus, producing rapid antidepressant effects, and stimulates hippocampal neurogenesis and synaptogenesis.", "research_summary": "Shows better TREK-1 binding affinity and longer in-vivo action (23 hours vs spadin's 7 hours). Demonstrates antidepressant efficacy in mouse behavioral tests and neuroprotection in stroke and post-stroke-depression models. All evidence is preclinical; no human trials published.", "citations": [ { "title": "Shortened Spadin Analogs Display Better TREK-1 Inhibition, Stability and Antidepressant Activity", "authors_year": "Djillani et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28955242/" } ], "reported_benefits": [ "antidepressant effect (rapid onset in animal models)", "neuroprotection in stroke models", "neurogenesis stimulation" ], "dosing_protocols": [ { "route": "Intraperitoneal injection (research only)", "protocol": "Mouse models: 0.03-3 μg/kg; no human dosing established." } ], "side_effects": [ "no human data", "good tolerability at therapeutic doses in animal studies" ], "safety_notes": "Zero human safety data. Crosses the blood-brain barrier. Not recommended for self-administration outside research settings.", "community_notes": "Virtually no self-experimenter reports. Too obscure and research-only at present.", "related": [ "semax", "cerebrolysin" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [], "related": [ "peptide:cerebrolysin", "peptide:semax" ], "conflicts": [], "sourceRefs": [ "pmid:28955242" ] }, "peptide:p21": { "id": "peptide:p21", "path": "/peptides/p21.html", "title": "P21", "summary": "CNTF-derived peptide with claimed neurogenic potential; adamantane-conjugated variant designed for blood-brain barrier penetration.", "aliases": [ "P-21" ], "kind": "peptide", "categories": [ "nootropics-cognitive", "longevity" ], "legacy": { "name": "P21", "full_name": "P21 neurogenic peptide (CNTF-derived)", "aliases": [ "P-21" ], "categories": [ "nootropics-cognitive", "longevity" ], "tagline": "CNTF-derived peptide with claimed neurogenic potential; adamantane-conjugated variant designed for blood-brain barrier penetration.", "status": "Investigational research compound; adamantane variant not approved for human use", "origin": "Proposed to derive from or mimic the activity domain of ciliary neurotrophic factor (CNTF). The adamantane-conjugated variant was engineered for better blood-brain-barrier penetration via the adamantane cage structure.", "mechanism": "Proposed as a CNTF mimetic, activating CNTF receptor signaling (gp130/STAT3, PI3K/Akt) to support neuronal survival, differentiation, and neurogenesis. The adamantane conjugate adds lipophilicity to improve CNS delivery.", "research_summary": "Primary literature on P21 as a therapeutic peptide is very thin; most PubMed hits are for the unrelated cyclin-dependent kinase inhibitor p21 protein. No peer-reviewed clinical trials or systematic preclinical reports exist. Evidence quality is very low.", "citations": [ { "title": "The effect of exogenous ciliary neurotrophic factor on cell cycle and neural differentiation markers of in vitro model cells", "authors_year": "Ghasemi et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33890305/" } ], "reported_benefits": [ "neurogenesis stimulation (theoretical)", "neuroprotection (theoretical)", "appetite stimulation (anecdotal)" ], "dosing_protocols": [ { "route": "Subcutaneous injection (research; no human standard)", "protocol": "No validated human dose exists for either form." } ], "side_effects": [ "insufficient human data" ], "safety_notes": "Essentially unevaluated in humans. CNTF itself has mixed effects, neuroprotective at some doses, neurotoxic at high ones, and P21 may carry similar risks. Not recommended outside formal research.", "community_notes": "Occasionally mentioned in nootropic forums with anecdotal cognitive and appetite claims. Use is rare, evidence speculative.", "related": [ "cerebrolysin", "semax" ], "variant_note": "The adamantane-conjugated form (sometimes marketed as 'Adamax') is a blood-brain-barrier-penetration modification of the same peptide, with essentially no published pharmacology or safety data beyond community discussion.", "mixing_notes": { "clinic_combos": [], "anecdotal_combos": [ "selank", "semax" ], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [], "related": [ "peptide:cerebrolysin", "peptide:semax" ], "conflicts": [], "sourceRefs": [ "pmid:33890305" ] }, "peptide:pnc27": { "id": "peptide:pnc27", "path": "/peptides/pnc27.html", "title": "PNC27", "summary": "CANCER RESEARCH ONLY: p53-derived peptide inducing tumor cell necrosis through HDM-2 interaction; no human clinical trials, and no longevity or anti-aging protocol exists.", "aliases": [ "PNC-27" ], "kind": "peptide", "categories": [ "longevity" ], "legacy": { "name": "PNC27", "full_name": "PNC-27; p53-derived HDM-2-targeting membrane-disrupting peptide", "aliases": [ "PNC-27" ], "categories": [ "longevity" ], "tagline": "CANCER RESEARCH ONLY: p53-derived peptide inducing tumor cell necrosis through HDM-2 interaction; no human clinical trials, and no longevity or anti-aging protocol exists.", "status": "Preclinical oncology research only; no human trials", "origin": "A 32-residue chimeric peptide fusing a p53-derived HDM-2 (MDM2) binding domain to a cell-penetrating penetratin leader sequence, built to target the p53-MDM2 interaction specifically in cancer cells that overexpress membrane-associated HDM-2.", "mechanism": "Binds membrane-associated HDM-2 with high affinity, forming complexes that dimerize and create transmembrane pores. This causes rapid necrosis selectively in cells expressing surface HDM-2, a feature of transformed, not normal, cells.", "research_summary": "Shows selective tumor cell killing in multiple cancer xenograft mouse models (pancreatic, leukemia, colon, ovarian) and ex vivo patient-derived samples. NO human clinical trials exist or are registered. All data are preclinical mouse xenograft or ex vivo findings, not evidence of human safety or efficacy.", "citations": [ { "title": "Anti-Cancer Peptide PNC-27 Kills Cancer Cells by Unique Interactions with Plasma Membrane-Bound hdm-2 and with Mitochondrial Membranes Causing Mitochondrial Disruption", "authors_year": "Krzesaj et al. 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38802154/" }, { "title": "PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis", "authors_year": "Sarafraz-Yazdi et al. 2022", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/35625682/" } ], "reported_benefits": [ "tumor cell necrosis in vitro and in xenograft models", "efficacy against chemotherapy-resistant cancers (preclinical)" ], "dosing_protocols": [ { "route": "Intravenous or intraperitoneal (mouse studies only)", "protocol": "Mouse models: ~50-100 μg/kg; NO human dosing exists or should be attempted." } ], "side_effects": [ "NO HUMAN DATA", "membrane-pore-forming mechanism could plausibly cause severe tissue damage if misapplied in vivo" ], "safety_notes": "CRITICAL: this is a cancer-research tool, not an approved or investigational human therapeutic. Zero human trials, zero healthy-volunteer data. Self-administration would be extremely dangerous and no evidence supports it.", "community_notes": "Some longevity forums mistakenly categorize PNC27 as a life-extension peptide. It isn't — it's pure oncology research. Legitimate anecdotal human use essentially doesn't exist.", "related": [] }, "research": [], "related": [], "conflicts": [], "sourceRefs": [ "pmid:38802154", "pmid:35625682" ] }, "peptide:thymalin": { "id": "peptide:thymalin", "path": "/peptides/thymalin.html", "title": "Thymalin", "summary": "Thymic bioregulator from the Khavinson family with long-term human mortality follow-up and immune-modulating effects.", "aliases": [ "thymus peptide" ], "kind": "peptide", "categories": [ "bioregulators", "longevity", "recovery-healing" ], "legacy": { "name": "Thymalin", "full_name": "Thymic peptide bioregulator", "aliases": [ "thymus peptide" ], "categories": [ "bioregulators", "longevity", "recovery-healing" ], "tagline": "Thymic bioregulator from the Khavinson family with long-term human mortality follow-up and immune-modulating effects.", "status": "Approved in Russia and Eastern Europe; used in clinical practice", "origin": "Isolated from thymic tissue extracts, developed by Vladimir Khavinson's laboratory at the St. Petersburg Institute of Bioregulation and Gerontology, part of the Russian bioregulation-therapy tradition emerging in the late 1980s-90s.", "mechanism": "Stimulates differentiation of T lymphocyte precursors into mature CD4+/CD8+ T cells, reduces apoptosis of aging thymocytes, and modulates cytokine balance (lower IL-6/IL-1β, higher IL-10), normalizing immune homeostasis in aging.", "research_summary": "A long-running Russian/Ukrainian cohort study (~266 elderly participants over 6-8 years) reported a 2.0-2.1-fold reduction in all-cause mortality in the Thymalin group versus controls, and 2.5-fold when combined with Epithalamin. Secondary outcomes included fewer acute respiratory infections and cardiovascular events. These are large effect sizes from small, Russian-led trials with limited Western replication, a caveat that applies to the whole bioregulator family.", "citations": [ { "title": "Peptides of pineal gland and thymus prolong human life", "authors_year": "Khavinson & Morozov 2003", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/14523363/" }, { "title": "Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19", "authors_year": "Khavinson et al. 2021", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/33575961/" } ], "reported_benefits": [ "immune function restoration", "reduced infection rates in elderly", "reduced cardiovascular disease incidence", "improved wound healing" ], "dosing_protocols": [ { "route": "Intramuscular or subcutaneous injection", "protocol": "Typical Russian protocol: 10-20 mg IM daily or every other day for 10-20 days, repeated every 6-12 months." } ], "side_effects": [ "rare mild local inflammation", "rare transient fever", "rare allergic reaction" ], "safety_notes": "Derived from animal thymic tissue, carrying a theoretical (undocumented) prion-disease risk. 15+ years of Russian clinical use report no serious adverse events. Not tested in pregnancy.", "community_notes": "Available in Russia/Eastern Europe; some Western users order through offshore channels. Anecdotal reports of reduced illness frequency; no Western regulatory pathway exists.", "related": [ "vilon", "epithalon", "pinealon", "thymosin-alpha-1" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ghk-cu", "ghrp-6", "ipamorelin", "pinealon", "selank", "semax", "tb-500", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [ { "id": "catalog:peptide:thymalin", "title": "Thymalin", "summary": "A thymic peptide extract used in Eastern Europe for immune dysfunction, with limited evidence outside Russian clinical practice.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Thymalin is a thymic peptide extract isolated from calf thymus, used in clinical practice primarily in Russia and parts of Eastern Europe for immune dysfunction. Small single-region prospective randomized trials have reported effects on T-cell restoration and lymphocyte markers in patients with immune suppression, including in older adults and those treated for COVID-19. However, clinical evidence consists mainly of studies within the Russian medical tradition, with no large independently conducted Western randomized controlled trials or Phase III datasets published in peer-reviewed journals outside this medical network. Replication by independent research institutions outside Russia has not occurred.", "verdict": { "benefits": [ "Small trials report effects on T-cell markers and lymphocyte recovery in immunocompromised patients" ], "risks": [ "Clinical evidence is limited to small single-region trials within Russian medical networks", "No large independently conducted randomized controlled trials in Western regulatory contexts", "Limited reproducibility; research findings have not been independently replicated outside Russia", "Long-term safety and efficacy unknown" ], "bottomLine": "Thymalin shows effects on immune markers in small Russian trials, but lacks independent large-scale Western clinical validation and is not approved outside Eastern Europe." }, "originalLinks": [ { "title": "Peptide Drug Thymalin Regulates Immune Status in Severe COVID-19 Older Patients", "url": "https://link.springer.com/article/10.1134/S2079057021040068" }, { "title": "A nonrandomized phase 2 trial of oral thymic peptides in hospitalized patients with Covid-19", "url": "https://www.medrxiv.org/content/10.1101/2021.12.05.21267318.full.pdf" }, { "title": "Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518946/" } ], "links": [ { "title": "Peptide Drug Thymalin Regulates Immune Status in Severe COVID-19 Older Patients", "url": "https://link.springer.com/article/10.1134/S2079057021040068" }, { "title": "A nonrandomized phase 2 trial of oral thymic peptides in hospitalized patients with Covid-19", "url": "https://www.medrxiv.org/content/10.1101/2021.12.05.21267318.full.pdf" }, { "title": "Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518946/" } ], "protocols": [], "community": [ { "description": "A protocol from Path To Peptides documents 10 mg administered intramuscularly once daily for a 5-10 day course, with cycles repeating every 6-12 months as a community-reported pattern.", "source": { "title": "Thymalin Protocol Guide", "url": "https://www.pathtopeptides.com/thymalin-protocol.html" }, "origins": [ "evidence.json#/catalog:peptide:thymalin/community/0" ] }, { "description": "A lower-dose variant described on Path To Peptides involves 5 mg daily for 5-10 days for anti-aging or maintenance use.", "source": { "title": "Thymalin Protocol Guide", "url": "https://www.pathtopeptides.com/thymalin-protocol.html" }, "origins": [ "evidence.json#/catalog:peptide:thymalin/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:thymalin/community/0", "url": "https://www.pathtopeptides.com/thymalin-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:thymalin/community/1", "url": "https://www.pathtopeptides.com/thymalin-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [ "peptide:epithalon", "peptide:pinealon", "peptide:thymosin-alpha-1", "peptide:vilon" ], "conflicts": [], "sourceRefs": [ "pmid:14523363", "pmid:33575961", "https://link.springer.com/article/10.1134/S2079057021040068", "https://www.medrxiv.org/content/10.1101/2021.12.05.21267318.full.pdf", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518946/", "https://www.pathtopeptides.com/thymalin-protocol.html" ] }, "peptide:vilon": { "id": "peptide:vilon", "path": "/peptides/vilon.html", "title": "Vilon", "summary": "Short-form thymic dipeptide bioregulator with immunomodulatory and T-cell differentiation effects.", "aliases": [ "lysyl-glutamic acid" ], "kind": "peptide", "categories": [ "bioregulators", "longevity" ], "legacy": { "name": "Vilon", "full_name": "Thymic dipeptide (Lysyl-Glutamic acid, Lys-Glu)", "aliases": [ "lysyl-glutamic acid" ], "categories": [ "bioregulators", "longevity" ], "tagline": "Short-form thymic dipeptide bioregulator with immunomodulatory and T-cell differentiation effects.", "status": "Available in Russia and some Eastern European countries", "origin": "A short dipeptide (Lys-Glu) isolated from thymic tissue extracts as part of Khavinson's bioregulation program, a 'short-form' analog of longer preparations like Thymalin.", "mechanism": "Stimulates differentiation of CD5+ lymphocyte precursors into mature CD4+/CD8+ T cells and promotes thymocyte proliferation (Ki-67 expression) in organotypic thymic culture; also modulates pineal lymphoid tissue differentiation.", "research_summary": "Multiple small in-vitro studies from Khavinson's laboratory show Vilon stimulates T-cell/B-cell differentiation from precursors in thymic and pineal cultures. No human clinical trials with mortality or large-cohort endpoints exist for Vilon specifically; evidence comes exclusively from Russian research institutions and remains unreplicated in the West.", "citations": [ { "title": "Immunomodulating effects of Vilon and its analogue in the culture of human and animal thymus cells", "authors_year": "Sevostianova et al. 2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23486604/" } ], "reported_benefits": [ "T-cell differentiation/maturation", "immune cell proliferation", "potential thymic rejuvenation" ], "dosing_protocols": [ { "route": "Intramuscular or subcutaneous injection", "protocol": "Typical Russian dosing: 5-10 mg IM daily or alternate-day for 10 days, repeated seasonally." } ], "side_effects": [ "minimal documented; rare local injection-site reaction" ], "safety_notes": "Simple dipeptide with likely low intrinsic toxicity, but no Western toxicology or safety monitoring data are published.", "community_notes": "Less well-known than Thymalin in Western communities; most references are Russian or translated. Availability outside Russia is limited.", "related": [ "thymalin", "epithalon", "pinealon" ] }, "research": [], "related": [ "peptide:epithalon", "peptide:pinealon", "peptide:thymalin" ], "conflicts": [], "sourceRefs": [ "pmid:23486604" ] }, "peptide:pinealon": { "id": "peptide:pinealon", "path": "/peptides/pinealon.html", "title": "Pinealon", "summary": "Pineal-derived peptide bioregulator with cognitive and neuroprotective positioning.", "aliases": [ "pineal peptide" ], "kind": "peptide", "categories": [ "bioregulators", "nootropics-cognitive" ], "legacy": { "name": "Pinealon", "full_name": "Pineal-gland peptide bioregulator (distinct short peptide, not to be confused with epithalon)", "aliases": [ "pineal peptide" ], "categories": [ "bioregulators", "nootropics-cognitive" ], "tagline": "Pineal-derived peptide bioregulator with cognitive and neuroprotective positioning.", "status": "Available in Russia and some international peptide suppliers", "origin": "A peptide bioregulator from pineal-gland-tissue isolation work by Khavinson's group, positioned for cognitive and CNS support. A distinct product from Epitalon/epithalon, though closely related in research tradition and often confused with it in marketing.", "mechanism": "Proposed to act as a tissue-specific bioregulator supporting pineal and CNS cell function, with claimed effects on neuronal signaling molecule expression and antioxidant activity in brain tissue.", "research_summary": "Evidence is limited to small Khavinson-group studies, largely unreplicated in Western literature. Human data are essentially anecdotal reports of improved sleep and mood in older adults. Overall evidence quality is very low.", "citations": [ { "title": "Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture", "authors_year": "Khavinson et al. 2011", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22803060/" } ], "reported_benefits": [ "sleep quality support", "circadian rhythm support (theoretical)", "cognitive support claims", "antioxidant effects (theoretical)" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection, or oral capsule", "protocol": "Reported Russian protocols: 10 mg IM daily for 10 days, or oral capsule courses; poorly standardized." } ], "side_effects": [ "insufficient human data; animal studies show good tolerability" ], "safety_notes": "Extremely limited safety data. No formal toxicology or long-term human studies published.", "community_notes": "Appears in Western longevity and biohacker circles, sometimes marketed under names overlapping with Epitalon, which causes confusion between the two. Claims often exceed evidence.", "related": [ "epithalon", "thymalin", "cerebrolysin" ], "mixing_notes": { "clinic_combos": [ "bpc-157", "cjc-1295", "cjc-1295-dac", "epithalon", "ipamorelin", "kisspeptin", "pt-141", "selank", "tb-500", "thymalin", "thymosin-alpha-1" ], "anecdotal_combos": [], "reported_avoid": [ "aod-9604", "ara-290", "mots-c", "nad" ] } }, "research": [], "related": [ "peptide:cerebrolysin", "peptide:epithalon", "peptide:thymalin" ], "conflicts": [], "sourceRefs": [ "pmid:22803060" ] }, "peptide:testagen": { "id": "peptide:testagen", "path": "/peptides/testagen.html", "title": "Testagen", "summary": "Testis-targeted bioregulator peptide from the Khavinson family, proposed for testicular and vascular function.", "aliases": [ "testis peptide" ], "kind": "peptide", "categories": [ "bioregulators", "sexual-health" ], "legacy": { "name": "Testagen", "full_name": "Testicular/vascular bioregulator peptide", "aliases": [ "testis peptide" ], "categories": [ "bioregulators", "sexual-health" ], "tagline": "Testis-targeted bioregulator peptide from the Khavinson family, proposed for testicular and vascular function.", "status": "Experimental research compound; minimal published data", "origin": "A peptide bioregulator derived from testicular-tissue peptide extraction, developed within Khavinson's bioregulation research framework alongside thymic and pineal preparations. Specific isolation methodology isn't well documented in English-language literature.", "mechanism": "Proposed to support testicular function and testosterone production through tissue-specific bioregulatory effects (theoretical Leydig-cell stimulation and vascular support), analogous to Thymalin's action on thymic tissue.", "research_summary": "Zero peer-reviewed research articles specifically on Testagen are indexed in PubMed. Vendor/community sources reference it as a 'testis bioregulator' with claims about testosterone and fertility, entirely anecdotal and unsupported by published studies, the lowest evidence tier of the bioregulator family.", "citations": [], "reported_benefits": [ "testosterone support (community claim, unproven)", "erectile function support (community claim, unproven)", "fertility support (community claim, unproven)" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection", "protocol": "No standardized dosing; online reports suggest 5-10 mg IM weekly, entirely unvalidated." } ], "side_effects": [ "unknown; no published data" ], "safety_notes": "No pharmacokinetics, toxicology, or human safety data published anywhere. Any hormonal claims are unproven; self-administration carries unknown risk.", "community_notes": "Appears in men's health forums with anecdotal libido/fertility claims; availability limited to a few international suppliers.", "related": [ "thymalin", "vilon" ] }, "research": [], "related": [ "peptide:thymalin", "peptide:vilon" ], "conflicts": [], "sourceRefs": [] }, "peptide:bronchogen": { "id": "peptide:bronchogen", "path": "/peptides/bronchogen.html", "title": "Bronchogen", "summary": "Organ-targeted bioregulator from the Khavinson lineage, aimed at bronchial and respiratory tissue.", "aliases": [ "AEDL peptide" ], "kind": "peptide", "categories": [ "bioregulators", "recovery-healing" ], "legacy": { "name": "Bronchogen", "full_name": "Bronchogen (Ala-Glu-Asp-Leu)", "aliases": [ "AEDL peptide" ], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted bioregulator from the Khavinson lineage, aimed at bronchial and respiratory tissue.", "status": "Approved in Russia", "origin": "Developed by Vladimir Khavinson's group at the St. Petersburg Institute of Bioregulation and Gerontology from amino-acid analysis of bronchial and respiratory tissue extracts; part of the Russian tissue-specific bioregulator program dating to the 1980s.", "mechanism": "Proposed to stimulate differentiation factors like CXCL12 and Hoxa3 in bronchial epithelial cells, especially in aging cultures, supporting lung tissue homeostasis.", "research_summary": "Research is limited and comes almost entirely from Khavinson's group. A 2012 study showed tissue-specific stimulation of differentiation markers in human bronchial epithelial cells in vitro; older work showed stimulatory effects in organotypic lung culture. No human trials or large-cohort data exist in English-language literature. Evidence is small-sample, Russian-led, and unreplicated in the West.", "citations": [ { "title": "Peptides tissue-specifically stimulate cell differentiation during their aging", "authors_year": "Khavinson et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22808515/" } ], "reported_benefits": [ "support for respiratory tissue structure", "enhancement of bronchial epithelial cell renewal (preclinical)", "potential immunoprotective effects on lung tissue" ], "dosing_protocols": [ { "route": "Intramuscular injection or oral tablet", "protocol": "Russian clinical use reports vary; community sourcing reports 10-20 mg subcutaneously, unstandardized in Western literature." } ], "side_effects": [ "minimal reported; low toxicity profile typical of short peptide preparations" ], "safety_notes": "No serious adverse effects reported in Russian studies. Sterility and purity of imported or self-compounded preparations can't be guaranteed, and long-term human safety is undocumented.", "community_notes": "Sourced by Western biohackers from Russian compounding services as part of the broader Khavinson suite; use is anecdotal with no systematic monitoring.", "related": [ "cardiogen", "cortagen", "livagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:cardiogen", "peptide:cortagen", "peptide:epithalon", "peptide:livagen", "peptide:pancragen", "peptide:prostamax", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:22808515" ] }, "peptide:cardiogen": { "id": "peptide:cardiogen", "path": "/peptides/cardiogen.html", "title": "Cardiogen", "summary": "Organ-targeted bioregulator from the Khavinson lineage aimed at cardiac tissue repair.", "aliases": [ "cardiac bioregulator" ], "kind": "peptide", "categories": [ "bioregulators", "longevity" ], "legacy": { "name": "Cardiogen", "full_name": "Cardiogen (cardiac tissue peptide bioregulator)", "aliases": [ "cardiac bioregulator" ], "categories": [ "bioregulators", "longevity" ], "tagline": "Organ-targeted bioregulator from the Khavinson lineage aimed at cardiac tissue repair.", "status": "Approved in Russia", "origin": "Developed by Khavinson's group from amino-acid analysis of bovine cardiac tissue extracts, registered in Russia as both an injectable (cytamin) and oral tablet (cytomax), dating to the 1980s-90s bioregulator program.", "mechanism": "Proposed to regulate cardiac cell proliferation and block apoptosis. In-vitro work shows stimulated myocardial explant growth and reduced p53 expression, pointing to a pro-survival, regenerative effect on heart tissue.", "research_summary": "Research is limited to small Russian studies. A 2009 organotypic-culture study showed stimulated myocardial proliferation and reduced apoptosis markers in both young and aged rat tissue; a related gene-expression study found an altered cardiac transcriptome after treatment. All evidence is in-vitro or animal; no human trials exist, and none of it is replicated in Western labs.", "citations": [ { "title": "[The effect of the amino acids and cardiogen on the development of myocard tissue culture from young and old rats]", "authors_year": "Chalisova et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20210190/" } ], "reported_benefits": [ "support for cardiac tissue repair/regeneration (preclinical)", "potential inhibition of myocardial apoptosis", "claimed anti-aging effects on heart tissue" ], "dosing_protocols": [ { "route": "Intramuscular injection or oral tablet", "protocol": "Community dosing reports: 10-20 mg subcutaneously; no standardized human protocol validated in literature." } ], "side_effects": [ "minimal reported; cardiac safety monitoring data unavailable" ], "safety_notes": "No serious adverse events reported, but the critical nature of cardiac tissue warrants caution, and no long-term human safety data exists. Anyone with pre-existing cardiac disease should get medical oversight before use.", "community_notes": "One of the more-discussed Khavinson peptides in Western longevity circles for cardiovascular aging; all anecdotal and uncontrolled.", "related": [ "bronchogen", "cortagen", "livagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:bronchogen", "peptide:cortagen", "peptide:epithalon", "peptide:livagen", "peptide:pancragen", "peptide:prostamax", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:20210190" ] }, "peptide:cortagen": { "id": "peptide:cortagen", "path": "/peptides/cortagen.html", "title": "Cortagen", "summary": "Organ-targeted Khavinson peptide aimed at cerebral cortex structure and cognitive function.", "aliases": [ "AEDP" ], "kind": "peptide", "categories": [ "bioregulators", "nootropics-cognitive" ], "legacy": { "name": "Cortagen", "full_name": "Cortagen (Ala-Glu-Asp-Pro, brain cortex peptide)", "aliases": [ "AEDP" ], "categories": [ "bioregulators", "nootropics-cognitive" ], "tagline": "Organ-targeted Khavinson peptide aimed at cerebral cortex structure and cognitive function.", "status": "Approved in Russia", "origin": "Synthesized from the amino-acid composition of a natural cerebral-cortex peptide extract related to Cortexin, derived from bovine brain-cortex tissue preparations, approved in Russia as injectable and oral formulations.", "mechanism": "Proposed to regulate cerebral cortex cell differentiation and reduce brain oxidative stress, with suggested effects on neurotrophic factor expression and circadian melatonin regulation in aging models.", "research_summary": "A 2007 study documented antioxidant effects and reduced oxidative-stress markers in rat cerebral cortex; earlier organotypic culture work established tissue-specific effects. Research comes almost entirely from Khavinson's group, and no human trials appear in English-language literature.", "citations": [ { "title": "Effects of bioactive tetrapeptides on free-radical processes", "authors_year": "Kozina et al. 2007", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18239817/" } ], "reported_benefits": [ "support for cortical cell renewal (preclinical)", "potential reduction in brain oxidative stress", "claimed cognitive/neuroprotective support" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Community dosing: 10-20 mg subcutaneously or intramuscularly; oral forms 10-30 mg; no validated human protocol." } ], "side_effects": [ "minimal reported; neurological monitoring data unavailable" ], "safety_notes": "No serious adverse events reported in Russian studies, but CNS effects are poorly characterized in humans, and long-term safety is undocumented.", "community_notes": "Discussed in Western nootropics and longevity communities for mental clarity and cognitive aging support. The evidence base is minimal and largely inaccessible to Western practitioners.", "related": [ "bronchogen", "cardiogen", "livagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:bronchogen", "peptide:cardiogen", "peptide:epithalon", "peptide:livagen", "peptide:pancragen", "peptide:prostamax", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:18239817" ] }, "peptide:livagen": { "id": "peptide:livagen", "path": "/peptides/livagen.html", "title": "Livagen", "summary": "Organ-targeted peptide bioregulator designed to support liver tissue repair and hepatic function.", "aliases": [ "KEDA" ], "kind": "peptide", "categories": [ "bioregulators", "recovery-healing" ], "legacy": { "name": "Livagen", "full_name": "Livagen (Lys-Glu-Asp-Ala, hepatic bioregulator)", "aliases": [ "KEDA" ], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted peptide bioregulator designed to support liver tissue repair and hepatic function.", "status": "Approved in Russia", "origin": "Synthesized from bovine liver tissue extract amino-acid analysis by Khavinson's group. Registered in Russia as injectable (cytamin/hepatamin) and oral tablet formulations, also known as tetrapeptide KEDA.", "mechanism": "Proposed to regulate hepatic cell regeneration, normalize immune/antioxidant status in liver tissue, and support structural homeostasis during metabolic dysfunction and aging.", "research_summary": "A 2020 review documented hepatoprotective and anti-aging properties in animal/in-vitro liver fibrosis models; older organotypic culture studies established tissue-specific effects in liver cultures from young vs aged rats. No human clinical trials identified in English-language literature; evidence is small-sample and unreplicated outside Russia.", "citations": [ { "title": "[The influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology]", "authors_year": "Kuznik et al. 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/32362099/" } ], "reported_benefits": [ "support for hepatic tissue repair/regeneration (preclinical)", "potential hepatoprotective effects", "claimed anti-aging effects on liver" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Community dosing: 10-20 mg subcutaneously or intramuscularly; oral forms 10-30 mg daily; unvalidated in humans." } ], "side_effects": [ "minimal reported; hepatotoxicity monitoring data unavailable" ], "safety_notes": "No serious adverse events reported in available studies. Anyone with pre-existing hepatic disease should avoid use without medical supervision.", "community_notes": "Discussed in Western biohacker circles for liver/metabolic health support; anecdotal only, with unassured purity when sourced outside Russia.", "related": [ "bronchogen", "cardiogen", "cortagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:bronchogen", "peptide:cardiogen", "peptide:cortagen", "peptide:epithalon", "peptide:pancragen", "peptide:prostamax", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:32362099" ] }, "peptide:pancragen": { "id": "peptide:pancragen", "path": "/peptides/pancragen.html", "title": "Pancragen", "summary": "Organ-targeted peptide bioregulator designed to support pancreatic function and glucose metabolism.", "aliases": [ "KEDT" ], "kind": "peptide", "categories": [ "bioregulators", "fat-loss" ], "legacy": { "name": "Pancragen", "full_name": "Pancragen (Lys-Glu-Asp-Trp, pancreatic bioregulator)", "aliases": [ "KEDT" ], "categories": [ "bioregulators", "fat-loss" ], "tagline": "Organ-targeted peptide bioregulator designed to support pancreatic function and glucose metabolism.", "status": "Approved in Russia", "origin": "Synthesized from bovine pancreatic tissue extract by Khavinson's group. Registered in Russia as injectable and oral formulations, and in Russian clinical practice for pancreatic and metabolic health since the 1990s.", "mechanism": "Proposed to regulate pancreatic islet and acinar cell differentiation, possibly via developmental transcription factors (Pdx1, Pax6, Pax4, Foxa2), normalizing insulin secretion and glucose tolerance.", "research_summary": "A 2013 study showed pancragen stimulated differentiation markers in pancreatic cell cultures, more so in aged cultures. Two primate studies (2014-2015) showed normalized glucose tolerance and insulin dynamics in aged rhesus monkeys, but with small samples (4-9 animals). No randomized human trials exist; evidence is limited to animal and cellular models.", "citations": [ { "title": "Effects of pancragen on the differentiation of pancreatic cells during their ageing", "authors_year": "Khavinson et al. 2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23486591/" }, { "title": "[Correction of impaired glucose tolerance using tetrapeptide (Pancragen) in old female rhesus monkeys]", "authors_year": "Goncharova et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28509500/" } ], "reported_benefits": [ "support for pancreatic cell regeneration (preclinical)", "potential normalization of glucose metabolism (primate data)", "claimed anti-diabetic effects" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Primate studies used 50-500 µg/animal/day for 10 days IM; community dosing 10-20 mg subcutaneously, unvalidated in humans." } ], "side_effects": [ "minimal reported; glucose/metabolic monitoring data limited" ], "safety_notes": "No serious adverse events reported in animal or in-vitro studies. People with diabetes should only use it under medical supervision given its potential glucose effects.", "community_notes": "Popular in metabolic-health biohacker circles for glucose control claims. Human evidence is entirely absent, and imported peptide quality is unassured.", "related": [ "bronchogen", "cardiogen", "cortagen", "livagen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:bronchogen", "peptide:cardiogen", "peptide:cortagen", "peptide:epithalon", "peptide:livagen", "peptide:prostamax", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:23486591", "pmid:28509500" ] }, "peptide:prostamax": { "id": "peptide:prostamax", "path": "/peptides/prostamax.html", "title": "Prostamax", "summary": "Organ-targeted peptide bioregulator designed to support prostate tissue structure and urogenital function.", "aliases": [ "Prostatilen" ], "kind": "peptide", "categories": [ "bioregulators", "sexual-health" ], "legacy": { "name": "Prostamax", "full_name": "Prostamax (also known as Prostatilen; prostate-derived peptide bioregulator)", "aliases": [ "Prostatilen" ], "categories": [ "bioregulators", "sexual-health" ], "tagline": "Organ-targeted peptide bioregulator designed to support prostate tissue structure and urogenital function.", "status": "Approved in Russia", "origin": "Derived from bovine prostate tissue extracts by Khavinson's group and collaborators. Registered in Russia as injectable (cytamin/prostatamin) and oral formulations, in Russian urology and gerontology practice since the 1980s-90s under the clinical name Prostatilen.", "mechanism": "Proposed to regulate prostate cell differentiation and regeneration and support structural integrity of prostate tissue, with theorized immunoprotective effects.", "research_summary": "Formal human clinical trials for Prostamax are absent from PubMed. A related study on vesugen showed tissue-specific stimulation in human prostate fibroblasts, suggesting a shared mechanism; a 1997 study of a related prostate peptide preparation showed protective effects in a rat decompression model. Evidence is largely Russian-language and unreplicated in the West.", "citations": [ { "title": "Peptides tissue-specifically stimulate cell differentiation during their aging", "authors_year": "Khavinson et al. 2012", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22808515/" } ], "reported_benefits": [ "support for prostate tissue structure (preclinical)", "claimed enhancement of prostate function", "possible support for urinary/sexual health" ], "dosing_protocols": [ { "route": "Subcutaneous/intramuscular injection or oral tablet", "protocol": "Community dosing: 10-20 mg subcutaneously or intramuscularly; oral forms 10-30 mg daily; unvalidated in humans." } ], "side_effects": [ "minimal reported; long-term monitoring data absent" ], "safety_notes": "No serious adverse events documented. Effects on hormone-sensitive prostate tissue aren't well characterized. Anyone with prostate cancer or significant prostate disease should avoid use without medical evaluation.", "community_notes": "Discussed in men's health and biohacker communities for prostate support and urinary flow. Anecdotal only; human research validation is absent.", "related": [ "bronchogen", "cardiogen", "cortagen", "livagen", "pancragen", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:bronchogen", "peptide:cardiogen", "peptide:cortagen", "peptide:epithalon", "peptide:livagen", "peptide:pancragen", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:22808515" ] }, "peptide:cartalax": { "id": "peptide:cartalax", "path": "/peptides/cartalax.html", "title": "Cartalax", "summary": "Organ-targeted Khavinson peptide aimed at cartilage and joint tissue regeneration.", "aliases": [], "kind": "peptide", "categories": [ "bioregulators", "recovery-healing" ], "legacy": { "name": "Cartalax", "full_name": "Cartalax (cartilage-targeted peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted Khavinson peptide aimed at cartilage and joint tissue regeneration.", "status": "Approved in Russia; research compound", "origin": "Synthesized by the St. Petersburg Institute of Bioregulation and Gerontology in the Khavinson organ-targeted bioregulator tradition, on the premise that short synthetic peptides can selectively influence specific tissues through epigenetic mechanisms.", "mechanism": "Proposed to activate cartilage cell proliferation and differentiation by interacting with DNA promoter regions in cartilage-specific genes, regulating chondrogenic markers and extracellular matrix proteins.", "research_summary": "No English-language peer-reviewed studies indexed in PubMed exist for Cartalax specifically. It's referenced only in Russian-language literature and commercial or community sources, unreplicated in Western academic literature. Evidence quality here is the lowest tier in the family.", "citations": [], "reported_benefits": [ "claimed joint cartilage regeneration", "claimed improved cartilage cell proliferation", "claimed reduced joint degeneration" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily or every other day for 10-20 days, repeated after 3-6 months." } ], "side_effects": [ "localized injection-site reactions when injected" ], "safety_notes": "Published safety data is limited. Russian regulatory approval suggests a history of use, but Western trials are absent, and compounded or imported preparation quality may vary.", "community_notes": "Community reports suggest positive effects on joint pain and mobility, entirely anecdotal. Typically sourced through import from Russia.", "related": [ "chonluten", "vesugen", "pancragen", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:chonluten", "peptide:epithalon", "peptide:pancragen", "peptide:thymosin-alpha-1", "peptide:vesugen" ], "conflicts": [], "sourceRefs": [] }, "peptide:chonluten": { "id": "peptide:chonluten", "path": "/peptides/chonluten.html", "title": "Chonluten", "summary": "Organ-targeted peptide for bronchial and pulmonary tissue support.", "aliases": [], "kind": "peptide", "categories": [ "bioregulators", "recovery-healing" ], "legacy": { "name": "Chonluten", "full_name": "Chonluten (bronchial/pulmonary peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "recovery-healing" ], "tagline": "Organ-targeted peptide for bronchial and pulmonary tissue support.", "status": "Approved in Russia; research compound", "origin": "Developed by the St. Petersburg Institute of Bioregulation and Gerontology as an organ-targeted bioregulator for lung and bronchial tissue, following the Khavinson model.", "mechanism": "Proposed to enhance proliferation and differentiation of bronchial and alveolar epithelial cells through epigenetic gene regulation, supporting airway repair and immune defense.", "research_summary": "No English-language peer-reviewed studies indexed in PubMed exist for Chonluten specifically. It's documented only in Russian-language literature and community sources; evidence quality is the family's lowest tier.", "citations": [], "reported_benefits": [ "claimed bronchial tissue repair", "claimed improved respiratory function", "claimed reduced respiratory tract inflammation" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily or every other day for 10-20 days, repeated seasonally." } ], "side_effects": [ "minimal systemic effects reported", "localized injection-site reactions possible" ], "safety_notes": "Published safety data outside Russian sources is limited. Not recommended in pregnancy, and compounded preparation quality varies.", "community_notes": "Some self-experimenters use it for chronic respiratory conditions; evidence is testimonial only.", "related": [ "bronchogen", "vesugen", "crystagen", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:bronchogen", "peptide:crystagen", "peptide:epithalon", "peptide:thymosin-alpha-1", "peptide:vesugen" ], "conflicts": [], "sourceRefs": [] }, "peptide:crystagen": { "id": "peptide:crystagen", "path": "/peptides/crystagen.html", "title": "Crystagen", "summary": "Organ-targeted Khavinson peptide aimed at immune activation and B-cell function.", "aliases": [], "kind": "peptide", "categories": [ "bioregulators", "longevity" ], "legacy": { "name": "Crystagen", "full_name": "Crystagen (immune-system-targeted peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "longevity" ], "tagline": "Organ-targeted Khavinson peptide aimed at immune activation and B-cell function.", "status": "Approved in Russia; limited Western literature", "origin": "Synthesized by the St. Petersburg Institute of Bioregulation and Gerontology as an immune-targeted bioregulator, part of the Khavinson family aimed at modulating tissue-specific immune function.", "mechanism": "Proposed to activate B-cell populations in the spleen by affecting proliferation and apoptosis regulation.", "research_summary": "A 2014 paper found Crystagen activates immune B-cells by modulating apoptosis, with a narrower overall cell-renewal effect than other family members like Vilon. The research base is small and mostly confined to Russian-language literature from the St. Petersburg Institute, with little independent Western replication.", "citations": [ { "title": "Molecular aspects of immunoprotective activity of peptides in spleen during the ageing process", "authors_year": "Khavinson et al. 2014", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28976144/" } ], "reported_benefits": [ "claimed B-cell immune activation", "claimed enhanced immune response in aging", "claimed reduced immune senescence" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily for 10-20 days, repeated every 3-6 months." } ], "side_effects": [ "generally well tolerated", "localized injection-site reactions possible" ], "safety_notes": "Safety data is limited to Russian studies. Not recommended for pregnant women or anyone with autoimmune conditions, where B-cell activation could be problematic.", "community_notes": "Community reports suggest immune-support benefits, often stacked with Vilon or Thymalin, entirely anecdotal.", "related": [ "thymalin", "vilon", "pinealon", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:epithalon", "peptide:pinealon", "peptide:thymalin", "peptide:thymosin-alpha-1", "peptide:vilon" ], "conflicts": [], "sourceRefs": [ "pmid:28976144" ] }, "peptide:ovagen": { "id": "peptide:ovagen", "path": "/peptides/ovagen.html", "title": "Ovagen", "summary": "Organ-targeted peptide supporting ovarian tissue function and reproductive health.", "aliases": [], "kind": "peptide", "categories": [ "bioregulators", "sexual-health" ], "legacy": { "name": "Ovagen", "full_name": "Ovagen (ovarian-tissue-targeted peptide bioregulator)", "aliases": [], "categories": [ "bioregulators", "sexual-health" ], "tagline": "Organ-targeted peptide supporting ovarian tissue function and reproductive health.", "status": "Approved in Russia; veterinary research applications documented", "origin": "Developed by the St. Petersburg Institute of Bioregulation and Gerontology as an ovarian-targeted bioregulator. Unlike most peptides in its family, it's been extensively used in veterinary reproduction research as an FSH alternative.", "mechanism": "Proposed to act as an FSH analog or potentiator, enhancing follicular development and oocyte maturation.", "research_summary": "Documented in peer-reviewed veterinary literature (dairy cattle, sheep, goats, 2003-2010) for improved follicle emergence and oocyte recovery in assisted reproduction. No human clinical trials for reproductive use turn up in PubMed. Evidence is moderate for veterinary use, essentially absent for human use.", "citations": [ { "title": "Effects of low-dose follicle-stimulating hormone administration on follicular dynamics and preovulatory follicle characteristics in dairy cows during the summer", "authors_year": "Friedman et al. 2010", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/20399062/" } ], "reported_benefits": [ "ovarian follicle stimulation (veterinary evidence)", "claimed improved fertility support in humans (unproven)" ], "dosing_protocols": [ { "route": "Subcutaneous or intramuscular injection", "protocol": "Veterinary applications: 2.2-4.4 mg on specific estrous-cycle days; human protocols not documented in Western literature." } ], "side_effects": [ "minimal reported in animal studies", "potential ovarian hyperstimulation (dose-dependent, theoretical in humans)" ], "safety_notes": "Safety data comes mainly from veterinary and Russian sources. Human reproductive use lacks Western clinical trials and needs medical supervision if attempted.", "community_notes": "Little community discussion. Most literature is veterinary and agricultural, not human self-experimentation.", "related": [ "testagen", "pancragen", "prostamax", "epithalon", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:epithalon", "peptide:pancragen", "peptide:prostamax", "peptide:testagen", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:20399062" ] }, "peptide:vesugen": { "id": "peptide:vesugen", "path": "/peptides/vesugen.html", "title": "Vesugen", "summary": "Organ-targeted peptide supporting vascular endothelial cell function and tissue regeneration.", "aliases": [ "KED peptide" ], "kind": "peptide", "categories": [ "bioregulators", "longevity" ], "legacy": { "name": "Vesugen", "full_name": "Vesugen (vascular-tissue-targeted peptide bioregulator, Lys-Glu-Asp / KED)", "aliases": [ "KED peptide" ], "categories": [ "bioregulators", "longevity" ], "tagline": "Organ-targeted peptide supporting vascular endothelial cell function and tissue regeneration.", "status": "Approved in Russia; PubMed-indexed research available", "origin": "Developed by the St. Petersburg Institute of Bioregulation and Gerontology as a vascular-targeted bioregulator. The tripeptide Lys-Glu-Asp (KED) was synthesized within the organ-targeted peptide tradition.", "mechanism": "Activates proliferation and renewal in vascular endothelial cells (increasing Ki-67, reducing p53), normalizes endothelin-1 expression in atherosclerotic endothelium, and increases SIRT1 expression involved in DNA repair.", "research_summary": "A 2016 paper described molecular mechanisms of vasoprotection including endothelin-1 normalization; a 2014 paper showed the KED tripeptide reduces adhesion molecules involved in atherosclerotic plaque formation. Other studies document effects on endothelial proliferation and erectile function in elderly men with atherosclerosis. Research base is small, a handful of PubMed-indexed studies, primarily from Russian institutions, with limited independent Western replication.", "citations": [ { "title": "Molecular aspects of vasoprotective peptide KED activity during atherosclerosis and restenosis", "authors_year": "Khavinson et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28539025/" }, { "title": "Molecular aspects of anti-atherosclerotic effects of short peptides", "authors_year": "Khavinson et al. 2014", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/25408528/" } ], "reported_benefits": [ "vascular endothelial cell regeneration (preclinical)", "claimed improved blood flow/circulation", "claimed reduced atherosclerotic plaque formation", "claimed improved erectile function in atherosclerosis-related ED" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Community reports: 10-20 mg daily or every other day for 10-20 days, repeated every 3-6 months." } ], "side_effects": [ "generally well tolerated", "localized injection-site reactions possible", "one study noted prooxidant activity in a chemiluminescence assay" ], "safety_notes": "Safety data comes primarily from Russian studies. Not recommended in pregnancy; patients on anticoagulants should consult a physician given the cardiovascular mechanism claims.", "community_notes": "Discussed in longevity communities for cardiovascular support, sometimes combined with other vascular-support peptides; entirely anecdotal.", "related": [ "epithalon", "pinealon", "pancragen", "cardiogen", "thymosin-alpha-1" ] }, "research": [], "related": [ "peptide:cardiogen", "peptide:epithalon", "peptide:pancragen", "peptide:pinealon", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:28539025", "pmid:25408528" ] }, "peptide:peg-mgf": { "id": "peptide:peg-mgf", "path": "/peptides/peg-mgf.html", "title": "PEG-MGF", "summary": "Native MGF with a polyethylene glycol tag bolted on to stretch its otherwise minutes-long half-life into something injectable a few times a week; the underlying human data is essentially borrowed from other pegylated IGF-1 work, not PEG-MGF itself.", "aliases": [ "Pegylated MGF", "PEG MGF" ], "kind": "peptide", "categories": [ "fitness-muscle" ], "legacy": { "name": "PEG-MGF", "full_name": "PEGylated Mechano Growth Factor", "aliases": [ "Pegylated MGF", "PEG MGF" ], "categories": [ "fitness-muscle" ], "tagline": "Native MGF with a polyethylene glycol tag bolted on to stretch its otherwise minutes-long half-life into something injectable a few times a week; the underlying human data is essentially borrowed from other pegylated IGF-1 work, not PEG-MGF itself.", "status": "Unapproved research compound, no regulatory approval for any human indication. Sold through the same research-chemical channels as unmodified MGF.", "origin": "MGF (mechano growth factor, the IGF-1Ec splice variant) is produced locally in muscle tissue after mechanical loading or damage and is cleared within minutes. PEG-MGF is a synthetic version with polyethylene glycol chains attached to the peptide backbone, a modification used across biologics (PEGylated interferons, PEGylated growth hormone, etc.) specifically to slow renal clearance and proteolysis.", "mechanism": "Proposed to act the same way as native MGF, binding IGF-1 receptors on satellite cells to trigger proliferation and fusion into myofibers, but with PEGylation increasing hydrodynamic size and shielding the peptide from clearance so it persists in circulation rather than acting only locally and briefly.", "research_summary": "No PubMed-indexed studies test PEG-MGF itself in animals or humans. What exists is indirect: a first-in-human trial of a differently PEGylated IGF-1 molecule (not MGF) showed PEGylation extended IGF-1 half-life from a matter of hours to roughly 140-200 hours and blunted the hypoglycemia and GH-suppression seen with unmodified IGF-1, demonstrating PEGylation's general effect on this protein family's pharmacokinetics. Separately, human muscle-biopsy studies confirm native MGF mRNA is induced transiently by resistance exercise and that this response is blunted in older adults. A 2026 narrative review of unregulated performance-enhancing peptides lists PEG-MGF among compounds being self-administered off-label and explicitly flags the absence of human pharmacokinetic or efficacy data for it specifically, contrasting it with better-studied compounds in the same drug class.", "reported_benefits": [ "claimed longer-lasting, more systemic muscle-building effect than native MGF (theoretical, extrapolated from PEGylation's known effect on IGF-1 half-life)", "reduced injection frequency compared to native MGF due to slower clearance", "same satellite-cell activation/hypertrophy claims made for native MGF, unverified for the pegylated form" ], "dosing_protocols": [ { "route": "Subcutaneous injection", "protocol": "Commonly reported at 200-500 mcg per injection, roughly 2x weekly, sometimes framed as once-weekly given the claimed extended half-life. No clinical dosing standard exists; these figures come from self-experimentation reporting, not trials." } ], "side_effects": [ "injection site irritation", "theoretical hypoglycemia risk from IGF-1 receptor activation", "unknown long-term effects of chronic PEG accumulation (a general PEGylation concern seen with other pegylated biologics, not established for PEG-MGF specifically)" ], "safety_notes": "There is no published human safety data for PEG-MGF as a distinct molecule. Safety claims lean entirely on data for native MGF and on unrelated PEGylated IGF-1/growth-hormone products, which is a real evidentiary gap, not a formality. Theoretical concerns carried over from the IGF-1 pathway generally (mitogenic signaling, malignancy risk in susceptible tissue) apply here too and are, if anything, amplified by the longer systemic exposure PEGylation is designed to produce.", "community_notes": "Discussed in bodybuilding and peptide self-experimentation circles as the 'systemic' counterpart to local MGF injections, used post-training with claims of prolonged muscle-building signaling. Reports are anecdotal; users generally acknowledge there's no controlled human trial behind the protocols being passed around.", "related": [ "mgf" ], "citations": [ { "title": "The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration", "authors_year": "Dominikowski et al. 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42395176/" }, { "title": "First-in-man study with a novel PEGylated recombinant human insulin-like growth factor-I", "authors_year": "Kletzl et al. 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28110155/" }, { "title": "Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro", "authors_year": "Philippou et al. 2009", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19567392/" }, { "title": "Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise", "authors_year": "Hameed et al. 2003", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/12562960/" } ] }, "research": [], "related": [ "peptide:mgf" ], "conflicts": [], "sourceRefs": [ "pmid:42395176", "pmid:28110155", "pmid:19567392", "pmid:12562960" ] }, "peptide:glutathione": { "id": "peptide:glutathione", "path": "/peptides/glutathione.html", "title": "Glutathione", "summary": "The body's main intracellular antioxidant tripeptide; oral supplementation genuinely raises body stores in trials, but the skin-lightening and detox claims built on top of that are much thinner.", "aliases": [ "GSH", "reduced glutathione", "L-glutathione" ], "kind": "peptide", "categories": [ "anti-aging" ], "legacy": { "name": "Glutathione", "full_name": "Glutathione (gamma-L-glutamyl-L-cysteinyl-glycine, GSH)", "aliases": [ "GSH", "reduced glutathione", "L-glutathione" ], "categories": [ "anti-aging" ], "tagline": "The body's main intracellular antioxidant tripeptide; oral supplementation genuinely raises body stores in trials, but the skin-lightening and detox claims built on top of that are much thinner.", "status": "Sold over-the-counter as an oral supplement, and used off-label as an IV or injectable product in wellness/aesthetic clinics; not FDA-approved for any indication marketed to consumers.", "origin": "A tripeptide (glutamate-cysteine-glycine) synthesized in nearly every cell, not obtained from diet as an intact peptide. It's the most abundant low-molecular-weight thiol in the body and central to redox buffering and detoxification.", "mechanism": "The cysteine thiol group lets glutathione cycle between reduced (GSH) and oxidized (GSSG) states, neutralizing reactive oxygen species and peroxides via glutathione peroxidase, and conjugating with xenobiotics via glutathione S-transferases for excretion. Proposed skin-lightening effects come from direct and indirect inhibition of tyrosinase and a shift in melanin synthesis from darker eumelanin toward lighter pheomelanin.", "research_summary": "Oral bioavailability was long assumed to be near zero because gut peptidases break glutathione down, but a 6-month randomized placebo-controlled trial in healthy adults showed daily oral GSH (250 or 1000 mg) did raise blood, erythrocyte, and buccal-cell glutathione levels in a dose- and time-dependent way, with levels falling back to baseline after a washout month. For the skin-lightening use case specifically, multiple human RCTs exist and reviews of them are mixed: some show modest melanin reduction with oral or topical glutathione, effects are inconsistent across body sites and populations, not long-lasting after stopping, and IV/parenteral glutathione carries real safety concerns (anaphylaxis, hepatotoxicity reports) that oral and topical forms don't. General antioxidant/longevity/detox benefit claims beyond raising measured GSH levels are not well supported by controlled human trials.", "reported_benefits": [ "reliably raises measured glutathione levels in blood and tissue with sustained oral dosing (best-supported claim)", "modest, inconsistent skin-lightening/depigmentation effect reported in some RCTs, not durable after discontinuation", "marketed general antioxidant/detox and anti-aging support, largely unproven beyond the biomarker changes above" ], "dosing_protocols": [ { "route": "Oral capsule", "protocol": "Trial doses of 250-1000 mg/day for up to 6 months raised body glutathione stores in a dose-dependent way; community use commonly mirrors this range." }, { "route": "IV infusion (clinic setting)", "protocol": "Widely used off-label for skin lightening at clinic-set doses with no standardized protocol; reviews note this route has the least standardization and the worst safety signal of the three." }, { "route": "Topical", "protocol": "Used in cosmetic formulations for localized skin-lightening effect; reported better tolerated than IV but with variable, non-durable results." } ], "side_effects": [ "oral: generally well tolerated, mild GI upset reported occasionally", "IV/parenteral: flushing, and rarer but serious reports of anaphylaxis and hepatotoxicity", "topical: mostly local irritation" ], "safety_notes": "Oral glutathione has the best safety and mechanistic evidence of the three routes and is where the strongest trial (Richie et al. 2014) sits. IV glutathione, despite being popular in aesthetic clinics for skin lightening, has weaker efficacy evidence and a real, documented risk of serious adverse events including anaphylaxis and liver injury; regulators in some countries have issued warnings against off-label IV use for this purpose. Long-term safety of sustained high-dose supplementation of any form isn't well characterized.", "community_notes": "Frequently paired with NAD+ in longevity and detox-focused wellness stacks, marketed as antioxidant/anti-aging support alongside NAD+'s energy-metabolism pitch. In cosmetic-focused communities it's discussed mainly for skin lightening, where users generally note effects fade if supplementation stops.", "related": [ "nad" ], "citations": [ { "title": "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione", "authors_year": "Richie et al. 2015", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/24791752/" }, { "title": "Exploring the Safety and Efficacy of Glutathione Supplementation for Skin Lightening: A Narrative Review", "authors_year": "Alzahrani et al. 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40013212/" }, { "title": "Systemic Glutathione as a Skin-Whitening Agent in Adult", "authors_year": "Sitohang & Ninditya 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/32373172/" }, { "title": "Glutathione as a skin whitening agent: Facts, myths, evidence and controversies", "authors_year": "Sonthalia et al. 2016", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/27088927/" } ] }, "research": [], "related": [ "peptide:nad" ], "conflicts": [], "sourceRefs": [ "pmid:24791752", "pmid:40013212", "pmid:32373172", "pmid:27088927" ] }, "peptide:fgl-l": { "id": "peptide:fgl-l", "path": "/peptides/fgl-l.html", "title": "FGL(L)", "summary": "A 15-amino-acid fragment of the neural cell adhesion molecule that activates FGFR1 in rodent brains — real synaptic-plasticity data, zero human trials.", "aliases": [ "FGL", "FG-Loop peptide", "FGLL", "NCAM mimetic peptide FGL" ], "kind": "peptide", "categories": [ "nootropics-cognitive" ], "legacy": { "name": "FGL(L)", "full_name": "FGL Peptide (NCAM-derived FG-Loop Peptide)", "aliases": [ "FGL", "FG-Loop peptide", "FGLL", "NCAM mimetic peptide FGL" ], "categories": [ "nootropics-cognitive" ], "tagline": "A 15-amino-acid fragment of the neural cell adhesion molecule that activates FGFR1 in rodent brains — real synaptic-plasticity data, zero human trials.", "status": "Unapproved research compound. No FDA/EMA approval, no clinical trials registered in humans as of 2026; all published work is in vitro or in rodent models.", "origin": "FGL is a synthetic 15-amino-acid peptide (sequence EVYVVAENQQGKSKA) corresponding to the second fibronectin type III (F3) module of the neural cell adhesion molecule (NCAM), first described by Cambon et al. (2004). It is not naturally circulating — it's a lab-designed mimetic of a binding loop within a much larger cell-surface protein.", "mechanism": "FGL binds and activates fibroblast growth factor receptor 1 (FGFR1), the same receptor NCAM engages via heterophilic interaction, without requiring the full NCAM protein. Downstream, this triggers PKC and CaMKII signaling that facilitates synaptic AMPA receptor delivery and NMDA-receptor-dependent long-term potentiation (LTP) in hippocampal neurons, and separately drives neurotrophic and anti-inflammatory effects (suppressing microglial activation via neuronal CD200 upregulation).", "research_summary": "All evidence is preclinical — cell culture and rodent studies, no human data. In rats, systemic or intracerebroventricular FGL improved spatial and fear-conditioning memory consolidation, facilitated hippocampal LTP in the dentate gyrus, and reduced amyloid-beta-induced CA1 pyramidal cell loss with partial rescue of social recognition memory in an Alzheimer's-relevant lesion model. In vitro, FGL promoted synaptogenesis, enhanced presynaptic function, mobilized neural stem cells, and suppressed neuroinflammatory microglial activation in aged rats. One study also found FGL alone (without amyloid-beta) reduced CA1 pyramidal cell counts by 40%, a caution against assuming benign effects outside disease models.", "reported_benefits": [ "Enhanced spatial learning and memory consolidation (rodent studies)", "Facilitated hippocampal long-term potentiation (LTP)", "Partial protection against amyloid-beta-induced neuronal loss and memory deficits (rodent AD model)", "Anti-inflammatory / anti-microglial activation effects in aged rat brain", "Promoted synaptogenesis and neural stem cell mobilization in vitro" ], "dosing_protocols": [ { "route": "Subcutaneous (rodent research dose)", "protocol": "Published rat studies typically used single or repeated doses in the range of ~1-3 mg/kg systemically; no human dosing data exists. Self-experimentation reports describing human doses are anecdotal extrapolations, not validated protocols." }, { "route": "Intracerebroventricular (research only)", "protocol": "Used exclusively in animal studies (microgram-range local infusion) to demonstrate direct CNS mechanism — not a route relevant to human self-use." } ], "side_effects": [ "Unknown in humans — no human safety data exists", "In rats, FGL alone (without pathology present) was associated with a reduction in CA1 pyramidal neuron counts in one study, suggesting effects may not be uniformly beneficial in a healthy brain", "Theoretical concern: FGFR1 agonism is not tissue-restricted to brain — systemic off-target growth-factor signaling effects are unstudied" ], "safety_notes": "FGL has never been tested in a human clinical trial; everything known comes from rodent behavioral studies and cell culture. The finding that FGL alone reduced CA1 neuron counts in non-lesioned tissue is a real red flag in the literature that self-experimentation communities often omit. Long-term safety, pharmacokinetics, immunogenicity (as a foreign peptide fragment), and optimal dosing are all unknown.", "community_notes": "FGL circulates in nootropic/longevity peptide forums as a theoretical 'NCAM mimetic' for memory enhancement, usually referenced alongside other FGFR-pathway peptides. Discussion tends to lean heavily on the Cambon 2004 and Knafo 2012 papers while glossing over the mixed CA1-neuron finding; actual self-reported use logs are sparse compared to better-established nootropic peptides.", "related": [ "semax", "selank", "cerebrolysin" ], "citations": [ { "title": "A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation", "authors_year": "Cambon K, Hansen SM, Venero C, et al. (2004)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/15115815/" }, { "title": "A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL", "authors_year": "Downer EJ, Cowley TR, Lyons A, et al. (2008)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/18468731/" }, { "title": "Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimetic peptide", "authors_year": "Corbett NJ, Gabbott PL, Klementiev B, et al. (2013)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23951173/" }, { "title": "Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement", "authors_year": "Knafo S, Venero C, Sánchez-Puelles C, et al. (2012)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22363206/" }, { "title": "The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo", "authors_year": "Dallérac G, Zerwas M, Novikova T, et al. (2011)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/21508096/" }, { "title": "The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo", "authors_year": "Klein R, Blaschke S, Neumaier B, et al. (2014)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/24817672/" } ] }, "research": [], "related": [ "peptide:cerebrolysin", "peptide:selank", "peptide:semax" ], "conflicts": [], "sourceRefs": [ "pmid:15115815", "pmid:18468731", "pmid:23951173", "pmid:22363206", "pmid:21508096", "pmid:24817672" ] }, "peptide:met-enkephalin": { "id": "peptide:met-enkephalin", "path": "/peptides/met-enkephalin.html", "title": "Met-Enkephalin", "summary": "An endogenous five-amino-acid opioid that quietly puts a brake on cell division — well-studied in oncology and immunology labs, but that's not the same as a validated self-use protocol.", "aliases": [ "OGF", "[Met5]-enkephalin", "Methionine enkephalin", "Opioid Growth Factor" ], "kind": "peptide", "categories": [ "bioregulators" ], "legacy": { "name": "Met-Enkephalin", "full_name": "Methionine-Enkephalin (Opioid Growth Factor, OGF)", "aliases": [ "OGF", "[Met5]-enkephalin", "Methionine enkephalin", "Opioid Growth Factor" ], "categories": [ "bioregulators" ], "tagline": "An endogenous five-amino-acid opioid that quietly puts a brake on cell division — well-studied in oncology and immunology labs, but that's not the same as a validated self-use protocol.", "status": "Endogenous human peptide (naturally produced). Not FDA-approved as a drug in its own right; investigated in early-phase oncology trials as 'OGF' biotherapy and mechanistically tied to low-dose naltrexone (LDN) research, which itself is used off-label.", "origin": "Met-enkephalin (Tyr-Gly-Gly-Phe-Met) is one of the body's native opioid peptides, derived from proteolytic processing of proenkephalin. Beyond its classical role as a weak opioid-receptor ligand, a specific pool of it functions as the 'opioid growth factor' (OGF) — an autocrine/paracrine signal that acts through a distinct, non-classical receptor (OGFr) to regulate cell replication.", "mechanism": "OGF (Met-enkephalin) binds OGFr and traffics into the cell nucleus, where it upregulates cyclin-dependent kinase inhibitors (p16, p21), delaying the G1/S transition of the cell cycle and slowing proliferation. This is the same axis proposed to underlie low-dose naltrexone's effects: brief opioid receptor blockade triggers compensatory upregulation of OGF and OGFr, amplifying the inhibitory signal once blockade wears off — a rebound mechanism distinct from naltrexone's classical opioid antagonism.", "research_summary": "Human data is limited mostly to small early-phase oncology trials using OGF as an adjunct biotherapy, plus indirect clinical experience via low-dose naltrexone (which is not the same compound but is mechanistically linked). The bulk of solid evidence is in vitro and in xenograft/animal models: the OGF-OGFr axis has been shown to inhibit proliferation across multiple human cancer cell lines (triple-negative breast, thyroid follicular, pancreatic, ovarian, colorectal, squamous cell), consistently via p16/p21-mediated cell-cycle arrest, and mutations in OGFr found in human tumors can blunt this response. Immune-modulating and wound-healing/homeostatic roles are also documented, chiefly in rodent models. No robust randomized controlled trial has established Met-enkephalin itself as a clinical therapy.", "reported_benefits": [ "Cell-cycle arrest / growth inhibition of cancer cell lines in vitro and in animal xenograft models", "Proposed synergy with chemotherapy agents (e.g., paclitaxel) in preclinical models", "Immune-modulatory and homeostatic signaling implicated in wound healing and autoimmune disease models", "Mechanistic basis cited for low-dose naltrexone's reported effects in autoimmune and oncology self-experimentation contexts" ], "dosing_protocols": [ { "route": "Intravenous (clinical trial context, historical)", "protocol": "Early oncology trials investigated OGF infusions in defined clinical protocols under medical supervision; these are not replicable or safe outside a trial/clinical setting and specific dosing is not something to extrapolate for self-use." }, { "route": "Subcutaneous (self-experimentation reports)", "protocol": "Community-reported use (loosely modeled on published rodent dosing, roughly 0.1-1 mg/kg equivalents scaled down) is speculative and not validated in controlled human studies — genuine dosing standards do not exist outside supervised trials." } ], "side_effects": [ "Because it interacts with opioid-receptor-adjacent pathways, theoretical risk of interaction with opioid medications or endogenous opioid tone", "Injection-site reactions reported anecdotally", "Unknown long-term effects of exogenous administration outside short clinical trial windows", "Tumor cells with OGFr mutations may not respond as expected, complicating any assumption of predictable growth-inhibitory effect" ], "safety_notes": "Met-enkephalin/OGF has real oncology-research pedigree, but that pedigree is early-phase and mechanistic, not a settled clinical protocol. It should not be conflated with low-dose naltrexone, which is a different molecule with a much larger (though still mostly off-label) human-use footprint. Self-administering a peptide whose only rigorous human data comes from monitored trials is a meaningfully different risk profile than trials themselves.", "community_notes": "In self-experimentation and biohacking circles, Met-enkephalin/OGF is discussed mostly as the 'mechanistic explanation' for why low-dose naltrexone might work in autoimmune and oncology-adjacent contexts, rather than as a peptide people commonly inject directly — actual first-hand use reports are far rarer than LDN reports themselves.", "related": [ "ll-37", "thymosin-alpha-1", "bpc-157" ], "citations": [ { "title": "The opioid growth factor-opioid growth factor receptor axis: homeostatic regulator of cell proliferation and its implications for health and disease", "authors_year": "McLaughlin PJ, Zagon IS (2012)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/22687282/" }, { "title": "Opioid growth factor - opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer", "authors_year": "Zagon IS, Porterfield NK, McLaughlin PJ (2013)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23918871/" }, { "title": "Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model", "authors_year": "Donahue RN, McLaughlin PJ, Zagon IS (2011)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/21807817/" }, { "title": "Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis", "authors_year": "McLaughlin PJ, Zagon IS, Park SS, et al. (2009)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/19835629/" }, { "title": "Mutations in the opioid growth factor receptor in human cancers alter receptor function", "authors_year": "Kren NP, Zagon IS, McLaughlin PJ (2015)", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/26005722/" } ] }, "research": [], "related": [ "peptide:bpc-157", "peptide:ll-37", "peptide:thymosin-alpha-1" ], "conflicts": [], "sourceRefs": [ "pmid:22687282", "pmid:23918871", "pmid:21807817", "pmid:19835629", "pmid:26005722" ] }, "peptide:leuphasyl": { "id": "peptide:leuphasyl", "path": "/peptides/leuphasyl.html", "title": "Leuphasyl", "summary": "A stabilized enkephalin fragment marketed as a topical, needle-free alternative to neuromuscular-blocking wrinkle treatments — the mechanism is plausible, the human wrinkle-reduction evidence is thin.", "aliases": [ "Pentapeptide-18", "Leu-DAP", "SNAP-8 alternative", "Enkephalin-analog pentapeptide" ], "kind": "peptide", "categories": [ "anti-aging" ], "legacy": { "name": "Leuphasyl", "full_name": "Pentapeptide-18", "aliases": [ "Pentapeptide-18", "Leu-DAP", "SNAP-8 alternative", "Enkephalin-analog pentapeptide" ], "categories": [ "anti-aging" ], "tagline": "A stabilized enkephalin fragment marketed as a topical, needle-free alternative to neuromuscular-blocking wrinkle treatments — the mechanism is plausible, the human wrinkle-reduction evidence is thin.", "status": "Unregulated cosmetic ingredient (not a drug); sold in serums/creams, not injectables. No FDA or EMA drug approval process applies because it isn't marketed as a therapeutic.", "origin": "Leuphasyl is a synthetic pentapeptide (Tyr-D-Ala-Gly-Phe-Leu) derived from the endogenous opioid peptide Leu-enkephalin, with a D-amino acid substitution at position 2 to resist enzymatic degradation and extend stability in topical formulations. It is a cosmetic-industry ingredient, not a pharmaceutical.", "mechanism": "Proposed to act at the neuromuscular junction interface in skin by binding opioid-receptor-like sites and dampening catecholamine and acetylcholine release, theoretically reducing the frequency and force of the micro-contractions in facial muscles that contribute to expression-line formation. This is distinct from Botox's mechanism (SNARE-protein cleavage) and from Argireline's (SNARE-complex assembly inhibition); Leuphasyl is generally pitched as complementary to both.", "research_summary": "Published data are almost entirely in vitro and in silico: molecular docking/dynamics and spectroscopic studies show Leuphasyl binding to inflammation- and matrix-remodeling targets (MMP-13, TGF-β, TNF-α pathways) and formulation studies confirm it is stable and non-cytotoxic to skin cell lines when delivered in lipid nanocarriers. No randomized, placebo-controlled human trial of Leuphasyl alone measuring wrinkle depth has been located on PubMed; manufacturer-reported efficacy claims are not independently peer-reviewed. By contrast, its usual co-formulant Argireline (acetyl hexapeptide-3) does have a small published RCT showing modest anti-wrinkle effects.", "reported_benefits": [ "Reported softening of expression lines (crow's feet, forehead lines) with regular topical use, per manufacturer and formulation literature", "Marketed as a synergistic partner to Argireline for combined 'triple mechanism' wrinkle serums", "Non-injectable, no downtime, compatible with routine skincare layering" ], "dosing_protocols": [ { "route": "topical", "protocol": "Typically formulated at 5-10% of a peptide-complex solution, itself included in a finished serum/cream at low single-digit percentages; applied once or twice daily to clean, dry skin, often in combination products with Argireline and/or Matrixyl-type peptides" } ], "side_effects": [ "Mild irritation or contact sensitivity in a minority of users, as with most concentrated peptide serums", "No systemic side effects reported given negligible dermal penetration at typical topical concentrations" ], "safety_notes": "Cosmetic peptides at these concentrations have a good short-term dermal safety record, but there is no dedicated long-term human safety dataset for Leuphasyl specifically, and efficacy claims rest almost entirely on industry-funded formulation studies rather than independent clinical trials.", "community_notes": "Discussed mainly in skincare/DIY-formulation circles as a budget, non-invasive component of 'peptide facial serums,' almost always stacked with Argireline; users report subtle, gradual softening rather than Botox-like results, and skepticism about marketing claims is common even among enthusiasts.", "related": [ "zinc-thymulin" ], "citations": [ { "title": "Pentapeptide-18 as an anti-aging candidate: Spectroscopic characterization and molecular interaction analysis", "authors_year": "Akhan et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41722287/" }, { "title": "Integrative In Silico and In Vitro Evaluation of Vialox and Leuphasyl Pentapeptides for Antiaging Applications", "authors_year": "Akhan et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42116636/" }, { "title": "Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18—Optimization, Characterization, and Cosmetic Application", "authors_year": "Pawłowska et al., 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39337562/" }, { "title": "D-tyrosine adds an anti-melanogenic effect to cosmetic peptides", "authors_year": "Park et al., 2020", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/31937863/" }, { "title": "The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study", "authors_year": "Wang et al., 2013", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/23417317/" } ] }, "research": [], "related": [ "peptide:zinc-thymulin" ], "conflicts": [], "sourceRefs": [ "pmid:41722287", "pmid:42116636", "pmid:39337562", "pmid:31937863", "pmid:23417317" ] }, "peptide:zinc-thymulin": { "id": "peptide:zinc-thymulin", "path": "/peptides/zinc-thymulin.html", "title": "Zinc-thymulin", "summary": "A zinc-dependent thymic hormone with real, decades-old immunology behind it, repackaged for topical hair-loss use on evidence that is mostly adjacent, not direct.", "aliases": [ "Zn-thymulin", "FTS (Facteur Thymique Sérique)", "Zinc-thymulin nonapeptide" ], "kind": "peptide", "categories": [ "anti-aging" ], "legacy": { "name": "Zinc-thymulin", "full_name": "Zinc-bound Thymulin (Zn-FTS, zinc-dependent thymic nonapeptide)", "aliases": [ "Zn-thymulin", "FTS (Facteur Thymique Sérique)", "Zinc-thymulin nonapeptide" ], "categories": [ "anti-aging" ], "tagline": "A zinc-dependent thymic hormone with real, decades-old immunology behind it, repackaged for topical hair-loss use on evidence that is mostly adjacent, not direct.", "status": "Not an approved drug for hair loss anywhere; sold as a cosmetic/topical ingredient in hair serums. Thymulin itself has a long research history in immunology, unrelated to any hair-specific approval.", "origin": "Thymulin is an endogenous nonapeptide hormone (Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn) produced by thymic epithelial cells; it is biologically inactive unless bound to a zinc ion, which is required for receptor binding and immune activity — hence 'zinc-thymulin.' In topical cosmetics, a synthesized or recombinant zinc-thymulin complex is applied to the scalp on the premise that local immune modulation in hair follicles can influence hair cycling and pigmentation.", "mechanism": "Physiologically, zinc-thymulin regulates T-lymphocyte differentiation and maturation and modulates cytokine expression. The hair-loss rationale extends this to the hair follicle's mini-immune environment: androgenetic alopecia and alopecia areata both involve local immune/inflammatory dysregulation around the follicle bulb, and zinc itself is an established cofactor for hair follicle keratinocyte turnover, so the proposed mechanism is restoring local immune balance and zinc-dependent follicular signaling rather than a direct androgen pathway effect.", "research_summary": "The zinc-thymulin biology (zinc-dependence, T-cell modulation, age-related decline) is well established in PubMed-indexed immunology and aging literature going back to the 1990s-2000s, mostly in the context of thymic involution and autoimmune disease, not hair. Separately, zinc deficiency is independently associated with alopecia areata and implicated as a modifiable factor in non-scarring hair loss in dermatology reviews. No PubMed-indexed clinical trial directly testing a topical zinc-thymulin formulation for androgenetic alopecia or hair pigmentation was found; the hair-specific application appears to be a cosmetic-industry extrapolation from these two separate literatures rather than a studied combination.", "reported_benefits": [ "Claimed reduction in hair shedding and support for hair density in androgenetic alopecia (manufacturer/industry claims, not independently trialed)", "Claimed support for maintaining hair pigmentation, based on zinc's and immune modulation's roles in follicle melanocyte function", "General scalp health support attributed to zinc's role in keratinocyte turnover" ], "dosing_protocols": [ { "route": "topical (scalp serum/solution)", "protocol": "Applied directly to scalp, typically once daily, as part of a hair-serum formulation; concentrations are not standardized across products and no clinical dosing protocol exists in the literature" } ], "side_effects": [ "Local scalp irritation possible with any concentrated topical actives", "No systemic toxicity expected at topical doses; injectable/systemic thymulin (studied in unrelated immunology contexts) is not the same use case as topical scalp application" ], "safety_notes": "The underlying zinc-thymulin biology is legitimate and well-studied, but that evidence base is about systemic immune function and thymic aging, not scalp application — safety and efficacy for topical hair use has essentially no direct human trial data, so claims should be treated as unproven extrapolation rather than established fact.", "community_notes": "Appears in peptide/hair-loss self-experimentation forums as a niche, 'immune-modulation angle' alternative or add-on to minoxidil/finasteride regimens, usually discussed with acknowledgment that evidence is indirect and results anecdotal; framed more as a plausible mechanism worth trying than a proven treatment.", "related": [ "leuphasyl" ], "citations": [ { "title": "Plasticity of neuroendocrine-thymus interactions during ontogeny and ageing: role of zinc and arginine", "authors_year": "Mocchegiani et al., 2006", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/16904953/" }, { "title": "The Role of Vitamins and Minerals in Hair Loss: A Review", "authors_year": "Almohanna et al., 2018", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/30547302/" }, { "title": "The Role of Micronutrients in Alopecia Areata: A Review", "authors_year": "Thompson et al., 2017", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/28508256/" }, { "title": "Altered thymic endocrine activity along with impairments of peripheral zinc metabolism and T-lymphocyte populations are associated with myasthenia gravis: a follow-up study", "authors_year": "Licastro et al., 1997", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/9258245/" } ] }, "research": [], "related": [ "peptide:leuphasyl" ], "conflicts": [], "sourceRefs": [ "pmid:16904953", "pmid:30547302", "pmid:28508256", "pmid:9258245" ] }, "peptide:slu-pp-332": { "id": "peptide:slu-pp-332", "path": "/peptides/slu-pp-332.html", "title": "SLU-PP-332", "summary": "A rodent-only 'exercise in a pill' compound that genuinely turns on exercise-like gene programs — but it is a small molecule, not a peptide, and has never been dosed in a human trial.", "aliases": [ "SLU-PP-332", "ERR pan-agonist SLU-PP-332" ], "kind": "peptide", "categories": [ "longevity" ], "legacy": { "name": "SLU-PP-332", "full_name": "SLU-PP-332 (synthetic pan-ERR agonist)", "aliases": [ "SLU-PP-332", "ERR pan-agonist SLU-PP-332" ], "categories": [ "longevity" ], "tagline": "A rodent-only 'exercise in a pill' compound that genuinely turns on exercise-like gene programs — but it is a small molecule, not a peptide, and has never been dosed in a human trial.", "status": "Preclinical research chemical only. No human trials registered or published; not approved or reviewed by any regulatory agency for any use. Sold in the gray-market research-chemical space alongside peptides, but it is chemically unrelated to peptides.", "origin": "IMPORTANT: SLU-PP-332 is NOT a peptide, despite being commonly sold and discussed alongside peptide research compounds. It is a synthetic small-molecule drug — a designed pan-agonist of the three estrogen-related receptor subtypes (ERRα, ERRβ, ERRγ), orphan nuclear receptors unrelated to estrogen signaling itself. It was developed and first reported by academic pharmacology labs (Washington University in St. Louis / Saint Louis University / University of Florida groups) as a chemical tool to probe ERR biology.", "mechanism": "ERRs are master transcriptional regulators of mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, and are activated physiologically during aerobic exercise. SLU-PP-332 binds and activates all three ERR subtypes (with highest potency at ERRα), driving an ERRα-dependent gene program that mimics acute aerobic exercise — including induction of Ddit4 and Slc25a25, increased type IIa oxidative muscle fiber content, and enhanced cellular respiration — without the animal actually exercising.", "research_summary": "All published evidence is preclinical: cell-based assays and mouse studies show SLU-PP-332 increases mitochondrial function and exercise endurance, reduces fat mass, and improves insulin sensitivity in diet-induced-obesity and metabolic syndrome mouse models. A 2026 structure-activity-relationship paper further characterizes its binding and identifies analogues (including the orally bioavailable follow-up compound SLU-PP-915) with improved pharmacokinetics. No human pharmacokinetic, safety, or efficacy data exist; a 2026 doping-control analytical paper characterizes its metabolites specifically because anti-doping labs are watching for illicit human use, which underscores that it is being taken by people despite zero human trials.", "reported_benefits": [ "In mice only: increased treadmill endurance, increased oxidative (type IIa) muscle fiber proportion, and improved aerobic capacity", "In mouse obesity/metabolic syndrome models: reduced fat mass, increased energy expenditure, improved insulin sensitivity", "Proposed (unproven in humans) as a mitochondrial-biogenesis and 'exercise mimetic' strategy for sarcopenia, metabolic disease, and aging-related muscle decline" ], "dosing_protocols": [ { "route": "not established for humans", "protocol": "All published dosing is intraperitoneal or oral administration in mice at research doses (mg/kg); no human dosing protocol exists, and self-administration in humans is unstudied off-label use of a research chemical with unknown human pharmacokinetics" } ], "side_effects": [ "No human safety data exists at all — side effect profile in humans is unknown", "Mouse studies report no evident toxicity at studied doses, but this does not establish human safety", "Flagged by anti-doping researchers as a potential performance-enhancing substance of concern, implying real-world human use is already occurring ahead of any safety data" ], "safety_notes": "This is the single largest gap in the whole profile: a compound with zero published human trials is being self-administered based on mouse data alone. Long-term effects of chronic ERR pan-activation in humans — including any off-target effects, since it hits all three ERR subtypes rather than a single isoform — are completely uncharacterized.", "community_notes": "Discussed in fitness/longevity research-chemical circles as a next-generation 'exercise mimetic,' often mentioned in the same breath as peptide compounds even though it is chemically distinct; self-experimenters extrapolate mouse dosing to humans by body-weight scaling, a practice with no validated basis and no reported pharmacokinetic grounding.", "related": [], "citations": [ { "title": "Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity", "authors_year": "Billon et al., 2023", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/36988910/" }, { "title": "A Synthetic ERR Agonist Alleviates Metabolic Syndrome", "authors_year": "Billon et al., 2024", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/37739806/" }, { "title": "An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity", "authors_year": "Billon et al., 2025", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41421047/" }, { "title": "Chemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling", "authors_year": "Okda et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41850449/" }, { "title": "[Pharmacological Activation of ERRα/β/γ as an Exercise Mimetic: Potential Therapeutic Applications]", "authors_year": "de Souza-Lima et al., 2026", "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42024694/" } ] }, "research": [], "related": [], "conflicts": [], "sourceRefs": [ "pmid:36988910", "pmid:37739806", "pmid:41421047", "pmid:41850449", "pmid:42024694" ] }, "library:context-alcohol": { "id": "library:context-alcohol", "path": "/library/context-alcohol.html", "title": "Alcohol", "summary": "Each drinking occasion recorded as its own entry, separate from any protocol.", "aliases": [], "kind": "context", "categories": [ "recovery-healing", "longevity", "nootropics-cognitive" ], "research": [ { "id": "catalog:context:alcohol", "title": "Alcohol", "summary": "Each drinking occasion recorded as its own entry, separate from any protocol.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "context", "evidenceTier": "systematic-review", "evidenceSummary": "Logging each drinking occasion mirrors how the Global Burden of Disease study measured population-level alcohol intake across 195 countries. That analysis found that the consumption level associated with the lowest total health loss, combining cancer, injury, and cardiovascular outcomes, was zero drinks per week.", "verdict": { "benefits": [ "Logging each drink creates a record that can be compared against population-level consumption data.", "Lower consumption levels are linked with lower risk across most alcohol-attributable disease categories in the Global Burden of Disease analysis.", "Tracking intake over time can reveal drinking patterns not visible from memory alone." ], "risks": [ "The Global Burden of Disease analysis found risk of death and disability rising with each additional drink, with zero consumption associated with the lowest total health loss.", "Alcohol is linked with increased cancer risk even at levels formerly viewed as moderate.", "Self-reported consumption logs are prone to underreporting in survey research." ], "bottomLine": "Population-level analysis found no consumption level associated with net health benefit once all outcomes were combined, with risk of harm rising from the first drink onward." }, "originalLinks": [ { "title": "Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/30146330/" } ], "links": [ { "title": "Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/30146330/" } ], "protocols": [ { "population": "General adult population across 195 countries and territories, ages 15 to 95 and older", "regimen": "Alcohol exposure estimated from 694 population data sources across a range of consumption categories from abstention upward, compared against relative risks for 23 linked health outcomes", "duration": "Twenty-six-year observation window, 1990 to 2016, analysed as part of the Global Burden of Disease Study 2016", "outcome": "Risk of death and disability rose with each additional standard drink, with no threshold below which additional health protection was gained relative to abstaining", "source": { "title": "Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/30146330/" }, "origins": [ "evidence.json#/catalog:context:alcohol/protocols/0" ] } ], "community": [ { "description": "NIAAA's Rethinking Drinking programme describes a printable four-week calendar card for recording individual drinks.", "source": { "title": "Alcohol Consumption Tracker - Rethinking Drinking - NIAAA", "url": "https://rethinkingdrinking.niaaa.nih.gov/tools/worksheets-more/alcohol-consumption-tracker" }, "origins": [ "evidence.json#/catalog:context:alcohol/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://rethinkingdrinking.niaaa.nih.gov/tools/worksheets-more/alcohol-consumption-tracker", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: NIAAA's Rethinking Drinking programme describes a printable four-week calendar card for recording individual drinks." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:context:alcohol/community/0", "url": "https://rethinkingdrinking.niaaa.nih.gov/tools/worksheets-more/alcohol-consumption-tracker", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:30146330", "https://rethinkingdrinking.niaaa.nih.gov/tools/worksheets-more/alcohol-consumption-tracker" ] }, "library:context-alcohol-free-day": { "id": "library:context-alcohol-free-day", "path": "/library/context-alcohol-free-day.html", "title": "Alcohol-free day", "summary": "A day with no alcohol, logged as its own positive entry rather than left as an absence.", "aliases": [], "kind": "context", "categories": [ "recovery-healing", "longevity" ], "research": [ { "id": "catalog:context:alcohol-free-day", "title": "Alcohol-free day", "summary": "A day with no alcohol, logged as its own positive entry rather than left as an absence.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "context", "evidenceTier": "clinical-study", "evidenceSummary": "Logging an alcohol-free day as its own entry echoes how researchers tracked participants in the 'Dry January' abstinence challenge. Prospective cohort studies of thousands of participants linked completing a month of alcohol-free days with measurable gains in self-rated wellbeing and drinking control that persisted for months afterward.", "verdict": { "benefits": [ "Completing a month of alcohol-free days was linked with higher self-rated wellbeing and greater drink-refusal self-efficacy at six-month follow-up in cohort data.", "Gains in wellbeing among challenge completers held without a later rebound in consumption in the tracked cohort.", "A visible log of alcohol-free days can make a pattern of moderation easier to notice over time." ], "risks": [ "Benefits observed among people who completed a structured alcohol-free challenge were not observed among a comparison group of adult drinkers who did not attempt it, so logging alone may not replicate the effect.", "People who sign up for alcohol-free challenges tend to be heavier drinkers than the general population, which limits how broadly these findings generalize.", "Cohort designs cannot rule out that people already inclined toward healthier drinking patterns were more likely to complete the challenge." ], "bottomLine": "Prospective cohort studies of a structured alcohol-free-month challenge found wellbeing and drinking-control gains among people who completed it, but the same gains did not appear in a comparison group of drinkers who did not attempt it." }, "originalLinks": [ { "title": "Voluntary temporary abstinence from alcohol during \"Dry January\" and subsequent alcohol use", "url": "https://pubmed.ncbi.nlm.nih.gov/26690637/" }, { "title": "Short- and Longer-Term Benefits of Temporary Alcohol Abstinence During 'Dry January' Are Not Also Observed Among Adult Drinkers in the General Population: Prospective Cohort Study", "url": "https://pubmed.ncbi.nlm.nih.gov/32391879/" } ], "links": [ { "title": "Voluntary temporary abstinence from alcohol during \"Dry January\" and subsequent alcohol use", "url": "https://pubmed.ncbi.nlm.nih.gov/26690637/" }, { "title": "Short- and Longer-Term Benefits of Temporary Alcohol Abstinence During 'Dry January' Are Not Also Observed Among Adult Drinkers in the General Population: Prospective Cohort Study", "url": "https://pubmed.ncbi.nlm.nih.gov/32391879/" } ], "protocols": [ { "population": "857 British adults (249 men, 608 women) participating in a month-long alcohol abstinence challenge", "regimen": "Baseline, one-month, and six-month follow-up questionnaires measuring alcohol consumption and drink refusal self-efficacy", "duration": "Six-month follow-up period after the abstinence month", "outcome": "Completing the alcohol-free month was linked with reduced later alcohol consumption and higher drink refusal self-efficacy at six months, without a rebound in consumption afterward", "source": { "title": "Voluntary temporary abstinence from alcohol during \"Dry January\" and subsequent alcohol use", "url": "https://pubmed.ncbi.nlm.nih.gov/26690637/" }, "origins": [ "evidence.json#/catalog:context:alcohol-free-day/protocols/0" ] }, { "population": "1,192 participants in the same alcohol abstinence challenge compared with 1,549 adult drinkers who did not attempt it", "regimen": "Online questionnaires in January, February, and August comparing wellbeing, drinking control, and alcohol intake between groups", "duration": "Eight-month prospective observation period", "outcome": "Wellbeing and drinking-control gains seen among challenge completers were not observed in the comparison group of drinkers who did not attempt a month of alcohol-free days", "source": { "title": "Short- and Longer-Term Benefits of Temporary Alcohol Abstinence During 'Dry January' Are Not Also Observed Among Adult Drinkers in the General Population: Prospective Cohort Study", "url": "https://pubmed.ncbi.nlm.nih.gov/32391879/" }, "origins": [ "evidence.json#/catalog:context:alcohol-free-day/protocols/1" ] } ], "community": [ { "description": "A Harvard Health guide to Dry January describes using the Try Dry app to record drinking and personal goals.", "source": { "title": "Take the Dry January challenge - Harvard Health", "url": "https://www.health.harvard.edu/healthy-aging-and-longevity/take-the-dry-january-challenge" }, "origins": [ "evidence.json#/catalog:context:alcohol-free-day/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.health.harvard.edu/healthy-aging-and-longevity/take-the-dry-january-challenge", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Harvard Health guide to Dry January describes using the Try Dry app to record drinking and personal goals." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:context:alcohol-free-day/community/0", "url": "https://www.health.harvard.edu/healthy-aging-and-longevity/take-the-dry-january-challenge", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:26690637", "pmid:32391879", "https://www.health.harvard.edu/healthy-aging-and-longevity/take-the-dry-january-challenge" ] }, "library:context-nicotine": { "id": "library:context-nicotine", "path": "/library/context-nicotine.html", "title": "Nicotine", "summary": "Nicotine or tobacco use recorded as an occurrence, separate from any protocol.", "aliases": [], "kind": "context", "categories": [ "longevity", "nootropics-cognitive" ], "research": [ { "id": "catalog:context:nicotine", "title": "Nicotine", "summary": "Nicotine or tobacco use recorded as an occurrence, separate from any protocol.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "context", "evidenceTier": "clinical-study", "evidenceSummary": "Logging nicotine or tobacco use as an occurrence mirrors how cohort studies quantify cigarettes smoked per day for mortality analysis. Two large prospective cohorts found that consistently smoking only a few cigarettes across adulthood still carried meaningfully higher mortality risk than never smoking.", "verdict": { "benefits": [ "Logging each use creates an objective count that self-recall alone tends to underestimate.", "A visible log of occurrences can make patterns of use easier to notice over time.", "Cohort data show mortality risk drops substantially after smoking cessation, with earlier quitting linked to larger reductions in risk." ], "risks": [ "Large cohort studies found even long-term smoking of ten or fewer cigarettes daily linked with meaningfully higher all-cause and lung cancer mortality than never smoking.", "No level of cigarette smoking studied in these cohorts was free of added mortality risk.", "Nicotine use is linked with cardiovascular and respiratory disease risk that scales with cumulative exposure." ], "bottomLine": "Two large prospective cohorts found that even low-intensity, long-term cigarette smoking carried meaningfully higher mortality risk than never smoking, with no threshold identified as risk-free." }, "originalLinks": [ { "title": "Association of Long-term, Low-Intensity Smoking With All-Cause and Cause-Specific Mortality in the National Institutes of Health-AARP Diet and Health Study", "url": "https://pubmed.ncbi.nlm.nih.gov/27918784/" }, { "title": "Low-intensity cigarette smoking and mortality risks: a pooled analysis of prospective cohort studies in Japan", "url": "https://pubmed.ncbi.nlm.nih.gov/34718588/" } ], "links": [ { "title": "Association of Long-term, Low-Intensity Smoking With All-Cause and Cause-Specific Mortality in the National Institutes of Health-AARP Diet and Health Study", "url": "https://pubmed.ncbi.nlm.nih.gov/27918784/" }, { "title": "Low-intensity cigarette smoking and mortality risks: a pooled analysis of prospective cohort studies in Japan", "url": "https://pubmed.ncbi.nlm.nih.gov/34718588/" } ], "protocols": [ { "population": "290,215 adults aged 59 to 82 in the NIH-AARP Diet and Health Study cohort, USA", "regimen": "Lifetime cigarette smoking history classified into categories including fewer than 1 and 1 to 10 cigarettes per day, compared with never smokers", "duration": "Cohort followed from 2004-2005 baseline through the end of 2011", "outcome": "Consistent long-term smokers of fewer than 1 or 1 to 10 cigarettes per day had substantially higher all-cause and lung cancer mortality than never smokers", "source": { "title": "Association of Long-term, Low-Intensity Smoking With All-Cause and Cause-Specific Mortality in the National Institutes of Health-AARP Diet and Health Study", "url": "https://pubmed.ncbi.nlm.nih.gov/27918784/" }, "origins": [ "evidence.json#/catalog:context:nicotine/protocols/0" ] }, { "population": "410,294 adults across nine Japanese population-based prospective cohorts", "regimen": "Current smokers grouped by cigarettes per day, from 1-2 up to 6-10, compared with never smokers", "duration": "Cohort baseline data collected 1983 to 1994, followed prospectively for mortality", "outcome": "All-cause mortality risk was higher at every smoking-intensity category studied and increased further with each additional cigarette per day", "source": { "title": "Low-intensity cigarette smoking and mortality risks: a pooled analysis of prospective cohort studies in Japan", "url": "https://pubmed.ncbi.nlm.nih.gov/34718588/" }, "origins": [ "evidence.json#/catalog:context:nicotine/protocols/1" ] } ], "community": [ { "description": "Smokefree.gov's quitSTART app includes tags for times or places associated with smoking urges as part of tracking a quit attempt.", "source": { "title": "quitSTART Quit Smoking App - Smokefree.gov", "url": "https://smokefree.gov/tools-tips/quitstart" }, "origins": [ "evidence.json#/catalog:context:nicotine/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://smokefree.gov/tools-tips/quitstart", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: Smokefree.gov's quitSTART app includes tags for times or places associated with smoking urges as part of tracking a quit attempt." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:context:nicotine/community/0", "url": "https://smokefree.gov/tools-tips/quitstart", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:27918784", "pmid:34718588", "https://smokefree.gov/tools-tips/quitstart" ] }, "library:context-routine": { "id": "library:context-routine", "path": "/library/context-routine.html", "title": "Context or routine", "summary": "Records situational context — travel, illness, high stress, a diet change — as timing information rather than a causal claim.", "aliases": [], "kind": "context", "categories": [ "recovery-healing", "longevity", "nootropics-cognitive" ], "research": [ { "id": "catalog:context:routine", "title": "Context or routine", "summary": "Records situational context — travel, illness, high stress, a diet change — as timing information rather than a causal claim.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "context", "evidenceTier": "reference", "evidenceSummary": "Recording timing and context around events, such as travel, illness, stress or diet changes, is descriptive: it does not show cause and effect. Context can help interpret patterns in other measurements but is not itself health evidence. The linked study is general reference on how habits form with repetition in daily life.", "verdict": { "benefits": [ "Notes on travel, illness, stress or diet give context for reading other measurements.", "The one linked study describes how habits form through repetition in daily life." ], "risks": [ "Descriptive only: context notes show timing, never cause and effect.", "Context is not health evidence on its own; the linked material is general reference." ], "bottomLine": "Context notes record what surrounded an event and help interpret other data, but they show no cause." }, "originalLinks": [ { "title": "CDC: Healthy living", "url": "https://www.cdc.gov/healthy-living/about/index.html" } ], "links": [ { "title": "How are habits formed: Modelling habit formation in the real world (Lally et al. 2010)", "url": "https://doi.org/10.1002/ejsp.674" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.sleepfoundation.org/sleep-faqs/how-to-wake-up-easier", "outcome": "no-practice-description", "reason": "The inspected guide gives expert recommendations for waking routines; those recommendations were not presented as observations of community practice." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "doi:10.1002/ejsp.674", "https://www.cdc.gov/healthy-living/about/index.html" ] }, "library:context-sleep": { "id": "library:context-sleep", "path": "/library/context-sleep.html", "title": "Sleep", "summary": "Sleep duration and quality as an entry in its own right, tracked across nights rather than pulled from a single device reading.", "aliases": [], "kind": "context", "categories": [ "recovery-healing", "nootropics-cognitive" ], "research": [ { "id": "catalog:context:sleep", "title": "Sleep", "summary": "Sleep duration and quality as an entry in its own right, tracked across nights rather than pulled from a single device reading.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "context", "evidenceTier": "reference", "evidenceSummary": "Sleep duration and quality logged as their own entry let a pattern emerge across weeks that a single night's device readout cannot show. A joint consensus statement from the American Academy of Sleep Medicine and the Sleep Research Society reviewed the existing evidence linking adult sleep duration to cardiovascular, metabolic, and cognitive outcomes.", "verdict": { "benefits": [ "Consistently sleeping seven or more hours nightly is associated with lower rates of cardiovascular disease, obesity, and impaired immune function in the consensus literature.", "Logging duration over weeks reveals patterns a single night's reading cannot show.", "Adequate sleep duration correlates with better next-day cognitive performance in the reviewed studies." ], "risks": [ "Self-reported sleep logs can diverge from objective sleep-tracking data.", "Consistently sleeping fewer than six hours nightly is linked with higher rates of hypertension, diabetes, depression, and mortality in cohort data.", "Sleeping beyond nine hours nightly is also linked with adverse health outcomes in some cohorts, though the direction of cause and effect is unclear." ], "bottomLine": "The joint AASM-SRS panel found sleeping seven or more hours nightly linked with better health outcomes in adults, based on a synthesis of existing cohort and experimental evidence rather than a new trial." }, "originalLinks": [ { "title": "Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society", "url": "https://pubmed.ncbi.nlm.nih.gov/26039963/" }, { "title": "Recommended Amount of Sleep for a Healthy Adult (full text, PMC)", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434546/" } ], "links": [ { "title": "Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society", "url": "https://pubmed.ncbi.nlm.nih.gov/26039963/" }, { "title": "Recommended Amount of Sleep for a Healthy Adult (full text, PMC)", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434546/" } ], "protocols": [ { "population": "Adults, reviewed by a multidisciplinary consensus panel", "regimen": "Sleep duration compared across categories from fewer than 6 hours nightly to 9 or more hours nightly, based on a modified RAND Appropriateness Method review of existing cohort and experimental literature", "duration": "Consensus review of accumulated longitudinal and experimental evidence, published 2015", "outcome": "The panel concluded that sleeping 7 or more hours per night on a regular basis is associated with optimal health, while consistently sleeping fewer than 7 hours is associated with adverse cardiometabolic, immune, and cognitive outcomes", "source": { "title": "Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society", "url": "https://pubmed.ncbi.nlm.nih.gov/26039963/" }, "origins": [ "evidence.json#/catalog:context:sleep/protocols/0" ] } ], "community": [ { "description": "The National Sleep Foundation's sleep diary has separate entries for waking and before bed, recorded daily.", "source": { "title": "NSF Sleep Diary - National Sleep Foundation", "url": "https://www.thensf.org/nsf-sleep-diary/" }, "origins": [ "evidence.json#/catalog:context:sleep/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.thensf.org/nsf-sleep-diary/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: The National Sleep Foundation's sleep diary has separate entries for waking and before bed, recorded daily." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:context:sleep/community/0", "url": "https://www.thensf.org/nsf-sleep-diary/", "claimMatch": "The earlier live reading supports only the bounded diary/traditional-use description; it does not establish effectiveness or a medical regimen.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "bounded-description-supported" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:26039963", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434546/", "https://www.thensf.org/nsf-sleep-diary/" ] }, "library:exercise-bodyweight": { "id": "library:exercise-bodyweight", "path": "/library/exercise-bodyweight.html", "title": "Bodyweight session", "summary": "Resistance training using body mass alone. Recorded by session, not by exercise.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:bodyweight", "title": "Bodyweight session", "summary": "Resistance training using body mass alone. Recorded by session, not by exercise.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "clinical-study", "evidenceSummary": "Bodyweight training uses body mass as the load. A controlled study in postmenopausal women compared bodyweight training with combined training over 24 weeks and found lower inflammatory markers and better functional fitness in both groups. A second study of a calisthenics programme reported changes in posture, strength and body composition. Both studies are small, and the first lost a large share of participants. There is no meta-analytic evidence behind this entry.", "verdict": { "benefits": [ "Lower inflammation markers and better functional fitness in one small controlled study", "The load is body mass itself, so no equipment is involved" ], "risks": [ "Two small studies only, one losing a large share of participants, and no meta-analysis", "Studied in postmenopausal women, so it may not carry to other groups", "One inflammation marker, IL-10, did not change in either group" ], "bottomLine": "Small studies in postmenopausal women found better functional fitness and lower inflammation; the evidence base is thin." }, "originalLinks": [ { "title": "PubMed: bodyweight session", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=bodyweight+resistance+training" } ], "links": [ { "title": "Bodyweight and Combined Training Reduce Chronic Low-Grade Inflammation and Improve Functional Fitness of Postmenopausal Women", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9610763/" }, { "title": "The effects of a calisthenics training intervention on posture, strength and body composition", "url": "https://doi.org/10.3233/ies-170001" } ], "protocols": [ { "population": "24 postmenopausal women who completed the study (14 combined training, 10 bodyweight training), mean age 64-65", "regimen": "45-minute sessions three times a week: bodyweight multi-articular exercises, or walking plus machine resistance work in the combined group", "duration": "24 weeks", "outcome": "Both groups lowered TNF-alpha and improved most functional fitness tests; only bodyweight training lowered IL-6, and neither group changed IL-10.", "source": { "title": "Bodyweight and Combined Training Reduce Chronic Low-Grade Inflammation and Improve Functional Fitness of Postmenopausal Women", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9610763/" }, "origins": [ "evidence.json#/catalog:exercise:bodyweight/protocols/0" ] } ], "community": [ { "description": "An American Council on Exercise guide describes bodyweight sessions using exercises such as push-ups, squats, lunges and planks without external weights.", "source": { "author": null, "title": "Body-weight Training: Don't Let a Lack of Equipment Keep You From Your Goals - ACE Fitness", "url": "https://www.acefitness.org/resources/everyone/blog/7038/body-weight-training-don-t-let-a-lack-of-equipment-keep-you-from-your-goals/" }, "origins": [ "evidence.json#/catalog:exercise:bodyweight/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.acefitness.org/resources/everyone/blog/7038/body-weight-training-don-t-let-a-lack-of-equipment-keep-you-from-your-goals/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: An American Council on Exercise guide describes bodyweight sessions using exercises such as push-ups, squats, lunges and planks without external weights." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:bodyweight/community/0", "url": "https://www.acefitness.org/resources/everyone/blog/7038/body-weight-training-don-t-let-a-lack-of-equipment-keep-you-from-your-goals/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9610763/", "doi:10.3233/ies-170001", "https://pubmed.ncbi.nlm.nih.gov/?term=bodyweight+resistance+training", "https://www.acefitness.org/resources/everyone/blog/7038/body-weight-training-don-t-let-a-lack-of-equipment-keep-you-from-your-goals/" ] }, "library:exercise-calisthenics": { "id": "library:exercise-calisthenics", "path": "/library/exercise-calisthenics.html", "title": "Calisthenics", "summary": "Skill-based bodyweight training. Recorded by session duration and effort.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:calisthenics", "title": "Calisthenics", "summary": "Skill-based bodyweight training. Recorded by session duration and effort.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "clinical-study", "evidenceSummary": "Calisthenics is strength training using body weight. Two small human intervention studies are linked: a 12-week calisthenics programme in adults with obesity, and a calisthenics intervention measuring posture, strength and body composition. Their full texts could not be read here, so only their topics, not their numbers, are confirmed. Evidence is limited to small short studies, with nothing linked on long-term adherence or injuries.", "verdict": { "benefits": [ "Two small human studies tested body-weight strength training for fitness, posture and body composition", "It is strength training that needs no equipment" ], "risks": [ "Only small, short studies, and their full texts could not be read, so the numbers are unconfirmed", "Nothing here covers injuries or whether people keep it up long term" ], "bottomLine": "Body-weight strength training rests on two small short studies, with no injury or long-term data here." }, "originalLinks": [ { "title": "PubMed: calisthenics", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=calisthenics" } ], "links": [ { "title": "Effects of a 12-Week Calisthenics Exercise Program on Physical Fitness in Adults With Obesity", "url": "https://onlinelibrary.wiley.com/doi/10.1002/ccd.70361" }, { "title": "The effects of a calisthenics training intervention on posture, strength and body composition", "url": "https://doi.org/10.3233/ies-170001" } ], "protocols": [], "community": [ { "description": "A Cleveland Clinic guide describes calisthenics as whole-body resistance exercises relying on body weight with little or no equipment.", "source": { "title": "Calisthenics Workout Routine and Benefits - Cleveland Clinic", "url": "https://health.clevelandclinic.org/calisthenics" }, "origins": [ "evidence.json#/catalog:exercise:calisthenics/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://health.clevelandclinic.org/calisthenics", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic guide describes calisthenics as whole-body resistance exercises relying on body weight with little or no equipment." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:calisthenics/community/0", "url": "https://health.clevelandclinic.org/calisthenics", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://onlinelibrary.wiley.com/doi/10.1002/ccd.70361", "doi:10.3233/ies-170001", "https://pubmed.ncbi.nlm.nih.gov/?term=calisthenics", "https://health.clevelandclinic.org/calisthenics" ] }, "library:exercise-cardio-zone2": { "id": "library:exercise-cardio-zone2", "path": "/library/exercise-cardio-zone2.html", "title": "Zone 2 cardio", "summary": "Sustained low-intensity aerobic work, conversational pace, for aerobic base.", "aliases": [], "kind": "exercise-plan", "categories": [ "longevity", "fitness-muscle" ], "research": [ { "id": "catalog:exercise:cardio-zone2", "title": "Zone 2 cardio", "summary": "Sustained low-intensity aerobic work, conversational pace, for aerobic base.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "reference", "evidenceSummary": "Zone 2 means steady aerobic exercise just below the first lactate or ventilatory threshold, as an expert panel of coaches and scientists defines it. A 2025 narrative review concludes that current evidence does not make Zone 2 the best intensity for mitochondrial or cardiorespiratory gains, and that higher intensities do at least as well, especially when training time is short. A laboratory study of 50 cyclists found the markers used to set Zone 2 vary widely between individuals. The expert panel also notes the expected adaptations are probably not unique to this intensity.", "verdict": { "benefits": [ "An expert panel expects broad aerobic adaptations, but says they are probably not unique to this intensity.", "It is a defined intensity, just below the first lactate or ventilatory threshold." ], "risks": [ "A 2025 review finds harder work does at least as well for fitness and mitochondria.", "The markers used to set the zone varied widely between cyclists in a lab study.", "Evidence here is reviews and expert opinion, not head-to-head trials." ], "bottomLine": "Zone 2 is a defined easy intensity whose claimed edge over harder training is not supported by reviews." }, "originalLinks": [ { "title": "PubMed: zone 2 training", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=aerobic+base+training+intensity" } ], "links": [ { "title": "Much Ado About Zone 2: A Narrative Review Assessing the Efficacy of Zone 2 Training for Improving Mitochondrial Capacity and Cardiorespiratory Fitness (Storoschuk et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40560504/" }, { "title": "What Is Zone 2 Training?: Experts' Viewpoint on Definition, Training Methods, and Expected Adaptations (Sitko et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40010355/" }, { "title": "Zone 2 Intensity: A Critical Comparison of Individual Variability in Different Submaximal Exercise Intensity Boundaries", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986187/" } ], "protocols": [ { "population": "expert panel of 14 applied sport scientists and professional coaches", "regimen": "continuous, variable or interval-type sessions at intensities immediately below the first lactate or ventilatory threshold", "duration": "not stated", "outcome": "The panel expected a broad range of central and peripheral adaptations, and noted these may not be unique to this intensity.", "source": { "title": "What Is Zone 2 Training?: Experts' Viewpoint on Definition, Training Methods, and Expected Adaptations (Sitko et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40010355/" }, "origins": [ "evidence.json#/catalog:exercise:cardio-zone2/protocols/0" ] } ], "community": [ { "description": "A Cleveland Clinic guide describes Zone 2 cardio as moderate-intensity activity during which conversation remains possible, in contrast to higher-intensity zones.", "source": { "title": "Exercise Heart Rate Zones Explained - Cleveland Clinic", "url": "https://health.clevelandclinic.org/exercise-heart-rate-zones-explained" }, "origins": [ "evidence.json#/catalog:exercise:cardio-zone2/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://health.clevelandclinic.org/exercise-heart-rate-zones-explained", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic guide describes Zone 2 cardio as moderate-intensity activity during which conversation remains possible, in contrast to higher-intensity zones." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:cardio-zone2/community/0", "url": "https://health.clevelandclinic.org/exercise-heart-rate-zones-explained", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:40560504", "pmid:40010355", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986187/", "https://pubmed.ncbi.nlm.nih.gov/?term=aerobic+base+training+intensity", "https://health.clevelandclinic.org/exercise-heart-rate-zones-explained" ] }, "library:exercise-climbing": { "id": "library:exercise-climbing", "path": "/library/exercise-climbing.html", "title": "Climbing", "summary": "Indoor or outdoor climbing, bouldering or roped, recorded by session.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:climbing", "title": "Climbing", "summary": "Indoor or outdoor climbing, bouldering or roped, recorded by session.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "clinical-study", "evidenceSummary": "A waitlist-controlled pilot trial tested an eight-week bouldering group program as a treatment for depression, integrating psychotherapeutic elements into indoor rock-climbing sessions without ropes. Participants who bouldered showed a significantly greater drop in depression scores than the waitlist group, an early signal that structured climbing sessions may support mood.", "verdict": { "benefits": [ "The bouldering group showed a significantly larger drop in depression scores than the waitlist group in this pilot trial.", "The number needed to treat was four, meaning a meaningful benefit was attributable to the program for roughly one in four participants.", "The eight-week structure combined physical activity with group-based psychotherapeutic elements." ], "risks": [ "This was a pilot study with a modest sample of 47 participants, and the authors called for further research before drawing firm conclusions.", "The comparison group was a waitlist rather than an active control, which can inflate apparent effect sizes.", "Findings on bouldering as a depression treatment have not yet been replicated at scale." ], "bottomLine": "An early waitlist-controlled pilot trial found an eight-week bouldering group program linked with a significantly greater reduction in depression scores than no treatment, though replication in larger trials is still needed." }, "originalLinks": [ { "title": "Indoor rock climbing (bouldering) as a new treatment for depression: study design of a waitlist-controlled randomized group pilot study and the first results", "url": "https://pubmed.ncbi.nlm.nih.gov/26302900/" } ], "links": [ { "title": "Indoor rock climbing (bouldering) as a new treatment for depression: study design of a waitlist-controlled randomized group pilot study and the first results", "url": "https://pubmed.ncbi.nlm.nih.gov/26302900/" } ], "protocols": [ { "population": "47 adults with depression completing a waitlist-controlled pilot study in Germany", "regimen": "Eight weekly three-hour bouldering group sessions combining structured indoor rock-climbing with brief psychotherapeutic interventions", "duration": "Eight-week intervention period with measurement at baseline and eight-week follow-up", "outcome": "The bouldering group showed a significantly larger reduction in Beck Depression Inventory scores than the waitlist group, with a number needed to treat of four", "source": { "title": "Indoor rock climbing (bouldering) as a new treatment for depression: study design of a waitlist-controlled randomized group pilot study and the first results", "url": "https://pubmed.ncbi.nlm.nih.gov/26302900/" }, "origins": [ "evidence.json#/catalog:exercise:climbing/protocols/0" ] } ], "community": [ { "description": "A Climbing magazine article illustrates hangboard practice for particular grip positions alongside time spent climbing.", "source": { "author": null, "title": "Should You Train or Just Go Climbing? - Climbing (Outside)", "url": "https://www.climbing.com/skills/training-value-effectiveness" }, "origins": [ "evidence.json#/catalog:exercise:climbing/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.climbing.com/skills/training-value-effectiveness", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Climbing magazine article illustrates hangboard practice for particular grip positions alongside time spent climbing." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:climbing/community/0", "url": "https://www.climbing.com/skills/training-value-effectiveness", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:26302900", "https://www.climbing.com/skills/training-value-effectiveness" ] }, "library:exercise-cycling": { "id": "library:exercise-cycling", "path": "/library/exercise-cycling.html", "title": "Cycling", "summary": "Indoor or outdoor. Recorded by duration and effort rather than route.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:cycling", "title": "Cycling", "summary": "Indoor or outdoor. Recorded by duration and effort rather than route.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "systematic-review", "evidenceSummary": "Cycling is aerobic exercise on a bike or trainer. A randomised trial in 120 middle-aged men with type 2 diabetes reported lower fasting glucose and blood pressure, less fat mass and better quality of life after a supervised programme. A randomised study in people with chronic stroke found both forced and voluntary cycling improved walking distance. A systematic review covers the health benefits of cycling more broadly. Evidence mixes single trials with one older review.", "verdict": { "benefits": [ "A randomised trial in men with type 2 diabetes found lower fasting glucose, blood pressure and fat mass.", "In chronic stroke, a randomised study found walking distance rose with cycling but not in controls.", "A systematic review covers the health benefits of cycling more broadly." ], "risks": [ "Evidence mixes single trials with one older review rather than a large pooled body.", "The trials were in specific groups, diabetes and stroke, so wider results are less certain." ], "bottomLine": "Randomised trials link cycling to better glucose, blood pressure and walking distance, mostly in specific patient groups." }, "originalLinks": [ { "title": "PubMed: cycling", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=cycling+exercise+health" } ], "links": [ { "title": "Pedalling towards better health: a randomised controlled trial of aerobic cycling to improve glycaemic control and quality of life in middle-aged men with type 2 diabetes (Tariq et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40771497/" }, { "title": "Forced and voluntary aerobic cycling interventions improve walking capacity in individuals with chronic stroke", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7796862/" }, { "title": "Health benefits of cycling: a systematic review (Oja et al. 2011)", "url": "https://doi.org/10.1111/j.1600-0838.2011.01299.x" } ], "protocols": [ { "population": "120 men aged 50-65 with type 2 diabetes, BMI over 25 and fasting glucose over 140 mg/dL", "regimen": "supervised aerobic cycling, 4 sessions a week, 50 minutes a session, against usual care", "duration": "12 weeks", "outcome": "Fasting glucose, systolic and diastolic blood pressure, fat mass and waist-to-hip ratio fell and quality-of-life scores improved versus control.", "source": { "title": "Pedalling towards better health: a randomised controlled trial of aerobic cycling to improve glycaemic control and quality of life in middle-aged men with type 2 diabetes (Tariq et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40771497/" }, "origins": [ "evidence.json#/catalog:exercise:cycling/protocols/0" ] }, { "population": "43 individuals with chronic stroke, randomised to forced cycling, voluntary cycling or a non-aerobic control", "regimen": "aerobic cycling at 60-80% of heart rate reserve with moderate to high cadence and resistance, 3 times a week, plus upper-extremity task practice", "duration": "8 weeks", "outcome": "Six-minute walk distance increased in both cycling groups but not in the non-aerobic control group.", "source": { "title": "Forced and voluntary aerobic cycling interventions improve walking capacity in individuals with chronic stroke", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7796862/" }, "origins": [ "evidence.json#/catalog:exercise:cycling/protocols/1" ] } ], "community": [ { "description": "A cycling club guide describes group-riding calls such as 'car back' and 'car up', alongside hand signals for turns and road hazards.", "source": { "title": "10 Tips for Safe Group Riding (League of American Bicyclists program)", "url": "https://gccfla.org/labtips.shtml" }, "origins": [ "evidence.json#/catalog:exercise:cycling/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://gccfla.org/labtips.shtml", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A cycling club guide describes group-riding calls such as 'car back' and 'car up', alongside hand signals for turns and road hazards." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:cycling/community/0", "url": "https://gccfla.org/labtips.shtml", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:40771497", "https://pmc.ncbi.nlm.nih.gov/articles/PMC7796862/", "doi:10.1111/j.1600-0838.2011.01299.x", "https://pubmed.ncbi.nlm.nih.gov/?term=cycling+exercise+health", "https://gccfla.org/labtips.shtml" ] }, "library:exercise-functional-fitness": { "id": "library:exercise-functional-fitness", "path": "/library/exercise-functional-fitness.html", "title": "Functional fitness", "summary": "Mixed-modal conditioning. Recorded by session rather than by movement.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:functional-fitness", "title": "Functional fitness", "summary": "Mixed-modal conditioning. Recorded by session rather than by movement.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "clinical-study", "evidenceSummary": "In a randomised trial of 43 postmenopausal women, both single-set and multiple-set functional training increased upper and lower limb muscle power and improved most functional fitness tests over 24 weeks. Multiple-set training lowered TNF-alpha and IL-6, while single-set training lowered only TNF-alpha. A review notes that high-intensity functional training lacks a settled definition and is far less studied than interval training. A workplace trial found strength training transferred to untrained memory tasks, while multi-modal training improved mainly the trained tasks.", "verdict": { "benefits": [ "A randomised trial found more muscle power and better functional fitness with either set scheme", "Two inflammation markers fell in the multiple-set group, one in the single-set group", "Strength training carried over to untrained memory tasks in a workplace trial" ], "risks": [ "Trials are small and run in postmenopausal women, so results may not carry to other groups", "High-intensity functional training has no settled definition and is far less studied than intervals" ], "bottomLine": "Small randomised trials link functional training to more muscle power and better everyday fitness; the term is unsettled." }, "originalLinks": [ { "title": "PubMed: functional fitness", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=functional+fitness+training" } ], "links": [ { "title": "A single-set functional training program increases muscle power, improves functional fitness, and reduces pro-inflammatory cytokines in postmenopausal women: A randomized clinical trial", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075356/" }, { "title": "High-Intensity Functional Training (HIFT): Definition and Research Implications for Improved Fitness", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162410/" }, { "title": "A Comparison of the Effects of Short-Term Physical and Combined Multi-Modal Training on Cognitive Functions", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223650/" } ], "protocols": [ { "population": "43 postmenopausal women aged about 63", "regimen": "Circuit of 14 functional exercises, 8-12 repetitions, 3 times a week: one set (22-minute sessions) or two sets (44-minute sessions)", "duration": "24 weeks, 72 sessions", "outcome": "Both set schemes raised muscle power and functional fitness; the multiple-set group lowered TNF-alpha and IL-6, the single-set group only TNF-alpha.", "source": { "title": "A single-set functional training program increases muscle power, improves functional fitness, and reduces pro-inflammatory cytokines in postmenopausal women: A randomized clinical trial", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075356/" }, "origins": [ "evidence.json#/catalog:exercise:functional-fitness/protocols/0" ] }, { "population": "102 employees aged 20-61 at a German car manufacturer", "regimen": "One 30-35 minute session a week: circuit resistance training, or 10-15 minutes strength plus 15 minutes dual-task agility board work", "duration": "12 weeks", "outcome": "Strength training transferred to untrained working-memory updating and immediate-recall tasks; combined training improved mainly the trained agility-board tasks.", "source": { "title": "A Comparison of the Effects of Short-Term Physical and Combined Multi-Modal Training on Cognitive Functions", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223650/" }, "origins": [ "evidence.json#/catalog:exercise:functional-fitness/protocols/1" ] } ], "community": [ { "description": "An American Council on Exercise guide describes functional sessions organised around combinations of movement patterns, including hinging, squatting, pushing and pulling.", "source": { "title": "Creating Functional-Training Programs for Every Type of Client - ACE Fitness", "url": "https://www.acefitness.org/resources/pros/expert-articles/7208/creating-functional-training-programs-for-every-type-of-client/" }, "origins": [ "evidence.json#/catalog:exercise:functional-fitness/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.acefitness.org/resources/pros/expert-articles/7208/creating-functional-training-programs-for-every-type-of-client/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: An American Council on Exercise guide describes functional sessions organised around combinations of movement patterns, including hinging, squatting, pushing and pulling." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:functional-fitness/community/0", "url": "https://www.acefitness.org/resources/pros/expert-articles/7208/creating-functional-training-programs-for-every-type-of-client/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075356/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162410/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223650/", "https://pubmed.ncbi.nlm.nih.gov/?term=functional+fitness+training", "https://www.acefitness.org/resources/pros/expert-articles/7208/creating-functional-training-programs-for-every-type-of-client/" ] }, "library:exercise-hiit": { "id": "library:exercise-hiit", "path": "/library/exercise-hiit.html", "title": "HIIT session", "summary": "High-intensity intervals. Recorded by session duration and effort rather than by interval structure.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:hiit", "title": "HIIT session", "summary": "High-intensity intervals. Recorded by session duration and effort rather than by interval structure.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "systematic-review", "evidenceSummary": "An umbrella review of 133 systematic reviews found high-intensity interval training improves body composition, cardiovascular and metabolic measures and mental health, with effects comparable to or better than moderate continuous training in several conditions, though the underlying studies vary a lot. A meta-analysis in recreationally active women reported gains in fitness and body composition. A separate systematic review examined safety in patients with cardiovascular disease. Evidence is large and pooled, but heterogeneous.", "verdict": { "benefits": [ "An umbrella review of 133 systematic reviews found gains in body composition, heart and metabolic health", "Effects matched or beat steady moderate training in several conditions", "Pooled trials in recreationally active women showed better fitness and body composition" ], "risks": [ "The underlying studies vary widely, so pooled effects hide a lot of difference", "Safety in people with existing cardiovascular disease was reviewed separately, not settled here" ], "bottomLine": "Interval training has broad pooled evidence for fitness and metabolic health, from widely differing studies." }, "originalLinks": [ { "title": "PubMed: high intensity interval training", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=high+intensity+interval+training" } ], "links": [ { "title": "The Impact of High-Intensity Interval Training on Cardiometabolic, Neurologic, Oncologic, and Pain-Related Outcomes: A Comprehensive Review of Systematic Reviews", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12692769/" }, { "title": "High‐intensity interval training and cardiorespiratory fitness in adults: An umbrella review of systematic reviews and meta‐analyses", "url": "https://onlinelibrary.wiley.com/doi/10.1111/sms.14652" }, { "title": "Effects of high-intensity interval training on physical fitness and body composition in recreationally active females: a systematic review and meta-analysis", "url": "https://www.nature.com/articles/s41598-025-11809-x" }, { "title": "High-Intensity Interval Training for Patients With Cardiovascular Disease—Is It Safe? A Systematic Review", "url": "https://www.ahajournals.org/doi/10.1161/JAHA.118.009305" } ], "protocols": [ { "population": "adults across 133 systematic reviews of high-intensity interval training", "regimen": "intervals reaching or passing 90% of VO2 max or maximum heart rate with active recovery at 40-60% of peak VO2, sessions of 8-30 minutes, 2-3 times a week", "duration": "the reviews report benefits mainly between weeks 6 and 12", "outcome": "The reviews reported improvements in cardiometabolic, neurologic, oncologic and pain-related outcomes, with wide variation between the underlying studies.", "source": { "title": "The Impact of High-Intensity Interval Training on Cardiometabolic, Neurologic, Oncologic, and Pain-Related Outcomes: A Comprehensive Review of Systematic Reviews", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12692769/" }, "origins": [ "evidence.json#/catalog:exercise:hiit/protocols/0" ] } ], "community": [ { "description": "A Cleveland Clinic guide describes HIIT sessions as repeated higher-intensity activity intervals alternated with lower-intensity recovery.", "source": { "title": "HIIT Workouts: They're Good for Everyone! - Cleveland Clinic", "url": "https://health.clevelandclinic.org/think-you-cant-do-high-intensity-interval-training-think-again" }, "origins": [ "evidence.json#/catalog:exercise:hiit/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://health.clevelandclinic.org/think-you-cant-do-high-intensity-interval-training-think-again", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic guide describes HIIT sessions as repeated higher-intensity activity intervals alternated with lower-intensity recovery." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:hiit/community/0", "url": "https://health.clevelandclinic.org/think-you-cant-do-high-intensity-interval-training-think-again", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC12692769/", "https://onlinelibrary.wiley.com/doi/10.1111/sms.14652", "https://www.nature.com/articles/s41598-025-11809-x", "https://www.ahajournals.org/doi/10.1161/JAHA.118.009305", "https://pubmed.ncbi.nlm.nih.gov/?term=high+intensity+interval+training", "https://health.clevelandclinic.org/think-you-cant-do-high-intensity-interval-training-think-again" ] }, "library:exercise-hiking": { "id": "library:exercise-hiking", "path": "/library/exercise-hiking.html", "title": "Hiking", "summary": "Extended low-intensity effort, usually irregular. Recorded by duration.", "aliases": [], "kind": "exercise-plan", "categories": [ "longevity", "fitness-muscle" ], "research": [ { "id": "catalog:exercise:hiking", "title": "Hiking", "summary": "Extended low-intensity effort, usually irregular. Recorded by duration.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "reference", "evidenceSummary": "Hiking is long, low-intensity walking outdoors. An integrative review reports better cardiovascular function, lower chronic disease risk, better immune function, lower stress and improved mood among hikers, and social benefits too. A cross-sectional study using exercise testing on real trails found that effort and cardiorespiratory strain vary widely between people and routes, so generic trail advice fits poorly. The evidence is reviews and observational work, not controlled trials, and a popular-science article covers the same ground.", "verdict": { "benefits": [ "An integrative review reports better heart function, mood, stress and immune measures among hikers.", "The same review notes social benefits alongside the physical ones." ], "risks": [ "Evidence is reviews and observational work, so cause and effect is not established.", "Effort and heart strain varied widely between people on the same trail.", "One linked source is a popular-science article rather than research." ], "bottomLine": "Observational reviews link hiking to better heart health and mood; strain varies widely between people." }, "originalLinks": [ { "title": "PubMed: hiking", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=hiking+exercise+health" } ], "links": [ { "title": "An integrative review of the physical, mental, and socioeconomic benefits of outdoor hiking", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819716/" }, { "title": "Why hiking is uniquely beneficial for your body and your brain", "url": "https://www.nationalgeographic.com/science/article/benefits-hiking-brain-heart-mental-health" }, { "title": "Are hiking recommendations one-size-fits-all? Insights into cardiovascular safety and trail demands", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12698341/" } ], "protocols": [ { "population": "72 adults, mean age 43.5, about a quarter with a chronic condition such as hypertension, diabetes or coronary artery disease", "regimen": "a maximal treadmill cardiopulmonary exercise test, then an 8.2 km trail with 300 m of ascent signposted as easy, walked in both directions", "duration": "two sessions within one week", "outcome": "Average hiking time was 97 minutes at 4.2 km/h, and exercise intensity varied widely between participants on the same trail.", "source": { "title": "Are hiking recommendations one-size-fits-all? Insights into cardiovascular safety and trail demands", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12698341/" }, "origins": [ "evidence.json#/catalog:exercise:hiking/protocols/0" ] } ], "community": [ { "description": "The American Hiking Society describes foot-only trails as one setting for hiking, managed for pedestrian travel away from motorised vehicles.", "source": { "title": "Hiking Trails Policy - American Hiking Society", "url": "https://americanhiking.org/resources/hiking-trails-policy/" }, "origins": [ "evidence.json#/catalog:exercise:hiking/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://americanhiking.org/resources/hiking-trails-policy/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: The American Hiking Society describes foot-only trails as one setting for hiking, managed for pedestrian travel away from motorised vehicles." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:hiking/community/0", "url": "https://americanhiking.org/resources/hiking-trails-policy/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819716/", "https://www.nationalgeographic.com/science/article/benefits-hiking-brain-heart-mental-health", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12698341/", "https://pubmed.ncbi.nlm.nih.gov/?term=hiking+exercise+health", "https://americanhiking.org/resources/hiking-trails-policy/" ] }, "library:exercise-martial-arts": { "id": "library:exercise-martial-arts", "path": "/library/exercise-martial-arts.html", "title": "Martial arts", "summary": "Class or sparring. Recorded by session duration and effort.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:martial-arts", "title": "Martial arts", "summary": "Class or sparring. Recorded by session duration and effort.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "systematic-review", "evidenceSummary": "Martial arts cover many practices, from tai chi to karate and judo. A systematic review of 28 studies of hard martial arts in adults reported improvements in balance, cognitive function and psychological health, while noting weak study quality. A review on older adults describes possible mechanisms, including BDNF, neuroplasticity and social support that reduces loneliness. A survey of 268 practitioners found perceived health benefits that did not depend on training frequency. The evidence is mostly review-level and varied.", "verdict": { "benefits": [ "A review of 28 studies reported better balance, thinking and psychological health in adults.", "A review in older adults describes social support that reduces loneliness." ], "risks": [ "The same review rated the quality of its studies as weak.", "A survey of practitioners measured perceived benefits, not measured ones.", "Evidence is review-level and lumps very different practices under one name." ], "bottomLine": "Reviews link martial arts to better balance, thinking and mood, but the underlying studies are weak and mixed." }, "originalLinks": [ { "title": "PubMed: martial arts", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=martial+arts+training+health" } ], "links": [ { "title": "Effects of martial arts on health status: A systematic review", "url": "https://onlinelibrary.wiley.com/doi/10.1111/j.1756-5391.2010.01107.x" }, { "title": "Health benefits of hard martial arts in adults: a systematic review (Origua et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29157151/" }, { "title": "Perceived health benefits of martial arts and combat sports", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13135931/" }, { "title": "Neural mechanisms and social support for mental health in old age by martial arts exercise", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827584/" } ], "protocols": [], "community": [ { "description": "One Harvard Health guide describes a tai chi class combining a warm-up with instruction and practice of movement forms.", "source": { "title": "The health benefits of tai chi - Harvard Health", "url": "https://www.health.harvard.edu/exercise-and-fitness/the-health-benefits-of-tai-chi" }, "origins": [ "evidence.json#/catalog:exercise:martial-arts/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.health.harvard.edu/exercise-and-fitness/the-health-benefits-of-tai-chi", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: One Harvard Health guide describes a tai chi class combining a warm-up with instruction and practice of movement forms." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:martial-arts/community/0", "url": "https://www.health.harvard.edu/exercise-and-fitness/the-health-benefits-of-tai-chi", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://onlinelibrary.wiley.com/doi/10.1111/j.1756-5391.2010.01107.x", "pmid:29157151", "https://pmc.ncbi.nlm.nih.gov/articles/PMC13135931/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827584/", "https://pubmed.ncbi.nlm.nih.gov/?term=martial+arts+training+health", "https://www.health.harvard.edu/exercise-and-fitness/the-health-benefits-of-tai-chi" ] }, "library:exercise-pilates": { "id": "library:exercise-pilates", "path": "/library/exercise-pilates.html", "title": "Pilates", "summary": "Mat or reformer work focused on core control and alignment.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:pilates", "title": "Pilates", "summary": "Mat or reformer work focused on core control and alignment.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "systematic-review", "evidenceSummary": "A Cochrane systematic review pooling ten randomised controlled trials examined Pilates as an exercise-based treatment for nonspecific low back pain. Compared with minimal intervention, Pilates was linked with reduced pain and disability in the short and medium term, though evidence did not show it outperforming other exercise programs.", "verdict": { "benefits": [ "Pilates was linked with reduced pain and disability compared with minimal intervention in the pooled trials, with low-to-moderate quality evidence.", "Effects on pain persisted at intermediate-term follow-up in several of the pooled trials.", "The pooled trials found effect sizes ranging from small to medium compared with minimal intervention." ], "risks": [ "The reviewers found no conclusive evidence that Pilates outperformed other forms of exercise therapy for low back pain.", "Trial quality varied, with three of the ten pooled trials rated at high risk of bias.", "Sample sizes in the pooled trials were modest, totaling 510 participants across ten trials." ], "bottomLine": "A Cochrane systematic review found Pilates linked with reduced pain and disability for low back pain compared with minimal intervention, but found no clear advantage over other exercise types." }, "originalLinks": [ { "title": "Pilates for low back pain", "url": "https://pubmed.ncbi.nlm.nih.gov/26133923/" }, { "title": "Pilates for Low Back Pain: Complete Republication of a Cochrane Review", "url": "https://pubmed.ncbi.nlm.nih.gov/26679894/" } ], "links": [ { "title": "Pilates for low back pain", "url": "https://pubmed.ncbi.nlm.nih.gov/26133923/" }, { "title": "Pilates for Low Back Pain: Complete Republication of a Cochrane Review", "url": "https://pubmed.ncbi.nlm.nih.gov/26679894/" } ], "protocols": [ { "population": "510 participants with acute, subacute, or chronic nonspecific low back pain across ten randomised controlled trials", "regimen": "Pilates-based exercise programs compared against minimal intervention or against other forms of exercise therapy", "duration": "Short-term and intermediate-term follow-up periods across the pooled trials, review published 2015", "outcome": "Pilates reduced pain and disability more than minimal intervention with low-to-moderate quality evidence, but showed no clear advantage over other exercise types", "source": { "title": "Pilates for low back pain", "url": "https://pubmed.ncbi.nlm.nih.gov/26133923/" }, "origins": [ "evidence.json#/catalog:exercise:pilates/protocols/0" ] } ], "community": [ { "description": "A Cleveland Clinic guide describes Pilates routines performed on a mat or on apparatus such as a reformer.", "source": { "title": "Pilates 101: What It Is and Health Benefits - Cleveland Clinic", "url": "https://health.clevelandclinic.org/everything-you-want-to-know-about-pilates" }, "origins": [ "evidence.json#/catalog:exercise:pilates/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://health.clevelandclinic.org/everything-you-want-to-know-about-pilates", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic guide describes Pilates routines performed on a mat or on apparatus such as a reformer." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:pilates/community/0", "url": "https://health.clevelandclinic.org/everything-you-want-to-know-about-pilates", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:26133923", "pmid:26679894", "https://health.clevelandclinic.org/everything-you-want-to-know-about-pilates" ] }, "library:exercise-resistance-session": { "id": "library:exercise-resistance-session", "path": "/library/exercise-resistance-session.html", "title": "Resistance training session", "summary": "A training day recorded at session level: body part or split, duration, and perceived effort.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:resistance-session", "title": "Resistance training session", "summary": "A training day recorded at session level: body part or split, duration, and perceived effort.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "systematic-review", "evidenceSummary": "Resistance training means working muscles against a load. An overview of systematic reviews in adults reports benefits for strength, function and several health markers. A systematic review of randomised trials in coronary heart disease rehabilitation examined exercise capacity, quality of life and strength, mostly with resistance training added to aerobic training. A meta-analysis of seven trials during chemotherapy found better lower-body strength but no clear effect on quality of life or fatigue. Benefits vary by population and outcome.", "verdict": { "benefits": [ "An overview of systematic reviews reports gains in strength, function and several health markers", "Added to aerobic training, it beat aerobic alone on fitness, quality of life and heart function" ], "risks": [ "During chemotherapy only lower-body strength improved; fatigue and quality of life did not", "Whether resistance training beats aerobic training on its own is still unclear", "Benefits vary a lot by population and by which outcome is measured" ], "bottomLine": "Systematic reviews support resistance training for strength and function, with benefits varying by population and outcome." }, "originalLinks": [ { "title": "ACSM: Guidelines for Exercise Testing and Prescription", "url": "https://acsm.org/education-resources/books/guidelines-exercise-testing-prescription/" } ], "links": [ { "title": "Efficacy and Safety of Resistance Training for Coronary Heart Disease Rehabilitation: A Systematic Review of Randomized Controlled Trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8602574/" }, { "title": "Exploring the Role of Resistance Training in the Prevention and Management of Chronic Conditions: A Narrative Review", "url": "https://doi.org/10.3390/clinpract16080157" }, { "title": "Resistance training and health in adults: an overview of systematic reviews", "url": "https://cdnsciencepub.com/doi/10.1139/apnm-2020-0245" }, { "title": "Effects of resistance training on quality of life, fatigue, physical function, and muscular strength during chemotherapy", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330399/" } ], "protocols": [ { "population": "2,465 participants with coronary heart disease across 38 randomised trials", "regimen": "resistance training added to aerobic training, compared with aerobic training, usual care, health education or physical therapy", "duration": "not stated", "outcome": "Resistance plus aerobic beat aerobic alone on peak oxygen uptake, quality of life, muscle strength and ejection fraction; resistance versus aerobic stayed unclear.", "source": { "title": "Efficacy and Safety of Resistance Training for Coronary Heart Disease Rehabilitation: A Systematic Review of Randomized Controlled Trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8602574/" }, "origins": [ "evidence.json#/catalog:exercise:resistance-session/protocols/0" ] }, { "population": "561 adults undergoing chemotherapy across 7 randomised trials", "regimen": "2-4 sessions a week, 1-4 sets of 8-20 repetitions at 50-80% of one-repetition maximum, sessions of 20-70 minutes", "duration": "19 weeks on average (SD 7.7 weeks)", "outcome": "A small significant gain in lower-body strength (SMD 0.33); no significant effect on quality of life, fatigue, physical function or upper-body strength.", "source": { "title": "Effects of resistance training on quality of life, fatigue, physical function, and muscular strength during chemotherapy", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330399/" }, "origins": [ "evidence.json#/catalog:exercise:resistance-session/protocols/1" ] } ], "community": [ { "description": "A Cleveland Clinic guide describes resistance sessions using free weights, machines or resistance bands, with muscles working against an external load.", "source": { "title": "What Is Strength Training and Its Benefits? - Cleveland Clinic", "url": "https://health.clevelandclinic.org/strength-training" }, "origins": [ "evidence.json#/catalog:exercise:resistance-session/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://health.clevelandclinic.org/strength-training", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic guide describes resistance sessions using free weights, machines or resistance bands, with muscles working against an external load." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:resistance-session/community/0", "url": "https://health.clevelandclinic.org/strength-training", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC8602574/", "doi:10.3390/clinpract16080157", "https://cdnsciencepub.com/doi/10.1139/apnm-2020-0245", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330399/", "https://acsm.org/education-resources/books/guidelines-exercise-testing-prescription/", "https://health.clevelandclinic.org/strength-training" ] }, "library:exercise-rowing": { "id": "library:exercise-rowing", "path": "/library/exercise-rowing.html", "title": "Rowing", "summary": "Machine or water. Full-body conditioning recorded by duration and effort.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:rowing", "title": "Rowing", "summary": "Machine or water. Full-body conditioning recorded by duration and effort.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "clinical-study", "evidenceSummary": "Rowing works most of the body while raising heart rate. A study of 30 breast cancer survivors with no control group reported better flexibility, grip strength, walking distance and body composition after a rowing programme. A randomised trial of upper-body rowing in adults with spinal cord injury found no change in heart-rate variability or blood pressure responses. Evidence is limited to small studies in specific groups. Comparisons with running and claims about heart size are not supported by these sources.", "verdict": { "benefits": [ "In breast cancer survivors, an uncontrolled study reported better strength, flexibility and lean mass", "Rowing works most of the body while raising heart rate" ], "risks": [ "A randomised trial in adults with spinal cord injury found no heart-rate or blood pressure change", "Evidence is small studies in specific groups; the fitness study had no control group", "Claims that rowing beats running, or changes heart size, are not supported here" ], "bottomLine": "Rowing improved fitness in one uncontrolled study and changed nothing cardiovascular in a randomised trial." }, "originalLinks": [ { "title": "PubMed: rowing", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=rowing+exercise+health" } ], "links": [ { "title": "Rowing Training in Breast Cancer Survivors: A Longitudinal Study of Physical Fitness", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400517/" }, { "title": "Effects of 12 weeks of upper-body rowing exercise on autonomic cardiovascular control and vascular structure in spinal cord-injured humans", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12857515/" } ], "protocols": [ { "population": "30 breast cancer survivors, mean age 54, single group with no control", "regimen": "rowing training three sessions a week, 60 to 90 minutes a session, intensity rising across three 4-week stages (Borg 5-8)", "duration": "12 weeks", "outcome": "Grip strength, chair stand, flexibility, six-minute walk distance and lean mass increased; body fat and resting heart rate fell.", "source": { "title": "Rowing Training in Breast Cancer Survivors: A Longitudinal Study of Physical Fitness", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400517/" }, "origins": [ "evidence.json#/catalog:exercise:rowing/protocols/0" ] }, { "population": "15 wheelchair-dependent adults with chronic spinal cord injury (8 exercise, 7 control)", "regimen": "supervised indoor upper-body rowing, three 30-minute sessions a week at moderate to vigorous intensity (RPE 12-17)", "duration": "12 weeks", "outcome": "Brachial artery diameter increased; heart-rate variability, blood pressure responses to sit-up testing and carotid measures did not change.", "source": { "title": "Effects of 12 weeks of upper-body rowing exercise on autonomic cardiovascular control and vascular structure in spinal cord-injured humans", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12857515/" }, "origins": [ "evidence.json#/catalog:exercise:rowing/protocols/1" ] } ], "community": [ { "description": "Concept2's indoor rowing guide describes a four-part stroke: the catch, drive, finish and recovery.", "source": { "title": "Indoor Rowing Technique - Concept2", "url": "https://www.concept2.com/training/rowing-technique" }, "origins": [ "evidence.json#/catalog:exercise:rowing/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.concept2.com/indoor-rowers/training/technique", "outcome": "not-found", "reason": "The initial citation returned HTTP 404. The description was checked against the current canonical page before publication." }, { "url": "https://www.concept2.com/training/rowing-technique", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: Concept2's indoor rowing guide describes a four-part stroke: the catch, drive, finish and recovery." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:rowing/community/0", "url": "https://www.concept2.com/training/rowing-technique", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400517/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12857515/", "https://pubmed.ncbi.nlm.nih.gov/?term=rowing+exercise+health", "https://www.concept2.com/training/rowing-technique" ] }, "library:exercise-running": { "id": "library:exercise-running", "path": "/library/exercise-running.html", "title": "Running", "summary": "Recorded by distance, duration and effort. Pace belongs in the note, not the schedule.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:running", "title": "Running", "summary": "Recorded by distance, duration and effort. Pace belongs in the note, not the schedule.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "reference", "evidenceSummary": "Two review articles summarise observational studies linking regular running to lower all-cause and cardiovascular death rates and to less chronic disease. Both are narrative reviews of cohort data rather than randomised trials, so cause and effect is not established. They also describe risks at the high end: heart tissue damage, arrhythmias and exercise-induced hypertension with very high intensity or very long distances, and rare sudden cardiac death in marathon and ultra-endurance running. The reviews conclude benefits come at moderate levels of running.", "verdict": { "benefits": [ "Two reviews of cohort studies link regular running to lower all-cause and cardiovascular death rates.", "The same reviews link running to less chronic disease, with benefits at moderate levels." ], "risks": [ "Both reviews summarise observational data, so cause and effect is not established.", "At very high intensity or distance they describe heart tissue damage and arrhythmias.", "Sudden cardiac death is rare but reported in marathon and ultra-endurance running." ], "bottomLine": "Observational reviews tie moderate running to lower death rates, and flag heart risks at the extreme end." }, "originalLinks": [ { "title": "PubMed: running", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=running+exercise+health" } ], "links": [ { "title": "Effects of Running on Chronic Diseases and Cardiovascular and All-Cause Mortality", "url": "https://doi.org/10.1016/j.mayocp.2015.08.001" }, { "title": "The Impact of Running on Cardiovascular Health: A Comprehensive Review of Benefits and Risks", "url": "https://apcz.umk.pl/QS/article/view/56445" } ], "protocols": [], "community": [ { "description": "The Road Runners Club of America describes run-walk-run sessions with alternating running and walking intervals, attributing the method to Jeff Galloway.", "source": { "title": "Road Runners Club of America - For Runners", "url": "https://www.rrca.org/education/for-runners/" }, "origins": [ "evidence.json#/catalog:exercise:running/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.rrca.org/education/for-runners/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: The Road Runners Club of America describes run-walk-run sessions with alternating running and walking intervals, attributing the method to Jeff Galloway." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:running/community/0", "url": "https://www.rrca.org/education/for-runners/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "doi:10.1016/j.mayocp.2015.08.001", "https://apcz.umk.pl/QS/article/view/56445", "https://pubmed.ncbi.nlm.nih.gov/?term=running+exercise+health", "https://www.rrca.org/education/for-runners/" ] }, "library:exercise-swimming": { "id": "library:exercise-swimming", "path": "/library/exercise-swimming.html", "title": "Swimming", "summary": "Recorded by duration and effort. Stroke and distance belong in the note.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:swimming", "title": "Swimming", "summary": "Recorded by duration and effort. Stroke and distance belong in the note.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "systematic-review", "evidenceSummary": "Swimming is whole-body aerobic exercise done in water. A systematic review and meta-analysis of 18 trials found aquatic exercise reduced mood and anxiety symptoms (standardised mean difference -0.77), though the swimming-only subgroup was not statistically significant. A quasi-experimental study in 40 adults with type 2 diabetes and high blood pressure reported improvements in cholesterol and other metabolic risk factors after regular swimming. A systematic review of 20 non-randomised studies in early adolescents reports better cardiorespiratory fitness and bone and body-composition outcomes, but rated most studies at high risk of bias.", "verdict": { "benefits": [ "Pooled trials of water-based exercise found mood and anxiety symptoms fell.", "In adults with diabetes and high blood pressure, cholesterol and other risk factors improved." ], "risks": [ "The swimming-only part of the mood analysis was not statistically significant.", "The adolescent review rated most of its studies at high risk of bias.", "The metabolic study was quasi-experimental, not randomised." ], "bottomLine": "Water exercise improved mood and metabolic markers in trials, though swimming alone was not separately proven for mood." }, "originalLinks": [ { "title": "PubMed: swimming", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=swimming+exercise+health" } ], "links": [ { "title": "Effects of aquatic exercise on mood and anxiety symptoms: A systematic review and meta-analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714032/" }, { "title": "Regular swimming exercise improves metabolic syndrome risk factors: a quasi-experimental study", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938372/" }, { "title": "Effects of Swimming Exercise on Early Adolescents' Physical Conditioning and Physical Health: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417868/" } ], "protocols": [ { "population": "40 adults with type 2 diabetes and hypertension, mean age 52", "regimen": "2-hour pool sessions 3 times a week: 20 min warm-up, 10 min aerobic exercise, 85 min free swimming, 5 min cool-down, water at 29-33 C", "duration": "16 weeks", "outcome": "Blood glucose, total and LDL cholesterol, triglycerides, blood pressure, BMI and body fat fell and HDL rose in the swimming group; controls did not change.", "source": { "title": "Regular swimming exercise improves metabolic syndrome risk factors: a quasi-experimental study", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938372/" }, "origins": [ "evidence.json#/catalog:exercise:swimming/protocols/0" ] }, { "population": "423 participants across 18 aquatic exercise trials, mostly older adults and people with chronic conditions", "regimen": "aquatic exercise sessions of 41-240 minutes, most 45-60 minutes, usually 2-3 times a week", "duration": "1 to 32 weeks across the trials, most 3 to 24 weeks", "outcome": "Pooled mood and anxiety symptoms fell (SMD -0.77); the swimming-only subgroup was not significant (SMD -0.51, CI -1.14 to 0.12).", "source": { "title": "Effects of aquatic exercise on mood and anxiety symptoms: A systematic review and meta-analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714032/" }, "origins": [ "evidence.json#/catalog:exercise:swimming/protocols/1" ] }, { "population": "early adolescents aged 10-15 across 20 non-randomised studies, 21-234 participants per study", "regimen": "swimming sessions from 45 minutes in recreational programmes to over 120 minutes in competitive training, up to 10 sessions a week", "duration": "3 to 36 months of follow-up, most 6 to 24 months", "outcome": "The studies reported better cardiorespiratory fitness, bone mineral density and body composition, but most were rated at high risk of bias.", "source": { "title": "Effects of Swimming Exercise on Early Adolescents' Physical Conditioning and Physical Health: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417868/" }, "origins": [ "evidence.json#/catalog:exercise:swimming/protocols/2" ] } ], "community": [ { "description": "US Masters Swimming describes adult swimming clubs and workout groups organised through local swimming committees.", "source": { "title": "What is U.S. Masters Swimming? - U.S. Masters Swimming", "url": "https://www.usms.org/about/what-is-us-masters-swimming" }, "origins": [ "evidence.json#/catalog:exercise:swimming/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.usms.org/about-usms/what-is-usms", "outcome": "not-found", "reason": "The initial citation returned HTTP 404. The description was checked against the current canonical page before publication." }, { "url": "https://www.usms.org/about/what-is-us-masters-swimming", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: US Masters Swimming describes adult swimming clubs and workout groups organised through local swimming committees." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:swimming/community/0", "url": "https://www.usms.org/about/what-is-us-masters-swimming", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714032/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938372/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417868/", "https://pubmed.ncbi.nlm.nih.gov/?term=swimming+exercise+health", "https://www.usms.org/about/what-is-us-masters-swimming" ] }, "library:exercise-team-sport": { "id": "library:exercise-team-sport", "path": "/library/exercise-team-sport.html", "title": "Team sport", "summary": "Football, basketball and the like — recorded by session rather than by drill.", "aliases": [], "kind": "exercise-plan", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:exercise:team-sport", "title": "Team sport", "summary": "Football, basketball and the like — recorded by session rather than by drill.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "clinical-study", "evidenceSummary": "A cross-sectional analysis of self-reported data from over 1.2 million adults in the United States compared self-reported mental health burden across different exercise categories. Popular team sports were linked with the largest reduction in poor mental health days relative to not exercising, ahead of cycling and gym-based activity.", "verdict": { "benefits": [ "Individuals who exercised reported fewer poor mental health days than matched non-exercisers, with popular team sports showing the largest association among exercise types studied.", "The team-sport association held after matching for age, income, education, and prior depression diagnosis.", "Durations around forty-five minutes and frequencies of three to five times weekly were linked with the greatest reductions in poor mental health days." ], "risks": [ "This was a cross-sectional, self-reported dataset, so the analysis cannot establish that team sport participation causes better mental health rather than reflecting it.", "People with more severe mental health burden may be less able to participate in team sports in the first place, a pattern the study design cannot rule out.", "The largest reported association does not mean more exercise was uniformly better; very high exercise volumes did not show additional benefit in the dataset." ], "bottomLine": "A large cross-sectional analysis of self-reported data found popular team sports linked with the largest reduction in poor mental health days among exercise types studied, though the design cannot establish cause and effect." }, "originalLinks": [ { "title": "Association between physical exercise and mental health in 1·2 million individuals in the USA between 2011 and 2015: a cross-sectional study", "url": "https://pubmed.ncbi.nlm.nih.gov/30099000/" } ], "links": [ { "title": "Association between physical exercise and mental health in 1·2 million individuals in the USA between 2011 and 2015: a cross-sectional study", "url": "https://pubmed.ncbi.nlm.nih.gov/30099000/" } ], "protocols": [ { "population": "1,237,194 adults aged 18 and older from the 2011, 2013, and 2015 CDC Behavioral Risk Factor Surveillance System survey, USA", "regimen": "Self-reported exercise type, frequency, duration, and intensity compared against self-reported days of poor mental health in the past month, matched for demographic and health covariates", "duration": "Cross-sectional survey data collected across three survey years, 2011 to 2015", "outcome": "Individuals who exercised reported fewer poor mental health days than matched non-exercisers, with the largest association seen for popular team sports, followed by cycling and gym-based aerobic activity", "source": { "title": "Association between physical exercise and mental health in 1·2 million individuals in the USA between 2011 and 2015: a cross-sectional study", "url": "https://pubmed.ncbi.nlm.nih.gov/30099000/" }, "origins": [ "evidence.json#/catalog:exercise:team-sport/protocols/0" ] } ], "community": [ { "description": "A County Health Rankings description of adult recreational leagues lists soccer, softball, kickball and basketball at different playing levels.", "source": { "title": "Recreational sports leagues for adults - County Health Rankings & Roadmaps", "url": "https://www.countyhealthrankings.org/strategies-and-solutions/what-works-for-health/strategies/recreational-sports-leagues-for-adults" }, "origins": [ "evidence.json#/catalog:exercise:team-sport/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.countyhealthrankings.org/strategies-and-solutions/what-works-for-health/strategies/recreational-sports-leagues-for-adults", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A County Health Rankings description of adult recreational leagues lists soccer, softball, kickball and basketball at different playing levels." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:team-sport/community/0", "url": "https://www.countyhealthrankings.org/strategies-and-solutions/what-works-for-health/strategies/recreational-sports-leagues-for-adults", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:30099000", "https://www.countyhealthrankings.org/strategies-and-solutions/what-works-for-health/strategies/recreational-sports-leagues-for-adults" ] }, "library:exercise-walking": { "id": "library:exercise-walking", "path": "/library/exercise-walking.html", "title": "Walking", "summary": "Low-intensity steady movement, the most frequently logged and least often planned.", "aliases": [], "kind": "exercise-plan", "categories": [ "longevity", "fitness-muscle" ], "research": [ { "id": "catalog:exercise:walking", "title": "Walking", "summary": "Low-intensity steady movement, the most frequently logged and least often planned.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "exercise", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 42 studies with 1,843 participants in walking groups found lower systolic and diastolic blood pressure, resting heart rate, body fat, body mass index and total cholesterol, higher VO2 max, and lower depression scores, with no notable adverse effects. A systematic review of 13 studies on brisk walking in older adults found better cardiorespiratory fitness, muscular strength and body composition, with conflicting results for balance. A review of walking and healthy ageing summarises observational evidence on lower risk of cardiovascular disease, diabetes and cognitive decline.", "verdict": { "benefits": [ "Pooled trials of walking groups found lower blood pressure, body fat, cholesterol and depression scores", "Reviews report better fitness and strength in older adults, with no notable adverse effects", "Observational data links higher step counts to less heart disease, diabetes and dementia" ], "risks": [ "Effects on blood sugar and HDL or LDL cholesterol were unclear, and balance results conflicted", "The disease-risk findings are observational, so they show association rather than cause" ], "bottomLine": "Walking shows broad, consistent benefits across pooled trials, with the disease-risk findings resting on observational data." }, "originalLinks": [ { "title": "PubMed: walking", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=walking+exercise+health" } ], "links": [ { "title": "Is there evidence that walking groups have health benefits? A systematic review and meta-analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453623/" }, { "title": "Effect of Brisk Walking on Health-Related Physical Fitness Balance and Life Satisfaction Among the Elderly: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841590/" }, { "title": "The multifaceted benefits of walking for healthy aging: from Blue Zones to molecular mechanisms", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643563/" } ], "protocols": [ { "population": "1,843 participants in walking groups across 42 studies", "regimen": "group walking, from self-selected and low intensity to brisk walking and high-intensity intervals; 75% of interventions fell below moderate activity guidelines", "duration": "168 to 8,580 minutes of walking over a period of 3 weeks to 1 year", "outcome": "Pooled falls in blood pressure (-3.72/-3.14 mmHg), resting heart rate, body fat, BMI, total cholesterol and depression; evidence unclear for glucose and HDL/LDL.", "source": { "title": "Is there evidence that walking groups have health benefits? A systematic review and meta-analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453623/" }, "origins": [ "evidence.json#/catalog:exercise:walking/protocols/0" ] }, { "population": "older adults in 13 studies, with 9 to 68 participants each", "regimen": "brisk walking 3-7 times a week, 15-60 minutes a session, at 40-85% of heart rate reserve or 40-80% of maximum heart rate", "duration": "12 to 52 weeks", "outcome": "Cardiorespiratory fitness, muscular strength and body composition improved; balance results conflicted and the single flexibility study found no improvement.", "source": { "title": "Effect of Brisk Walking on Health-Related Physical Fitness Balance and Life Satisfaction Among the Elderly: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841590/" }, "origins": [ "evidence.json#/catalog:exercise:walking/protocols/1" ] }, { "population": "adults and older adults in the observational studies the review covers", "regimen": "daily step counts: about 9,800 steps a day, with 3,800 a day as a minimum dose, and as few as 6,000 a day in adults over 60", "duration": "not stated", "outcome": "The review reports lower risk of dementia, cardiovascular disease, type 2 diabetes and death at higher step counts, with pace a stronger predictor than volume.", "source": { "title": "The multifaceted benefits of walking for healthy aging: from Blue Zones to molecular mechanisms", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643563/" }, "origins": [ "evidence.json#/catalog:exercise:walking/protocols/2" ] } ], "community": [ { "description": "CDC's activity guide lists brisk walking as an example of moderate-intensity physical activity.", "source": { "title": "CDC - Physical Activity Basics", "url": "https://www.cdc.gov/physical-activity-basics/guidelines/index.html" }, "origins": [ "evidence.json#/catalog:exercise:walking/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.cdc.gov/physical-activity-basics/guidelines/index.html", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: CDC's activity guide lists brisk walking as an example of moderate-intensity physical activity." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:exercise:walking/community/0", "url": "https://www.cdc.gov/physical-activity-basics/guidelines/index.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453623/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841590/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643563/", "https://pubmed.ncbi.nlm.nih.gov/?term=walking+exercise+health", "https://www.cdc.gov/physical-activity-basics/guidelines/index.html" ] }, "library:food-protocol-16-8": { "id": "library:food-protocol-16-8", "path": "/library/food-protocol-16-8.html", "title": "16:8 time-restricted eating", "summary": "Sixteen-hour daily fast with an eight-hour eating window. Tracked by window adherence rather than food content.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:food-protocol:16-8", "title": "16:8 time-restricted eating", "summary": "Sixteen-hour daily fast with an eight-hour eating window. Tracked by window adherence rather than food content.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "Time-restricted eating keeps food to a set window each day. A meta-analysis of eight randomised trials in adults with overweight or obesity found a mean weight loss of about 1.5 kg and lower fat mass, with no clear change in lean mass. It found an improvement in insulin resistance but no clear effect on other glucose or lipid measures. A larger meta-analysis of 23 randomised trials found small reductions in fasting glucose, insulin and insulin resistance. Effects are consistent but modest, and the trials are short.", "verdict": { "benefits": [ "Pooled randomised trials in adults with overweight or obesity found modest weight and fat loss", "Insulin resistance improved, and a larger pooled analysis found small falls in fasting glucose and insulin" ], "risks": [ "The weight effect is small, around one and a half kilograms, and lean mass did not change", "No clear effect on most glucose and lipid measures, and the trials are short" ], "bottomLine": "Time-restricted eating produced small but consistent weight and insulin changes in short randomised trials." }, "originalLinks": [ { "title": "PubMed: time-restricted eating", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=time+restricted+eating" } ], "links": [ { "title": "Is time-restricted eating (8/16) beneficial for body weight and metabolism of obese and overweight adults? A systematic review and meta-analysis of randomized controlled trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10002957/" }, { "title": "Effect of 8-Hour Time-Restricted Eating (16/8 TRE) on Glucose Metabolism and Lipid Profile in Adults: A Systematic Review and Meta-Analysis (Wong et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41351878/" } ], "protocols": [ { "population": "adults with overweight or obesity, 464 people across 8 randomised trials", "regimen": "8-hour eating window with 16-hour fast, most trials using 12:00-20:00 or 08:00-16:00", "duration": "6 weeks to 12 months, most trials 8-12 weeks", "outcome": "Weight fell 1.48 kg and fat mass about 1.1 kg versus control; lean mass, glucose, HbA1c and lipids did not change significantly.", "source": { "title": "Is time-restricted eating (8/16) beneficial for body weight and metabolism of obese and overweight adults? A systematic review and meta-analysis of randomized controlled trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10002957/" }, "origins": [ "evidence.json#/catalog:food-protocol:16-8/protocols/0" ] }, { "population": "adults, 1,280 people across 23 randomised controlled trials", "regimen": "16-hour fast with an 8-hour daily eating window (16/8 time-restricted eating), compared with a control diet", "duration": "varied by trial; subgroup analysis separated trials running longer than 6 months", "outcome": "Small reductions in fasting glucose, insulin and HOMA-IR and a modest rise in HDL-C; no significant effect on the other lipid markers.", "source": { "title": "Effect of 8-Hour Time-Restricted Eating (16/8 TRE) on Glucose Metabolism and Lipid Profile in Adults: A Systematic Review and Meta-Analysis (Wong et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41351878/" }, "origins": [ "evidence.json#/catalog:food-protocol:16-8/protocols/1" ] } ], "community": [ { "description": "A nutrition guide describes the popular 16:8 pattern as a daily 16-hour fast with meals in the remaining eight-hour window.", "source": { "title": "Pros and Cons of Intermittent Fasting - Healthline", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" }, "origins": [ "evidence.json#/catalog:food-protocol:16-8/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide explicitly describes a popular daily 16-hour fast and eight-hour eating window.", "checks": [ { "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "outcome": "verified-description", "reason": "The live guide explicitly describes a popular daily 16-hour fast and eight-hour eating window." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:16-8/community/0", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC10002957/", "pmid:41351878", "https://pubmed.ncbi.nlm.nih.gov/?term=time+restricted+eating", "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" ] }, "library:food-protocol-18-6": { "id": "library:food-protocol-18-6", "path": "/library/food-protocol-18-6.html", "title": "18:6 time-restricted eating", "summary": "Eighteen-hour fast with a six-hour eating window. A tighter variant of 16:8.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:food-protocol:18-6", "title": "18:6 time-restricted eating", "summary": "Eighteen-hour fast with a six-hour eating window. A tighter variant of 16:8.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "reference", "evidenceSummary": "This is a tighter form of time-restricted eating, with a long fast and a short eating window. A 2025 scoping review of 81 human studies of time-restricted eating reports better body composition, insulin sensitivity, lipids and inflammation, while noting that people often eat less overall at the same time. A randomised trial in people with type 2 diabetes is testing this pattern over a year, but it is a published protocol with no results yet. No linked study reports outcomes for this specific window.", "verdict": { "benefits": [ "A review of 81 studies of time-restricted eating reports better body composition and insulin sensitivity.", "The same review reports better lipids and lower inflammation." ], "risks": [ "No linked study reports outcomes for this specific eating window.", "People often ate less overall, so benefits may come from that rather than timing.", "The trial in type 2 diabetes is a published protocol with no results yet." ], "bottomLine": "Time-restricted eating looks favourable in review, but this tighter window has no results of its own here." }, "originalLinks": [ { "title": "PubMed: time-restricted eating", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=time+restricted+eating" } ], "links": [ { "title": "Time-Restricted Eating in Metabolic and Clinical Health: a Current Evidence and Mechanistic Insights (Minari 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41478598/" }, { "title": "Time Restricted EAting for Type 2 diabetes and MEtabolic health: The TEA TIME trial study protocol (Retnakaran et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41818195/" } ], "protocols": [ { "population": "adults with overweight or obesity and type 2 diabetes of under 10 years' duration", "regimen": "18 hours of fasting with a 6-hour eating window between 2 and 8 PM each day, versus standard lifestyle recommendations", "duration": "52 weeks", "outcome": "No results reported: this is a published study protocol and the trial is ongoing.", "source": { "title": "Time Restricted EAting for Type 2 diabetes and MEtabolic health: The TEA TIME trial study protocol (Retnakaran et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41818195/" }, "origins": [ "evidence.json#/catalog:food-protocol:18-6/protocols/0" ] }, { "population": "81 human studies of time-restricted eating in a scoping review", "regimen": "the review describes protocols such as 16:8 and 14:10 eating windows", "duration": "not stated", "outcome": "The review reports better body composition, insulin sensitivity, lipids and inflammation, while noting benefits may coincide with eating less overall.", "source": { "title": "Time-Restricted Eating in Metabolic and Clinical Health: a Current Evidence and Mechanistic Insights (Minari 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41478598/" }, "origins": [ "evidence.json#/catalog:food-protocol:18-6/protocols/1" ] } ], "community": [ { "description": "A Cleveland Clinic podcast includes an 18-hour daily fast among time-restricted eating patterns, corresponding to a six-hour eating window.", "source": { "title": "What is Intermittent Fasting? (Love Your Heart podcast) - Cleveland Clinic", "url": "https://my.clevelandclinic.org/podcasts/love-your-heart/what-is-intermittent-fasting" }, "origins": [ "evidence.json#/catalog:food-protocol:18-6/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://my.clevelandclinic.org/podcasts/love-your-heart/what-is-intermittent-fasting", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic podcast includes an 18-hour daily fast among time-restricted eating patterns, corresponding to a six-hour eating window." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:18-6/community/0", "url": "https://my.clevelandclinic.org/podcasts/love-your-heart/what-is-intermittent-fasting", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:41478598", "pmid:41818195", "https://pubmed.ncbi.nlm.nih.gov/?term=time+restricted+eating", "https://my.clevelandclinic.org/podcasts/love-your-heart/what-is-intermittent-fasting" ] }, "library:food-protocol-5-2": { "id": "library:food-protocol-5-2", "path": "/library/food-protocol-5-2.html", "title": "5:2 intermittent fasting", "summary": "Normal eating five days a week with two non-consecutive restricted days of roughly 500–600 kcal.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:food-protocol:5-2", "title": "5:2 intermittent fasting", "summary": "Normal eating five days a week with two non-consecutive restricted days of roughly 500–600 kcal.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "The 5:2 pattern mixes normal eating days with strongly reduced-intake days. A randomised controlled trial in 60 adults with fatty liver disease compared it with daily calorie restriction and reported improvements in liver measures. A systematic review and meta-analysis of intermittent fasting in people with impaired glucose and lipid metabolism found small reductions in fasting glucose, HbA1c, insulin, insulin resistance, BMI and weight. Neither source reports long-term outcomes. The evidence is meta-analytic but built on short studies.", "verdict": { "benefits": [ "A randomised trial in fatty liver disease found less steatosis and fibrosis than daily calorie restriction.", "Pooled trials found small falls in fasting glucose, HbA1c, insulin resistance, weight and cholesterol." ], "risks": [ "The metabolic changes were small, and weight loss matched daily calorie restriction.", "Neither source reports long-term outcomes; the pooled studies were short." ], "bottomLine": "The 5:2 pattern produced small metabolic gains and better liver measures, but only in short studies." }, "originalLinks": [ { "title": "PubMed: intermittent fasting 5:2", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=5%3A2+intermittent+fasting" } ], "links": [ { "title": "Effect of 5:2 intermittent fasting diet versus daily calorie restriction eating on metabolic-associated fatty liver disease—a randomized controlled trial", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11368853/" }, { "title": "Effect of Intermittent Fasting Diet on Glucose and Lipid Metabolism and Insulin Resistance in Patients with Impaired Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8970877/" } ], "protocols": [ { "population": "54 adults with metabolic-associated fatty liver disease who completed the trial, 27 per arm", "regimen": "5:2 fasting: 600 kcal/day for women and 800 kcal/day for men on two days, customary eating on five, versus daily calorie restriction", "duration": "12 weeks", "outcome": "Hepatic steatosis (29.6% vs 59.3%) and fibrosis (3.7% vs 25.9%) were less frequent than with daily restriction; weight loss was similar in both arms.", "source": { "title": "Effect of 5:2 intermittent fasting diet versus daily calorie restriction eating on metabolic-associated fatty liver disease—a randomized controlled trial", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11368853/" }, "origins": [ "evidence.json#/catalog:food-protocol:5-2/protocols/0" ] }, { "population": "about 276 people with impaired glucose and lipid metabolism across 10 randomised trials", "regimen": "trials used alternate-day fasting, modified fasting under 25% of needs, 500-600 kcal fasting days, time-restricted feeding and Ramadan fasting", "duration": "5 weeks to 12 months", "outcome": "Pooled fasting glucose fell 0.15 mmol/L, HbA1c 0.08%, HOMA-IR 0.31, weight 1.87 kg and total cholesterol 0.32 mmol/L.", "source": { "title": "Effect of Intermittent Fasting Diet on Glucose and Lipid Metabolism and Insulin Resistance in Patients with Impaired Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8970877/" }, "origins": [ "evidence.json#/catalog:food-protocol:5-2/protocols/1" ] } ], "community": [ { "description": "A nutrition guide describes the 5:2 pattern as five usual eating days each week and two days limited to 500-600 kcal.", "source": { "title": "Pros and Cons of Intermittent Fasting - Healthline", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" }, "origins": [ "evidence.json#/catalog:food-protocol:5-2/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide describes five usual eating days and two restricted days. The description identifies the named pattern, not a recommendation to adopt it.", "checks": [ { "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "outcome": "verified-description", "reason": "The live guide describes five usual eating days and two restricted days. The description identifies the named pattern, not a recommendation to adopt it." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:5-2/community/0", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC11368853/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC8970877/", "https://pubmed.ncbi.nlm.nih.gov/?term=5%3A2+intermittent+fasting", "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" ] }, "library:food-protocol-adf": { "id": "library:food-protocol-adf", "path": "/library/food-protocol-adf.html", "title": "Alternate-day fasting", "summary": "Alternating fast days and normal eating days.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:food-protocol:adf", "title": "Alternate-day fasting", "summary": "Alternating fast days and normal eating days.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "Alternate-day fasting alternates fasting days with normal eating days. A systematic review and meta-analysis of seven randomised controlled trials with 269 adults found lower body weight and BMI, plus lower total cholesterol, LDL, triglycerides, fat mass and blood pressure, compared with controls. Fasting blood sugar and insulin resistance did not differ, and lean mass also fell. A network meta-analysis of 24 trials found intermittent fasting produced weight loss similar to steady calorie restriction.", "verdict": { "benefits": [ "Pooled randomised trials found lower weight, BMI, fat mass, cholesterol and blood pressure" ], "risks": [ "Lean mass fell alongside fat mass", "Blood sugar and insulin resistance did not improve", "Across 24 trials the weight loss was no different from steady calorie restriction" ], "bottomLine": "Alternate-day fasting lowered weight and lipids in pooled trials, matched plain calorie restriction, and also cut lean mass." }, "originalLinks": [ { "title": "PubMed: alternate day fasting", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=alternate+day+fasting" } ], "links": [ { "title": "Health Effects of Alternate-Day Fasting in Adults: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7732631/" }, { "title": "A meta-analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time-restricted eating for weight loss (Elortegui et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36349432/" } ], "protocols": [ { "population": "269 adults across seven randomised controlled trials", "regimen": "4:3 alternate-day fasting: 25% of energy needs on fasting days, unrestricted eating on the alternating feeding days", "duration": "Trials ran 4 to 48 weeks", "outcome": "Weight, BMI, fat mass, lean mass, total and LDL cholesterol, triglycerides and blood pressure fell; HDL, fasting glucose and insulin resistance did not.", "source": { "title": "Health Effects of Alternate-Day Fasting in Adults: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7732631/" }, "origins": [ "evidence.json#/catalog:food-protocol:adf/protocols/0" ] }, { "population": "1,768 people across 24 randomised controlled trials in the general population", "regimen": "Alternate-day fasting, the 5:2 diet and time-restricted eating, compared with continuous calorie restriction", "duration": "Not stated", "outcome": "Intermittent fasting gave weight loss no different from continuous calorie restriction (mean difference 0.26 kg, 95% CI -0.31 to 0.84).", "source": { "title": "A meta-analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time-restricted eating for weight loss (Elortegui et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36349432/" }, "origins": [ "evidence.json#/catalog:food-protocol:adf/protocols/1" ] } ], "community": [ { "description": "A nutrition guide lists alternate-day fasting among popular patterns, alternating a fasting day with a day of eating.", "source": { "title": "Pros and Cons of Intermittent Fasting - Healthline", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" }, "origins": [ "evidence.json#/catalog:food-protocol:adf/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide lists alternate-day fasting and describes fasting every other day; no efficacy or adherence claim is repeated.", "checks": [ { "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "outcome": "verified-description", "reason": "The live guide lists alternate-day fasting and describes fasting every other day; no efficacy or adherence claim is repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:adf/community/0", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC7732631/", "pmid:36349432", "https://pubmed.ncbi.nlm.nih.gov/?term=alternate+day+fasting", "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" ] }, "library:food-protocol-calorie-protein-target": { "id": "library:food-protocol-calorie-protein-target", "path": "/library/food-protocol-calorie-protein-target.html", "title": "Calorie or protein target", "summary": "A daily calorie or protein target, tracked by adherence rather than by the food itself.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss", "fitness-muscle" ], "research": [ { "id": "catalog:food-protocol:calorie-protein-target", "title": "Calorie or protein target", "summary": "A daily calorie or protein target, tracked by adherence rather than by the food itself.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "Logging adherence to a daily calorie or protein target follows the same self-monitoring principle that systematic reviews link to outcomes from structured eating plans. Diaries and app-based tracking of intake were consistently associated with greater weight loss, and separately, higher total protein intake was linked with larger gains in muscle size and strength during resistance training.", "verdict": { "benefits": [ "Self-monitoring of dietary intake was consistently linked with greater weight loss across the studies reviewed by Burke and colleagues.", "Higher total protein intake during resistance training was linked with larger gains in strength and fat-free mass in the pooled trials.", "A logged daily target gives an objective record of adherence rather than relying on memory." ], "risks": [ "Protein intake beyond a threshold identified in the pooled trials showed no further gains in fat-free mass, so higher totals were not linked with proportionally greater benefit.", "Most self-monitoring studies reviewed relied on self-report, a source of measurement error.", "Evidence linking adherence to a target with better outcomes is largely correlational rather than causal." ], "bottomLine": "Self-monitoring of dietary intake against a set target was consistently linked with greater weight loss, and higher protein intake during resistance training was linked with larger strength and muscle gains up to a point beyond which returns diminished." }, "originalLinks": [ { "title": "Self-monitoring in weight loss: a systematic review of the literature", "url": "https://pubmed.ncbi.nlm.nih.gov/21185970/" }, { "title": "A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults", "url": "https://pubmed.ncbi.nlm.nih.gov/28698222/" } ], "links": [ { "title": "Self-monitoring in weight loss: a systematic review of the literature", "url": "https://pubmed.ncbi.nlm.nih.gov/21185970/" }, { "title": "A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults", "url": "https://pubmed.ncbi.nlm.nih.gov/28698222/" } ], "protocols": [ { "population": "Adults enrolled in behavioral weight-management programs, drawn from 22 studies published 1993 to 2009", "regimen": "Self-monitoring of diet, exercise, or body weight using paper diaries, personal digital assistants, or electronic scales", "duration": "Review spanning sixteen years of published weight-loss intervention studies", "outcome": "Greater adherence to self-monitoring of dietary intake was consistently associated with greater weight loss across the reviewed studies", "source": { "title": "Self-monitoring in weight loss: a systematic review of the literature", "url": "https://pubmed.ncbi.nlm.nih.gov/21185970/" }, "origins": [ "evidence.json#/catalog:food-protocol:calorie-protein-target/protocols/0" ] }, { "population": "1,863 healthy adults across 49 randomised controlled trials of resistance training", "regimen": "Dietary protein supplementation added to resistance training programs, with total daily protein intake tracked across a wide range", "duration": "Resistance training programs lasting six weeks or longer across the pooled trials", "outcome": "Protein intake above a threshold identified in the pooled trials showed no further gains in fat-free mass, while intake below that threshold was associated with smaller strength and muscle-size gains", "source": { "title": "A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults", "url": "https://pubmed.ncbi.nlm.nih.gov/28698222/" }, "origins": [ "evidence.json#/catalog:food-protocol:calorie-protein-target/protocols/1" ] } ], "community": [ { "description": "MyFitnessPal describes food logging that records calories and macronutrients, including protein, against personal goals.", "source": { "title": "MyFitnessPal (official site)", "url": "https://www.myfitnesspal.com/" }, "origins": [ "evidence.json#/catalog:food-protocol:calorie-protein-target/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.myfitnesspal.com/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: MyFitnessPal describes food logging that records calories and macronutrients, including protein, against personal goals." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:calorie-protein-target/community/0", "url": "https://www.myfitnesspal.com/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:21185970", "pmid:28698222", "https://www.myfitnesspal.com/" ] }, "library:food-protocol-carb-cycling": { "id": "library:food-protocol-carb-cycling", "path": "/library/food-protocol-carb-cycling.html", "title": "Carb cycling", "summary": "Carbohydrate intake varied across the week, commonly aligned to training days.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss", "fitness-muscle" ], "research": [ { "id": "catalog:food-protocol:carb-cycling", "title": "Carb cycling", "summary": "Carbohydrate intake varied across the week, commonly aligned to training days.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "A systematic review and meta-analysis in trained endurance athletes found that periodising carbohydrate intake does not reliably improve performance compared with keeping carbohydrate high. A five-week trial in 17 well-trained cyclists found no advantage over an energy-matched high-carbohydrate diet on lactate steady state, substrate use or body composition. An eight-week trial in 24 recreational runners found fat oxidation rose on low carbohydrate and reverted when carbohydrate returned, with better running economy at lactate threshold in the periodised group but no difference in performance. Evidence is small trials plus one meta-analysis.", "verdict": { "benefits": [ "One trial found fat oxidation rose while carbohydrate was low, and running economy improved" ], "risks": [ "Pooled endurance performance did not differ from ordinary training in trained athletes", "A trial in well-trained cyclists found no advantage on any measured outcome", "The fat-burning shift reverted once carbohydrate returned, and performance did not improve" ], "bottomLine": "Periodising carbohydrate shifted fuel use but did not improve endurance performance in pooled trials." }, "originalLinks": [ { "title": "PubMed: carbohydrate periodisation", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=carbohydrate+periodization" } ], "links": [ { "title": "Performance effects of periodized carbohydrate restriction in endurance trained athletes – a systematic review and meta-analysis", "url": "https://jissn.biomedcentral.com/articles/10.1186/s12970-021-00435-3" }, { "title": "A Five-Week Periodized Carbohydrate Diet Does Not Improve Maximal Lactate Steady-State Exercise Capacity", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10820927/" }, { "title": "Periodized carbohydrate intake influences metabolic flexibility and indices of running economy during endurance training", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851979/" } ], "protocols": [ { "population": "endurance-trained athletes across 9 studies, VO2 max at least 55 (women) or 60 (men) ml/kg/min", "regimen": "training or recovery sessions with restricted carbohydrate availability at least three times a week, against normal high-carbohydrate availability", "duration": "interventions of one week or longer", "outcome": "Pooled endurance performance did not differ from control training (SMD 0.17, 95% CI -0.15 to 0.49, P = 0.29).", "source": { "title": "Performance effects of periodized carbohydrate restriction in endurance trained athletes – a systematic review and meta-analysis", "url": "https://jissn.biomedcentral.com/articles/10.1186/s12970-021-00435-3" }, "origins": [ "evidence.json#/catalog:food-protocol:carb-cycling/protocols/0" ] }, { "population": "17 highly trained male cyclists at U23 national level, VO2 peak about 71 ml/kg/min", "regimen": "\"fuel for the work required\": carbohydrate withheld from the previous lunch through recovery around 13 zone 1-2 sessions, then refed, against energy-matched high carbohydrate", "duration": "5 weeks, 66 hours of identical training", "outcome": "Both groups improved maximal lactate steady state equally; periodising carbohydrate gave no advantage in any measured outcome.", "source": { "title": "A Five-Week Periodized Carbohydrate Diet Does Not Improve Maximal Lactate Steady-State Exercise Capacity", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10820927/" }, "origins": [ "evidence.json#/catalog:food-protocol:carb-cycling/protocols/1" ] }, { "population": "24 recreationally active male runners aged 18-40, VO2 peak 51 ml/kg/min", "regimen": "4 weeks at 50 g or less carbohydrate a day with over 60% of energy from fat, then 4 weeks at 50-60% of energy from carbohydrate, 5 running sessions a week", "duration": "8 weeks", "outcome": "Fat oxidation rose then reverted once carbohydrate returned and running economy improved, but peak speed, time to exhaustion and VO2 peak did not differ.", "source": { "title": "Periodized carbohydrate intake influences metabolic flexibility and indices of running economy during endurance training", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851979/" }, "origins": [ "evidence.json#/catalog:food-protocol:carb-cycling/protocols/2" ] } ], "community": [ { "description": "A Precision Nutrition guide describes carb cycling as alternating higher-carbohydrate workout days with lower-carbohydrate non-workout days.", "source": { "title": "Carb Cycling: What It Is, How It Works, and How to Do It - Precision Nutrition", "url": "https://www.precisionnutrition.com/all-about-carb-cycling" }, "origins": [ "evidence.json#/catalog:food-protocol:carb-cycling/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.precisionnutrition.com/all-about-carb-cycling", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Precision Nutrition guide describes carb cycling as alternating higher-carbohydrate workout days with lower-carbohydrate non-workout days." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:carb-cycling/community/0", "url": "https://www.precisionnutrition.com/all-about-carb-cycling", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://jissn.biomedcentral.com/articles/10.1186/s12970-021-00435-3", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10820927/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851979/", "https://pubmed.ncbi.nlm.nih.gov/?term=carbohydrate+periodization", "https://www.precisionnutrition.com/all-about-carb-cycling" ] }, "library:food-protocol-carnivore": { "id": "library:food-protocol-carnivore", "path": "/library/food-protocol-carnivore.html", "title": "Carnivore / zero carb", "summary": "Animal foods only, with carbohydrate intake close to zero. Fibre and micronutrient coverage are the open questions.", "aliases": [], "kind": "food-protocol", "categories": [ "longevity" ], "research": [ { "id": "catalog:food-protocol:carnivore", "title": "Carnivore / zero carb", "summary": "Animal foods only, with carbohydrate intake close to zero. Fibre and micronutrient coverage are the open questions.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "The carnivore diet is an almost entirely animal-based way of eating. A scoping review found only nine human studies, with small samples, short durations and weak designs. Some reported weight loss, more satiety and better inflammatory or metabolic markers, while risks included possible shortfalls in vitamins C and D, calcium, magnesium, iodine and fibre, and raised LDL and total cholesterol. One case described worsening health. The review concluded that the quality of evidence is very limited.", "verdict": { "benefits": [ "Some of the nine human studies reported weight loss, more satiety and better metabolic markers.", "Survey respondents reported better digestion, mood and cognition, all self-reported." ], "risks": [ "A scoping review found only nine small, short, weakly designed studies and called the evidence very limited.", "Reported harms include raised LDL and total cholesterol.", "Possible shortfalls in vitamins C and D, calcium, magnesium, iodine and fibre; one case worsened." ], "bottomLine": "Carnivore eating has very limited human evidence, with reported weight loss set against raised cholesterol." }, "originalLinks": [ { "title": "PubMed: carnivore diet", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=carnivore+diet" } ], "links": [ { "title": "Carnivore Diet: A Scoping Review of the Current Evidence, Potential Benefits and Risks", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12845189/" }, { "title": "Beliefs and Experiences of Individuals Following a Zero-Carb Diet", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8699012/" }, { "title": "Assessing the Nutrient Composition of a Carnivore Diet: A Case Study Model", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11722875/" } ], "protocols": [ { "population": "about 2,300 people across 9 human studies, from single cases to one survey of 2,029 respondents", "regimen": "predominantly red meat, eggs, dairy and organ meat with plant foods excluded; roughly 70-75% of energy as fat, 25-30% protein, under 5% carbohydrate", "duration": "43 days to about 6 years; survey respondents reported a median of 12-14 months", "outcome": "Studies reported weight loss, more satiety and lower inflammatory markers, alongside raised LDL and total cholesterol in 27% and micronutrient shortfalls.", "source": { "title": "Carnivore Diet: A Scoping Review of the Current Evidence, Potential Benefits and Risks", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12845189/" }, "origins": [ "evidence.json#/catalog:food-protocol:carnivore/protocols/0" ] }, { "population": "170 adults from 25 countries recruited through Twitter, mean age 42.8", "regimen": "almost entirely animal foods - beef, fatty fish, pork, eggs, dairy, poultry - with fruit and vegetables rarely eaten and water the main drink", "duration": "at least 6 months before the survey; 99% intended to continue indefinitely", "outcome": "Respondents reported better digestion, metabolic markers, mood and cognition, plus social stigma, lack of clinician support and high food cost; all self-reported.", "source": { "title": "Beliefs and Experiences of Individuals Following a Zero-Carb Diet", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8699012/" }, "origins": [ "evidence.json#/catalog:food-protocol:carnivore/protocols/1" ] } ], "community": [ { "description": "A Cleveland Clinic guide describes carnivore eating around meat, fish, eggs and limited dairy, excluding plant foods.", "source": { "title": "The Carnivore Diet: Should You Try It? - Cleveland Clinic", "url": "https://health.clevelandclinic.org/the-carnivore-diet" }, "origins": [ "evidence.json#/catalog:food-protocol:carnivore/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://health.clevelandclinic.org/the-carnivore-diet", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic guide describes carnivore eating around meat, fish, eggs and limited dairy, excluding plant foods." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:carnivore/community/0", "url": "https://health.clevelandclinic.org/the-carnivore-diet", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC12845189/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC8699012/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC11722875/", "https://pubmed.ncbi.nlm.nih.gov/?term=carnivore+diet", "https://health.clevelandclinic.org/the-carnivore-diet" ] }, "library:food-protocol-extended-fast": { "id": "library:food-protocol-extended-fast", "path": "/library/food-protocol-extended-fast.html", "title": "Extended fast", "summary": "A fast beyond 24 hours. Electrolytes and refeeding become the practical concerns as duration grows.", "aliases": [], "kind": "food-protocol", "categories": [ "longevity", "fat-loss" ], "research": [ { "id": "catalog:food-protocol:extended-fast", "title": "Extended fast", "summary": "A fast beyond 24 hours. Electrolytes and refeeding become the practical concerns as duration grows.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "clinical-study", "evidenceSummary": "An observational study of 1,422 people in a supervised multi-day fasting programme reported falls in weight, waist circumference and blood pressure, better blood lipids and glucose control, and adverse effects in under 1% of participants. Most reported no hunger after the first days, and 84% of those with existing complaints said these improved. A narrative review of human trials adds that prolonged fasting causes moderate weight loss, of which about two-thirds is lean mass, and that metabolic gains faded a few months after refeeding. Reported problems include metabolic acidosis, headache and insomnia.", "verdict": { "benefits": [ "An observational programme in 1,422 people reported lower weight and pressure, better lipids and glucose.", "Adverse effects were reported in under 1% of that supervised group." ], "risks": [ "About two-thirds of the weight lost was lean mass.", "A few months after normal eating resumed, no metabolic benefit remained.", "Reported problems include metabolic acidosis, headache and insomnia." ], "bottomLine": "Supervised multi-day fasting lowered weight and blood pressure, but much of the loss was lean mass and gains faded." }, "originalLinks": [ { "title": "PubMed: prolonged fasting", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=prolonged+fasting" } ], "links": [ { "title": "Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6314618/" }, { "title": "Efficacy and safety of prolonged water fasting: a narrative review of human trials (Ezpeleta et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/37377031/" } ], "protocols": [ { "population": "1,422 people in a supervised fasting programme at a specialist clinic", "regimen": "Buchinger fasting on 200-250 kcal a day with a moderate-intensity lifestyle programme and daily medical monitoring", "duration": "fasting periods of 5, 10, 15 or 20 days (each plus or minus 2 days)", "outcome": "Weight fell 3.2 kg at 5 days to 8.6 kg at 20 days, blood pressure dropped, 93.2% reported no hunger, and under 1% had adverse effects.", "source": { "title": "Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6314618/" }, "origins": [ "evidence.json#/catalog:food-protocol:extended-fast/protocols/0" ] }, { "population": "adults in human trials of prolonged fasting, as summarised by the review", "regimen": "prolonged fasting: little or no food or caloric drink, across the trials the review covered", "duration": "5-20 days", "outcome": "Weight fell 2-10%, about two-thirds of it lean mass; blood pressure fell; 3-4 months after the fast no metabolic benefit remained.", "source": { "title": "Efficacy and safety of prolonged water fasting: a narrative review of human trials (Ezpeleta et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/37377031/" }, "origins": [ "evidence.json#/catalog:food-protocol:extended-fast/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The proposed source is a commercial fasting clinic's promotional page; its supporting excerpt makes benefit claims rather than independently documenting the proposed community routine.", "checks": [ { "url": "https://www.healthpromoting.com/about-water-only-fasting", "outcome": "no-practice-description", "reason": "The proposed source is a commercial fasting clinic's promotional page; its supporting excerpt makes benefit claims rather than independently documenting the proposed community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC6314618/", "pmid:37377031", "https://pubmed.ncbi.nlm.nih.gov/?term=prolonged+fasting" ] }, "library:food-protocol-full-day-fast": { "id": "library:food-protocol-full-day-fast", "path": "/library/food-protocol-full-day-fast.html", "title": "24-hour fast", "summary": "A full calendar day with no food, logged as one entry per day rather than a start and end time.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:food-protocol:full-day-fast", "title": "24-hour fast", "summary": "A full calendar day with no food, logged as one entry per day rather than a start and end time.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "clinical-study", "evidenceSummary": "A three-week randomised controlled trial in lean, healthy adults compared true 24-hour alternate-day fasting against a matched degree of continuous daily energy restriction, and against alternate-day fasting with no net energy deficit. True 24-hour fasting reduced body mass but lost less fat than the matched continuous restriction, and postprandial cardiometabolic markers and adipose tissue gene expression did not differ between groups.", "verdict": { "benefits": [ "A 24-hour fast repeated on alternate days lowered body mass in a 3-week randomised trial" ], "risks": [ "The same trial found this lost less fat than a matched degree of continuous daily restriction", "Fasting without a net energy deficit did not significantly reduce body or fat mass" ], "bottomLine": "A single day of complete fasting cuts intake for that day; the trial evidence shows this loses less fat than the same calorie deficit spread evenly across days." }, "originalLinks": [ { "title": "PubMed: 24-hour fasting RCT (Templeman et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34135111/" } ], "links": [ { "title": "A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults (Templeman et al. 2021, Science Translational Medicine)", "url": "https://pubmed.ncbi.nlm.nih.gov/34135111/" } ], "protocols": [ { "population": "36 lean, healthy adults split into three groups of 12", "regimen": "24-hour fasting on alternate days, at either 150% or 200% energy intake on feeding days, compared with 75% energy intake every day with no fasting", "duration": "3 weeks", "outcome": "Daily restriction cut fat mass by 1.75 kg; alternate-day fasting with the same net deficit cut it by only 0.74 kg, and fasting without a net deficit did not significantly reduce fat mass.", "source": { "title": "A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults (Templeman et al. 2021, Science Translational Medicine)", "url": "https://pubmed.ncbi.nlm.nih.gov/34135111/" }, "origins": [ "evidence.json#/catalog:food-protocol:full-day-fast/protocols/0" ] } ], "community": [ { "description": "A nutrition guide describes Eat Stop Eat as a 24-hour fast once or twice per week, outside a study setting.", "source": { "title": "Pros and Cons of Intermittent Fasting - Healthline", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" }, "origins": [ "evidence.json#/catalog:food-protocol:full-day-fast/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide explicitly describes Eat Stop Eat as a 24-hour fast once or twice per week, outside an intervention-trial description.", "checks": [ { "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "outcome": "verified-description", "reason": "The live guide explicitly describes Eat Stop Eat as a 24-hour fast once or twice per week, outside an intervention-trial description." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:full-day-fast/community/0", "url": "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:34135111", "https://www.healthline.com/nutrition/6-ways-to-do-intermittent-fasting" ] }, "library:food-protocol-keto": { "id": "library:food-protocol-keto", "path": "/library/food-protocol-keto.html", "title": "Ketogenic diet", "summary": "Very low carbohydrate intake, typically under 50 g daily, to sustain nutritional ketosis.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:food-protocol:keto", "title": "Ketogenic diet", "summary": "Very low carbohydrate intake, typically under 50 g daily, to sustain nutritional ketosis.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "An umbrella review of 17 meta-analyses covering 68 randomised trials graded the evidence on ketogenic diets. High-quality evidence supported lower seizure frequency and lower triglycerides, and also a rise in LDL cholesterol. Most underlying trials were small (median 42 participants) and short (median 13 weeks), so long-term outcomes are unknown. A separate systematic review of mood and anxiety disorders found only 12 low-quality, mostly uncontrolled studies.", "verdict": { "benefits": [ "High-quality evidence from an umbrella review: fewer seizures in children with epilepsy.", "High-quality evidence for lower triglycerides." ], "risks": [ "The same high-quality evidence shows LDL cholesterol rises in type 2 diabetes.", "Underlying trials were mostly small and short, so long-term outcomes are unknown.", "For mood and anxiety, only 12 low-quality studies exist; one panic-disorder case worsened." ], "bottomLine": "Ketogenic diets have strong evidence for fewer seizures and lower triglycerides, alongside higher LDL." }, "originalLinks": [ { "title": "PubMed: ketogenic diet", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=ketogenic+diet" } ], "links": [ { "title": "Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10210275/" }, { "title": "Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10134254/" } ], "protocols": [ { "population": "68 randomised trials, median 42 participants each", "regimen": "Ketogenic diets; the standard form limits carbohydrate to under 50 g a day or under 10% of energy, other forms to under 10-50 g a day", "duration": "Median follow-up 13 weeks", "outcome": "High-quality evidence for fewer seizures in children with epilepsy, lower triglycerides, and higher LDL cholesterol at 12 months in type 2 diabetes.", "source": { "title": "Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10210275/" }, "origins": [ "evidence.json#/catalog:food-protocol:keto/protocols/0" ] }, { "population": "389 people with mood or anxiety disorders across 12 studies, nine of them case reports", "regimen": "Low-carbohydrate or ketogenic diets ranging from 0 to under 130 g carbohydrate a day; five studies did not report carbohydrate intake", "duration": "2 weeks to 3 years", "outcome": "Studies reported mood stabilisation and fewer symptoms, but no high-quality evidence; one panic-disorder case had higher anxiety, and relapse followed stopping.", "source": { "title": "Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10134254/" }, "origins": [ "evidence.json#/catalog:food-protocol:keto/protocols/1" ] } ], "community": [ { "description": "A keto diet guide describes the standard version as roughly 70% of energy from fat, 20% from protein and 10% from carbohydrate; it also describes a cyclical variant with five keto days and two higher-carbohydrate days.", "source": { "title": "A Detailed Beginner's Guide to the Ketogenic Diet - Healthline", "url": "https://www.healthline.com/nutrition/ketogenic-diet-101" }, "origins": [ "evidence.json#/catalog:food-protocol:keto/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide documents both the stated standard macro proportions and a cyclical variant. The description reports those versions, not health outcomes.", "checks": [ { "url": "https://www.healthline.com/nutrition/ketogenic-diet-101", "outcome": "verified-description", "reason": "The live guide documents both the stated standard macro proportions and a cyclical variant. The description reports those versions, not health outcomes." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:keto/community/0", "url": "https://www.healthline.com/nutrition/ketogenic-diet-101", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC10210275/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC10134254/", "https://pubmed.ncbi.nlm.nih.gov/?term=ketogenic+diet", "https://www.healthline.com/nutrition/ketogenic-diet-101" ] }, "library:food-protocol-low-carb": { "id": "library:food-protocol-low-carb", "path": "/library/food-protocol-low-carb.html", "title": "Low carbohydrate", "summary": "Reduced carbohydrate intake without necessarily reaching ketosis, commonly 50–130 g daily.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:food-protocol:low-carb", "title": "Low carbohydrate", "summary": "Reduced carbohydrate intake without necessarily reaching ketosis, commonly 50–130 g daily.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "A systematic review of 15 controlled trials in type 2 diabetes found that low-carbohydrate approaches, with or without calorie restriction, produced clinically meaningful weight loss and lower HbA1c, with neither approach clearly better at 12 and 24 months. Average weight loss tracked the fall in HbA1c, suggesting sustained weight loss drives remission. A meta-analysis of randomised trials (18 studies, 2,204 adults) found a modest HbA1c advantage at one year, plus better triglycerides and HDL cholesterol. Whether cutting carbohydrates helps beyond weight loss is still unclear.", "verdict": { "benefits": [ "A review of 15 controlled trials in type 2 diabetes found meaningful weight loss and lower HbA1c.", "Pooled randomised trials found a modest HbA1c edge at one year, with better triglycerides and HDL." ], "risks": [ "Whether cutting carbohydrates helps beyond the weight loss itself is still unclear.", "Low-carbohydrate and calorie-restricted eating were not clearly different at one and two years.", "Weight, total and LDL cholesterol and diastolic pressure did not differ at one year." ], "bottomLine": "Low-carbohydrate eating lowered HbA1c and weight in type 2 diabetes, with the benefit tracking the weight loss." }, "originalLinks": [ { "title": "PubMed: low carbohydrate diet", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=low+carbohydrate+diet" } ], "links": [ { "title": "Restricting carbohydrates and calories in the treatment of type 2 diabetes: a systematic review of the effectiveness of 'low carbohydrate' interventions with differing energy levels", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8453456/" }, { "title": "The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials (Huntriss et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29269890/" } ], "protocols": [ { "population": "adults with type 2 diabetes, mostly obese, across 15 controlled trials", "regimen": "carbohydrate under 130 g a day or under 26% of energy, individual trials prescribing from under 20 g a day upwards, with or without energy restriction", "duration": "3 to 24 months", "outcome": "Trials reported meaningful weight loss and lower HbA1c; severe energy restriction was no better than ad libitum low-carbohydrate feeding, and weight loss tracked HbA1c.", "source": { "title": "Restricting carbohydrates and calories in the treatment of type 2 diabetes: a systematic review of the effectiveness of 'low carbohydrate' interventions with differing energy levels", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8453456/" }, "origins": [ "evidence.json#/catalog:food-protocol:low-carb/protocols/0" ] }, { "population": "2,204 adults with type 2 diabetes across 18 randomised trials", "regimen": "low-carbohydrate diets as each trial defined them; the review judged under 130 g a day achievable and under 50 g a day unrealistic in this group", "duration": "meta-analysis pooled the seven trials reporting at 1 year", "outcome": "At one year HbA1c was 0.28% lower, triglycerides and systolic pressure lower, HDL higher; weight, total and LDL cholesterol and diastolic pressure did not differ.", "source": { "title": "The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials (Huntriss et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29269890/" }, "origins": [ "evidence.json#/catalog:food-protocol:low-carb/protocols/1" ] } ], "community": [ { "description": "A Diet Doctor guide distinguishes stricter ketogenic eating from moderate and more liberal low-carbohydrate patterns.", "source": { "title": "How low carb is low carb? - Diet Doctor", "url": "https://www.dietdoctor.com/low-carb/how-low-carb-is-low-carb" }, "origins": [ "evidence.json#/catalog:food-protocol:low-carb/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.dietdoctor.com/low-carb/how-low-carb-is-low-carb", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Diet Doctor guide distinguishes stricter ketogenic eating from moderate and more liberal low-carbohydrate patterns." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:low-carb/community/0", "url": "https://www.dietdoctor.com/low-carb/how-low-carb-is-low-carb", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC8453456/", "pmid:29269890", "https://pubmed.ncbi.nlm.nih.gov/?term=low+carbohydrate+diet", "https://www.dietdoctor.com/low-carb/how-low-carb-is-low-carb" ] }, "library:food-protocol-mediterranean": { "id": "library:food-protocol-mediterranean", "path": "/library/food-protocol-mediterranean.html", "title": "Mediterranean", "summary": "Pattern emphasising olive oil, fish, vegetables, legumes and whole grains. Among the best-evidenced dietary patterns.", "aliases": [], "kind": "food-protocol", "categories": [ "longevity" ], "research": [ { "id": "catalog:food-protocol:mediterranean", "title": "Mediterranean", "summary": "Pattern emphasising olive oil, fish, vegetables, legumes and whole grains. Among the best-evidenced dietary patterns.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "The Mediterranean diet emphasises olive oil, vegetables, legumes, whole grains and fish. An updated systematic review of 24 studies found that closer adherence goes with lower overall mortality and lower cardiovascular disease risk, both in the general population and in people who already have heart disease. A second systematic review graded the evidence as high for primary and secondary cardiovascular prevention and moderate for preventing type 2 diabetes. Most of this evidence is observational, so it shows association rather than proof of cause.", "verdict": { "benefits": [ "Closer adherence tracks lower death rates and fewer cardiovascular events across 24 studies", "One review graded the evidence high for heart disease prevention, moderate for type 2 diabetes" ], "risks": [ "Most of this evidence is observational, so it shows association rather than proof of cause" ], "bottomLine": "Consistent evidence links Mediterranean-style eating to less heart disease and lower mortality, though mostly observational." }, "originalLinks": [ { "title": "PubMed: Mediterranean diet", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=mediterranean+diet" } ], "links": [ { "title": "Mediterranean Diet for Primary and Secondary Prevention of Cardiovascular Disease and Mortality: An Updated Systematic Review", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10421390/" }, { "title": "Mediterranean Diet and Cardiodiabesity: A Systematic Review through Evidence-Based Answers to Key Clinical Questions", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471908/" } ], "protocols": [ { "population": "adults in the 24 studies reviewed, both without and with existing cardiovascular disease", "regimen": "the review describes trials assigning a Mediterranean diet supplemented with extra-virgin olive oil or with nuts, against control diets advised to reduce fat", "duration": "the trials it cites ran 46 months to 7 years", "outcome": "The review reports that closer adherence went with lower all-cause mortality and fewer cardiovascular events; most of the evidence it pools is observational.", "source": { "title": "Mediterranean Diet for Primary and Secondary Prevention of Cardiovascular Disease and Mortality: An Updated Systematic Review", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10421390/" }, "origins": [ "evidence.json#/catalog:food-protocol:mediterranean/protocols/0" ] }, { "population": "healthy and at-risk adults in the studies reviewed", "regimen": "Mediterranean dietary patterns; the review quotes one included study supplementing 33 g of olive oil a day and 56 g of nuts a week", "duration": "at least 6 months of follow-up for inclusion; included studies ran from 1 year to 25 years", "outcome": "The review graded the evidence high for cardiovascular prevention and weight reduction and moderate for preventing type 2 diabetes.", "source": { "title": "Mediterranean Diet and Cardiodiabesity: A Systematic Review through Evidence-Based Answers to Key Clinical Questions", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471908/" }, "origins": [ "evidence.json#/catalog:food-protocol:mediterranean/protocols/1" ] } ], "community": [ { "description": "A Mediterranean diet guide describes a flexible pattern of vegetables, fruits, whole grains, legumes, nuts and olive oil, with fish and seafood at least twice a week and fewer processed foods.", "source": { "title": "Beginner's Guide to the Mediterranean Diet - Healthline", "url": "https://www.healthline.com/nutrition/mediterranean-diet-meal-plan" }, "origins": [ "evidence.json#/catalog:food-protocol:mediterranean/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide describes the stated food pattern and includes fish and seafood at least twice weekly. No outcome claims are repeated.", "checks": [ { "url": "https://www.healthline.com/nutrition/mediterranean-diet-meal-plan", "outcome": "verified-description", "reason": "The live guide describes the stated food pattern and includes fish and seafood at least twice weekly. No outcome claims are repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:mediterranean/community/0", "url": "https://www.healthline.com/nutrition/mediterranean-diet-meal-plan", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC10421390/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471908/", "https://pubmed.ncbi.nlm.nih.gov/?term=mediterranean+diet", "https://www.healthline.com/nutrition/mediterranean-diet-meal-plan" ] }, "library:food-protocol-omad": { "id": "library:food-protocol-omad", "path": "/library/food-protocol-omad.html", "title": "OMAD (one meal a day)", "summary": "A single daily eating occasion, effectively a 23:1 window. Hitting protein and micronutrient targets in one sitting is the practical difficulty.", "aliases": [], "kind": "food-protocol", "categories": [ "fat-loss", "fitness-muscle" ], "research": [ { "id": "catalog:food-protocol:omad", "title": "OMAD (one meal a day)", "summary": "A single daily eating occasion, effectively a 23:1 window. Hitting protein and micronutrient targets in one sitting is the practical difficulty.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "No linked study tested one meal a day directly. A scoping review of 81 studies of time-restricted eating reports better body composition, insulin sensitivity, lipids and inflammation, but it excluded prolonged fasting and looked at wider eating windows. A meta-analysis of intermittent fasting covering 64 reports found alternate-day fasting gave the largest metabolic gains, with people who have obesity or metabolic syndrome benefiting most. Evidence for this specific pattern is therefore indirect, and nutrient adequacy in a single meal is not addressed by these sources.", "verdict": { "benefits": [ "No linked study tested one meal a day directly; the evidence here is indirect" ], "risks": [ "The scoping review covered wider eating windows and excluded prolonged fasting", "A pooled analysis found alternate-day fasting, not this pattern, gave the strongest metabolic changes", "Whether a single meal covers nutrient needs is not addressed by these sources" ], "bottomLine": "Eating once a day has no direct study in these sources; the evidence comes from broader fasting research." }, "originalLinks": [ { "title": "PubMed: one meal a day", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=one+meal+a+day+fasting" } ], "links": [ { "title": "Time-Restricted Eating in Metabolic and Clinical Health: a Current Evidence and Mechanistic Insights (Minari 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41478598/" }, { "title": "Effects of Intermittent Fasting on Regulation of Metabolic Homeostasis: A Systematic Review and Meta-Analysis in Health and Metabolic-Related Disorders", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10253889/" } ], "protocols": [ { "population": "adults across 81 studies of time-restricted eating, excluding alternate-day and prolonged fasting", "regimen": "time-restricted eating protocols such as 16:8 and 14:10 daily eating windows", "duration": "not stated", "outcome": "The review reports better body composition, insulin sensitivity, lipids and inflammation, with early feeding giving better glycaemic outcomes.", "source": { "title": "Time-Restricted Eating in Metabolic and Clinical Health: a Current Evidence and Mechanistic Insights (Minari 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41478598/" }, "origins": [ "evidence.json#/catalog:food-protocol:omad/protocols/0" ] }, { "population": "4,052 participants across 64 studies of intermittent fasting", "regimen": "alternate-day fasting (1+1, 5:2, 4:3), time-restricted fasting with eating windows of 4-16 hours, and Ramadan fasting", "duration": "about 2-8 weeks up to one year", "outcome": "Weight, BMI, waist and total cholesterol were similar across regimes; alternate-day fasting gave the strongest lipid, insulin and blood-pressure changes.", "source": { "title": "Effects of Intermittent Fasting on Regulation of Metabolic Homeostasis: A Systematic Review and Meta-Analysis in Health and Metabolic-Related Disorders", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10253889/" }, "origins": [ "evidence.json#/catalog:food-protocol:omad/protocols/1" ] } ], "community": [ { "description": "A Healthline guide describes one-meal-a-day eating as concentrating daily food intake into one meal rather than several meals.", "source": { "title": "What Is OMAD? Is the One Meal a Day Diet Healthy? - Healthline", "url": "https://www.healthline.com/health/one-meal-a-day" }, "origins": [ "evidence.json#/catalog:food-protocol:omad/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.healthline.com/health/one-meal-a-day", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Healthline guide describes one-meal-a-day eating as concentrating daily food intake into one meal rather than several meals." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:omad/community/0", "url": "https://www.healthline.com/health/one-meal-a-day", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:41478598", "https://pmc.ncbi.nlm.nih.gov/articles/PMC10253889/", "https://pubmed.ncbi.nlm.nih.gov/?term=one+meal+a+day+fasting", "https://www.healthline.com/health/one-meal-a-day" ] }, "library:food-protocol-paleo": { "id": "library:food-protocol-paleo", "path": "/library/food-protocol-paleo.html", "title": "Paleo", "summary": "Excludes grains, legumes, dairy and refined foods. Carbohydrate intake is unrestricted from whole-food sources.", "aliases": [], "kind": "food-protocol", "categories": [ "longevity" ], "research": [ { "id": "catalog:food-protocol:paleo", "title": "Paleo", "summary": "Excludes grains, legumes, dairy and refined foods. Carbohydrate intake is unrestricted from whole-food sources.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "A GRADE-assessed systematic review and meta-analysis pooled 19 randomised trials and 12 cohort studies of the Paleolithic diet. The trials showed modest improvements in fasting insulin, cholesterol, LDL, triglycerides, body weight, BMI and diastolic blood pressure. The cohorts linked high adherence with about 10% lower all-cause and cancer mortality. An earlier meta-analysis of four small trials (98 people) found no difference from other healthy diets on glucose and insulin measures, and a StatPearls chapter gives background.", "verdict": { "benefits": [ "A meta-analysis of 19 randomised trials found modest gains in insulin, lipids, weight and diastolic pressure.", "Pooled cohorts linked high adherence with about 10% lower all-cause and cancer mortality." ], "risks": [ "The cohort mortality link is observational, so cause and effect is not established.", "An earlier meta-analysis of four small trials found no edge over other healthy diets.", "Improvements in the trials were modest rather than large." ], "bottomLine": "Pooled trials show modest metabolic gains on a Paleolithic diet; earlier work found no edge over other diets." }, "originalLinks": [ { "title": "PubMed: paleolithic diet", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=paleolithic+diet" } ], "links": [ { "title": "The Paleolithic diet and chronic disease risk: a GRADE-assessed systematic review and dose-response meta-analysis (Bahrami et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41129328/" }, { "title": "The Effect of the Paleolithic Diet vs. Healthy Diets on Glucose and Insulin Homeostasis: A Systematic Review and Meta-Analysis (Jamka et al. 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/31973038/" }, { "title": "Paleolithic Diet - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK482457/" } ], "protocols": [ { "population": "19 randomised trials and 12 prospective cohorts pooled in the review", "regimen": "a Paleolithic diet against control diets in the trials; high versus low adherence to a Paleolithic pattern in the cohorts", "duration": "not stated", "outcome": "Trials showed lower fasting insulin, cholesterol, LDL, triglycerides, weight, BMI and diastolic pressure; cohorts showed 10% lower all-cause and cancer mortality.", "source": { "title": "The Paleolithic diet and chronic disease risk: a GRADE-assessed systematic review and dose-response meta-analysis (Bahrami et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41129328/" }, "origins": [ "evidence.json#/catalog:food-protocol:paleo/protocols/0" ] }, { "population": "98 subjects with altered glucose metabolism across 4 randomised trials", "regimen": "a Paleolithic diet compared with a Mediterranean diet, a diabetes diet or a diet recommended by the Dutch Health Council", "duration": "not stated", "outcome": "No difference from the comparison diets on fasting glucose, fasting insulin, HbA1c, HOMA-IR, or glucose and insulin area under the curve.", "source": { "title": "The Effect of the Paleolithic Diet vs. Healthy Diets on Glucose and Insulin Homeostasis: A Systematic Review and Meta-Analysis (Jamka et al. 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/31973038/" }, "origins": [ "evidence.json#/catalog:food-protocol:paleo/protocols/1" ] } ], "community": [ { "description": "A paleo diet guide describes a modern version built around unprocessed meat, fish, eggs, vegetables, fruit, nuts and seeds, generally leaving out legumes, dairy and grains; it also notes that some followers allow modern foods.", "source": { "title": "The Paleo Diet: A Beginner's Guide Plus Recipe Ideas - Healthline", "url": "https://www.healthline.com/nutrition/paleo-diet-meal-plan-and-menu" }, "origins": [ "evidence.json#/catalog:food-protocol:paleo/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide lists the food groups in the description, identifies grains, dairy and legumes as restricted groups, and discusses flexible modern variants.", "checks": [ { "url": "https://www.healthline.com/nutrition/paleo-diet-meal-plan-and-menu", "outcome": "verified-description", "reason": "The live guide lists the food groups in the description, identifies grains, dairy and legumes as restricted groups, and discusses flexible modern variants." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:paleo/community/0", "url": "https://www.healthline.com/nutrition/paleo-diet-meal-plan-and-menu", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:41129328", "pmid:31973038", "https://www.ncbi.nlm.nih.gov/books/NBK482457/", "https://pubmed.ncbi.nlm.nih.gov/?term=paleolithic+diet", "https://www.healthline.com/nutrition/paleo-diet-meal-plan-and-menu" ] }, "library:food-protocol-vegan": { "id": "library:food-protocol-vegan", "path": "/library/food-protocol-vegan.html", "title": "Vegan", "summary": "Excludes all animal products. B12 supplementation is required; iron, zinc, omega-3 and iodine warrant attention.", "aliases": [], "kind": "food-protocol", "categories": [ "longevity" ], "research": [ { "id": "catalog:food-protocol:vegan", "title": "Vegan", "summary": "Excludes all animal products. B12 supplementation is required; iron, zinc, omega-3 and iodine warrant attention.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "reference", "evidenceSummary": "A scoping review of 70 studies found vitamin B12 deficiency is common in people eating vegan diets, because B12 comes almost entirely from animal foods. Supplements or fortified foods are the way deficiency is prevented and treated in this literature. The review notes gaps: no randomised trials comparing different B12 forms or amounts in vegetarians. A related paper sets out supplementation guidance for vegan complementary feeding. These are reviews and guidance, not trials.", "verdict": { "benefits": [ "The linked material covers vitamin B12 supply only and reports no health benefit of the diet itself." ], "risks": [ "Vitamin B12 deficiency is common on vegan diets, as B12 comes almost entirely from animal foods.", "No randomised trials compare different B12 forms or amounts in vegetarians.", "The sources are reviews and guidance, not trials." ], "bottomLine": "The evidence here is about vitamin B12 deficiency on vegan diets and how supplements address it, not the diet's benefits." }, "originalLinks": [ { "title": "NIH ODS: Vitamin B12", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" } ], "links": [ { "title": "Exploring Vitamin B12 Supplementation in the Vegan Population: A Scoping Review of the Evidence", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11124153/" }, { "title": "Toward Supplementation Guidelines for Vegan Complementary Feeding", "url": "https://onlinelibrary.wiley.com/doi/full/10.1002/fsn3.4565" }, { "title": "Knowledge, Attitudes and Application of Critical Nutrient Supplementation in Vegan Diets among Healthcare Professionals", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777782/" } ], "protocols": [ { "population": "vegetarians and vegans with mild vitamin B12 deficiency, in one trial described by the review", "regimen": "oral vitamin B12 at 50 µg daily compared with 2000 µg once a week", "duration": "not stated", "outcome": "The review reports no differences between the daily and weekly dosing groups.", "source": { "title": "Exploring Vitamin B12 Supplementation in the Vegan Population: A Scoping Review of the Evidence", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11124153/" }, "origins": [ "evidence.json#/catalog:food-protocol:vegan/protocols/0" ] } ], "community": [ { "description": "The Vegan Society describes vegan eating as excluding animal-derived foods, including meat, fish, dairy, eggs and honey.", "source": { "title": "Definition of Veganism - The Vegan Society", "url": "https://www.vegansociety.com/go-vegan/definition-veganism" }, "origins": [ "evidence.json#/catalog:food-protocol:vegan/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.vegansociety.com/go-vegan/definition-veganism", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: The Vegan Society describes vegan eating as excluding animal-derived foods, including meat, fish, dairy, eggs and honey." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:vegan/community/0", "url": "https://www.vegansociety.com/go-vegan/definition-veganism", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC11124153/", "https://onlinelibrary.wiley.com/doi/full/10.1002/fsn3.4565", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777782/", "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/", "https://www.vegansociety.com/go-vegan/definition-veganism" ] }, "library:food-protocol-vegetarian": { "id": "library:food-protocol-vegetarian", "path": "/library/food-protocol-vegetarian.html", "title": "Vegetarian", "summary": "Excludes meat and fish while retaining dairy and eggs.", "aliases": [], "kind": "food-protocol", "categories": [ "longevity" ], "research": [ { "id": "catalog:food-protocol:vegetarian", "title": "Vegetarian", "summary": "Excludes meat and fish while retaining dairy and eggs.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "food-protocol", "evidenceTier": "systematic-review", "evidenceSummary": "Vegetarian eating excludes meat and fish while allowing dairy and eggs. A systematic review and meta-analysis of randomised trials looked at vegetarian and vegan patterns in adults with type 2 diabetes. Another meta-analysis in people with or at high risk of cardiovascular disease found reductions in LDL cholesterol, HbA1c and body weight against non-vegetarian diets. A broad review covers both benefits and possible nutrient shortfalls. Effects on long-term cardiovascular events remain unclear.", "verdict": { "benefits": [ "In type 2 diabetes, pooled trials found lower HbA1c and BMI with moderate certainty", "In people with or at high risk of heart disease, LDL cholesterol, HbA1c and weight fell" ], "risks": [ "Fasting glucose, and LDL in one analysis, showed no meaningful change; blood pressure did not move", "A broad review flags possible nutrient shortfalls", "Effects on long-term cardiovascular events remain unclear" ], "bottomLine": "Trials show modest gains in blood sugar, weight and LDL, with nutrient gaps and long-term event data unresolved." }, "originalLinks": [ { "title": "PubMed: vegetarian diet", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=vegetarian+diet" } ], "links": [ { "title": "Vegetarian and Vegan Dietary Patterns to Treat Adult Type 2 Diabetes: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540868/" }, { "title": "Vegetarian Dietary Patterns and Cardiometabolic Risk in People With or at High Risk of Cardiovascular Disease", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369207/" }, { "title": "Vegetarian and vegan diets: benefits and drawbacks", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516628/" } ], "protocols": [ { "population": "770 adults with type 2 diabetes across seven randomised trials", "regimen": "Vegetarian or vegan dietary patterns, predominantly vegan, against non-vegetarian diets", "duration": "12 to 74 weeks, averaging about 26 weeks", "outcome": "HbA1c fell 0.40% and BMI 0.96 kg/m2 with moderate certainty; fasting blood glucose and LDL cholesterol showed no meaningful difference.", "source": { "title": "Vegetarian and Vegan Dietary Patterns to Treat Adult Type 2 Diabetes: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540868/" }, "origins": [ "evidence.json#/catalog:food-protocol:vegetarian/protocols/0" ] }, { "population": "1,878 people with or at high risk of cardiovascular disease across 20 randomised trials", "regimen": "Vegan, lacto-ovo-vegetarian or lacto-vegetarian diets against usual diet or active control diets", "duration": "Mean 25.4 weeks, range 2 to 24 months", "outcome": "LDL cholesterol fell 6.6 mg/dL, HbA1c 0.24% and body weight 3.4 kg; systolic blood pressure did not change significantly.", "source": { "title": "Vegetarian Dietary Patterns and Cardiometabolic Risk in People With or at High Risk of Cardiovascular Disease", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369207/" }, "origins": [ "evidence.json#/catalog:food-protocol:vegetarian/protocols/1" ] } ], "community": [ { "description": "The Academy of Nutrition and Dietetics describes lacto-ovo vegetarian eating as including dairy and eggs alongside plant foods while excluding meat, poultry and fish.", "source": { "title": "Vegetarianism: The Basic Facts - Academy of Nutrition and Dietetics (eatright.org)", "url": "https://www.eatright.org/health/wellness/vegetarian-and-plant-based/vegetarianism-the-basic-facts" }, "origins": [ "evidence.json#/catalog:food-protocol:vegetarian/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.eatright.org/health/wellness/vegetarian-and-plant-based/vegetarianism-the-basic-facts", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: The Academy of Nutrition and Dietetics describes lacto-ovo vegetarian eating as including dairy and eggs alongside plant foods while excluding meat, poultry and fish." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:food-protocol:vegetarian/community/0", "url": "https://www.eatright.org/health/wellness/vegetarian-and-plant-based/vegetarianism-the-basic-facts", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540868/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369207/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516628/", "https://pubmed.ncbi.nlm.nih.gov/?term=vegetarian+diet", "https://www.eatright.org/health/wellness/vegetarian-and-plant-based/vegetarianism-the-basic-facts" ] }, "library:hormone-anastrozole": { "id": "library:hormone-anastrozole", "path": "/library/hormone-anastrozole.html", "title": "Anastrozole", "summary": "Aromatase inhibitor, recorded alongside testosterone protocols where oestradiol management is part of the plan.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:anastrozole", "title": "Anastrozole", "summary": "Aromatase inhibitor, recorded alongside testosterone protocols where oestradiol management is part of the plan.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Anastrozole is an FDA-approved aromatase inhibitor for hormone receptor-positive breast cancer in postmenopausal women, used as adjuvant treatment, first-line treatment of advanced disease, and after tamoxifen. It blocks aromatase, the enzyme that makes oestrogen from androgens. The label warns about more ischaemic cardiac events in women with existing heart disease, falls in bone mineral density and rises in total cholesterol. It is contraindicated before menopause and in pregnancy. This is regulator-approved labelling.", "verdict": { "benefits": [ "Hormone receptor-positive breast cancer in postmenopausal women.", "Adjuvant treatment, as first-line treatment of advanced disease, and after tamoxifen.", "Blocks the enzyme that makes oestrogen from androgens" ], "risks": [ "The label warns of more ischaemic cardiac events in women with existing heart disease", "Bone mineral density falls and total cholesterol rises", "Contraindicated before menopause and in pregnancy; the best adjuvant duration is unknown" ], "bottomLine": "An approved breast cancer medicine whose label flags cardiac events, bone loss and higher cholesterol.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: anastrozole", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=anastrozole" } ], "links": [ { "title": "Arimidex (anastrozole) tablet FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020541s026lbl.pdf" }, { "title": "Treatment of ER-positive breast cancer with FDA-approved aromatase inhibitors (Kim 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41678931/" }, { "title": "Anastrozole tablets prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca9d4aff-ffdf-4a46-ad20-e47e5886a19e" } ], "protocols": [ { "population": "postmenopausal women with advanced breast cancer, per the US label", "regimen": "one 1 mg tablet by mouth once a day, with or without food", "duration": "continued until tumour progression, per the label", "outcome": "The label carries this as the approved regimen for advanced breast cancer.", "source": { "title": "Anastrozole tablets prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca9d4aff-ffdf-4a46-ad20-e47e5886a19e" }, "origins": [ "evidence.json#/catalog:hormone:anastrozole/protocols/0" ] }, { "population": "postmenopausal women with hormone-receptor-positive early breast cancer, per the US label", "regimen": "one 1 mg tablet by mouth once a day", "duration": "the label says the optimal duration is unknown; the ATAC trial ran five years", "outcome": "The label states the optimal duration of adjuvant therapy is not known.", "source": { "title": "Anastrozole tablets prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca9d4aff-ffdf-4a46-ad20-e47e5886a19e" }, "origins": [ "evidence.json#/catalog:hormone:anastrozole/protocols/1" ] } ], "community": [ { "description": "Community members on a bodybuilding forum report using 0.5 mg of anastrozole twice weekly when managing estradiol during TRT with 200 mg testosterone weekly.", "source": { "title": "Anastrozole Dosage 200Mg TRT | EliteFitness.com Bodybuilding Forums", "url": "https://www.elitefitness.com/forum/threads/anastrozole-dosage-200mg-trt.1333113/" }, "origins": [ "evidence.json#/catalog:hormone:anastrozole/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:anastrozole/community/0", "url": "https://www.elitefitness.com/forum/threads/anastrozole-dosage-200mg-trt.1333113/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 50, "source": "FDA label, Arimidex" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020541s026lbl.pdf", "pmid:41678931", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca9d4aff-ffdf-4a46-ad20-e47e5886a19e", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=anastrozole", "https://www.elitefitness.com/forum/threads/anastrozole-dosage-200mg-trt.1333113/" ] }, "library:hormone-andarine": { "id": "library:hormone-andarine", "path": "/library/hormone-andarine.html", "title": "Andarine (S4)", "summary": "A selective androgen receptor modulator whose development was abandoned due to vision side effects.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:andarine", "title": "Andarine (S4)", "summary": "A selective androgen receptor modulator whose development was abandoned due to vision side effects.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "Andarine (S4, GTX-007) is a selective androgen receptor modulator originally developed by GTx, Inc. for musculoskeletal diseases and benign prostatic hyperplasia. Clinical development was abandoned after preclinical identification of visual side effects (night blindness, yellow tint to vision) linked to ocular androgen receptor binding. No Phase I human trials published.", "verdict": { "benefits": [ "Preclinical anabolic effects in muscle and bone", "Potent lean mass and fat loss in animal models" ], "risks": [ "Development abandoned due to vision side effects (night blindness, yellow tinting)", "No published Phase I human trials", "Binding to ocular androgen receptors causes visual disturbances" ], "bottomLine": "Preclinical only; clinical development halted due to reversible but significant vision effects." }, "originalLinks": [ { "title": "S4 (Andarine) SARM - MorePlatesMoreDates", "url": "https://moreplatesmoredates.com/andarine-s4/" }, { "title": "Selective Androgen Receptor Modulator for Prostate - ClinicalTrials.gov", "url": "https://cdn.clinicaltrials.gov/large-docs/97/NCT02499497/Prot_SAP_000.pdf" } ], "links": [ { "title": "S4 (Andarine) SARM - MorePlatesMoreDates", "url": "https://moreplatesmoredates.com/andarine-s4/" }, { "title": "Selective Androgen Receptor Modulator for Prostate - ClinicalTrials.gov", "url": "https://cdn.clinicaltrials.gov/large-docs/97/NCT02499497/Prot_SAP_000.pdf" } ], "protocols": [], "community": [ { "description": "A fitness guide describes andarine protocols ranging from 25 to 75 mg per day, with 50 mg daily or less noted as ideal for most users, divided into two equal doses due to the compound's 3-6 hour half-life.", "source": { "title": "S4 (Andarine) Guide for Beginners: Benefits, Risks, Dosage and Stacks", "url": "https://swolverine.com/blogs/blog/s4-andarine-guide-for-beginners-benefits-risks-dosage-amp-stacks" }, "origins": [ "evidence.json#/catalog:hormone:andarine/community/0" ] }, { "description": "A supplement resource documents andarine cutting protocol of 25 mg daily for 6-8 weeks, and bulking protocols using 50 mg of andarine for 8 weeks, with advanced users potentially extending cycles to 10 weeks if post-cycle therapy is planned.", "source": { "title": "Andarine S4 - Guide to Effects, Dosing, Cycles and Side Effects", "url": "https://enhancedpeptides.com/andarine-s4-the-complete-guide/" }, "origins": [ "evidence.json#/catalog:hormone:andarine/community/1" ] }, { "description": "A fitness reference documents andarine dosing of 30 mg daily divided into three 10 mg portions, or 50 mg daily for advanced users, cycled for 8 to 12 weeks, with a note that post-cycle therapy is recommended after use.", "source": { "title": "Andarine S4 Complete Guide: Benefits, Uses, Dosage (2026)", "url": "https://muscleandbrawn.com/sarms/andarine-s4/" }, "origins": [ "evidence.json#/catalog:hormone:andarine/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:andarine/community/0", "url": "https://swolverine.com/blogs/blog/s4-andarine-guide-for-beginners-benefits-risks-dosage-amp-stacks", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:andarine/community/1", "url": "https://enhancedpeptides.com/andarine-s4-the-complete-guide/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:andarine/community/2", "url": "https://muscleandbrawn.com/sarms/andarine-s4/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 4.5, "lowerHours": 3, "source": "Gao, Kim & Dalton 2006, Pharm Res 23(8):1641-1658, PMID 16841196 — rats and dogs only, no human PK trial exists", "upperHours": 6 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://moreplatesmoredates.com/andarine-s4/", "https://cdn.clinicaltrials.gov/large-docs/97/NCT02499497/Prot_SAP_000.pdf", "https://swolverine.com/blogs/blog/s4-andarine-guide-for-beginners-benefits-risks-dosage-amp-stacks", "https://enhancedpeptides.com/andarine-s4-the-complete-guide/", "https://muscleandbrawn.com/sarms/andarine-s4/" ] }, "library:hormone-boldenone-undecylenate": { "id": "library:hormone-boldenone-undecylenate", "path": "/library/hormone-boldenone-undecylenate.html", "title": "Boldenone Undecylenate (Equipoise)", "summary": "An anabolic steroid developed for veterinary use that was never FDA-approved for human medicine.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:boldenone-undecylenate", "title": "Boldenone Undecylenate (Equipoise)", "summary": "An anabolic steroid developed for veterinary use that was never FDA-approved for human medicine.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "Boldenone undecylenate (Equipoise) is a synthetic anabolic steroid originally developed for veterinary use, primarily in horses. It was marketed as Parenabol for human use in the 1950s-1970s but was discontinued and never received modern FDA approval. It is not approved for any human medical condition.", "verdict": { "benefits": [], "risks": [ "Not approved for human use; safety and efficacy in humans not established under modern standards", "Schedule III controlled substance in the United States", "No current medical indication" ], "bottomLine": "Never approved for human medical use despite historical veterinary application; classified as a controlled substance.", "approvalStatus": "Never approved for human use (veterinary only)." }, "originalLinks": [ { "title": "Boldenone Undecylenate - Wikipedia", "url": "https://en.wikipedia.org/wiki/Boldenone_undecylenate" }, { "title": "Boldenone - ScienceDirect Overview", "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/boldenone" } ], "links": [ { "title": "Boldenone Undecylenate - Wikipedia", "url": "https://en.wikipedia.org/wiki/Boldenone_undecylenate" }, { "title": "Boldenone - ScienceDirect Overview", "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/boldenone" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 336, "source": "Westreich, in Ruiz & Strain, Lowinson and Ruiz's Substance Abuse (2011), p.358 — compiled reference, no controlled human PK trial; boldenone is primarily a veterinary compound" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://en.wikipedia.org/wiki/Boldenone_undecylenate", "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/boldenone" ] }, "library:hormone-cabergoline": { "id": "library:hormone-cabergoline", "path": "/library/hormone-cabergoline.html", "title": "Cabergoline", "summary": "An FDA-approved dopamine agonist used to treat hyperprolactinemic disorders.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:cabergoline", "title": "Cabergoline", "summary": "An FDA-approved dopamine agonist used to treat hyperprolactinemic disorders.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Cabergoline is a long-acting dopamine agonist approved by the FDA under the brand name Dostinex for treatment of hyperprolactinemic disorders, whether idiopathic or due to pituitary adenomas. It exerts direct inhibitory effects on prolactin secretion through D2 receptor agonism. FDA labeling warns against postpartum lactation suppression due to serious adverse reaction risks.", "verdict": { "benefits": [ "Treatment of hyperprolactinemic disorders, idiopathic or pituitary adenoma-related." ], "risks": [ "Black box warning against use for postpartum lactation suppression", "Contraindicated with D-antagonists (phenothiazines, butyrophenones, metoclopramide)", "Cardiac valvulopathy risk with long-term use" ], "bottomLine": "FDA-approved dopamine agonist for hyperprolactinemia with black box warning limiting certain uses.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DOSTINEX (cabergoline) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/020664s016lbl.pdf" }, { "title": "Cabergoline - Drugs.com Monograph", "url": "https://www.drugs.com/monograph/cabergoline.html" } ], "links": [ { "title": "DOSTINEX (cabergoline) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/020664s016lbl.pdf" }, { "title": "Cabergoline - Drugs.com Monograph", "url": "https://www.drugs.com/monograph/cabergoline.html" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 66, "source": "FDA label, Dostinex: elimination half-life estimated from urinary data, 63 to 69 hours (midpoint shown — the range rounds to the same day count)" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/020664s016lbl.pdf", "https://www.drugs.com/monograph/cabergoline.html" ] }, "library:hormone-clomiphene-citrate": { "id": "library:hormone-clomiphene-citrate", "path": "/library/hormone-clomiphene-citrate.html", "title": "Clomiphene Citrate", "summary": "An FDA-approved selective estrogen receptor modulator used to induce ovulation in women with infertility.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:clomiphene-citrate", "title": "Clomiphene Citrate", "summary": "An FDA-approved selective estrogen receptor modulator used to induce ovulation in women with infertility.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Clomiphene citrate is an FDA-approved selective estrogen receptor modulator (SERM) approved on February 1, 1967, for treatment of ovulatory dysfunction in women desiring pregnancy. It induces ovulation in patients with anovulatory or oligo-ovulatory infertility and is commonly used in polycystic ovarian syndrome and other causes of infertility. Six-month live birth rate ranges from 20-40%.", "verdict": { "benefits": [ "Ovulation induction in women with anovulatory or oligo-ovulatory infertility.", "Widely used for PCOS-related infertility" ], "risks": [ "Ovarian hyperstimulation syndrome", "Multiple pregnancy risk", "Visual disturbances", "Mood changes" ], "bottomLine": "FDA-approved SERM for fertility with documented efficacy and established safety profile when used under medical supervision.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "Clomid (clomiphene citrate) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016131s026lbl.pdf" }, { "title": "Clomiphene - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK559292/" }, { "title": "Clomiphene citrate at 50: the dawning of assisted reproduction", "url": "https://www.fertstert.org/article/S0015-0282(17)31697-7/fulltext" } ], "links": [ { "title": "Clomid (clomiphene citrate) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016131s026lbl.pdf" }, { "title": "Clomiphene - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK559292/" }, { "title": "Clomiphene citrate at 50: the dawning of assisted reproduction", "url": "https://www.fertstert.org/article/S0015-0282(17)31697-7/fulltext" } ], "protocols": [ { "population": "Women with anovulatory or oligo-ovulatory infertility", "regimen": "Oral administration for ovulation induction", "duration": "Typical course spans multiple cycles", "outcome": "Induces ovulation; six-month live birth rates of 20-40% reported", "source": { "title": "Clomiphene citrate at 50: the dawning of assisted reproduction", "url": "https://www.fertstert.org/article/S0015-0282(17)31697-7/fulltext" }, "origins": [ "evidence.json#/catalog:hormone:clomiphene-citrate/protocols/0" ] } ], "community": [ { "description": "A steroid community profile documents athletic use protocols ranging from 50-100 mg daily for 4-6 weeks, while medical protocols vary from 300 mg on day 1 followed by 100 mg daily for 10 days, then 50 mg daily.", "source": { "title": "Clomid (Clomiphene Citrate) - EliteFitness Steroid Profiles", "url": "https://www.elitefitness.com/steroid_profiles/Clomid-Clomiphene-Citrate.html" }, "origins": [ "evidence.json#/catalog:hormone:clomiphene-citrate/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:clomiphene-citrate/community/0", "url": "https://www.elitefitness.com/steroid_profiles/Clomid-Clomiphene-Citrate.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016131s026lbl.pdf", "https://www.ncbi.nlm.nih.gov/books/NBK559292/", "https://www.fertstert.org/article/S0015-0282(17)31697-7/fulltext", "https://www.elitefitness.com/steroid_profiles/Clomid-Clomiphene-Citrate.html" ] }, "library:hormone-dhea": { "id": "library:hormone-dhea", "path": "/library/hormone-dhea.html", "title": "DHEA", "summary": "An adrenal steroid precursor to estrogens and androgens, sold over the counter and studied separately in a prescription vaginal form.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:dhea", "title": "DHEA", "summary": "An adrenal steroid precursor to estrogens and androgens, sold over the counter and studied separately in a prescription vaginal form.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Dehydroepiandrosterone (DHEA) is a steroid hormone produced mainly by the adrenal glands that serves as a precursor for estrogens and androgens. It is sold as an unregulated dietary supplement in the United States, while a synthetic form named prasterone has been evaluated in randomized trials for adrenal insufficiency and received FDA approval as a vaginal insert for menopause-related vulvovaginal atrophy. Regulatory status therefore differs sharply by formulation, indication, and country.", "verdict": { "benefits": [ "FDA-approved prescription form (prasterone) demonstrated reduced dyspareunia and improved vaginal tissue markers compared with placebo in postmenopausal women.", "Widely available over the counter in the United States as a dietary supplement, unlike most steroid hormone precursors.", "Long track record of study as a substrate for downstream androgen and estrogen synthesis in adrenal insufficiency research." ], "risks": [ "Oral supplement forms sold in the United States are not FDA-reviewed for safety, purity, or the claims made on their labels.", "Randomized trials in adrenal insufficiency have found little to no benefit on fatigue, cognitive function, or sexual function despite raising hormone levels.", "Long-term safety data outside the vaginal-insert indication and outside adrenal insufficiency populations remains limited." ], "bottomLine": "DHEA's regulatory status is indication- and formulation-specific: an FDA-approved vaginal insert exists for menopausal dyspareunia, while oral DHEA sold as a dietary supplement carries no such review.", "approvalStatus": "FDA-approved only as a vaginal insert (prasterone); the oral supplement is not FDA-reviewed." }, "originalLinks": [ { "title": "INTRAROSA (prasterone) vaginal insert label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=df731acd-7276-4fef-b037-bc7f30c112cb" }, { "title": "Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/18000094/" } ], "links": [ { "title": "INTRAROSA (prasterone) vaginal insert label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=df731acd-7276-4fef-b037-bc7f30c112cb" }, { "title": "Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/18000094/" } ], "protocols": [ { "population": "postmenopausal women aged 40 to 80 with moderate to severe dyspareunia due to vulvar and vaginal atrophy", "regimen": "one 6.5 mg prasterone vaginal insert placed once daily at bedtime", "duration": "two twelve-week randomized, double-blind, placebo-controlled efficacy trials, plus a fifty-two-week open-label safety extension", "outcome": "FDA approval based on co-primary endpoints of reduced dyspareunia severity and improved vaginal cytology and pH compared with placebo", "source": { "title": "INTRAROSA (prasterone) vaginal insert label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=df731acd-7276-4fef-b037-bc7f30c112cb" }, "origins": [ "evidence.json#/catalog:hormone:dhea/protocols/0" ] }, { "population": "106 adults (44 men, 62 women) with primary adrenal insufficiency (Addison's disease)", "regimen": "oral micronized DHEA at 50 mg once daily versus placebo", "duration": "twelve months, randomized double-blind design", "outcome": "modest improvement on one SF-36 subscale, with circulating DHEA-S and androstenedione rising in both sexes; no significant benefit on fatigue, cognition, or sexual function was found", "source": { "title": "Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/18000094/" }, "origins": [ "evidence.json#/catalog:hormone:dhea/protocols/1" ] } ], "community": [ { "description": "Supplement product vendors recommend DHEA at 50 mg administered daily as a single capsule, with indication that doses may be adjusted to 100 mg daily if directed by a healthcare provider.", "source": { "title": "Swanson Ultra DHEA 50 mg - Swanson Vitamins", "url": "https://www.swansonvitamins.com/p/swanson-ultra-dhea-50-mg-120-caps" }, "origins": [ "evidence.json#/catalog:hormone:dhea/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The vendor label retrieved on 2026-10-15 supports a daily 50 mg capsule statement, but the imported adjustment to 100 mg was not verified. Retained as a disputed historical account, not a dose recommendation.", "This is a commercial product label, not independent clinical evidence or a representative community cohort. The separately cited vaginal prasterone label must not be read as approval of oral DHEA supplementation." ], "community": [ { "origin": "evidence.json#/catalog:hormone:dhea/community/0", "url": "https://www.swansonvitamins.com/p/swanson-ultra-dhea-50-mg-120-caps", "claimMatch": "The vendor label retrieved on 2026-10-15 supports a daily 50 mg capsule statement, but the imported adjustment to 100 mg was not verified. Retained as a disputed historical account, not a dose recommendation. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "disputed-support" } ] }, "pk": { "hours": 20, "source": "Legrain et al. 2000, J Clin Endocrinol Metab, PMID 10999810: apparent terminal half-life of blood DHEA is more than 20 hours after oral dosing" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=df731acd-7276-4fef-b037-bc7f30c112cb", "pmid:18000094", "https://www.swansonvitamins.com/p/swanson-ultra-dhea-50-mg-120-caps" ] }, "library:hormone-drostanolone": { "id": "library:hormone-drostanolone", "path": "/library/hormone-drostanolone.html", "title": "Drostanolone (Masteron)", "summary": "An anabolic steroid approved for palliative treatment of advanced breast cancer in postmenopausal women.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:drostanolone", "title": "Drostanolone (Masteron)", "summary": "An anabolic steroid approved for palliative treatment of advanced breast cancer in postmenopausal women.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Drostanolone (Masteron) is an anabolic steroid derived from dihydrotestosterone. It was approved by the FDA for palliative treatment of advanced metastatic breast cancer in postmenopausal women, where it inhibited cancer growth. However, it is rarely used today due to other available options.", "verdict": { "benefits": [ "Palliative treatment of advanced metastatic breast cancer in postmenopausal women." ], "risks": [ "Androgenic side effects", "Virilization in women", "Liver toxicity", "Lipid abnormalities" ], "bottomLine": "Regulatory approval for advanced breast cancer, but now rarely used due to superior alternative treatments.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "Drugs@FDA: Drolban (drostanolone) NDA 012936", "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=012936" }, { "title": "Drostanolone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Drostanolone" }, { "title": "Drostanolone Propionate - DrugBank", "url": "https://go.drugbank.com/drugs/DB14655" } ], "links": [ { "title": "Drugs@FDA: Drolban (drostanolone) NDA 012936", "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=012936" }, { "title": "Drostanolone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Drostanolone" }, { "title": "Drostanolone Propionate - DrugBank", "url": "https://go.drugbank.com/drugs/DB14655" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 48, "source": "Llewellyn, Anabolics (Molecular Nutrition LLC, 2011), p.517 — compiled pharmacology reference; historically used clinically as Drolban/Masteril, no modern dedicated PK trial" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=012936", "https://en.wikipedia.org/wiki/Drostanolone", "https://go.drugbank.com/drugs/DB14655" ] }, "library:hormone-enclomiphene": { "id": "library:hormone-enclomiphene", "path": "/library/hormone-enclomiphene.html", "title": "Enclomiphene", "summary": "The active isomer of clomiphene with potential for raising testosterone while preserving fertility, but not FDA-approved.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:enclomiphene", "title": "Enclomiphene", "summary": "The active isomer of clomiphene with potential for raising testosterone while preserving fertility, but not FDA-approved.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "Enclomiphene is the active isomer of clomiphene citrate (the other isomer, zuclomiphene, may antagonize desired effects). It functions as a non-steroidal SERM, antagonizing estrogen receptors in the hypothalamus to increase gonadotropin-releasing hormone and stimulate endogenous testosterone production. Unlike testosterone replacement therapy, it preserves spermatogenesis. Not FDA-approved; used through compounding under specialist supervision.", "verdict": { "benefits": [ "May raise testosterone in hypogonadal men while preserving fertility (unlike TRT)", "Maintains FSH/LH levels and intratesticular testosterone" ], "risks": [ "Available only through compounding under specialist judgment", "Limited long-term human data" ], "bottomLine": "Preclinical evidence and specialized use only; not FDA-approved despite in vitro efficacy and small clinical studies.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "Clomiphene or Enclomiphene for Male Hypogonadism - PubMed Central", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12510335/" }, { "title": "Enclomiphene and Fertility - Good Health by Hims", "url": "https://www.hims.com/blog/enclomiphene-and-fertility" }, { "title": "Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404117/" } ], "links": [ { "title": "Clomiphene or Enclomiphene for Male Hypogonadism - PubMed Central", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12510335/" }, { "title": "Enclomiphene and Fertility - Good Health by Hims", "url": "https://www.hims.com/blog/enclomiphene-and-fertility" }, { "title": "Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404117/" } ], "protocols": [ { "population": "Men with secondary hypogonadism", "regimen": "Oral SERM; increase in total testosterone compared to placebo", "duration": "Studies varied in duration", "outcome": "Significant increase in total testosterone (273.76 ng/dL above placebo); non-significant difference vs. topical testosterone gel; preserved sperm concentration", "source": { "title": "Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404117/" }, "origins": [ "evidence.json#/catalog:hormone:enclomiphene/protocols/0" ] } ], "community": [ { "description": "A community protocol guide identifies 12.5 mg daily as the standard 'community sweet spot', with post-cycle therapy at 12.5 mg for 4 weeks and moderate-to-heavy cycle recovery extending to 12.5-25 mg daily for 6-8 weeks.", "source": { "title": "Enclomiphene Dosage & Protocol - Biomogging", "url": "https://www.biomogging.com/compounds/enclomiphene" }, "origins": [ "evidence.json#/catalog:hormone:enclomiphene/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:enclomiphene/community/0", "url": "https://www.biomogging.com/compounds/enclomiphene", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC12510335/", "https://www.hims.com/blog/enclomiphene-and-fertility", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404117/", "https://www.biomogging.com/compounds/enclomiphene" ] }, "library:hormone-estradiol": { "id": "library:hormone-estradiol", "path": "/library/hormone-estradiol.html", "title": "Oestradiol", "summary": "Oestrogen used in feminising HRT and menopausal HRT. Available as tablets, patches, gel and injectable esters.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:estradiol", "title": "Oestradiol", "summary": "Oestrogen used in feminising HRT and menopausal HRT. Available as tablets, patches, gel and injectable esters.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Oestradiol is an approved oestrogen medicine with an FDA prescribing label. The label covers menopausal symptoms and other conditions linked to low oestrogen. In February 2026 the FDA approved labelling changes for six menopausal hormone therapy products, removing boxed-warning statements about cardiovascular disease, breast cancer and probable dementia. This is regulator-level information rather than new trial evidence.", "verdict": { "benefits": [ "Treats menopausal symptoms.", "Labelled as replacement in female hypoestrogenism due to hypogonadism.", "In February 2026 the FDA removed boxed warnings on heart disease, cancer and dementia from six products." ], "risks": [ "The label still carries boxed warnings on endometrial cancer and cardiovascular risk.", "The 2026 change is a regulatory labelling decision, not new trial evidence." ], "bottomLine": "Oestradiol is an FDA-approved oestrogen for menopausal and low-oestrogen conditions, with boxed warnings.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "EMA: product information", "url": "https://www.ema.europa.eu/en/glossary-terms/product-information" } ], "links": [ { "title": "Depo-Estradiol (estradiol cypionate injection) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/085470s015lbl.pdf" }, { "title": "FDA approves labelling changes to menopausal hormone therapy products (2025)", "url": "https://www.fda.gov/news-events/press-announcements/fda-approves-labeling-changes-menopausal-hormone-therapy-products" } ], "protocols": [ { "population": "women with moderate to severe vasomotor symptoms of the menopause, per the US Depo-Estradiol label", "regimen": "1 to 5 mg estradiol cypionate injected intramuscularly every 3 to 4 weeks", "duration": "short-term cyclic use, with attempts to stop or taper at 3- to 6-month intervals", "outcome": "The label lists this as the approved regimen for menopausal vasomotor symptoms and carries boxed warnings on endometrial cancer and cardiovascular risk.", "source": { "title": "Depo-Estradiol (estradiol cypionate injection) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/085470s015lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:estradiol/protocols/0" ] }, { "population": "women with hypoestrogenism due to hypogonadism, per the US Depo-Estradiol label", "regimen": "1.5 to 2 mg estradiol cypionate injected intramuscularly at monthly intervals", "duration": "ongoing, per the label, with reassessment at 3- to 6-month intervals", "outcome": "The label lists this as the approved regimen for female hypoestrogenism due to hypogonadism.", "source": { "title": "Depo-Estradiol (estradiol cypionate injection) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/085470s015lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:estradiol/protocols/1" ] } ], "community": [ { "description": "A community-focused HRT platform documents that most estradiol patch users receive 100 mcg patches applied two at a time, lasting 3-4 days, which totals approximately 400 mcg per week as an average weekly dosage.", "source": { "title": "Estrogen Patches for hormone replacement therapy", "url": "https://www.folxhealth.com/library/estrogen-patches-for-hormone-replacement-therapy-what-where-and-how" }, "origins": [ "evidence.json#/catalog:hormone:estradiol/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The imported patch account mixes labelled delivery-rate units, patch counts and a weekly total. The stated weekly arithmetic is not verified and must not be used to calculate an administered dose." ], "community": [ { "origin": "evidence.json#/catalog:hormone:estradiol/community/0", "url": "https://www.folxhealth.com/library/estrogen-patches-for-hormone-replacement-therapy-what-where-and-how", "claimMatch": "The imported patch account mixes labelled delivery-rate units, patch counts and a weekly total. The stated weekly arithmetic is not verified and must not be used to calculate an administered dose. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unit-interpretation-unverified" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/085470s015lbl.pdf", "https://www.fda.gov/news-events/press-announcements/fda-approves-labeling-changes-menopausal-hormone-therapy-products", "https://www.ema.europa.eu/en/glossary-terms/product-information", "https://www.folxhealth.com/library/estrogen-patches-for-hormone-replacement-therapy-what-where-and-how" ] }, "library:hormone-exemestane": { "id": "library:hormone-exemestane", "path": "/library/hormone-exemestane.html", "title": "Exemestane", "summary": "An FDA-approved steroidal aromatase inhibitor used to treat hormone receptor-positive breast cancer.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:exemestane", "title": "Exemestane", "summary": "An FDA-approved steroidal aromatase inhibitor used to treat hormone receptor-positive breast cancer.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Exemestane (Aromasin) is a steroidal aromatase inhibitor that covalently and irreversibly binds aromatase, inactivating it. FDA approved on October 21, 1999, for advanced breast cancer in postmenopausal women after tamoxifen failure. Approved October 5, 2005, for adjuvant treatment of early breast cancer after 2-3 years of tamoxifen.", "verdict": { "benefits": [ "Advanced breast cancer in postmenopausal women who have stopped responding to tamoxifen.", "Adjuvant treatment of early breast cancer." ], "risks": [ "Lipid abnormalities", "Bone loss and increased fracture risk", "Arthralgia", "Hot flashes" ], "bottomLine": "FDA-approved steroidal aromatase inhibitor with irreversible mechanism for hormone receptor-positive breast cancer.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: exemestane", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=exemestane" }, { "title": "Exemestane Hormonal Therapy - LBBC", "url": "https://www.lbbc.org/about-breast-cancer/treatments/hormonal-therapy/aromatase-inhibitors/exemestane" }, { "title": "Endocrinological Evaluation of Exemestane - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2034036/" } ], "links": [ { "title": "DailyMed: exemestane", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=exemestane" }, { "title": "Exemestane Hormonal Therapy - LBBC", "url": "https://www.lbbc.org/about-breast-cancer/treatments/hormonal-therapy/aromatase-inhibitors/exemestane" }, { "title": "Endocrinological Evaluation of Exemestane - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2034036/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 24, "source": "FDA label, Aromasin: mean terminal half-life about 24 hours" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=exemestane", "https://www.lbbc.org/about-breast-cancer/treatments/hormonal-therapy/aromatase-inhibitors/exemestane", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2034036/" ] }, "library:hormone-gw-501516": { "id": "library:hormone-gw-501516", "path": "/library/hormone-gw-501516.html", "title": "GW-501516 (Cardarine)", "summary": "A peroxisome proliferator-activated receptor agonist that was never approved for human use.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:gw-501516", "title": "GW-501516 (Cardarine)", "summary": "A peroxisome proliferator-activated receptor agonist that was never approved for human use.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "GW-501516 (Cardarine) is a peroxisome proliferator-activated receptor delta (PPARδ) agonist investigated for dyslipidemia and metabolic disorders. It activates PPARδ with 1000-fold selectivity over PPARα. Research indicates effects on lipid metabolism, mitochondrial respiration, and metabolic disorders. However, it was never approved for human use and is not FDA-approved.", "verdict": { "benefits": [ "Selective PPARδ agonist; effects on lipid and glucose metabolism in preclinical models" ], "risks": [ "Concerns about cancer risk from animal studies" ], "bottomLine": "Preclinical research only; development abandoned before approval; not approved for human use.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "GW501516 - DrugBank", "url": "https://go.drugbank.com/drugs/DB05416" }, { "title": "Metabolomic Study of GW501516 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421799/" } ], "links": [ { "title": "GW501516 - DrugBank", "url": "https://go.drugbank.com/drugs/DB05416" }, { "title": "Metabolomic Study of GW501516 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421799/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://go.drugbank.com/drugs/DB05416", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421799/" ] }, "library:hormone-letrozole": { "id": "library:hormone-letrozole", "path": "/library/hormone-letrozole.html", "title": "Letrozole", "summary": "An FDA-approved aromatase inhibitor used to treat hormone receptor-positive breast cancer.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:letrozole", "title": "Letrozole", "summary": "An FDA-approved aromatase inhibitor used to treat hormone receptor-positive breast cancer.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Letrozole is an aromatase inhibitor approved by the FDA in 1997 for treatment of advanced breast cancer in postmenopausal women and approved in 1998 following prior antiestrogen failure. It blocks aromatase enzyme activity, lowering estrogen levels. FDA approvals include adjuvant and extended adjuvant treatment of early breast cancer and first/second-line treatment of advanced disease.", "verdict": { "benefits": [ "Adjuvant treatment of early breast cancer in postmenopausal women.", "Extended adjuvant treatment after 5 years of tamoxifen.", "First/second-line treatment of advanced breast cancer" ], "risks": [ "Lipid changes", "Bone loss and increased fracture risk", "Arthralgia", "Hypercholesterolemia" ], "bottomLine": "FDA-approved aromatase inhibitor for hormone receptor-positive breast cancer with established efficacy.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: letrozole", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=letrozole" }, { "title": "FDA Approves Femara as First-Line Therapy", "url": "https://www.cancernetwork.com/view/fda-approves-femara-first-line-therapy" }, { "title": "Letrozole in Breast Cancer Treatment - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/11895893/" } ], "links": [ { "title": "DailyMed: letrozole", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=letrozole" }, { "title": "FDA Approves Femara as First-Line Therapy", "url": "https://www.cancernetwork.com/view/fda-approves-femara-first-line-therapy" }, { "title": "Letrozole in Breast Cancer Treatment - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/11895893/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 48, "source": "FDA label, Femara: terminal elimination half-life about 2 days" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=letrozole", "https://www.cancernetwork.com/view/fda-approves-femara-first-line-therapy", "pmid:11895893" ] }, "library:hormone-levothyroxine": { "id": "library:hormone-levothyroxine", "path": "/library/hormone-levothyroxine.html", "title": "Levothyroxine (T4)", "summary": "Synthetic T4. Absorption is materially reduced by calcium, iron and magnesium, so timing separation is part of the protocol.", "aliases": [], "kind": "medication-hormone", "categories": [ "longevity" ], "research": [ { "id": "catalog:hormone:levothyroxine", "title": "Levothyroxine (T4)", "summary": "Synthetic T4. Absorption is materially reduced by calcium, iron and magnesium, so timing separation is part of the protocol.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Levothyroxine is synthetic thyroxine (T4). A clinical reference states it is FDA-approved for primary, secondary and tertiary hypothyroidism, and for thyrotropin suppression in well-differentiated thyroid cancer. A systematic review of 63 studies found that food, coffee, soy, fibre and calcium or iron supplements all reduced how much of the drug was absorbed. The same review found morning and bedtime intake equally effective. The interaction evidence is review-level and the authors call parts of it limited.", "verdict": { "benefits": [ "Hypothyroidism and for thyrotropin suppression in well-differentiated thyroid cancer.", "It is synthetic thyroxine, replacing the hormone the thyroid would make" ], "risks": [ "Food, coffee, soy, fibre and calcium or iron supplements all cut how much is absorbed", "A lower start is advised where cardiac disease is present", "The interaction evidence is review-level, and the authors call parts of it limited" ], "bottomLine": "An approved thyroid hormone replacement whose absorption is reduced by coffee, food and several supplements.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "EMA: levothyroxine", "url": "https://www.ema.europa.eu/en/medicines/human/referrals/levothyroxine-containing-medicinal-products" } ], "links": [ { "title": "Synthroid (levothyroxine sodium) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e11ad30-1041-4520-10b0-8f9d30d30fcc" }, { "title": "Levothyroxine - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK539808/" }, { "title": "Levothyroxine Interactions with Food and Dietary Supplements–A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002057/" } ], "protocols": [ { "population": "people with primary, secondary or tertiary hypothyroidism, and thyrotropin-dependent well-differentiated thyroid cancer, per the US label", "regimen": "a single daily dose, about 1.6 mcg/kg/day for full replacement in adults, on an empty stomach half an hour to an hour before breakfast", "duration": "ongoing, per the label", "outcome": "The label lists it as replacement therapy in hypothyroidism and as an adjunct to surgery and radioiodine in thyroid cancer, with lower starting doses where cardiac disease is present.", "source": { "title": "Synthroid (levothyroxine sodium) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e11ad30-1041-4520-10b0-8f9d30d30fcc" }, "origins": [ "evidence.json#/catalog:hormone:levothyroxine/protocols/0" ] }, { "population": "people taking levothyroxine across 63 studies of food and supplement interactions", "regimen": "review of intake timing and co-ingestion: tablets taken 30-60 minutes before breakfast, morning versus bedtime, with coffee, soy, fibre, calcium or iron", "duration": "not stated", "outcome": "Coffee lowered serum T4 by 29-36% and a one-hour gap prevented it; calcium and iron reduced absorption; morning and bedtime intake were comparable.", "source": { "title": "Levothyroxine Interactions with Food and Dietary Supplements–A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002057/" }, "origins": [ "evidence.json#/catalog:hormone:levothyroxine/protocols/1" ] } ], "community": [ { "description": "A health optimization blog describes the reported protocol where levothyroxine is taken in the morning on an empty stomach, with a minimum 4-hour separation before consuming calcium supplements.", "source": { "title": "Levothyroxine and Calcium: Timing Guide for Safe Use", "url": "https://www.doctronic.ai/blog/calcium-and-levothyroxine/" }, "origins": [ "evidence.json#/catalog:hormone:levothyroxine/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:levothyroxine/community/0", "url": "https://www.doctronic.ai/blog/calcium-and-levothyroxine/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 168, "source": "FDA label, Synthroid" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e11ad30-1041-4520-10b0-8f9d30d30fcc", "https://www.ncbi.nlm.nih.gov/books/NBK539808/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002057/", "https://www.ema.europa.eu/en/medicines/human/referrals/levothyroxine-containing-medicinal-products", "https://www.doctronic.ai/blog/calcium-and-levothyroxine/" ] }, "library:hormone-lgd-4033": { "id": "library:hormone-lgd-4033", "path": "/library/hormone-lgd-4033.html", "title": "LGD-4033 (Ligandrol)", "summary": "A selective androgen receptor modulator investigated in clinical trials but not FDA-approved for human use.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:lgd-4033", "title": "LGD-4033 (Ligandrol)", "summary": "A selective androgen receptor modulator investigated in clinical trials but not FDA-approved for human use.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "LGD-4033 (Ligandrol) is a selective androgen receptor modulator developed by Ligand Pharmaceuticals. A Phase I trial (Basaria et al. 2013) in 76 healthy men found dose-dependent lean mass gains over 21 days. Despite extensive human trials (over 25 controlled studies, 1,700+ subjects), no SARM has received FDA approval.", "verdict": { "benefits": [ "Selective androgen receptor activity in muscle and bone", "Lean mass gains demonstrated in short-term study" ], "risks": [ "Limited long-term human safety data", "Suppression of endogenous testosterone" ], "bottomLine": "Preclinical and early-stage research only; no FDA approval despite extensive clinical trials on 1,700+ subjects.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "Basaria et al. 2013, J Gerontol A Biol Sci Med Sci - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22459616/" }, { "title": "LGD-4033 SARM Research - Ligand Pharmaceuticals", "url": "https://investor.ligand.com/news-and-events/press-releases/news-details/2009/Ligand-Initiates-Clinical-Trial-with-the-Selective-Androgen-Receptor-Modulator-LGD-4033-a-Potential-Treatment-of-Muscle-and-Bone-Disorders-06-17-2009/default.aspx" }, { "title": "LGD-4033 - Wikipedia", "url": "https://en.wikipedia.org/wiki/LGD-4033" } ], "links": [ { "title": "Basaria et al. 2013, J Gerontol A Biol Sci Med Sci - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22459616/" }, { "title": "LGD-4033 SARM Research - Ligand Pharmaceuticals", "url": "https://investor.ligand.com/news-and-events/press-releases/news-details/2009/Ligand-Initiates-Clinical-Trial-with-the-Selective-Androgen-Receptor-Modulator-LGD-4033-a-Potential-Treatment-of-Muscle-and-Bone-Disorders-06-17-2009/default.aspx" }, { "title": "LGD-4033 - Wikipedia", "url": "https://en.wikipedia.org/wiki/LGD-4033" } ], "protocols": [ { "population": "76 healthy men, randomized double-blind placebo-controlled", "regimen": "Oral 0.1, 0.3, or 1.0 mg/day", "duration": "21 days", "outcome": "1.21 kg lean mass gain at 1.0 mg/day; well-tolerated with minimal adverse effects", "source": { "title": "Basaria et al. 2013, J Gerontol A Biol Sci Med Sci - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22459616/" }, "origins": [ "evidence.json#/catalog:hormone:lgd-4033/protocols/0" ] } ], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 30, "lowerHours": 24, "source": "Basaria et al. 2013, J Gerontol A Biol Sci Med Sci 68(1):87-95, PMID 22459616 — Phase 1 human PK trial", "upperHours": 36 } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:22459616", "https://investor.ligand.com/news-and-events/press-releases/news-details/2009/Ligand-Initiates-Clinical-Trial-with-the-Selective-Androgen-Receptor-Modulator-LGD-4033-a-Potential-Treatment-of-Muscle-and-Bone-Disorders-06-17-2009/default.aspx", "https://en.wikipedia.org/wiki/LGD-4033" ] }, "library:hormone-liothyronine": { "id": "library:hormone-liothyronine", "path": "/library/hormone-liothyronine.html", "title": "Liothyronine (T3)", "summary": "Synthetic T3. Short half-life, so it is often split across the day rather than taken once.", "aliases": [], "kind": "medication-hormone", "categories": [ "longevity" ], "research": [ { "id": "catalog:hormone:liothyronine", "title": "Liothyronine (T3)", "summary": "Synthetic T3. Short half-life, so it is often split across the day rather than taken once.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Liothyronine is synthetic T3 with an FDA-approved label (Cytomel). It is approved as replacement in hypothyroidism, as an adjunct in managing well-differentiated thyroid cancer by suppressing TSH, and as a diagnostic agent in thyroid suppression tests. The label carries a boxed warning that thyroid hormones must not be used for obesity or weight loss, and that amounts beyond hormonal needs can cause serious toxicity.", "verdict": { "benefits": [ "Replacement therapy in hypothyroidism.", "An adjunct in well-differentiated thyroid cancer, by suppressing TSH.", "A diagnostic agent in thyroid suppression tests." ], "risks": [ "A boxed warning states thyroid hormones must not be used for obesity or weight loss.", "The label warns that amounts beyond hormonal needs can cause serious toxicity." ], "bottomLine": "Liothyronine is FDA-approved thyroid hormone replacement, with a boxed warning against use for weight loss.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: liothyronine", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=liothyronine" } ], "links": [ { "title": "CYTOMEL (liothyronine sodium) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/010379s054lbl.pdf" }, { "title": "Liothyronine sodium tablets FDA prescribing information", "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/115a84c2-0126-4dd7-816e-1873875f1e49/spl-doc" } ], "protocols": [ { "population": "Adults with hypothyroidism, per the US label", "regimen": "25 mcg orally once daily to start, increased by 25 mcg daily every 1 or 2 weeks; usual maintenance 25 mcg to 75 mcg once daily", "duration": "Ongoing, per the label", "outcome": "Approved as replacement therapy in hypothyroidism; the label's boxed warning states thyroid hormones must not be used for obesity or weight loss.", "source": { "title": "Liothyronine sodium tablets FDA prescribing information", "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/115a84c2-0126-4dd7-816e-1873875f1e49/spl-doc" }, "origins": [ "evidence.json#/catalog:hormone:liothyronine/protocols/0" ] }, { "population": "People with well-differentiated thyroid cancer needing TSH suppression, per the US label", "regimen": "Dose targeted to keep TSH within the desired therapeutic range, which the label says may require higher doses", "duration": "Ongoing, per the label", "outcome": "Approved as an adjunct to surgery and radioiodine in managing well-differentiated thyroid cancer.", "source": { "title": "Liothyronine sodium tablets FDA prescribing information", "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/115a84c2-0126-4dd7-816e-1873875f1e49/spl-doc" }, "origins": [ "evidence.json#/catalog:hormone:liothyronine/protocols/1" ] }, { "population": "People undergoing a thyroid suppression test, per the US label", "regimen": "75 mcg to 100 mcg daily, with radioactive iodine uptake measured before and after the administration", "duration": "7 days", "outcome": "Approved as a diagnostic agent in thyroid suppression tests.", "source": { "title": "Liothyronine sodium tablets FDA prescribing information", "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/115a84c2-0126-4dd7-816e-1873875f1e49/spl-doc" }, "origins": [ "evidence.json#/catalog:hormone:liothyronine/protocols/2" ] } ], "community": [ { "description": "A performance optimization guide documents that community members using T3 for fat loss typically begin at 25-50 mcg once daily, with increases of 12.5 mcg every 5-7 days for those on intermediate protocols.", "source": { "title": "Liothyronine (T3) Cycle — Dosage, Contest Prep & GH Stack", "url": "https://www.biomogging.com/compounds/liothyronine" }, "origins": [ "evidence.json#/catalog:hormone:liothyronine/community/0" ] }, { "description": "Users on thyroid patient forums describe splitting their T3 dose to manage absorption peaks, with examples including 10 mcg at 5am, 7.5 mcg at 1pm, and 2.5 mcg at 4pm to smooth the effect over the day.", "source": { "title": "T3 split dose experiences | Thyroid UK HealthUnlocked", "url": "https://healthunlocked.com/thyroiduk/posts/147796886/splitting-t3-dose" }, "origins": [ "evidence.json#/catalog:hormone:liothyronine/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:liothyronine/community/0", "url": "https://www.biomogging.com/compounds/liothyronine", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:liothyronine/community/1", "url": "https://healthunlocked.com/thyroiduk/posts/147796886/splitting-t3-dose", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 60, "source": "FDA label, Cytomel: biological half-life about 2 1/2 days" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/010379s054lbl.pdf", "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/115a84c2-0126-4dd7-816e-1873875f1e49/spl-doc", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=liothyronine", "https://www.biomogging.com/compounds/liothyronine", "https://healthunlocked.com/thyroiduk/posts/147796886/splitting-t3-dose" ] }, "library:hormone-mesterolone": { "id": "library:hormone-mesterolone", "path": "/library/hormone-mesterolone.html", "title": "Mesterolone (Proviron)", "summary": "An anabolic steroid used clinically to treat male hypogonadism and low testosterone.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:mesterolone", "title": "Mesterolone (Proviron)", "summary": "An anabolic steroid used clinically to treat male hypogonadism and low testosterone.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "reference", "evidenceSummary": "Mesterolone (Proviron) is an anabolic steroid used clinically to treat low testosterone, hypogonadism, oligozoospermia, and Leydig cell failure. Structurally similar to dihydrotestosterone, it has been used primarily since the early 1960s. Regulatory status varies by country; approval status in the United States is limited.", "verdict": { "benefits": [ "Indicated for treatment of male hypogonadism and associated fertility issues" ], "risks": [ "Weak anabolic activity compared to other steroids", "Androgenic side effects", "Cardiac remodelling and lipid profile changes" ], "bottomLine": "Regulatory approval for hypogonadism with weak anabolic properties and potential cardiac effects requiring monitoring." }, "originalLinks": [ { "title": "Mesterolone - DrugBank", "url": "https://go.drugbank.com/drugs/DB13587" }, { "title": "Mesterolone on Cardiac Remodelling - PubMed Central", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2613982/" } ], "links": [ { "title": "Mesterolone - DrugBank", "url": "https://go.drugbank.com/drugs/DB13587" }, { "title": "Mesterolone on Cardiac Remodelling - PubMed Central", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2613982/" } ], "protocols": [], "community": [ { "description": "Users on EliteFitness forum report 50 mg daily for 8 weeks as a standard approach, with 25-50 mg daily described as good for most people.", "source": { "title": "How Do You Run Proviron? - EliteFitness Forum", "url": "https://www.elitefitness.com/forum/threads/how-do-you-run-proviron.1490647/" }, "origins": [ "evidence.json#/catalog:hormone:mesterolone/community/0" ] }, { "description": "Forum members discuss proviron dosing of 25 mg daily as effective, with 50 mg typical for those seeking additional effects when stacked with other compounds.", "source": { "title": "Proviron Uses and Dosage - EliteFitness", "url": "https://www.elitefitness.com/articles/proviron-mesterolone/" }, "origins": [ "evidence.json#/catalog:hormone:mesterolone/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:mesterolone/community/0", "url": "https://www.elitefitness.com/forum/threads/how-do-you-run-proviron.1490647/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:mesterolone/community/1", "url": "https://www.elitefitness.com/articles/proviron-mesterolone/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 12.5, "lowerHours": 12, "source": "DrugBank clinical-pharmacology monograph", "upperHours": 13 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://go.drugbank.com/drugs/DB13587", "https://pmc.ncbi.nlm.nih.gov/articles/PMC2613982/", "https://www.elitefitness.com/forum/threads/how-do-you-run-proviron.1490647/", "https://www.elitefitness.com/articles/proviron-mesterolone/" ] }, "library:hormone-methandienone": { "id": "library:hormone-methandienone", "path": "/library/hormone-methandienone.html", "title": "Methandienone (Dianabol)", "summary": "An anabolic steroid whose FDA approval was revoked in 1985 and is no longer approved for human use.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:methandienone", "title": "Methandienone (Dianabol)", "summary": "An anabolic steroid whose FDA approval was revoked in 1985 and is no longer approved for human use.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "reference", "evidenceSummary": "Methandienone (Dianabol) is an orally active synthetic anabolic steroid. The FDA accepted it as 'Probably Effective' in 1970 for post-menopausal osteoporosis and pituitary-deficient dwarfism. However, CIBA withdrew it from the U.S. market in 1983 and the FDA revoked its approval entirely in 1985. It is no longer approved for human use.", "verdict": { "benefits": [ "Historical regulatory approval (revoked) for osteoporosis and dwarfism" ], "risks": [ "FDA approval revoked in 1985", "Hepatotoxicity", "Lipid abnormalities", "Virilization in women" ], "bottomLine": "No longer FDA-approved; regulatory approval was revoked in 1985 despite historical acceptance for specific conditions.", "approvalStatus": "FDA approval revoked in 1985." }, "originalLinks": [ { "title": "NCATS Inxight Drugs — Methandrostenolone", "url": "https://drugs.ncats.io/drug/COZ1R7EOCC" }, { "title": "Metandienone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Metandienone" } ], "links": [ { "title": "NCATS Inxight Drugs — Methandrostenolone", "url": "https://drugs.ncats.io/drug/COZ1R7EOCC" }, { "title": "Metandienone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Metandienone" } ], "protocols": [], "community": [ { "description": "A protocol shared on Swolverine describes beginner methandienone dosing at 15–25 mg daily for 4–6 weeks with split dosing, intermediate at 30–40 mg daily, and advanced at 50–60 mg daily for maximum 4 weeks due to liver strain.", "source": { "title": "Dianabol Dosage Guide: How Much Dbol Should You Take Per Day", "url": "https://swolverine.com/blogs/blog/dianabol-dosage-guide-how-much-dbol-should-you-take-per-day" }, "origins": [ "evidence.json#/catalog:hormone:methandienone/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:methandienone/community/0", "url": "https://swolverine.com/blogs/blog/dianabol-dosage-guide-how-much-dbol-should-you-take-per-day", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 4.5, "lowerHours": 3, "source": "Llewellyn, Anabolics (2011); Ruiz & Strain, Lowinson and Ruiz's Substance Abuse (2011), p.358 — compiled pharmacology references", "upperHours": 6 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://drugs.ncats.io/drug/COZ1R7EOCC", "https://en.wikipedia.org/wiki/Metandienone", "https://swolverine.com/blogs/blog/dianabol-dosage-guide-how-much-dbol-should-you-take-per-day" ] }, "library:hormone-methenolone": { "id": "library:hormone-methenolone", "path": "/library/hormone-methenolone.html", "title": "Methenolone (Primobolan)", "summary": "An anabolic steroid with limited clinical use and documented risks of androgenic and hepatic toxicity.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:methenolone", "title": "Methenolone (Primobolan)", "summary": "An anabolic steroid with limited clinical use and documented risks of androgenic and hepatic toxicity.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "Methenolone (Primobolan) is available as oral tablets (17-acetate) and intramuscular injection (17-enanthate). Human metabolism studies after oral administration show parent steroid detection in urine for up to 90 hours. Limited clinical evidence exists; main risks relate to excessive androgens and 17-alpha-alkylated oral steroid hepatotoxicity.", "verdict": { "benefits": [], "risks": [ "Limited approved human use", "Menstrual irregularities and virilization in women", "Impotence and cardiovascular disease in men", "Liver damage with oral formulation", "Psychiatric changes during and after use" ], "bottomLine": "Preclinical evidence with human metabolism data; significant androgenic and hepatic risks limit approved clinical use.", "approvalStatus": "Limited, largely historical approved human use." }, "originalLinks": [ { "title": "Studies on Anabolic Steroids—Methenolone Acetate Metabolites - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/2242348/" }, { "title": "Methenolone (PIM 907) - INCHEM", "url": "https://www.inchem.org/documents/pims/pharm/pim907.htm" } ], "links": [ { "title": "Studies on Anabolic Steroids—Methenolone Acetate Metabolites - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/2242348/" }, { "title": "Methenolone (PIM 907) - INCHEM", "url": "https://www.inchem.org/documents/pims/pharm/pim907.htm" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 252, "source": "Westreich, in Ruiz & Strain, Lowinson and Ruiz's Substance Abuse (2011), p.358 — enanthate ester (Primobolan Depot)" } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:2242348", "https://www.inchem.org/documents/pims/pharm/pim907.htm" ] }, "library:hormone-mk-2866": { "id": "library:hormone-mk-2866", "path": "/library/hormone-mk-2866.html", "title": "MK-2866 (Ostarine)", "summary": "A selective androgen receptor modulator tested in over 1,700 subjects that failed FDA approval for muscle wasting.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:mk-2866", "title": "MK-2866 (Ostarine)", "summary": "A selective androgen receptor modulator tested in over 1,700 subjects that failed FDA approval for muscle wasting.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "MK-2866 (Ostarine, Enobosarm) is a nonsteroidal selective androgen receptor modulator studied in over 25 controlled clinical trials involving 1,700+ subjects—the largest SARM clinical dataset. However, it failed Phase III trials for lung cancer-associated muscle wasting in mid-2013. Despite extensive research, no SARM compound has received FDA approval.", "verdict": { "benefits": [ "Selective AR activity in muscle and bone", "No aromatization to estrogen; no 5-alpha reduction" ], "risks": [ "Classified as Investigational New Drug (IND)", "Suppression of endogenous testosterone" ], "bottomLine": "Extensive clinical research (1,700+ subjects) failed to achieve FDA approval; remains investigational.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "Ostarine (MK-2866) Clinical Trials - MorePlatesMoreDates", "url": "https://moreplatesmoredates.com/ostarine-results/" }, { "title": "Enobosarm - Wikipedia", "url": "https://en.wikipedia.org/wiki/Enobosarm" } ], "links": [ { "title": "Ostarine (MK-2866) Clinical Trials - MorePlatesMoreDates", "url": "https://moreplatesmoredates.com/ostarine-results/" }, { "title": "Enobosarm - Wikipedia", "url": "https://en.wikipedia.org/wiki/Enobosarm" } ], "protocols": [], "community": [ { "description": "A bodybuilding resource documents ostarine protocols reporting 20 mg daily for 8 weeks as typical for men pursuing fat loss and muscle retention, with extended cycles to 12 weeks conducted only if health markers remain within acceptable ranges.", "source": { "title": "Ostarine (MK-2866): Results, Before and After Pictures, Dosages", "url": "https://insidebodybuilding.com/ostarine-mk-2866/" }, "origins": [ "evidence.json#/catalog:hormone:mk-2866/community/0" ] }, { "description": "A fitness guide describes female ostarine protocols of 10 mg daily for 4 to 8 weeks, with case studies documenting cycles using 12.5 mg initially then 25 mg for subsequent weeks.", "source": { "title": "Ostarine (MK-2866): Results, Before and After Pictures, Dosages", "url": "https://insidebodybuilding.com/ostarine-mk-2866/" }, "origins": [ "evidence.json#/catalog:hormone:mk-2866/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:mk-2866/community/0", "url": "https://insidebodybuilding.com/ostarine-mk-2866/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:mk-2866/community/1", "url": "https://insidebodybuilding.com/ostarine-mk-2866/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 19, "lowerHours": 14, "source": "Human clinical PK data (Dalton JT group trials; Jones et al. 2013 metabolite study, PMID 27105861) — most rigorously human-studied SARM on this list", "upperHours": 24 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://moreplatesmoredates.com/ostarine-results/", "https://en.wikipedia.org/wiki/Enobosarm", "https://insidebodybuilding.com/ostarine-mk-2866/" ] }, "library:hormone-nandrolone-decanoate": { "id": "library:hormone-nandrolone-decanoate", "path": "/library/hormone-nandrolone-decanoate.html", "title": "Nandrolone decanoate", "summary": "Long-acting 19-nortestosterone ester. Suppresses natural production and is detectable long after use.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:nandrolone-decanoate", "title": "Nandrolone decanoate", "summary": "Long-acting 19-nortestosterone ester. Suppresses natural production and is detectable long after use.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Nandrolone decanoate is a synthetic anabolic-androgenic steroid. A meta-analysis of seven small randomised trials in postmenopausal women with osteoporosis reported fewer fractures, modest bone density gains, less pain and more muscle mass, at low to moderate certainty. The same analysis found more mild virilising effects such as acne, hirsutism and voice change. A systematic review of nandrolone use and abuse catalogues the side effects reported with illicit use. The trials behind this are small and mostly old.", "verdict": { "benefits": [ "Pooled small trials in postmenopausal osteoporosis found fewer fractures, more bone and muscle, less pain.", "The US label states it raises haemoglobin and red cell mass in anaemia of renal insufficiency." ], "risks": [ "Mild virilising effects such as acne, hirsutism and voice change were more common than with placebo.", "The supporting trials are small, mostly old, and rated low to moderate certainty.", "A systematic review catalogues the side effects reported with illicit use." ], "bottomLine": "Nandrolone cut fractures and raised bone and muscle in small old trials, at the cost of virilising side effects." }, "originalLinks": [ { "title": "DailyMed: nandrolone decanoate", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=nandrolone+decanoate" } ], "links": [ { "title": "Nandrolone decanoate injection — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a586b484-1b46-40b9-9508-fd28002ad383" }, { "title": "Nandrolone Decanoate: Use, Abuse and Side Effects", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7696474/" }, { "title": "Nandrolone Decanoate for Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748007/" } ], "protocols": [ { "population": "people with the anaemia of renal insufficiency, per the US label", "regimen": "deep intramuscular injection into the gluteal muscle: 50-100 mg weekly in women, 100-200 mg weekly in men, 25-50 mg every 3-4 weeks in children aged 2-13", "duration": "ongoing and preferably intermittent, per the label, stopped if there is no improvement in the first six months", "outcome": "The label states nandrolone decanoate has been shown to increase haemoglobin and red cell mass in the anaemia of renal insufficiency.", "source": { "title": "Nandrolone decanoate injection — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a586b484-1b46-40b9-9508-fd28002ad383" }, "origins": [ "evidence.json#/catalog:hormone:nandrolone-decanoate/protocols/0" ] }, { "population": "293 postmenopausal women with osteoporosis across seven randomised placebo-controlled trials", "regimen": "nandrolone decanoate 50 mg intramuscularly every three weeks in all trials but one, which used 50 mg every four weeks", "duration": "6 to 24 months of follow-up, most trials 12 months", "outcome": "Fractures fell (RR 0.37), bone density, bone mineral content and muscle mass rose and pain fell; mild virilising adverse events were more common than with placebo.", "source": { "title": "Nandrolone Decanoate for Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748007/" }, "origins": [ "evidence.json#/catalog:hormone:nandrolone-decanoate/protocols/1" ] } ], "community": [ { "description": "Community-reported protocols indicate 200–400 mg per week via intramuscular injection weekly for beginners, with experienced users dosing 300–600 mg per week every 5–7 days over 8–12 week cycles.", "source": { "title": "Nandrolone Decanoate: How to Take It Safely and Effectively", "url": "https://projectclear.com/nandrolone-decanoate-how-to-take-it-safely-and-effectively/" }, "origins": [ "evidence.json#/catalog:hormone:nandrolone-decanoate/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:nandrolone-decanoate/community/0", "url": "https://projectclear.com/nandrolone-decanoate-how-to-take-it-safely-and-effectively/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 216, "lowerHours": 144, "source": "FDA label, Deca-Durabolin", "upperHours": 288 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a586b484-1b46-40b9-9508-fd28002ad383", "https://pmc.ncbi.nlm.nih.gov/articles/PMC7696474/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748007/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=nandrolone+decanoate", "https://projectclear.com/nandrolone-decanoate-how-to-take-it-safely-and-effectively/" ] }, "library:hormone-oxandrolone": { "id": "library:hormone-oxandrolone", "path": "/library/hormone-oxandrolone.html", "title": "Oxandrolone (Anavar)", "summary": "An anabolic steroid FDA-approved for protein catabolism secondary to corticosteroids and osteoporosis-related bone pain.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing", "fitness-muscle" ], "research": [ { "id": "catalog:hormone:oxandrolone", "title": "Oxandrolone (Anavar)", "summary": "An anabolic steroid FDA-approved for protein catabolism secondary to corticosteroids and osteoporosis-related bone pain.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Oxandrolone is an anabolic steroid approved by the FDA as adjunctive therapy to offset protein catabolism from prolonged corticosteroid administration and for relief of bone pain from osteoporosis. A boxed warning notes serious risks including liver damage, lipid changes, accelerated bone maturation in children, and bleeding interactions with warfarin.", "verdict": { "benefits": [ "Protein-catabolic states secondary to prolonged corticosteroid use.", "Bone pain relief in osteoporosis." ], "risks": [ "Boxed warning: liver toxicity including peliosis hepatis and liver tumors", "Significant lipid changes (decreased HDL, increased LDL)", "Accelerated epiphyseal closure in children", "Hepatotoxicity and cholestatic jaundice", "Increased bleeding risk with warfarin" ], "bottomLine": "FDA-approved for specific catabolic and pain indications with a boxed warning for serious hepatic and cardiovascular risks requiring medical supervision.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "Label: OXANDROLONE tablet - DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6f42739-5bfc-4b76-8795-e93fa58f3d29" }, { "title": "StatPearls - Oxandrolone", "url": "https://www.ncbi.nlm.nih.gov/books/NBK557608/" } ], "links": [ { "title": "Label: OXANDROLONE tablet - DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6f42739-5bfc-4b76-8795-e93fa58f3d29" }, { "title": "StatPearls - Oxandrolone", "url": "https://www.ncbi.nlm.nih.gov/books/NBK557608/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 9.9, "lowerHours": 9.4, "source": "Miller & Btaiche 2009, Pharmacotherapy 29(2):213-226, PMID 19170590", "upperHours": 10.4 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6f42739-5bfc-4b76-8795-e93fa58f3d29", "https://www.ncbi.nlm.nih.gov/books/NBK557608/" ] }, "library:hormone-oxymetholone": { "id": "library:hormone-oxymetholone", "path": "/library/hormone-oxymetholone.html", "title": "Oxymetholone (Anadrol)", "summary": "An FDA-approved anabolic steroid used to treat anemias caused by deficient red-cell production.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:oxymetholone", "title": "Oxymetholone (Anadrol)", "summary": "An FDA-approved anabolic steroid used to treat anemias caused by deficient red-cell production.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Oxymetholone is an FDA-approved anabolic steroid indicated for treating anemias caused by deficient red-cell production, including aplastic anemia, myelofibrosis, and anemia related to administration of myelotoxic drugs. It has been studied for HIV-associated wasting and other catabolic conditions with varying success.", "verdict": { "benefits": [ "Anemias caused by deficient red-cell production, including aplastic anemia." ], "risks": [ "Significant hepatotoxicity (cholestatic jaundice is the most important hepatic side effect)", "Virilization in women", "Lipid abnormalities", "Cardiovascular effects" ], "bottomLine": "FDA-approved for specific anemias; remains approved but hepatotoxicity is a major safety concern requiring monitoring.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "ANADROL-50 (oxymetholone) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/16848s021lbl.pdf" }, { "title": "Review of Oxymetholone - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/11440282/" } ], "links": [ { "title": "ANADROL-50 (oxymetholone) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/16848s021lbl.pdf" }, { "title": "Review of Oxymetholone - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/11440282/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/16848s021lbl.pdf", "pmid:11440282" ] }, "library:hormone-pregnenolone": { "id": "library:hormone-pregnenolone", "path": "/library/hormone-pregnenolone.html", "title": "Pregnenolone", "summary": "A cholesterol-derived steroid precursor to progesterone and DHEA, sold as an unregulated supplement.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:pregnenolone", "title": "Pregnenolone", "summary": "A cholesterol-derived steroid precursor to progesterone and DHEA, sold as an unregulated supplement.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "clinical-study", "evidenceSummary": "Pregnenolone is an endogenous steroid synthesized from cholesterol that serves as the biosynthetic precursor to progesterone, DHEA, and other downstream steroid hormones, earning it the nickname of the body's mother hormone. It is sold in the United States as an unregulated dietary supplement and has been studied in placebo-controlled psychiatric trials for conditions including bipolar depression and schizophrenia. No government regulatory agency has approved it as a prescription drug.", "verdict": { "benefits": [ "Placebo-controlled trials have reported improvements in negative symptoms and some cognitive measures in schizophrenia when added to antipsychotic treatment.", "Occurs naturally as the shared precursor for progesterone, DHEA, and downstream sex and adrenal steroid hormones.", "Sold over the counter in the United States, giving researchers easy access to a well-characterized neurosteroid for study." ], "risks": [ "A twelve-week placebo-controlled trial in bipolar depression found no significant benefit over placebo on the primary mood outcome.", "As an unregulated dietary supplement, product purity, actual hormone content, and manufacturing quality are not independently verified by any regulator.", "Evidence remains limited to small, short-duration psychiatric trials; long-term safety and effects in healthy adults are not well characterized." ], "bottomLine": "Pregnenolone is an unregulated over-the-counter steroid precursor with mixed results across small placebo-controlled psychiatric trials, and no regulatory agency has evaluated or approved it as a drug.", "approvalStatus": "Not FDA- or EMA-approved; sold as an unregulated supplement." }, "originalLinks": [ { "title": "A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/24917198/" }, { "title": "Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/19339966/" } ], "links": [ { "title": "A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/24917198/" }, { "title": "Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/19339966/" } ], "protocols": [ { "population": "80 adults with bipolar disorder in a current depressive episode", "regimen": "oral pregnenolone titrated up to 500 mg per day versus placebo, added to existing mood-stabilizer treatment", "duration": "twelve weeks, randomized, double-blind, placebo-controlled", "outcome": "no statistically significant difference from placebo on the Hamilton Depression Rating Scale, the trial's primary endpoint", "source": { "title": "A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/24917198/" }, "origins": [ "evidence.json#/catalog:hormone:pregnenolone/protocols/0" ] }, { "population": "adults with schizophrenia or schizoaffective disorder on stable antipsychotic treatment", "regimen": "adjunctive oral pregnenolone at 500 mg per day versus placebo", "duration": "eight weeks, randomized, double-blind, placebo-controlled proof-of-concept trial", "outcome": "improvements in negative symptoms and select cognitive measures compared with placebo, with the rise in serum pregnenolone correlated to cognitive gains", "source": { "title": "Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia — PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/19339966/" }, "origins": [ "evidence.json#/catalog:hormone:pregnenolone/protocols/1" ] } ], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:24917198", "pmid:19339966" ] }, "library:hormone-progesterone": { "id": "library:hormone-progesterone", "path": "/library/hormone-progesterone.html", "title": "Progesterone (micronised)", "summary": "Bioidentical progesterone used in HRT. Oral dosing is sedating, which is why it is usually taken at night.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:progesterone", "title": "Progesterone (micronised)", "summary": "Bioidentical progesterone used in HRT. Oral dosing is sedating, which is why it is usually taken at night.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Micronised progesterone is chemically identical to the body's own progesterone and has an FDA-approved label (Prometrium). The linked label covers protection of the womb lining against endometrial hyperplasia in women taking oestrogen, with trial figures over up to three years of treatment. That label version carries a boxed warning drawn from the Women's Health Initiative about cardiovascular risk, breast cancer and probable dementia with oestrogen plus progestin. A 2025 FDA press release announces the removal of warnings it describes as misleading from hormone replacement products.", "verdict": { "benefits": [ "Protect the womb lining in women on oestrogen, and for secondary amenorrhoea.", "In the label trial, endometrial hyperplasia was 6% on the combination against 64% on oestrogen alone" ], "risks": [ "That label version carries a boxed warning on heart disease, breast cancer and probable dementia", "A 2025 FDA press release announces removing warnings it calls misleading, so labelling is in flux" ], "bottomLine": "Micronised progesterone is an approved medicine that protects the womb lining, with boxed warnings now under revision.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: progesterone", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=progesterone" } ], "links": [ { "title": "PROMETRIUM (progesterone USP) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019781s017,020843s011lbl.pdf" }, { "title": "HHS advances women's health, removes misleading FDA warnings on hormone replacement therapy", "url": "https://www.fda.gov/news-events/press-announcements/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy" } ], "protocols": [ { "population": "postmenopausal women with a uterus receiving daily conjugated estrogens, per the US Prometrium label", "regimen": "200 mg micronised progesterone orally as a single daily dose at bedtime, for 12 days sequentially per 28-day cycle", "duration": "ongoing, per the label", "outcome": "The label lists this as the approved regimen for prevention of endometrial hyperplasia.", "source": { "title": "PROMETRIUM (progesterone USP) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019781s017,020843s011lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:progesterone/protocols/0" ] }, { "population": "women with secondary amenorrhoea, per the US Prometrium label", "regimen": "400 mg micronised progesterone orally as a single daily dose at bedtime", "duration": "10 days", "outcome": "The label lists this as the approved regimen for treatment of secondary amenorrhoea.", "source": { "title": "PROMETRIUM (progesterone USP) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019781s017,020843s011lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:progesterone/protocols/1" ] }, { "population": "358 postmenopausal women with an intact uterus, in the randomised double-blind trial described in the label", "regimen": "conjugated estrogens 0.625 mg a day plus Prometrium 200 mg a day for 12 days per 28-day cycle, against conjugated estrogens alone or placebo", "duration": "up to 36 months", "outcome": "Endometrial hyperplasia occurred in 6% on the combination against 64% on conjugated estrogens alone.", "source": { "title": "PROMETRIUM (progesterone USP) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019781s017,020843s011lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:progesterone/protocols/2" ] } ], "community": [ { "description": "An HRT health platform reports that many women in their community begin with 100 mg of micronized progesterone taken nightly as an oral capsule, often combined with an estrogen patch.", "source": { "title": "What Is The Lowest Dose of Progesterone For HRT?", "url": "https://www.joinmidi.com/post/low-dose-progesterone" }, "origins": [ "evidence.json#/catalog:hormone:progesterone/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:progesterone/community/0", "url": "https://www.joinmidi.com/post/low-dose-progesterone", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019781s017,020843s011lbl.pdf", "https://www.fda.gov/news-events/press-announcements/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=progesterone", "https://www.joinmidi.com/post/low-dose-progesterone" ] }, "library:hormone-rad140": { "id": "library:hormone-rad140", "path": "/library/hormone-rad140.html", "title": "RAD140 (Testolone)", "summary": "A selective androgen receptor modulator with preclinical promise but limited human data and reported serious adverse effects.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:rad140", "title": "RAD140 (Testolone)", "summary": "A selective androgen receptor modulator with preclinical promise but limited human data and reported serious adverse effects.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "RAD140 (Testolone) is a selective androgen receptor modulator showing potent anabolic activity in preclinical studies. Limited human research exists: six micro-dose excretion studies on five volunteers each, and a Phase I trial on metastatic breast cancer efficacy. Three published cases reported drug-induced liver damage in male users; another reported acute myocarditis.", "verdict": { "benefits": [ "Selective AR binding in preclinical models; minimal prostate activation", "Neuroprotection shown in cultured neurons" ], "risks": [ "Not FDA-approved; minimal human clinical data", "Three published cases of serious drug-induced liver damage", "One case of acute myocarditis and congestive heart failure", "No long-term human safety studies" ], "bottomLine": "Preclinical promise but very limited human data; serious hepatic and cardiac adverse events reported in case studies." }, "originalLinks": [ { "title": "Preclinical Assessment of RAD140 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274021/" }, { "title": "Human In Vivo Metabolism of RAD140 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325264/" } ], "links": [ { "title": "Preclinical Assessment of RAD140 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274021/" }, { "title": "Human In Vivo Metabolism of RAD140 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325264/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 52.5, "lowerHours": 45, "source": "LoRusso et al. 2022, Clin Breast Cancer 22(1):67-77, PMID 34565686 — Phase 1 human PK trial", "upperHours": 60 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274021/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325264/" ] }, "library:hormone-sr9009": { "id": "library:hormone-sr9009", "path": "/library/hormone-sr9009.html", "title": "SR9009 (Stenabolic)", "summary": "A REV-ERB agonist research compound with significant off-target effects that is not FDA-approved.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:sr9009", "title": "SR9009 (Stenabolic)", "summary": "A REV-ERB agonist research compound with significant off-target effects that is not FDA-approved.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "SR9009 (Stenabolic) is a synthetic REV-ERBα/REV-ERBβ agonist used as a research tool for circadian rhythm regulation, metabolism, and mitochondrial biogenesis. It activates REV-ERB signaling to regulate circadian clock genes and metabolic pathways. Important limitation: SR9009 is 100-fold more active toward LXRα than REV-ERBs, suggesting observed effects may derive from off-target activity.", "verdict": { "benefits": [ "REV-ERB agonism in preclinical models; effects on circadian rhythm and metabolism" ], "risks": [ "Not FDA-approved; research use only", "Significant off-target LXRα activity (100-fold over REV-ERB activity)", "Effects may not be due to intended REV-ERB mechanism", "No human safety or efficacy data" ], "bottomLine": "Research tool only with major off-target activity; preclinical effects may not reflect intended mechanism." }, "originalLinks": [ { "title": "SR9009 REV-ERB Agonist - MedKoo", "url": "https://www.medkoo.com/products/14012" }, { "title": "In Vitro Metabolic Studies of SR9009 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085709/" } ], "links": [ { "title": "SR9009 REV-ERB Agonist - MedKoo", "url": "https://www.medkoo.com/products/14012" }, { "title": "In Vitro Metabolic Studies of SR9009 - PubMed Central", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085709/" } ], "protocols": [], "community": [ { "description": "A protocol documented on Path To Peptides describes 20-30 mg administered orally in split doses 3-4 times daily for 8-12 weeks as a community-reported approach, though the source notes this route has poor bioavailability (~2%).", "source": { "title": "SR-9009 Protocol Guide", "url": "https://www.pathtopeptides.com/sr-9009-protocol.html" }, "origins": [ "evidence.json#/catalog:hormone:sr9009/community/0" ] }, { "description": "A sublingual administration pattern shared on Path To Peptides involves 10-20 mg held under the tongue 3 times daily, split across 8-12 week cycles.", "source": { "title": "SR-9009 Protocol Guide", "url": "https://www.pathtopeptides.com/sr-9009-protocol.html" }, "origins": [ "evidence.json#/catalog:hormone:sr9009/community/1" ] }, { "description": "An injectable protocol described on Path To Peptides details 10 mg administered subcutaneously twice daily across 8-12 week cycles.", "source": { "title": "SR-9009 Protocol Guide", "url": "https://www.pathtopeptides.com/sr-9009-protocol.html" }, "origins": [ "evidence.json#/catalog:hormone:sr9009/community/2" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:sr9009/community/0", "url": "https://www.pathtopeptides.com/sr-9009-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:sr9009/community/1", "url": "https://www.pathtopeptides.com/sr-9009-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:sr9009/community/2", "url": "https://www.pathtopeptides.com/sr-9009-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.medkoo.com/products/14012", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085709/", "https://www.pathtopeptides.com/sr-9009-protocol.html" ] }, "library:hormone-stanozolol": { "id": "library:hormone-stanozolol", "path": "/library/hormone-stanozolol.html", "title": "Stanozolol (Winstrol)", "summary": "A synthetic anabolic steroid that was FDA-approved for hereditary angioedema but is now discontinued.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:stanozolol", "title": "Stanozolol (Winstrol)", "summary": "A synthetic anabolic steroid that was FDA-approved for hereditary angioedema but is now discontinued.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Stanozolol is a synthetic anabolic steroid developed in 1962 and approved by the FDA specifically for hereditary angioedema (HAE) to decrease the frequency and severity of attacks. It is rarely used today due to other available treatments. The FDA approved product was voluntarily withdrawn from the U.S. market in 2010.", "verdict": { "benefits": [ "Prophylactic treatment to decrease frequency and severity of hereditary angioedema attacks." ], "risks": [ "Virilization in women", "Liver toxicity", "Cholestatic jaundice", "Androgenic effects" ], "bottomLine": "Regulatory approval for hereditary angioedema, but discontinued in the U.S.; safer alternatives now available for this indication.", "approvalStatus": "FDA-approved for hereditary angioedema, but discontinued in the US." }, "originalLinks": [ { "title": "Drugs@FDA: Winstrol (stanozolol) NDA 012885", "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=012885" }, { "title": "NCATS Inxight Drugs — Stanozolol", "url": "https://drugs.ncats.io/drug/4R1VB9P8V3" }, { "title": "Winstrol (Stanozolol) for Hereditary Angioedema", "url": "https://angioedemanews.com/winstrol-hereditary-angioedema-therapy-prevents-swelling-flare-ups/" } ], "links": [ { "title": "Drugs@FDA: Winstrol (stanozolol) NDA 012885", "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=012885" }, { "title": "NCATS Inxight Drugs — Stanozolol", "url": "https://drugs.ncats.io/drug/4R1VB9P8V3" }, { "title": "Winstrol (Stanozolol) for Hereditary Angioedema", "url": "https://angioedemanews.com/winstrol-hereditary-angioedema-therapy-prevents-swelling-flare-ups/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 9, "source": "Ruiz & Strain (eds.), Lowinson and Ruiz's Substance Abuse (2011), p.358 — oral tablet; the IM aqueous suspension form runs closer to 24 h" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=012885", "https://drugs.ncats.io/drug/4R1VB9P8V3", "https://angioedemanews.com/winstrol-hereditary-angioedema-therapy-prevents-swelling-flare-ups/" ] }, "library:hormone-sustanon-250": { "id": "library:hormone-sustanon-250", "path": "/library/hormone-sustanon-250.html", "title": "Sustanon 250", "summary": "Blend of four testosterone esters with staggered release, from fast-acting propionate to slow decanoate.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:sustanon-250", "title": "Sustanon 250", "summary": "Blend of four testosterone esters with staggered release, from fast-acting propionate to slow decanoate.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "reference", "evidenceSummary": "Sustanon is a brand name for a mixed testosterone ester preparation given by intramuscular injection. A reference page on testosterone isocaproate lists it as one component of these mixed preparations and describes their action as longer than single short esters. The other link is a private clinic's guide to testosterone therapy, not a regulator document. No approving regulator label is cited here, so this rests on general reference material only.", "verdict": { "benefits": [ "Reference material describes mixed testosterone esters as acting longer than single short esters" ], "risks": [ "No approving regulator label is cited here, only a reference page and a private clinic's guide", "No trial evidence for this preparation appears in these sources" ], "bottomLine": "A mixed testosterone ester covered here by general reference material, with no regulator label or trial." }, "originalLinks": [ { "title": "EMA: product information", "url": "https://www.ema.europa.eu/en/glossary-terms/product-information" } ], "links": [ { "title": "Sustanon: HRT Guide for Trans Men & Non-Binary People", "url": "https://www.gendergp.com/medical-guide/sustanon/" }, { "title": "Testosterone isocaproate - Wikipedia", "url": "https://en.wikipedia.org/wiki/Testosterone_isocaproate" } ], "protocols": [], "community": [ { "description": "Community consensus dosing for Sustanon 250 centers on 300–500 mg per week for entry-level cycles, administered in twice-weekly (Monday/Thursday) splits, with more advanced protocols using every-3-day or every-other-day injection frequencies to achieve flatter hormone curves.", "source": { "title": "Sustanon 250 Cycle Guide — Dosage, Protocol & PCT", "url": "https://www.biomogging.com/compounds/sustanon-250" }, "origins": [ "evidence.json#/catalog:hormone:sustanon-250/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:sustanon-250/community/0", "url": "https://www.biomogging.com/compounds/sustanon-250", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 264, "lowerHours": 24, "source": "Four esters; blended release", "upperHours": 504 } } ], "related": [ "library:hormone-testosterone-decanoate", "library:hormone-testosterone-isocaproate", "library:hormone-testosterone-phenylpropionate", "library:hormone-testosterone-propionate" ], "conflicts": [], "sourceRefs": [ "https://www.gendergp.com/medical-guide/sustanon/", "https://en.wikipedia.org/wiki/Testosterone_isocaproate", "https://www.ema.europa.eu/en/glossary-terms/product-information", "https://www.biomogging.com/compounds/sustanon-250" ] }, "library:hormone-tamoxifen": { "id": "library:hormone-tamoxifen", "path": "/library/hormone-tamoxifen.html", "title": "Tamoxifen", "summary": "An FDA-approved selective estrogen receptor modulator used to treat hormone receptor-positive breast cancer.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:hormone:tamoxifen", "title": "Tamoxifen", "summary": "An FDA-approved selective estrogen receptor modulator used to treat hormone receptor-positive breast cancer.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Tamoxifen was the first selective estrogen receptor modulator (SERM) approved by the FDA in 1977. It reduces cancer recurrence risk by 50% during the first 5 years and 33% during years 5-9 in estrogen receptor-positive early breast cancer. FDA-approved for early breast cancer, ductal carcinoma in situ, and risk reduction in high-risk women.", "verdict": { "benefits": [ "Reducing recurrence and death in early-stage ER+ breast cancer.", "DCIS and risk reduction in high-risk women." ], "risks": [ "Endometrial cancer risk", "Thromboembolic events", "Hot flashes", "Sexual dysfunction" ], "bottomLine": "First SARM approved by FDA with robust evidence of benefit in hormone receptor-positive breast cancer.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: tamoxifen", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=tamoxifen" }, { "title": "Use of SERMs for Adjuvant Therapy - Johns Hopkins University", "url": "https://pure.johnshopkins.edu/en/publications/use-of-serms-for-the-adjuvant-therapy-of-early-stage-breast-cance-6/" }, { "title": "Tamoxifen - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK532905/" }, { "title": "Treating ER-positive breast cancer: SERMs and SERDs review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018393/" } ], "links": [ { "title": "DailyMed: tamoxifen", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=tamoxifen" }, { "title": "Use of SERMs for Adjuvant Therapy - Johns Hopkins University", "url": "https://pure.johnshopkins.edu/en/publications/use-of-serms-for-the-adjuvant-therapy-of-early-stage-breast-cance-6/" }, { "title": "Tamoxifen - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK532905/" }, { "title": "Treating ER-positive breast cancer: SERMs and SERDs review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018393/" } ], "protocols": [ { "population": "Women with estrogen receptor-positive early breast cancer", "regimen": "Median 5 years of tamoxifen therapy", "duration": "5 years; extended therapy studied", "outcome": "50% reduction in recurrence risk during years 1-5; 33% reduction during years 5-9", "source": { "title": "Treating ER-positive breast cancer: SERMs and SERDs review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018393/" }, "origins": [ "evidence.json#/catalog:hormone:tamoxifen/protocols/0" ] } ], "community": [ { "description": "A steroid community profile documents post-cycle use at 10 mg daily for males (sufficient to prevent estrogenic side effects) and 25 mg daily for females, with initiation 3-4 weeks after anabolic steroid use, with general dosing at 10-30 mg daily.", "source": { "title": "Nolvadex (Tamoxifen Citrate) - EliteFitness Steroid Profiles", "url": "https://www.elitefitness.com/steroid_profiles/Nolvadex-Tamoxifen-Citrate.html" }, "origins": [ "evidence.json#/catalog:hormone:tamoxifen/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:tamoxifen/community/0", "url": "https://www.elitefitness.com/steroid_profiles/Nolvadex-Tamoxifen-Citrate.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 144, "lowerHours": 120, "source": "FDA label, tamoxifen citrate: terminal elimination half-life 5 to 7 days", "upperHours": 168 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=tamoxifen", "https://pure.johnshopkins.edu/en/publications/use-of-serms-for-the-adjuvant-therapy-of-early-stage-breast-cance-6/", "https://www.ncbi.nlm.nih.gov/books/NBK532905/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018393/", "https://www.elitefitness.com/steroid_profiles/Nolvadex-Tamoxifen-Citrate.html" ] }, "library:hormone-testosterone-cypionate": { "id": "library:hormone-testosterone-cypionate", "path": "/library/hormone-testosterone-cypionate.html", "title": "Testosterone cypionate", "summary": "Long-acting testosterone ester, half-life around eight days, which is why weekly or twice-weekly injection is typical.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-cypionate", "title": "Testosterone cypionate", "summary": "Long-acting testosterone ester, half-life around eight days, which is why weekly or twice-weekly injection is typical.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Testosterone cypionate is an injectable testosterone ester with an FDA-approved label (Depo-Testosterone). The label approves it as replacement therapy in men with primary hypogonadism or hypogonadotropic hypogonadism. It states that safety and efficacy in age-related (late-onset) hypogonadism have not been established. It is contraindicated in men with known or suspected prostate or breast cancer.", "verdict": { "benefits": [ "Replacement therapy in men with primary or hypogonadotropic hypogonadism." ], "risks": [ "The label states safety and efficacy in age-related hypogonadism are not established.", "Contraindicated in men with known or suspected prostate or breast cancer." ], "bottomLine": "Testosterone cypionate is FDA-approved for diagnosed hypogonadism; age-related decline sits outside the label.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: testosterone cypionate", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+cypionate" } ], "links": [ { "title": "Depo-Testosterone (testosterone cypionate injection) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/085635s040lbl.pdf" } ], "protocols": [ { "population": "men with primary hypogonadism or hypogonadotropic hypogonadism, per the US label", "regimen": "50-400 mg by deep intramuscular injection into the gluteal muscle every two to four weeks", "duration": "ongoing, per the label", "outcome": "The label approves this dosing as replacement therapy, and states safety and efficacy in age-related hypogonadism have not been established.", "source": { "title": "Depo-Testosterone (testosterone cypionate injection) FDA Label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/085635s040lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-cypionate/protocols/0" ] } ], "community": [ { "description": "Clinical and community guidelines reference 100-200 mg testosterone cypionate administered weekly via intramuscular injection as standard TRT dosing.", "source": { "title": "Testosterone Cypionate Weekly Injection Protocol", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5686655/" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-cypionate/community/0" ] }, { "description": "A user forum discussion describes a protocol of approximately 100-150 mg testosterone cypionate administered once weekly for TRT, noted as a standard practice among TRT clinicians.", "source": { "title": "Forms of Testosterone Replacement - BowTiedLoon's Newsletter", "url": "https://bowtiedloon.substack.com/p/forms-of-testosterone-replacement" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-cypionate/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The first community citation is a clinical article, not a community dosing guideline. Its study population and route must not be generalised to the imported claim of standard intramuscular TRT dosing." ], "community": [ { "origin": "evidence.json#/catalog:hormone:testosterone-cypionate/community/0", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5686655/", "claimMatch": "The first community citation is a clinical article, not a community dosing guideline. Its study population and route must not be generalised to the imported claim of standard intramuscular TRT dosing. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "population-and-route-limited" }, { "origin": "evidence.json#/catalog:hormone:testosterone-cypionate/community/1", "url": "https://bowtiedloon.substack.com/p/forms-of-testosterone-replacement", "claimMatch": "The first community citation is a clinical article, not a community dosing guideline. Its study population and route must not be generalised to the imported claim of standard intramuscular TRT dosing. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "population-and-route-limited" } ] }, "pk": { "hours": 168, "lowerHours": 144, "source": "FDA label, Depo-Testosterone", "upperHours": 192 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/085635s040lbl.pdf", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+cypionate", "https://pmc.ncbi.nlm.nih.gov/articles/PMC5686655/", "https://bowtiedloon.substack.com/p/forms-of-testosterone-replacement" ] }, "library:hormone-testosterone-decanoate": { "id": "library:hormone-testosterone-decanoate", "path": "/library/hormone-testosterone-decanoate.html", "title": "Testosterone decanoate", "summary": "The longest-acting ester in Sustanon, qualitatively between enanthate and undecanoate but never marketed or studied on its own.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-decanoate", "title": "Testosterone decanoate", "summary": "The longest-acting ester in Sustanon, qualitatively between enanthate and undecanoate but never marketed or studied on its own.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "reference", "evidenceSummary": "Testosterone decanoate is the longest-acting ester in Sustanon-type blends, qualitatively described in the clinical-pharmacology literature as releasing more slowly than enanthate and more quickly than undecanoate, but it has never been marketed or formally studied as a standalone injectable. It has been used as one component of male-contraceptive combination trials, which report outcomes for the combination rather than an isolated single-compound pharmacokinetic figure for decanoate itself, so no half-life is reported here.", "verdict": { "benefits": [ "Contributes the longest release phase to blended esters such as Sustanon." ], "risks": [ "No formal single-compound pharmacokinetic figure has been published; reported data comes from combination contraceptive trials, not an isolated study.", "Never marketed or studied as a standalone injectable." ], "bottomLine": "The longest-acting ester in blends such as Sustanon, qualitatively described but never formally studied or marketed alone." }, "originalLinks": [ { "title": "Testosterone esters — Wikipedia overview", "url": "https://en.wikipedia.org/wiki/Testosterone_ester" } ], "links": [ { "title": "Testosterone ester — Wikipedia overview", "url": "https://en.wikipedia.org/wiki/Testosterone_ester" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://en.wikipedia.org/wiki/Testosterone_ester" ] }, "library:hormone-testosterone-enanthate": { "id": "library:hormone-testosterone-enanthate", "path": "/library/hormone-testosterone-enanthate.html", "title": "Testosterone enanthate", "summary": "Long-acting testosterone ester with a half-life close to cypionate. Largely interchangeable for scheduling.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-enanthate", "title": "Testosterone enanthate", "summary": "Long-acting testosterone ester with a half-life close to cypionate. Largely interchangeable for scheduling.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Testosterone enanthate injection is approved by the US FDA as testosterone replacement therapy in adult males with conditions linked to low or absent natural testosterone. The label states that safety and effectiveness were not established in men with age-related hypogonadism or in males under 18. In July 2025 the label removed its boxed warning about blood pressure increases and its cardiovascular-risk warning, while still warning that testosterone can raise blood pressure. An FDA presentation on testosterone replacement describes the same class indication. The evidence here is regulator-approved product labelling, not a new trial.", "verdict": { "benefits": [ "Testosterone replacement in adult males with low or absent natural testosterone." ], "risks": [ "Safety and effectiveness were not established in age-related low testosterone or in males under 18.", "The label still warns that testosterone can raise blood pressure.", "In July 2025 the boxed blood-pressure warning and the cardiovascular-risk warning were removed." ], "bottomLine": "Testosterone enanthate is FDA-approved replacement for men with low testosterone, but not proven for age-related decline.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: testosterone enanthate", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+enanthate" } ], "links": [ { "title": "FDA label for Testosterone Enanthate Injection", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209863s020lbl.pdf" }, { "title": "Testosterone Replacement Therapy: Current Regulatory Landscape", "url": "https://www.fda.gov/media/123591/download" } ], "protocols": [ { "population": "adult males with primary or hypogonadotropic hypogonadism, per the US label for Xyosted testosterone enanthate injection", "regimen": "75 mg injected subcutaneously in the abdomen once a week, adjusted on trough testosterone measured 7 days after the most recent dose", "duration": "ongoing, per the label", "outcome": "The label states safety and efficacy were not established in men with age-related hypogonadism or in males under 18.", "source": { "title": "FDA label for Testosterone Enanthate Injection", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209863s020lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-enanthate/protocols/0" ] } ], "community": [ { "description": "Community users report beginner testosterone enanthate cycles at 500 mg per week, with advanced protocols using 500–750 mg per week combined with additional compounds, and cutting cycles as low as 250 mg every other day.", "source": { "title": "Testosterone Enanthate Cycle Guide", "url": "https://muscleandbrawn.com/anabolics/testosterone-enanthate-cycle/" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-enanthate/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:testosterone-enanthate/community/0", "url": "https://muscleandbrawn.com/anabolics/testosterone-enanthate-cycle/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 120, "lowerHours": 108, "source": "FDA label", "upperHours": 132 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209863s020lbl.pdf", "https://www.fda.gov/media/123591/download", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+enanthate", "https://muscleandbrawn.com/anabolics/testosterone-enanthate-cycle/" ] }, "library:hormone-testosterone-gel": { "id": "library:hormone-testosterone-gel", "path": "/library/hormone-testosterone-gel.html", "title": "Testosterone gel (transdermal)", "summary": "Daily transdermal testosterone, dosed by pump actuations or sachets rather than injection volume.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-gel", "title": "Testosterone gel (transdermal)", "summary": "Daily transdermal testosterone, dosed by pump actuations or sachets rather than injection volume.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Testosterone gel is approved by the US FDA as testosterone replacement therapy in males with primary hypogonadism or hypogonadotropic hypogonadism. Both linked labels carry a boxed warning that children exposed to treated skin have developed signs of virilization. The 2025 label removed its cardiovascular-risk warning and added warnings on venous blood clots and blood pressure increases. Labels also state that different topical products can give different testosterone exposure. This is regulator-approved labelling, not trial evidence.", "verdict": { "benefits": [ "Testosterone replacement in males with diagnosed hypogonadism." ], "risks": [ "Boxed warning: children exposed to treated skin have developed signs of virilization", "The 2025 label dropped the cardiovascular warning and added blood clot and blood pressure warnings", "Different topical products can give different testosterone exposure" ], "bottomLine": "Approved labelling rather than trial evidence: it treats diagnosed hypogonadism and carries a boxed skin-transfer warning.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: testosterone gel", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+gel" } ], "links": [ { "title": "AndroGel (testosterone) gel FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021015s036lbl.pdf" }, { "title": "VOGELXO (testosterone) gel FDA label 2025", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204399s016lbl.pdf" } ], "protocols": [ { "population": "Males with primary hypogonadism or hypogonadotropic hypogonadism, per the US label", "regimen": "50 mg of testosterone applied once daily to clean dry skin of the shoulders, upper arms and/or abdomen, adjustable between 25 mg and 100 mg daily", "duration": "Ongoing, per the label; dose changes after at least 14 days", "outcome": "Approved as testosterone replacement therapy; the boxed warning records virilization in children exposed to treated skin.", "source": { "title": "AndroGel (testosterone) gel FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021015s036lbl.pdf" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-gel/protocols/0" ] } ], "community": [ { "description": "FDA-approved testosterone gel formulations begin at 40–60 mg daily applied topically, with dose titration in 10–25 mg increments based on serum testosterone levels, reaching maximum doses of 100–120 mg daily depending on the specific gel product.", "source": { "title": "Pharmacology of testosterone replacement therapy preparations", "url": "https://tau.amegroups.org/article/view/11328/13164" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-gel/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:testosterone-gel/community/0", "url": "https://tau.amegroups.org/article/view/11328/13164", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 2, "source": "Transdermal; steady state in 24-48 h" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021015s036lbl.pdf", "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204399s016lbl.pdf", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+gel", "https://tau.amegroups.org/article/view/11328/13164" ] }, "library:hormone-testosterone-isocaproate": { "id": "library:hormone-testosterone-isocaproate", "path": "/library/hormone-testosterone-isocaproate.html", "title": "Testosterone isocaproate", "summary": "A mid-length testosterone ester that only ever appears as one component of a blend such as Sustanon.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-isocaproate", "title": "Testosterone isocaproate", "summary": "A mid-length testosterone ester that only ever appears as one component of a blend such as Sustanon.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "reference", "evidenceSummary": "Testosterone isocaproate is a mid-length testosterone ester used exclusively as one of the four esters in Sustanon-type blends. No dedicated human pharmacokinetic study of this ester in isolation was located in the literature search performed for this entry; every published pharmacokinetic figure for isocaproate is confounded with the other esters (propionate, phenylpropionate, decanoate) it is always co-administered with in the same injection, so no single-compound half-life can honestly be reported here.", "verdict": { "benefits": [ "Contributes a mid-length release phase to blended esters such as Sustanon." ], "risks": [ "No dedicated single-compound human pharmacokinetic study exists for this ester alone; published data is confounded with the other esters in the same blend.", "Never marketed or studied as a standalone injectable." ], "bottomLine": "A mid-length testosterone ester known only as one component of blends such as Sustanon; no half-life for the isolated compound has been established." }, "originalLinks": [ { "title": "Testosterone esters — Wikipedia overview", "url": "https://en.wikipedia.org/wiki/Testosterone_ester" } ], "links": [ { "title": "Testosterone ester — Wikipedia overview", "url": "https://en.wikipedia.org/wiki/Testosterone_ester" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://en.wikipedia.org/wiki/Testosterone_ester" ] }, "library:hormone-testosterone-phenylpropionate": { "id": "library:hormone-testosterone-phenylpropionate", "path": "/library/hormone-testosterone-phenylpropionate.html", "title": "Testosterone phenylpropionate", "summary": "A mid-length testosterone ester, almost always used as one component of a blend such as Sustanon rather than on its own.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-phenylpropionate", "title": "Testosterone phenylpropionate", "summary": "A mid-length testosterone ester, almost always used as one component of a blend such as Sustanon rather than on its own.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "reference", "evidenceSummary": "Testosterone phenylpropionate is a mid-length testosterone ester, hydrolysed to free testosterone after release from an intramuscular oil depot. It is one of four esters in Sustanon-type blends and has rarely been formulated or studied as a standalone injectable. Compiled clinical-pharmacology references (e.g. Wright & Burgess, Long Acting Injections and Implants, Springer 2012) describe a depot release lasting roughly eight days for this ester, but no dedicated single-compound human pharmacokinetic trial for phenylpropionate alone was located; the figure is a compiled reference value, not a primary study result.", "verdict": { "benefits": [ "Contributes a mid-length release phase to blended esters such as Sustanon, between the fast propionate and the slow decanoate." ], "risks": [ "No dedicated single-compound human pharmacokinetic study exists; the release-duration figure comes from a compiled clinical-pharmacology reference, not a primary trial.", "Never marketed or studied as a standalone injectable." ], "bottomLine": "A mid-length testosterone ester known mainly as one component of blends such as Sustanon, with no dedicated human PK trial of its own." }, "originalLinks": [ { "title": "Testosterone esters — Wikipedia overview", "url": "https://en.wikipedia.org/wiki/Testosterone_ester" } ], "links": [ { "title": "Testosterone ester — Wikipedia overview", "url": "https://en.wikipedia.org/wiki/Testosterone_ester" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 192, "source": "Compiled clinical-pharmacology reference (Wright & Burgess, Long Acting Injections and Implants, 2012) — depot release duration, not a dedicated single-compound PK trial" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://en.wikipedia.org/wiki/Testosterone_ester" ] }, "library:hormone-testosterone-propionate": { "id": "library:hormone-testosterone-propionate", "path": "/library/hormone-testosterone-propionate.html", "title": "Testosterone propionate", "summary": "Short-acting testosterone ester, half-life around two to three days, requiring frequent injection.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-propionate", "title": "Testosterone propionate", "summary": "Short-acting testosterone ester, half-life around two to three days, requiring frequent injection.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "reference", "evidenceSummary": "Testosterone propionate is a short-acting ester of testosterone. The linked sources are review articles: one revisits the medicinal use of testosterone and related steroids, the other reviews testosterone replacement and the prostate. They describe therapeutic uses and safety questions for this drug class rather than trials of propionate itself. This is general reference reading, not trial evidence for this particular ester.", "verdict": { "benefits": [ "Review articles describe therapeutic uses for testosterone and related steroids as a class" ], "risks": [ "The sources are reviews of the drug class, not trials of this short-acting ester", "The same reviews raise open safety questions, including effects on the prostate" ], "bottomLine": "A short-acting testosterone ester backed here by class-level reviews, not trials of the ester itself." }, "originalLinks": [ { "title": "DailyMed: testosterone propionate", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+propionate" } ], "links": [ { "title": "Medicinal Use of Testosterone and Related Steroids Revisited", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919692/" }, { "title": "The effects of testosterone replacement therapy on the prostate: a clinical perspective", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392157/" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 19.200000000000003, "source": "Published ester PK" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919692/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392157/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=testosterone+propionate" ] }, "library:hormone-testosterone-undecanoate": { "id": "library:hormone-testosterone-undecanoate", "path": "/library/hormone-testosterone-undecanoate.html", "title": "Testosterone undecanoate", "summary": "A long-acting testosterone ester, given as an intramuscular depot or an oral capsule, for confirmed male hypogonadism.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:testosterone-undecanoate", "title": "Testosterone undecanoate", "summary": "A long-acting testosterone ester, given as an intramuscular depot or an oral capsule, for confirmed male hypogonadism.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "regulatory", "evidenceSummary": "Testosterone undecanoate is a long-acting ester of testosterone, delivered either as an intramuscular depot injection or as an oral capsule formulated for lymphatic absorption. It is approved in the European Union as an injectable depot for male hypogonadism and in the United States as an oral capsule for the same indication, with regulatory review covering pharmacokinetics, cardiovascular safety, and hepatic effects in adult men with confirmed testosterone deficiency.", "verdict": { "benefits": [ "Regulatory-reviewed option for restoring serum testosterone to the normal range in men with confirmed hypogonadism.", "Available in both a long-acting intramuscular depot form and an oral capsule form, reviewed by the EMA and FDA respectively.", "Extensive postmarketing history as one of the original approved testosterone replacement therapies, first approved in the 1950s." ], "risks": [ "FDA labeling carries a boxed warning for increases in blood pressure with the oral capsule form.", "Depot injection formulations have been associated with rare pulmonary oil microembolism reactions at the time of injection.", "Long-term cardiovascular and prostate safety in men without confirmed hypogonadism has not been established in either label." ], "bottomLine": "Testosterone undecanoate is a regulator-approved testosterone replacement therapy for men with confirmed hypogonadism, with distinct EU depot-injection and US oral-capsule labels covering different regimens and monitoring requirements.", "approvalStatus": "EMA-approved (depot injection) and FDA-approved (oral capsule), as separate formulations." }, "originalLinks": [ { "title": "Nebido 1000 mg/4 ml Summary of Product Characteristics (EMC/UK)", "url": "https://www.medicines.org.uk/emc/product/14631/smpc" }, { "title": "JATENZO (testosterone undecanoate) capsule label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ed7b5d41-7475-4c10-99b9-b62b3434ae60" } ], "links": [ { "title": "Nebido 1000 mg/4 ml Summary of Product Characteristics (EMC/UK)", "url": "https://www.medicines.org.uk/emc/product/14631/smpc" }, { "title": "JATENZO (testosterone undecanoate) capsule label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ed7b5d41-7475-4c10-99b9-b62b3434ae60" } ], "protocols": [ { "population": "adult men with hypogonadism confirmed by clinical features and biochemical testing", "regimen": "1000 mg testosterone undecanoate given by deep intramuscular injection, with the interval between the first two injections shortened to six weeks and every injection thereafter spaced ten to fourteen weeks apart", "duration": "ongoing replacement therapy, dosed every ten to fourteen weeks after the initial loading interval", "outcome": "European regulatory labeling establishing testosterone undecanoate depot injection as a testosterone replacement therapy that restores serum testosterone to the normal range in hypogonadal men", "source": { "title": "Nebido 1000 mg/4 ml Summary of Product Characteristics (EMC/UK)", "url": "https://www.medicines.org.uk/emc/product/14631/smpc" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-undecanoate/protocols/0" ] }, { "population": "adult men with primary hypogonadism or hypogonadotropic hypogonadism confirmed by low morning serum testosterone on two separate days; not established for age-related hypogonadism", "regimen": "oral capsules taken twice daily with food, at a labeled starting dosage of 237 mg in the morning and 237 mg in the evening, titrated between 158 mg and 396 mg twice daily based on serum testosterone measured six hours after the morning dose", "duration": "dose adjustment assessed at least seven days after initiation or any dosage change, with periodic monitoring thereafter", "outcome": "FDA-approved oral testosterone replacement shown in labeling trials to raise serum testosterone into the normal range in hypogonadal men, carrying a boxed warning for blood pressure increase", "source": { "title": "JATENZO (testosterone undecanoate) capsule label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ed7b5d41-7475-4c10-99b9-b62b3434ae60" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-undecanoate/protocols/1" ] } ], "community": [ { "description": "A clinical TRT reference documents a standard testosterone undecanoate protocol of 1000 mg given initially, followed by a second 1000 mg dose at six weeks, then 1000 mg maintenance injections administered every 10–12 weeks based on blood work.", "source": { "title": "Microdosing TRT – The Future of Testosterone Replacement Therapy - The Men's Health Clinic", "url": "https://themenshealthclinic.co.uk/microdosing-trt-the-future-of-testosterone-replacement-therapy/" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-undecanoate/community/0" ] }, { "description": "The same source documents an alternative protocol of 125 mg testosterone undecanoate administered via deep intramuscular injection weekly to maintain more consistent testosterone levels throughout treatment cycles.", "source": { "title": "Microdosing TRT – The Future of Testosterone Replacement Therapy - The Men's Health Clinic", "url": "https://themenshealthclinic.co.uk/microdosing-trt-the-future-of-testosterone-replacement-therapy/" }, "origins": [ "evidence.json#/catalog:hormone:testosterone-undecanoate/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:testosterone-undecanoate/community/0", "url": "https://themenshealthclinic.co.uk/microdosing-trt-the-future-of-testosterone-replacement-therapy/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:testosterone-undecanoate/community/1", "url": "https://themenshealthclinic.co.uk/microdosing-trt-the-future-of-testosterone-replacement-therapy/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 657.5999999999999, "lowerHours": 501.59999999999997, "source": "Nieschlag & Behre, Andrology (Springer, 2010) pp.441-446; Saad et al. 2007, Asian J Androl, PMID 17486268 — range reflects tea-seed-oil vs castor-oil vehicle", "upperHours": 813.5999999999999 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.medicines.org.uk/emc/product/14631/smpc", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ed7b5d41-7475-4c10-99b9-b62b3434ae60", "https://themenshealthclinic.co.uk/microdosing-trt-the-future-of-testosterone-replacement-therapy/" ] }, "library:hormone-trenbolone": { "id": "library:hormone-trenbolone", "path": "/library/hormone-trenbolone.html", "title": "Trenbolone", "summary": "A synthetic anabolic steroid with no approved human indication and extensive reports of severe adverse effects.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:trenbolone", "title": "Trenbolone", "summary": "A synthetic anabolic steroid with no approved human indication and extensive reports of severe adverse effects.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "Trenbolone is a synthetic nandrolone analogue first synthesized in the 1960s for veterinary use to enhance cattle growth. A human form, Parabolan, was briefly marketed in France starting in 1980 for muscle-wasting conditions but was withdrawn in 1987 due to significant adverse effects. No approved human medical indication exists.", "verdict": { "benefits": [], "risks": [ "90% of users report adverse effects", "Severe cardiovascular, hepatic, renal toxicity", "Psychiatric effects including aggression at higher doses", "Limited controlled human safety data" ], "bottomLine": "No approved human medical use; only animal studies and anecdotal reports, with documented serious toxicity.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "Adverse Effects of Trenbolone - ResearchGate", "url": "https://www.researchgate.net/publication/390366632_ADVERSE_EFFECTS_OF_TRENBOLONE_A_STRUCTURED_REVIEW_OF_CASE_REPORTS_IN_HUMANS" }, { "title": "Trenbolone and Psychological Distress - ScienceDirect", "url": "https://www.sciencedirect.com/science/article/pii/S0955395924003207" } ], "links": [ { "title": "Adverse Effects of Trenbolone - ResearchGate", "url": "https://www.researchgate.net/publication/390366632_ADVERSE_EFFECTS_OF_TRENBOLONE_A_STRUCTURED_REVIEW_OF_CASE_REPORTS_IN_HUMANS" }, { "title": "Trenbolone and Psychological Distress - ScienceDirect", "url": "https://www.sciencedirect.com/science/article/pii/S0955395924003207" } ], "protocols": [], "community": [ { "description": "An intermediate protocol shared on Swolverine describes trenbolone enanthate dosed at 300–400 mg per week for 8–10 weeks, administered twice weekly, combined with testosterone enanthate 200–300 mg/week.", "source": { "title": "Unlocking the Power of Trenbolone Enanthate: Benefits, Risks, and Expert Tips for Bodybuilders", "url": "https://swolverine.com/blogs/blog/unlocking-the-power-of-trenbolone-enanthate-benefits-risks-and-expert-tips-for-bodybuilders" }, "origins": [ "evidence.json#/catalog:hormone:trenbolone/community/0" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:trenbolone/community/0", "url": "https://swolverine.com/blogs/blog/unlocking-the-power-of-trenbolone-enanthate-benefits-risks-and-expert-tips-for-bodybuilders", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 72, "source": "Ruiz & Strain (eds.), Lowinson and Ruiz's Substance Abuse (2011), p.358 — compiled reference, no human clinical PK trial; a veterinary/livestock compound (as Finaplix)" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.researchgate.net/publication/390366632_ADVERSE_EFFECTS_OF_TRENBOLONE_A_STRUCTURED_REVIEW_OF_CASE_REPORTS_IN_HUMANS", "https://www.sciencedirect.com/science/article/pii/S0955395924003207", "https://swolverine.com/blogs/blog/unlocking-the-power-of-trenbolone-enanthate-benefits-risks-and-expert-tips-for-bodybuilders" ] }, "library:hormone-trestolone": { "id": "library:hormone-trestolone", "path": "/library/hormone-trestolone.html", "title": "Trestolone (MENT)", "summary": "A research compound investigated for male contraception that never received FDA approval.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle", "sexual-health" ], "research": [ { "id": "catalog:hormone:trestolone", "title": "Trestolone (MENT)", "summary": "A research compound investigated for male contraception that never received FDA approval.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "Trestolone (7α-methyl-19-nortestosterone, MENT) was first synthesized in 1963 and investigated by the Population Council as a candidate for male hormonal contraception and hypogonadism treatment. Despite promising results in the 1990s, it failed to receive FDA approval. No IND application renewal since 2010; Schedule III controlled substance.", "verdict": { "benefits": [ "Research suggested potential for male contraception and hypogonadism treatment" ], "risks": [ "No FDA approval; IND application not renewed since 2010", "Uncertain long-term prostate and cancer safety", "Schedule III controlled substance", "Absence of long-term human safety data" ], "bottomLine": "Preclinical and early-stage research only; never received FDA approval despite promising initial results.", "approvalStatus": "Never received FDA approval; its IND application lapsed in 2010." }, "originalLinks": [ { "title": "Investigations Into Human Metabolism of Trestolone - PubMed Central", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12983052/" }, { "title": "Trestolone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Trestolone" } ], "links": [ { "title": "Investigations Into Human Metabolism of Trestolone - PubMed Central", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12983052/" }, { "title": "Trestolone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Trestolone" } ], "protocols": [], "community": [ { "description": "Users on Biomogging report trestolone acetate dosing of 25-30 mg daily for entry level, 35-50 mg daily for most users, and 60-75 mg daily for advanced users administered via daily subcutaneous injection.", "source": { "title": "Trestolone (MENT) Compound Profile - Biomogging", "url": "https://www.biomogging.com/compounds/trestolone" }, "origins": [ "evidence.json#/catalog:hormone:trestolone/community/0" ] }, { "description": "A protocol shared on Biomogging describes splitting doses above 40 mg daily into AM and PM administrations, with 6-10 week cycles typical, often stacked with 150-200 mg weekly testosterone base.", "source": { "title": "Trestolone Administration and Dosing - Biomogging", "url": "https://www.biomogging.com/compounds/trestolone" }, "origins": [ "evidence.json#/catalog:hormone:trestolone/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:trestolone/community/0", "url": "https://www.biomogging.com/compounds/trestolone", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:trestolone/community/1", "url": "https://www.biomogging.com/compounds/trestolone", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC12983052/", "https://en.wikipedia.org/wiki/Trestolone", "https://www.biomogging.com/compounds/trestolone" ] }, "library:hormone-turinabol": { "id": "library:hormone-turinabol", "path": "/library/hormone-turinabol.html", "title": "Turinabol (Chlorodehydromethyltestosterone)", "summary": "An anabolic steroid with historical use in East German doping programs and no modern approved indication.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:turinabol", "title": "Turinabol (Chlorodehydromethyltestosterone)", "summary": "An anabolic steroid with historical use in East German doping programs and no modern approved indication.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "Turinabol (4-chlorodehydromethyltestosterone) is an anabolic steroid introduced in the 1960s for recovery after major surgery. It was infamously administered to approximately ten thousand East German athletes as part of a systematic state-sponsored doping program. Modern controlled human trials do not exist; banned by WADA.", "verdict": { "benefits": [], "risks": [ "Muscle tightness, acne, functional liver damage", "Amenorrhea in women", "WADA banned substance", "Obtained from uncontrolled sources with contamination risk" ], "bottomLine": "No approved medical use; controlled human safety and efficacy data absent.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "Controlled Administration of Dehydrochloromethyltestosterone - bioRxiv", "url": "https://www.biorxiv.org/content/10.1101/2021.08.02.454719.full.pdf" }, { "title": "Chlorodehydromethyltestosterone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Chlorodehydromethyltestosterone" } ], "links": [ { "title": "Controlled Administration of Dehydrochloromethyltestosterone - bioRxiv", "url": "https://www.biorxiv.org/content/10.1101/2021.08.02.454719.full.pdf" }, { "title": "Chlorodehydromethyltestosterone - Wikipedia", "url": "https://en.wikipedia.org/wiki/Chlorodehydromethyltestosterone" } ], "protocols": [], "community": [ { "description": "A dosage protocol reported on Swolverine describes beginners starting at 20-40 mg daily divided into 2-3 doses throughout the day for 6-8 week cycles, with conservative progression to 30-40 mg by week 3-4.", "source": { "title": "Turinabol for Beginners: Cycle, Dosage, and What to Expect", "url": "https://swolverine.com/blogs/blog/turinabol-for-beginners-cycle-dosage-and-what-to-expect" }, "origins": [ "evidence.json#/catalog:hormone:turinabol/community/0" ] }, { "description": "A community protocol on Swolverine shows intermediate doses of 40-60 mg daily and advanced users reporting 60-80 mg daily within 6-8 week cycles, with emphasis on liver support.", "source": { "title": "Unlocking Gains - The Ultimate Guide to a Turinabol Cycle", "url": "https://swolverine.com/blogs/blog/unlocking-gains-the-ultimate-guide-to-a-turinabol-cycle-for-maximum-muscle-growth" }, "origins": [ "evidence.json#/catalog:hormone:turinabol/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:hormone:turinabol/community/0", "url": "https://swolverine.com/blogs/blog/turinabol-for-beginners-cycle-dosage-and-what-to-expect", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:hormone:turinabol/community/1", "url": "https://swolverine.com/blogs/blog/unlocking-gains-the-ultimate-guide-to-a-turinabol-cycle-for-maximum-muscle-growth", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.biorxiv.org/content/10.1101/2021.08.02.454719.full.pdf", "https://en.wikipedia.org/wiki/Chlorodehydromethyltestosterone", "https://swolverine.com/blogs/blog/turinabol-for-beginners-cycle-dosage-and-what-to-expect", "https://swolverine.com/blogs/blog/unlocking-gains-the-ultimate-guide-to-a-turinabol-cycle-for-maximum-muscle-growth" ] }, "library:hormone-yk-11": { "id": "library:hormone-yk-11", "path": "/library/hormone-yk-11.html", "title": "YK-11", "summary": "An experimental selective androgen receptor modulator with myostatin-inhibiting properties and documented neurological risks.", "aliases": [], "kind": "medication-hormone", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:hormone:yk-11", "title": "YK-11", "summary": "An experimental selective androgen receptor modulator with myostatin-inhibiting properties and documented neurological risks.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "hormone", "evidenceTier": "preclinical", "evidenceSummary": "YK-11 is a synthetic steroidal selective androgen receptor modulator first studied in 2011 by Japanese researcher Yuihi Kanno. It functions as a partial AR agonist and uniquely suppresses myostatin by upregulating follistatin. Recent research indicates YK-11 may promote oxidative stress and mitochondrial dysfunction, with potential neurological risks affecting memory consolidation.", "verdict": { "benefits": [ "Myostatin inhibition via follistatin upregulation in vitro" ], "risks": [ "No validated clinical studies to date", "Promotes oxidative stress and mitochondrial dysfunction", "Impairs memory consolidation at anabolic doses", "Safety, pharmacokinetics, and long-term effects poorly characterized" ], "bottomLine": "Experimental compound with preclinical myostatin-inhibiting promise but documented neurological and mitochondrial risks." }, "originalLinks": [ { "title": "YK11 Hippocampal Function - PubMed Central", "url": "https://pubmed.ncbi.nlm.nih.gov/38521455/" }, { "title": "YK-11 and Myostatin Inhibition - ChemicalBook", "url": "https://www.chemicalbook.com/article/side-effects-of-yk-11.htm" } ], "links": [ { "title": "YK11 Hippocampal Function - PubMed Central", "url": "https://pubmed.ncbi.nlm.nih.gov/38521455/" }, { "title": "YK-11 and Myostatin Inhibition - ChemicalBook", "url": "https://www.chemicalbook.com/article/side-effects-of-yk-11.htm" } ], "protocols": [], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:38521455", "https://www.chemicalbook.com/article/side-effects-of-yk-11.htm" ] }, "library:lab-marker-panel": { "id": "library:lab-marker-panel", "path": "/library/lab-marker-panel.html", "title": "Blood panel", "summary": "Records lab-provided values with units, reference ranges and collection context. No interpretation is applied.", "aliases": [], "kind": "lab-marker", "categories": [ "longevity" ], "research": [ { "id": "catalog:lab-marker:panel", "title": "Blood panel", "summary": "Records lab-provided values with units, reference ranges and collection context. No interpretation is applied.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "lab-marker", "evidenceTier": "reference", "evidenceSummary": "This entry records laboratory values with their units and reference ranges. The values are measurements, not diagnoses, and nothing here interprets them. A MedlinePlus consumer page explains how lab results and reference ranges are read. Collection details are kept so results can be compared later.", "verdict": { "benefits": [ "Records laboratory values with units and reference ranges so results can be compared later.", "Collection details are kept alongside the numbers." ], "risks": [ "The values are measurements, not diagnoses, and nothing here interprets them.", "A reference range describes a comparison group, not a verdict on one person." ], "bottomLine": "A lab panel records measured values with their units and ranges; it does not diagnose anything on its own." }, "originalLinks": [ { "title": "MedlinePlus: Understanding laboratory tests", "url": "https://medlineplus.gov/lab-tests/" } ], "links": [ { "title": "How to Understand Your Lab Results (MedlinePlus)", "url": "https://medlineplus.gov/lab-tests/how-to-understand-your-lab-results/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.cdc.gov/cholesterol/testing/index.html", "outcome": "no-practice-description", "reason": "The inspected CDC page explains cholesterol-panel contents and preparation advice. No community testing schedule was imported." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://medlineplus.gov/lab-tests/how-to-understand-your-lab-results/", "https://medlineplus.gov/lab-tests/" ] }, "library:medication-antacid": { "id": "library:medication-antacid", "path": "/library/medication-antacid.html", "title": "Antacid / PPI", "summary": "Omeprazole and similar. Relevant beyond the symptom: sustained acid suppression reduces absorption of magnesium, B12 and iron.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:antacid", "title": "Antacid / PPI", "summary": "Omeprazole and similar. Relevant beyond the symptom: sustained acid suppression reduces absorption of magnesium, B12 and iron.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "reference", "evidenceSummary": "Proton pump inhibitors block the H+/K+-ATPase pump in stomach parietal cells and so reduce acid. A 2025 review describes them as widely prescribed for reflux, peptic ulcer disease and prevention of gastrointestinal bleeding. The same review lists interactions, including omeprazole reducing the effect of clopidogrel, and links long-term use to vitamin B12 and calcium deficiency, fractures and more infections. This is a general review, not a regulator label or a trial.", "verdict": { "benefits": [ "A 2025 review describes these drugs as widely prescribed for reflux and peptic ulcer disease.", "They block the stomach's acid pump directly, and are used to prevent gastrointestinal bleeding." ], "risks": [ "Long-term use is linked to vitamin B12 and calcium deficiency, fractures and more infections.", "Omeprazole reduces the effect of clopidogrel.", "The single source is a general review, not a regulator label or a trial." ], "bottomLine": "Proton pump inhibitors cut stomach acid; long-term use is linked to nutrient deficiency, fractures and infections." }, "originalLinks": [ { "title": "DailyMed: omeprazole", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=omeprazole" } ], "links": [ { "title": "Pharmacodynamics, pharmacokinetics, interactions with other drugs, toxicity and clinical effectiveness of proton pump inhibitors", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325061/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. A product's list of available dosage forms, including a paediatric formulation, is not a reported community routine.", "checks": [ { "url": "https://www.nhs.uk/medicines/gaviscon/about-gaviscon/", "outcome": "no-practice-description", "reason": "A product's list of available dosage forms, including a paediatric formulation, is not a reported community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 1, "source": "FDA label, omeprazole; effect outlasts plasma level" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325061/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=omeprazole" ] }, "library:medication-antibiotic-course": { "id": "library:medication-antibiotic-course", "path": "/library/medication-antibiotic-course.html", "title": "Antibiotic course (generic)", "summary": "A placeholder for whatever you were prescribed, so the course is on the timeline without needing a catalogue entry per drug. Rename it to the actual antibiotic.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:antibiotic-course", "title": "Antibiotic course (generic)", "summary": "A placeholder for whatever you were prescribed, so the course is on the timeline without needing a catalogue entry per drug. Rename it to the actual antibiotic.", "uncertainty": "Deliberately generic. Dose, interval and duration come from your prescription, not from here — they vary by drug, indication and body weight.", "namespace": "medication", "evidenceTier": "reference", "evidenceSummary": "Antibiotics are prescription medicines used to treat bacterial infections, and approved uses, risks and monitoring differ for each drug. The two linked items cover antibiotic prophylaxis, including before dental procedures in people with joint replacements, rather than antibiotics in general. They are reference and conference material, not a regulator label or a large trial. No general claim about how well antibiotic courses work can be drawn from them.", "verdict": { "benefits": [ "Antibiotics are prescription medicines for bacterial infections, with uses set per drug" ], "risks": [ "The linked material covers prophylaxis before procedures, not antibiotic courses in general", "It is reference and conference material, not a regulator label or a large trial", "No general claim about how well antibiotic courses work follows from these sources" ], "bottomLine": "The sources here describe antibiotic prophylaxis before procedures and support no general claim about antibiotic courses." }, "originalLinks": [ { "title": "DailyMed: search by drug name", "url": "https://dailymed.nlm.nih.gov/dailymed/" }, { "title": "WHO: antibiotic resistance", "url": "https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance" } ], "links": [ { "title": "Antimicrobial Prophylaxis in Adults - Mayo Clinic Proceedings", "url": "https://doi.org/10.4065/75.1.98" }, { "title": "Antibiotic Prophylaxis before Dental Procedures to Prevent Prosthetic Joint Infections", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11777115/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.cdc.gov/antibiotic-use/index.html", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://www.cdc.gov/antibiotic-use/communication-resources/index.html", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://www.cdc.gov/antibiotic-use/took-your-last-dose.html", "outcome": "not-found", "reason": "Independent direct retrieval returned HTTP 404. No description was verified at this attempted address." }, { "url": "https://www.cdc.gov/antibiotic-use/materials-references/index.html", "outcome": "not-found", "reason": "Independent direct retrieval returned HTTP 404. No description was verified at this attempted address." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "doi:10.4065/75.1.98", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11777115/", "https://dailymed.nlm.nih.gov/dailymed/", "https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance" ] }, "library:medication-antihistamine": { "id": "library:medication-antihistamine", "path": "/library/medication-antihistamine.html", "title": "Antihistamine (non-drowsy)", "summary": "Cetirizine, loratadine and similar. Seasonal use is worth logging — allergy load itself affects sleep and training quality.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:antihistamine", "title": "Antihistamine (non-drowsy)", "summary": "Cetirizine, loratadine and similar. Seasonal use is worth logging — allergy load itself affects sleep and training quality.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "reference", "evidenceSummary": "Cetirizine and loratadine are second-generation antihistamines. A clinical reference states cetirizine is FDA-approved for allergic rhinitis and chronic hives, was approved in the United States in 1995 and later sold over the counter. A study of FDA adverse-event reports found strong drowsiness signals for both drugs, so the non-drowsy label does not mean drowsiness never occurs. That study counts spontaneous reports, not trial results. Evidence here is reference-level plus report-database analysis.", "verdict": { "benefits": [ "Cetirizine treats allergic rhinitis and chronic hives, and is sold over the counter." ], "risks": [ "Adverse-event reports show strong drowsiness signals for both cetirizine and loratadine", "The non-drowsy label does not mean drowsiness never happens", "That analysis counts spontaneous reports, not trial results" ], "bottomLine": "Approved over-the-counter allergy medicines that still show clear drowsiness signals in adverse reports.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: cetirizine", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=cetirizine" } ], "links": [ { "title": "Cetirizine - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK549776/" }, { "title": "High-risks drug adverse events associated with Cetirizine and Loratadine", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11387460/" } ], "protocols": [ { "population": "adults and children aged 12 and over with allergic rhinitis or chronic urticaria, per the FDA-approved indication this reference describes", "regimen": "cetirizine 5-10 mg by mouth once daily, with 2.5-10 mg once daily in younger age bands", "duration": "not stated", "outcome": "The reference states cetirizine is FDA-approved for allergic rhinitis and chronic urticaria, approved in the US in 1995 and later sold over the counter.", "source": { "title": "Cetirizine - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK549776/" }, "origins": [ "evidence.json#/catalog:medication:antihistamine/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The proposed text only lists medication classes and available dosage forms, not a reported community routine.", "checks": [ { "url": "https://www.nhs.uk/medicines/antihistamines/", "outcome": "no-practice-description", "reason": "The proposed text only lists medication classes and available dosage forms, not a reported community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 8, "source": "FDA label, cetirizine" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/books/NBK549776/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC11387460/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=cetirizine" ] }, "library:medication-aspirin": { "id": "library:medication-aspirin", "path": "/library/medication-aspirin.html", "title": "Aspirin", "summary": "NSAID, and an irreversible platelet inhibitor. The antiplatelet effect lasts the life of the platelet, roughly a week, long after the drug itself has cleared.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing", "longevity" ], "research": [ { "id": "catalog:medication:aspirin", "title": "Aspirin", "summary": "NSAID, and an irreversible platelet inhibitor. The antiplatelet effect lasts the life of the platelet, roughly a week, long after the drug itself has cleared.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Aspirin was the first antiplatelet medicine and irreversibly blocks the cyclooxygenase enzyme, cutting production of thromboxane A2, which drives platelet clumping. A pharmacology review describes antiplatelet therapy reducing cardiovascular risk after heart attack, bypass surgery and in atrial fibrillation, with aspirin still a mainstay. Neither linked source is a regulator label or a new trial; both are general reference texts. Dose-related trade-offs are not covered here.", "verdict": { "benefits": [ "Labelled for headache, muscle pain, toothache, menstrual pain, cold fever and minor arthritis pain.", "A pharmacology review describes aspirin as a mainstay of antiplatelet therapy after heart attack." ], "risks": [ "The cardiovascular material comes from general reference texts, not a label or a new trial.", "How effects change with the amount used is not covered by the sources here." ], "bottomLine": "Aspirin is a labelled pain and fever medicine and a long-standing antiplatelet drug, per reference texts." }, "originalLinks": [ { "title": "DailyMed: aspirin", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=aspirin" } ], "links": [ { "title": "Bayer Genuine Aspirin — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ca776c2-47ed-5107-e063-6394a90ac5df" }, { "title": "Aspirin: Pharmacology and Clinical Applications", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236360/" }, { "title": "Antiplatelet Medications - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK537062/" } ], "protocols": [ { "population": "Adults and children 12 years and over, per the US over-the-counter label", "regimen": "325 mg tablets: 1 or 2 tablets every 4 hours, or 3 tablets every 6 hours, not more than 12 tablets in 24 hours, with a full glass of water", "duration": "Not stated", "outcome": "Labelled to temporarily relieve headache, muscle pain, toothache, menstrual pain, the pain and fever of colds, and minor arthritis pain.", "source": { "title": "Bayer Genuine Aspirin — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ca776c2-47ed-5107-e063-6394a90ac5df" }, "origins": [ "evidence.json#/catalog:medication:aspirin/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt is expert advice about an enteric-coated product and includes a claimed stomach benefit; it does not document observed community use.", "checks": [ { "url": "https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/ask-the-experts/aspirin-stomach", "outcome": "no-practice-description", "reason": "The excerpt is expert advice about an enteric-coated product and includes a claimed stomach benefit; it does not document observed community use." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 3, "source": "FDA label, salicylate; dose-dependent" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ca776c2-47ed-5107-e063-6394a90ac5df", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236360/", "https://www.ncbi.nlm.nih.gov/books/NBK537062/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=aspirin" ] }, "library:medication-atorvastatin": { "id": "library:medication-atorvastatin", "path": "/library/medication-atorvastatin.html", "title": "Atorvastatin", "summary": "A statin that lowers LDL cholesterol by blocking an early step of hepatic cholesterol synthesis.", "aliases": [], "kind": "medication-hormone", "categories": [ "longevity" ], "research": [ { "id": "catalog:medication:atorvastatin", "title": "Atorvastatin", "summary": "A statin that lowers LDL cholesterol by blocking an early step of hepatic cholesterol synthesis.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Atorvastatin is a synthetic HMG-CoA reductase inhibitor, or statin, that lowers LDL cholesterol by blocking an early step in hepatic cholesterol synthesis. It is approved by the FDA to reduce the risk of myocardial infarction, stroke, and other cardiovascular events in adults with elevated cardiovascular risk, and separately to lower LDL cholesterol across several inherited and acquired lipid disorders, including pediatric familial hypercholesterolemia. Its cardiovascular outcome and safety data span numerous large randomized trials.", "verdict": { "benefits": [ "Reduce risk of myocardial infarction, stroke, revascularization, and angina in adults with elevated cardiovascular risk.", "One of the most extensively studied statins, with cardiovascular outcome trials spanning primary and secondary prevention populations.", "Approved down to pediatric familial hypercholesterolemia populations under specific age and diagnostic criteria." ], "risks": [ "Labeled risk of myopathy and rhabdomyolysis, a rare but serious muscle breakdown reaction.", "Not labeled for use during pregnancy or breastfeeding due to potential fetal harm.", "Liver enzyme elevations are a labeled adverse reaction requiring periodic monitoring." ], "bottomLine": "Atorvastatin is an FDA-approved, extensively studied statin for cardiovascular risk reduction and LDL lowering, labeled with monitoring requirements for muscle and liver effects.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "LIPITOR (atorvastatin calcium) tablet label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a60cc18b-0631-4cf0-b021-9f52224ece65" }, { "title": "LIPITOR full prescribing information — FDA AccessData", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020702s081lbl.pdf" } ], "links": [ { "title": "LIPITOR (atorvastatin calcium) tablet label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a60cc18b-0631-4cf0-b021-9f52224ece65" }, { "title": "LIPITOR full prescribing information — FDA AccessData", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020702s081lbl.pdf" } ], "protocols": [ { "population": "adults with multiple cardiovascular risk factors, established cardiovascular disease, or hyperlipidemia; pediatric patients ten years and older with heterozygous familial hypercholesterolemia", "regimen": "oral tablets at a labeled starting dosage of 10 or 20 mg once daily, with a dosage range of 10 mg to 80 mg once daily individualized to therapeutic response", "duration": "ongoing daily therapy, with response assessed as early as four weeks after initiation or dose change", "outcome": "FDA-approved labeling documenting reduced risk of myocardial infarction, stroke, revascularization procedures, and angina, along with LDL cholesterol reduction across studied populations", "source": { "title": "LIPITOR (atorvastatin calcium) tablet label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a60cc18b-0631-4cf0-b021-9f52224ece65" }, "origins": [ "evidence.json#/catalog:medication:atorvastatin/protocols/0" ] }, { "population": "adults and pediatric patients ten years and older across the labeled lipid-disorder and cardiovascular-risk-reduction indications", "regimen": "full prescribing information covering dosing in hepatic impairment, drug interactions, and pediatric dosing by Tanner stage", "duration": "chronic, ongoing oral therapy", "outcome": "complete FDA-approved prescribing information including labeled risk of myopathy and rhabdomyolysis and monitoring recommendations", "source": { "title": "LIPITOR full prescribing information — FDA AccessData", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020702s081lbl.pdf" }, "origins": [ "evidence.json#/catalog:medication:atorvastatin/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nhs.uk/medicines/atorvastatin/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 25, "lowerHours": 20, "source": "FDA label, Lipitor: parent-drug half-life is about 14 hours, but HMG-CoA reductase inhibitory activity (parent plus active metabolites) has a half-life of 20-30 hours, which is the figure usually quoted for dosing purposes", "upperHours": 30 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a60cc18b-0631-4cf0-b021-9f52224ece65", "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020702s081lbl.pdf" ] }, "library:medication-diclofenac-topical": { "id": "library:medication-diclofenac-topical", "path": "/library/medication-diclofenac-topical.html", "title": "Diclofenac gel (topical)", "summary": "Topical NSAID for a specific joint or muscle. Systemic exposure is a fraction of oral, which is the point.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:diclofenac-topical", "title": "Diclofenac gel (topical)", "summary": "Topical NSAID for a specific joint or muscle. Systemic exposure is a fraction of oral, which is the point.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Topical diclofenac is an NSAID applied to the skin. The linked FDA label covers diclofenac sodium topical solution 2%, approved for the pain of osteoarthritis of the knee, with initial US approval in 1988. It carries a boxed warning for serious cardiovascular and gastrointestinal events, as oral NSAIDs do. The label does not cover other joints or an over-the-counter gel.", "verdict": { "benefits": [ "A topical solution for the pain of osteoarthritis of the knee.", "First approved in the United States in 1988, so the profile is long established." ], "risks": [ "Boxed warning for serious cardiovascular and gastrointestinal events, as with oral NSAIDs.", "The label does not cover joints other than the knee, or an over-the-counter gel." ], "bottomLine": "Topical diclofenac is FDA-approved for knee osteoarthritis pain and carries a boxed heart and gut warning.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: diclofenac topical", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=diclofenac+sodium+topical" } ], "links": [ { "title": "Diclofenac Sodium topical gel FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207238ORig1s000lbl.pdf" }, { "title": "Diclofenac sodium topical gel 1% drug facts (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aee20924-79ab-400e-b9b6-418978914654" } ], "protocols": [ { "population": "adults with arthritis pain of the hand, wrist, elbow, foot, ankle or knee, per the US over-the-counter label", "regimen": "2 g applied to each affected hand, wrist or elbow, or 4 g to each affected foot, ankle or knee, four times a day; no more than 16 g a day on any one joint", "duration": "the label directs stopping at 21 days unless a doctor says otherwise", "outcome": "The label carries this regimen for temporary relief of arthritis pain.", "source": { "title": "Diclofenac sodium topical gel 1% drug facts (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aee20924-79ab-400e-b9b6-418978914654" }, "origins": [ "evidence.json#/catalog:medication:diclofenac-topical/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt describes UK prescription status and available forms, not a reported community routine.", "checks": [ { "url": "https://www.nhs.uk/medicines/diclofenac/about-diclofenac/", "outcome": "no-practice-description", "reason": "The excerpt describes UK prescription status and available forms, not a reported community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207238ORig1s000lbl.pdf", "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aee20924-79ab-400e-b9b6-418978914654", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=diclofenac+sodium+topical" ] }, "library:medication-dutasteride": { "id": "library:medication-dutasteride", "path": "/library/medication-dutasteride.html", "title": "Dutasteride", "summary": "An FDA-approved 5-alpha reductase inhibitor for benign prostatic hyperplasia, used off-label for hair loss.", "aliases": [], "kind": "medication-hormone", "categories": [ "anti-aging", "sexual-health" ], "research": [ { "id": "catalog:medication:dutasteride", "title": "Dutasteride", "summary": "An FDA-approved 5-alpha reductase inhibitor for benign prostatic hyperplasia, used off-label for hair loss.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Dutasteride (Avodart) is a 5-alpha reductase inhibitor approved by the FDA in 2001 for benign prostatic hyperplasia. It blocks both type 1 and type 2 5-alpha reductase enzymes, converting testosterone to DHT more effectively than finasteride. While FDA-approved only for BPH, it is prescribed off-label for male pattern baldness, where it is approved in South Korea (2009) and Japan (2015).", "verdict": { "benefits": [ "Benign prostatic hyperplasia in men." ], "risks": [ "Sexual dysfunction", "Decreased libido", "Off-label use for hair loss not FDA-approved in the U.S.", "Pregnancy category X (teratogenic)" ], "bottomLine": "FDA-approved for BPH only; off-label use for hair loss requires physician judgment and is approved in other countries only.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: dutasteride", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=dutasteride" }, { "title": "Dutasteride (Avodart) - American Hair Loss Association", "url": "https://www.americanhairloss.org/hair-loss-treatment/drug-therapy/dutasteride-avodart/" }, { "title": "Avodart Regulatory Status Global - HealthRX", "url": "https://healthrx.com/dutasteride/regulatory-status-global" } ], "links": [ { "title": "DailyMed: dutasteride", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=dutasteride" }, { "title": "Dutasteride (Avodart) - American Hair Loss Association", "url": "https://www.americanhairloss.org/hair-loss-treatment/drug-therapy/dutasteride-avodart/" }, { "title": "Avodart Regulatory Status Global - HealthRX", "url": "https://healthrx.com/dutasteride/regulatory-status-global" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nhs.uk/conditions/enlarged-prostate/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 840, "source": "FDA label, Avodart: terminal half-life about 5 weeks at steady state with daily dosing (single-dose values range 170-300 h depending on age)" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=dutasteride", "https://www.americanhairloss.org/hair-loss-treatment/drug-therapy/dutasteride-avodart/", "https://healthrx.com/dutasteride/regulatory-status-global" ] }, "library:medication-finasteride": { "id": "library:medication-finasteride", "path": "/library/medication-finasteride.html", "title": "Finasteride", "summary": "An FDA-approved 5-alpha reductase inhibitor used to treat benign prostatic hyperplasia.", "aliases": [], "kind": "medication-hormone", "categories": [ "anti-aging", "sexual-health" ], "research": [ { "id": "catalog:medication:finasteride", "title": "Finasteride", "summary": "An FDA-approved 5-alpha reductase inhibitor used to treat benign prostatic hyperplasia.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Finasteride (Proscar) is a 5-alpha reductase inhibitor approved by the FDA on June 19, 1992, for benign prostatic hyperplasia in men with enlarged prostate. It reduces DHT levels, causing prostate shrinkage and reducing risk of acute urinary retention and surgical intervention. FDA label was revised to note persistent erectile dysfunction and other sexual side effects after discontinuation.", "verdict": { "benefits": [ "Benign prostatic hyperplasia (BPH)", "Reduces risk of acute urinary retention and need for BPH-related surgery" ], "risks": [ "Persistent erectile dysfunction and sexual dysfunction reported after discontinuation", "Decreased libido", "Ejaculation disorders", "Rare reports of male breast cancer" ], "bottomLine": "FDA-approved for BPH with robust evidence, but updated label warns of persistent sexual side effects.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "PROSCAR (finasteride) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020180s049lbl.pdf" }, { "title": "Finasteride - Drugs.com", "url": "https://www.drugs.com/finasteride.html" } ], "links": [ { "title": "PROSCAR (finasteride) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020180s049lbl.pdf" }, { "title": "Finasteride - Drugs.com", "url": "https://www.drugs.com/finasteride.html" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nhs.uk/medicines/finasteride/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 9.5, "lowerHours": 3, "source": "FDA label, Proscar: single-dose half-life 3-16 hours in men 45-60y (6-15h in men over 70y)", "upperHours": 16 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020180s049lbl.pdf", "https://www.drugs.com/finasteride.html" ] }, "library:medication-ibuprofen": { "id": "library:medication-ibuprofen", "path": "/library/medication-ibuprofen.html", "title": "Ibuprofen", "summary": "NSAID. Regular use around training suppresses the inflammatory signal that drives adaptation, so a week of it is worth seeing next to your training log.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:ibuprofen", "title": "Ibuprofen", "summary": "NSAID. Regular use around training suppresses the inflammatory signal that drives adaptation, so a week of it is worth seeing next to your training log.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Ibuprofen is a non-steroidal anti-inflammatory drug. A standard clinical reference lists its FDA-approved uses, including mild to moderate pain, fever, period pain, osteoarthritis and rheumatoid disorders. It blocks cyclooxygenase enzymes, which lowers prostaglandin production and so reduces pain and inflammation. Known risks include stomach bleeding, kidney impairment and cardiovascular events. The sources are a reference text and a narrative review, not new trial data.", "verdict": { "benefits": [ "Mild to moderate pain, fever, period pain and arthritic conditions.", "The mechanism is established: blocking cyclooxygenase lowers prostaglandins, pain and inflammation" ], "risks": [ "Known risks include stomach bleeding, kidney impairment and cardiovascular events", "The sources are a reference text and a narrative review, not new trial data" ], "bottomLine": "Ibuprofen is an approved anti-inflammatory painkiller with well-known stomach, kidney and cardiovascular risks.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: ibuprofen", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=ibuprofen" }, { "title": "EMA: ibuprofen", "url": "https://www.ema.europa.eu/en/medicines/human/referrals/ibuprofen-dexibuprofen-containing-medicines" } ], "links": [ { "title": "Motrin IB (ibuprofen) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56846774-8413-c306-e063-6394a90a2be8" }, { "title": "Ibuprofen - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK542299/" }, { "title": "Intravenously Administered Nonsteroidal Anti-Inflammatory Drugs in Clinical Practice: A Narrative Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859530/" } ], "protocols": [ { "population": "adults and children 12 years and over, per the US over-the-counter Motrin IB label", "regimen": "one 200 mg tablet every 4 to 6 hours while symptoms last, two tablets if one does not help, not more than 6 tablets in 24 hours", "duration": "up to 10 days for pain and 3 days for fever without seeing a doctor", "outcome": "The label's approved uses are temporary relief of minor aches and pains and temporary reduction of fever.", "source": { "title": "Motrin IB (ibuprofen) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56846774-8413-c306-e063-6394a90a2be8" }, "origins": [ "evidence.json#/catalog:medication:ibuprofen/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The proposed text only lists available dosage forms; no community routine is documented.", "checks": [ { "url": "https://www.nhs.uk/medicines/ibuprofen-for-adults/", "outcome": "no-practice-description", "reason": "The proposed text only lists available dosage forms; no community routine is documented." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 2, "source": "FDA label; 1.8-2 h" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56846774-8413-c306-e063-6394a90a2be8", "https://www.ncbi.nlm.nih.gov/books/NBK542299/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859530/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=ibuprofen", "https://www.ema.europa.eu/en/medicines/human/referrals/ibuprofen-dexibuprofen-containing-medicines" ] }, "library:medication-insulin": { "id": "library:medication-insulin", "path": "/library/medication-insulin.html", "title": "Insulin glargine", "summary": "A long-acting basal insulin analogue for once-daily use in type 1 and type 2 diabetes.", "aliases": [], "kind": "medication-hormone", "categories": [ "longevity" ], "research": [ { "id": "catalog:medication:insulin", "title": "Insulin glargine", "summary": "A long-acting basal insulin analogue for once-daily use in type 1 and type 2 diabetes.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Insulin glargine is a long-acting recombinant human insulin analog engineered to provide a relatively steady, once-daily basal insulin profile. It is approved by the FDA to improve glycemic control in adults and children with type 1 diabetes and in adults with type 2 diabetes, and it is not intended for treating diabetic ketoacidosis. Regulatory review covered pharmacokinetics, cardiovascular outcomes, and immunogenicity across large clinical trial programs.", "verdict": { "benefits": [ "Both type 1 and type 2 diabetes, with regulatory review covering large clinical trial programs.", "Long-acting profile allows once-daily basal dosing, reviewed and labeled for use across vial, cartridge, and prefilled-pen presentations.", "Decades of postmarketing surveillance data since its original approval in 2000." ], "risks": [ "Carries a boxed warning against use for treating diabetic ketoacidosis, which requires a different insulin regimen.", "Hypoglycemia, allergic reactions, and injection-site lipodystrophy are labeled adverse reactions.", "Not studied in children under six years of age or in pediatric type 2 diabetes." ], "bottomLine": "Insulin glargine is an FDA-approved long-acting basal insulin analog for type 1 and type 2 diabetes, with labeling that individualizes dosing rather than specifying a single universal amount.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "LANTUS (insulin glargine) injection label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b861fdd9-e134-436e-8c0c-a60dd0006dd3" }, { "title": "LANTUS full prescribing information — FDA AccessData", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021081s076lbl.pdf" } ], "links": [ { "title": "LANTUS (insulin glargine) injection label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b861fdd9-e134-436e-8c0c-a60dd0006dd3" }, { "title": "LANTUS full prescribing information — FDA AccessData", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021081s076lbl.pdf" } ], "protocols": [ { "population": "adults and children age six and older with type 1 diabetes mellitus; adults with type 2 diabetes mellitus", "regimen": "subcutaneous injection once daily at the same time each day, via vial, cartridge, or prefilled SoloStar pen, at a labeled starting dosage for insulin-naive type 2 patients of 10 units or 0.2 units per kilogram daily, individually titrated thereafter", "duration": "ongoing daily basal dosing, titrated based on periodic blood glucose monitoring", "outcome": "FDA-approved basal insulin analog shown in labeling trials to improve glycemic control versus comparator insulin regimens", "source": { "title": "LANTUS (insulin glargine) injection label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b861fdd9-e134-436e-8c0c-a60dd0006dd3" }, "origins": [ "evidence.json#/catalog:medication:insulin/protocols/0" ] }, { "population": "adults and pediatric patients with type 1 or type 2 diabetes mellitus", "regimen": "full prescribing information covering dose individualization, injection site rotation, and storage conditions for vial, cartridge, and prefilled pen presentations", "duration": "chronic, ongoing basal insulin therapy", "outcome": "complete FDA-approved prescribing information including boxed warning against use for treating diabetic ketoacidosis and against insulin pump or intravenous use", "source": { "title": "LANTUS full prescribing information — FDA AccessData", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021081s076lbl.pdf" }, "origins": [ "evidence.json#/catalog:medication:insulin/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nhs.uk/medicines/insulin/insulin-for-type-1-diabetes/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://www.nhs.uk/medicines/insulin/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 12, "source": "Bolli et al. 2026, Diabetes Obes Metab, PMID 42046184 — modeled literature estimate, not a figure stated in the FDA label, which describes only a flat 24-hour release profile qualitatively" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b861fdd9-e134-436e-8c0c-a60dd0006dd3", "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021081s076lbl.pdf" ] }, "library:medication-metformin": { "id": "library:medication-metformin", "path": "/library/medication-metformin.html", "title": "Metformin", "summary": "A biguanide that lowers blood glucose by reducing hepatic glucose output, first-line for type 2 diabetes.", "aliases": [], "kind": "medication-hormone", "categories": [ "longevity" ], "research": [ { "id": "catalog:medication:metformin", "title": "Metformin", "summary": "A biguanide that lowers blood glucose by reducing hepatic glucose output, first-line for type 2 diabetes.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Metformin is a biguanide oral medication that lowers blood glucose primarily by reducing hepatic glucose production and improving peripheral insulin sensitivity. It is approved by the FDA as an adjunct to diet and exercise for improving glycemic control in adults and in pediatric patients with type 2 diabetes, and it remains the most widely prescribed first-line oral diabetes medication worldwide. Decades of clinical trial and epidemiological data cover its cardiovascular, renal, and metabolic effects.", "verdict": { "benefits": [ "First-line oral therapy for type 2 diabetes in adults and in pediatric patients ten and older.", "One of the most extensively studied oral diabetes medications, with decades of clinical trial and real-world outcome data.", "Labeled indication is as an adjunct to diet and exercise rather than a replacement for lifestyle management." ], "risks": [ "Carries a boxed warning for lactic acidosis, a rare but serious adverse reaction more likely with renal impairment, hepatic impairment, or excessive alcohol intake.", "Labeling notes potential reduction in vitamin B12 levels with long-term use.", "Gastrointestinal adverse effects such as nausea and diarrhea are commonly reported." ], "bottomLine": "Metformin is an FDA-approved, extensively studied first-line oral medication for type 2 diabetes, labeled with a boxed warning for lactic acidosis and periodic monitoring requirements.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "Metformin hydrochloride tablet label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56d13a1c-b289-4528-b23c-60f5427b4552" } ], "links": [ { "title": "Metformin hydrochloride tablet label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56d13a1c-b289-4528-b23c-60f5427b4552" } ], "protocols": [ { "population": "adults and pediatric patients ten years of age and older with type 2 diabetes mellitus", "regimen": "oral tablets starting at 500 mg twice daily or 850 mg once daily, titrated in adults to a maximum of 2550 mg per day in divided doses, and in pediatric patients to a maximum of 2000 mg per day in divided doses", "duration": "ongoing daily oral therapy as an adjunct to diet and exercise, with dosage adjusted based on glycemic response", "outcome": "FDA-approved first-line oral therapy shown in labeling trials to improve glycemic control, carrying a boxed warning for the rare risk of lactic acidosis", "source": { "title": "Metformin hydrochloride tablet label — DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56d13a1c-b289-4528-b23c-60f5427b4552" }, "origins": [ "evidence.json#/catalog:medication:metformin/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6544683/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6779524/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 6.2, "source": "FDA label, Glumetza: plasma half-life about 6.2 hours (whole-blood/erythrocyte half-life is longer, about 17.6 hours, due to red-cell partitioning)" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56d13a1c-b289-4528-b23c-60f5427b4552" ] }, "library:medication-minoxidil": { "id": "library:medication-minoxidil", "path": "/library/medication-minoxidil.html", "title": "Minoxidil", "summary": "An FDA-approved topical medication for pattern hair loss that extends the hair growth phase and increases follicle size.", "aliases": [], "kind": "medication-hormone", "categories": [ "anti-aging" ], "research": [ { "id": "catalog:medication:minoxidil", "title": "Minoxidil", "summary": "An FDA-approved topical medication for pattern hair loss that extends the hair growth phase and increases follicle size.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Minoxidil is an FDA-approved topical medication for androgenetic alopecia (pattern hair loss) in both men and women. Topical minoxidil was approved by the FDA for male pattern hair loss in 1988 and for female pattern hair loss in 1991. It is available over-the-counter in 2% and 5% solutions and 5% foam formulations in the United States. Minoxidil works by enlarging miniaturized hair follicles, extending the anagen (growth) phase of the hair cycle, and shortening the telogen (resting) phase, thereby decreasing hair loss and increasing hair thickness. It is converted to its active form, minoxidil sulfate, in the scalp by the enzyme SULT1A1. Topical minoxidil has been found safe and effective in meta-analysis with similar efficacy and safety across different concentrations.", "verdict": { "benefits": [ "Male and female pattern hair loss with demonstrated efficacy.", "Topical formulation has favorable safety profile with no significant difference across concentrations", "First-line therapy in most clinical scenarios" ], "risks": [ "Oral minoxidil (off-label) associated with hypertrichosis (unwanted hair growth)", "Cardiovascular events rare but reported at higher oral doses", "Topical application limited to scalp area" ], "bottomLine": "Minoxidil is an FDA-approved, over-the-counter topical treatment for pattern hair loss with established efficacy and favorable safety profile when used topically.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: minoxidil", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=minoxidil" }, { "title": "Male and Female Pattern Hair Loss: A Guide to Treatment", "url": "https://consultqd.clevelandclinic.org/male-and-female-pattern-hair-loss-a-guide-to-treatment" }, { "title": "Minoxidil: a comprehensive review", "url": "https://pubmed.ncbi.nlm.nih.gov/34159872/" }, { "title": "Minoxidil: Formulation, Dosage & Side-Effects", "url": "https://ishrs.org/patients/treatments-for-hair-loss/medications/minoxidil/" } ], "links": [ { "title": "DailyMed: minoxidil", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=minoxidil" }, { "title": "Male and Female Pattern Hair Loss: A Guide to Treatment", "url": "https://consultqd.clevelandclinic.org/male-and-female-pattern-hair-loss-a-guide-to-treatment" }, { "title": "Minoxidil: a comprehensive review", "url": "https://pubmed.ncbi.nlm.nih.gov/34159872/" }, { "title": "Minoxidil: Formulation, Dosage & Side-Effects", "url": "https://ishrs.org/patients/treatments-for-hair-loss/medications/minoxidil/" } ], "protocols": [ { "population": "Men and women with male or female pattern hair loss", "regimen": "Topical minoxidil solution (2% or 5%) or foam (5%) applied to scalp", "duration": "Ongoing; effects typically require months of continuous use", "outcome": "Decreased hair loss, increased hair thickness, and follicle enlargement", "source": { "title": "Male and Female Pattern Hair Loss: A Guide to Treatment", "url": "https://consultqd.clevelandclinic.org/male-and-female-pattern-hair-loss-a-guide-to-treatment" }, "origins": [ "evidence.json#/catalog:medication:minoxidil/protocols/0" ] } ], "community": [ { "description": "A clinical review reports off-label oral minoxidil use for alopecia alongside established topical formulations, without supplying a dosing routine here.", "source": { "title": "Low-Dose Oral Minoxidil for Alopecia: A Comprehensive Review (PMC)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10806356/" }, "origins": [ "evidence.json#/catalog:medication:minoxidil/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10806356/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A clinical review reports off-label oral minoxidil use for alopecia alongside established topical formulations, without supplying a dosing routine here." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:medication:minoxidil/community/0", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10806356/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=minoxidil", "https://consultqd.clevelandclinic.org/male-and-female-pattern-hair-loss-a-guide-to-treatment", "pmid:34159872", "https://ishrs.org/patients/treatments-for-hair-loss/medications/minoxidil/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC10806356/" ] }, "library:medication-naproxen": { "id": "library:medication-naproxen", "path": "/library/medication-naproxen.html", "title": "Naproxen", "summary": "Longer-acting NSAID, typically twice daily rather than every few hours.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:naproxen", "title": "Naproxen", "summary": "Longer-acting NSAID, typically twice daily rather than every few hours.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Naproxen is a non-steroidal anti-inflammatory drug. A standard clinical reference lists FDA-approved uses including acute gout, ankylosing spondylitis, bursitis, tendonitis, osteoarthritis, rheumatoid arthritis, pain and period pain. It blocks cyclooxygenase enzymes and is described as a first-line option for several painful inflammatory conditions. Like other NSAIDs it carries risks of stomach bleeding, kidney problems and cardiovascular events. The second source is a review of back-pain treatment options.", "verdict": { "benefits": [ "Gout, arthritis, tendonitis, bursitis, pain, period pain and fever.", "Described as a first-line option for several painful inflammatory conditions" ], "risks": [ "Like other anti-inflammatories it carries stomach bleeding, kidney and cardiovascular risks" ], "bottomLine": "An approved anti-inflammatory painkiller with a well-known profile of stomach, kidney and heart risks.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: naproxen", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=naproxen" } ], "links": [ { "title": "Aleve (naproxen sodium) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ca84972-f8c9-1881-e063-6294a90a9070" }, { "title": "Naproxen - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK525965/" }, { "title": "What a pain in the back: a review of current treatment options with a focus on naproxen sodium", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880755/" } ], "protocols": [ { "population": "adults and children 12 and over with minor aches, pains or fever, per the US over-the-counter label", "regimen": "1 caplet orally every 8 to 12 hours with a full glass of water; 2 caplets allowed in the first hour; no more than 3 caplets in 24 hours", "duration": "ongoing while symptoms last, per the label; stop after 10 days for pain or 3 days for fever unless a doctor says otherwise", "outcome": "The label states this temporarily relieves minor arthritis pain, muscular aches, backache, menstrual cramps, headache and toothache, and reduces fever.", "source": { "title": "Aleve (naproxen sodium) — US label (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ca84972-f8c9-1881-e063-6294a90a9070" }, "origins": [ "evidence.json#/catalog:medication:naproxen/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The proposed text only lists available dosage forms, not a reported community routine.", "checks": [ { "url": "https://www.nhs.uk/medicines/naproxen/", "outcome": "no-practice-description", "reason": "The proposed text only lists available dosage forms, not a reported community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 14, "source": "FDA label; 12-17 h" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ca84972-f8c9-1881-e063-6294a90a9070", "https://www.ncbi.nlm.nih.gov/books/NBK525965/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880755/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=naproxen" ] }, "library:medication-oral-rehydration": { "id": "library:medication-oral-rehydration", "path": "/library/medication-oral-rehydration.html", "title": "Oral rehydration salts", "summary": "Electrolyte replacement for illness, heat or heavy sweating.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing", "fitness-muscle" ], "research": [ { "id": "catalog:medication:oral-rehydration", "title": "Oral rehydration salts", "summary": "Electrolyte replacement for illness, heat or heavy sweating.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "reference", "evidenceSummary": "The World Health Organization publishes a monograph for making oral rehydration salts, including the newer lower-osmolarity formula. A review of acute gastroenteritis says WHO recommends oral rehydration salts as the first choice, because they replace fluid and salts, but they do not reduce stool volume, stool frequency or how long diarrhoea lasts. That review also describes proposed changes such as rice-based versions, zinc and probiotics. These are guidance and review sources rather than trial reports.", "verdict": { "benefits": [ "The WHO publishes a monograph for oral rehydration salts, including a lower-osmolarity formula.", "WHO recommends them as first choice in acute gastroenteritis, to replace fluid and salts." ], "risks": [ "They do not reduce stool volume, stool frequency or how long diarrhoea lasts.", "The sources here are guidance and a review, not trial reports.", "Rice-based versions, zinc and probiotics are proposals, not settled practice." ], "bottomLine": "Oral rehydration salts are WHO's first choice for replacing fluid and salts lost in diarrhoea." }, "originalLinks": [ { "title": "WHO: oral rehydration salts", "url": "https://www.who.int/publications/i/item/WHO-FCH-CAH-06.1" } ], "links": [ { "title": "Oral rehydration salts - WHO", "url": "https://www.who.int/publications/i/item/WHO-FCH-CAH-06.1" }, { "title": "Acute gastroenteritis—changes to the recommended original oral rehydrating salts: a review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773804/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.who.int/publications/i/item/WHO-FCH-CAH-06.1", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773804/" ] }, "library:medication-orforglipron": { "id": "library:medication-orforglipron", "path": "/library/medication-orforglipron.html", "title": "Orforglipron", "summary": "An oral small-molecule GLP-1 receptor agonist showing 10-11% weight loss in Phase III trials, pending regulatory approval in 2026.", "aliases": [], "kind": "medication-hormone", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:medication:orforglipron", "title": "Orforglipron", "summary": "An oral small-molecule GLP-1 receptor agonist showing 10-11% weight loss in Phase III trials, pending regulatory approval in 2026.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "clinical-study", "evidenceSummary": "Orforglipron (LY3502970) is an oral small-molecule GLP-1 receptor agonist being developed by Eli Lilly for obesity treatment. The ATTAIN-1 Phase III trial enrolled 3,127 adults with obesity over 72 weeks, demonstrating double-digit percentage mean weight loss, with the majority of participants achieving at least a 10% reduction and improvements in cardiometabolic parameters. The ATTAIN-2 trial evaluated orforglipron in adults with obesity or overweight and type 2 diabetes, with all studied amounts meeting primary and key secondary endpoints at 72 weeks. The highest-efficacy regimen, taken once daily without food or water restrictions, lowered weight by a clinically meaningful margin compared with placebo, with meaningful A1C reductions and improved cardiometabolic risk factors. Orforglipron is being developed as an oral medication taken on a daily schedule. With ATTAIN-2 completion, Lilly has the clinical data package required for global regulatory submissions in 2026.", "verdict": { "benefits": [ "Phase III trials (ATTAIN-1 and ATTAIN-2) demonstrate 10-11% weight loss", "Meaningful A1C reductions in patients with type 2 diabetes", "Once-daily oral administration without food/water restrictions", "Improvements in cardiometabolic risk factors demonstrated" ], "risks": [ "Not yet approved; regulatory submissions expected in 2026", "Gastrointestinal adverse events expected with GLP-1 agonist mechanism", "Long-term safety data beyond 72 weeks not yet available" ], "bottomLine": "Orforglipron is an oral GLP-1 receptor agonist showing 10-11% weight loss in Phase III trials, with regulatory submissions expected in 2026 for obesity and type 2 diabetes indications." }, "originalLinks": [ { "title": "Lilly's oral GLP-1, orforglipron, delivers weight loss of up to an average of 27.3 lbs in first of two pivotal Phase 3 trials in adults with obesity", "url": "https://hfsa.org/lillys-oral-glp-1-orforglipron-delivers-weight-loss-average-273-lbs-first-two-pivotal-phase-3" }, { "title": "Lilly's oral GLP-1, orforglipron, is successful in third Phase 3 trial, triggering global regulatory submissions this year for the treatment of obesity", "url": "https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-successful-third-phase-3-trial" }, { "title": "Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02165-8/abstract" } ], "links": [ { "title": "Lilly's oral GLP-1, orforglipron, delivers weight loss of up to an average of 27.3 lbs in first of two pivotal Phase 3 trials in adults with obesity", "url": "https://hfsa.org/lillys-oral-glp-1-orforglipron-delivers-weight-loss-average-273-lbs-first-two-pivotal-phase-3" }, { "title": "Lilly's oral GLP-1, orforglipron, is successful in third Phase 3 trial, triggering global regulatory submissions this year for the treatment of obesity", "url": "https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-successful-third-phase-3-trial" }, { "title": "Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02165-8/abstract" } ], "protocols": [ { "population": "3,127 adults with obesity (ATTAIN-1); additional patients with obesity and type 2 diabetes (ATTAIN-2)", "regimen": "Once-daily oral orforglipron 36 mg or placebo without food/water restrictions", "duration": "72 weeks (Phase III)", "outcome": "ATTAIN-1: 11.2% mean weight loss; ATTAIN-2: 10.5% mean weight loss vs. 2.2% placebo; meaningful A1C reduction", "source": { "title": "Lilly's oral GLP-1, orforglipron, delivers weight loss of up to an average of 27.3 lbs in first of two pivotal Phase 3 trials in adults with obesity", "url": "https://hfsa.org/lillys-oral-glp-1-orforglipron-delivers-weight-loss-average-273-lbs-first-two-pivotal-phase-3" }, "origins": [ "evidence.json#/catalog:medication:orforglipron/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.fda.gov/news-events/press-announcements/fda-approves-first-new-molecular-entity-under-national-priority-voucher-program", "outcome": "no-practice-description", "reason": "The inspected FDA announcement reports regulatory and clinical-trial information. Those facts were not repurposed as community practice." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 63.949999999999996, "lowerHours": 51.8, "source": "Ohwaki et al. 2026, J Diabetes Investig, PMID 41325139 — phase 1 ascending-dose study in Japanese participants, week-12 mean terminal half-life", "upperHours": 76.1 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://hfsa.org/lillys-oral-glp-1-orforglipron-delivers-weight-loss-average-273-lbs-first-two-pivotal-phase-3", "https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-successful-third-phase-3-trial", "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02165-8/abstract" ] }, "library:medication-paracetamol": { "id": "library:medication-paracetamol", "path": "/library/medication-paracetamol.html", "title": "Paracetamol (acetaminophen)", "summary": "Analgesic and antipyretic, not an anti-inflammatory. The usual choice when you want pain or fever relief without suppressing inflammation.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:paracetamol", "title": "Paracetamol (acetaminophen)", "summary": "Analgesic and antipyretic, not an anti-inflammatory. The usual choice when you want pain or fever relief without suppressing inflammation.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Paracetamol (acetaminophen) has an FDA-approved label; the linked one covers the intravenous form for mild to moderate pain, for moderate to severe pain alongside opioids, and for fever. The label carries a boxed warning about dosing errors and about acute liver failure, mostly when more than the recommended maximum is taken or when several paracetamol-containing products are combined. A 2026 review of cancer pain says the evidence for paracetamol there is limited and of low quality, with little added benefit next to strong opioids. Nothing in these links supports a specific rate of liver injury at normal use.", "verdict": { "benefits": [ "Mild to moderate pain, for severe pain alongside opioids, and for fever." ], "risks": [ "Boxed warning for dosing errors and acute liver failure, mainly past the label maximum.", "Combining several paracetamol-containing products is a named cause of that liver injury.", "In cancer pain the evidence is limited and low quality, adding little next to strong opioids." ], "bottomLine": "Paracetamol is an approved painkiller and fever medicine whose main danger is liver failure past the label maximum.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: acetaminophen", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=acetaminophen" }, { "title": "EMA: paracetamol", "url": "https://www.ema.europa.eu/en/medicines/human/referrals/paracetamol-containing-medicinal-products" } ], "links": [ { "title": "Acetaminophen Injection FDA label", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206968s000lbl.pdf" }, { "title": "Paracetamol and NSAIDs in Cancer Pain Management: Evidence Review and Treatment Considerations", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901147/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The proposed text only lists available dosage forms, not a reported community routine.", "checks": [ { "url": "https://www.nhs.uk/medicines/paracetamol-for-adults/", "outcome": "no-practice-description", "reason": "The proposed text only lists available dosage forms, not a reported community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 2, "source": "FDA label; 1.25-3 h" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206968s000lbl.pdf", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901147/", "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=acetaminophen", "https://www.ema.europa.eu/en/medicines/human/referrals/paracetamol-containing-medicinal-products" ] }, "library:medication-pentosan-polysulfate": { "id": "library:medication-pentosan-polysulfate", "path": "/library/medication-pentosan-polysulfate.html", "title": "Pentosan Polysulfate", "summary": "An FDA-approved medication for interstitial cystitis that restores bladder protective layer, with risk of vision changes from long-term use.", "aliases": [], "kind": "medication-hormone", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:medication:pentosan-polysulfate", "title": "Pentosan Polysulfate", "summary": "An FDA-approved medication for interstitial cystitis that restores bladder protective layer, with risk of vision changes from long-term use.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Pentosan polysulfate sodium (Elmiron) is an FDA-approved oral medication for relief of bladder pain or discomfort associated with interstitial cystitis, approved September 26, 1996. It is the most studied oral medication for interstitial cystitis, with evidence from over seven randomized trials involving 500+ patients (Grade B evidence). In one multicenter randomized controlled trial of 148 patients, 32% on pentosan polysulfate showed significant improvement compared with 16% on placebo. The mechanism involves restoration of the damaged glycosaminoglycan (GAG) protective layer on the bladder urothelium. However, post-marketing surveillance since approval has identified serious visual risks including progressive pigmentary maculopathy associated with long-term exposure that threatens vision.", "verdict": { "benefits": [ "Symptom relief in interstitial cystitis, shown in randomized trials.", "Addresses underlying GAG layer damage mechanism" ], "risks": [ "Post-marketing surveillance identified serious visual risk: progressive pigmentary maculopathy with long-term use", "Vision-threatening effects were not recognized in initial clinical trials", "21-year pharmacovigilance analysis documents previously unreported serious adverse events" ], "bottomLine": "Pentosan polysulfate is an FDA-approved medication for interstitial cystitis with demonstrated efficacy, but long-term use carries a risk of serious vision-threatening pigmentary eye changes identified through post-marketing surveillance.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "DailyMed: pentosan polysulfate", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=pentosan+polysulfate" }, { "title": "Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554761/" }, { "title": "Post-marketing safety of pentosan polysulfate sodium: a 21-year pharmacovigilance analysis of the FAERS database", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12872569/" }, { "title": "Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis", "url": "https://pubmed.ncbi.nlm.nih.gov/16706553/" } ], "links": [ { "title": "DailyMed: pentosan polysulfate", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=pentosan+polysulfate" }, { "title": "Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554761/" }, { "title": "Post-marketing safety of pentosan polysulfate sodium: a 21-year pharmacovigilance analysis of the FAERS database", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12872569/" }, { "title": "Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis", "url": "https://pubmed.ncbi.nlm.nih.gov/16706553/" } ], "protocols": [ { "population": "148 patients with interstitial cystitis", "regimen": "Pentosan polysulfate 100 mg three times daily oral", "duration": "Multicenter randomized controlled trial", "outcome": "32% showed significant improvement vs. 16% placebo; improved bladder pain and urinary urgency", "source": { "title": "Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis", "url": "https://pubmed.ncbi.nlm.nih.gov/16706553/" }, "origins": [ "evidence.json#/catalog:medication:pentosan-polysulfate/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://medlineplus.gov/druginfo/meds/a602007.html", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 23.5, "lowerHours": 20, "source": "FDA label, Elmiron: plasma radioactivity half-life about 20-27 hours across the 300/450 mg dose range (reflects total drug-related material, not necessarily unchanged parent)", "upperHours": 27 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=pentosan+polysulfate", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554761/", "https://pmc.ncbi.nlm.nih.gov/articles/PMC12872569/", "pmid:16706553" ] }, "library:medication-sildenafil": { "id": "library:medication-sildenafil", "path": "/library/medication-sildenafil.html", "title": "Sildenafil", "summary": "An FDA-approved phosphodiesterase-5 inhibitor used to treat erectile dysfunction and pulmonary arterial hypertension.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:medication:sildenafil", "title": "Sildenafil", "summary": "An FDA-approved phosphodiesterase-5 inhibitor used to treat erectile dysfunction and pulmonary arterial hypertension.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor approved by the FDA on March 27, 1998, as the first oral medication for erectile dysfunction. Subsequently approved for pulmonary arterial hypertension to improve exercise ability and delay clinical worsening in adults and pediatric patients (1-17 years). Under Viagra brand for ED; Revatio brand for PAH.", "verdict": { "benefits": [ "Erectile dysfunction in adults.", "Pulmonary arterial hypertension to improve exercise ability." ], "risks": [ "Headache", "Flushing", "Dyspepsia", "Nasal congestion", "Vision changes", "Priapism (rare)", "Cardiovascular events in susceptible patients" ], "bottomLine": "FDA-approved PDE5 inhibitor with established efficacy for two distinct approved indications.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "Label: SILDENAFIL CITRATE tablet - DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=49a95b25-08b3-4cfe-a60b-c5132c280be2" }, { "title": "Sildenafil - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK558978/" }, { "title": "FDA Approves Impotence Pill, Viagra - ScienceDaily", "url": "https://www.sciencedaily.com/releases/1998/04/980401074901.htm" } ], "links": [ { "title": "Label: SILDENAFIL CITRATE tablet - DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=49a95b25-08b3-4cfe-a60b-c5132c280be2" }, { "title": "Sildenafil - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK558978/" }, { "title": "FDA Approves Impotence Pill, Viagra - ScienceDaily", "url": "https://www.sciencedaily.com/releases/1998/04/980401074901.htm" } ], "protocols": [ { "population": "Adult men with erectile dysfunction", "regimen": "Oral phosphodiesterase-5 inhibitor; response dependent on sexual stimulation", "duration": "As-needed use per FDA indication", "outcome": "Improves erectile function compared to placebo", "source": { "title": "FDA Approves Impotence Pill, Viagra - ScienceDaily", "url": "https://www.sciencedaily.com/releases/1998/04/980401074901.htm" }, "origins": [ "evidence.json#/catalog:medication:sildenafil/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nhs.uk/medicines/sildenafil-viagra/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 4, "source": "FDA label, Viagra: parent and active N-desmethyl metabolite half-life about 4 hours" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=49a95b25-08b3-4cfe-a60b-c5132c280be2", "https://www.ncbi.nlm.nih.gov/books/NBK558978/", "https://www.sciencedaily.com/releases/1998/04/980401074901.htm" ] }, "library:medication-tadalafil": { "id": "library:medication-tadalafil", "path": "/library/medication-tadalafil.html", "title": "Tadalafil", "summary": "An FDA-approved phosphodiesterase-5 inhibitor used to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension.", "aliases": [], "kind": "medication-hormone", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:medication:tadalafil", "title": "Tadalafil", "summary": "An FDA-approved phosphodiesterase-5 inhibitor used to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "regulatory", "evidenceSummary": "Tadalafil is a phosphodiesterase-5 (PDE5) inhibitor approved by the FDA for three indications: erectile dysfunction, benign prostatic hyperplasia symptoms, and pulmonary arterial hypertension. Marketed as Cialis (ED/BPH), Adcirca (PAH), and in low-dose daily formulation for ED. Longer half-life than sildenafil enables once-daily dosing.", "verdict": { "benefits": [ "Erectile dysfunction.", "Benign prostatic hyperplasia symptoms.", "Pulmonary arterial hypertension." ], "risks": [ "Headache", "Flushing", "Dyspepsia", "Nasal congestion", "Back pain", "Priapism (rare)", "Vision and hearing changes" ], "bottomLine": "FDA-approved PDE5 inhibitor with three distinct approved indications and longer duration than sildenafil.", "approvalStatus": "FDA-approved." }, "originalLinks": [ { "title": "CIALIS (tadalafil) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021368s20s21lbl.pdf" }, { "title": "Tadalafil - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK603743/" } ], "links": [ { "title": "CIALIS (tadalafil) Label - FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021368s20s21lbl.pdf" }, { "title": "Tadalafil - StatPearls", "url": "https://www.ncbi.nlm.nih.gov/books/NBK603743/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nhs.uk/medicines/tadalafil/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 17.5, "source": "FDA label, Cialis: mean terminal half-life 17.5 hours" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021368s20s21lbl.pdf", "https://www.ncbi.nlm.nih.gov/books/NBK603743/" ] }, "library:medication-tesofensine": { "id": "library:medication-tesofensine", "path": "/library/medication-tesofensine.html", "title": "Tesofensine", "summary": "A neurotransmitter reuptake inhibitor showing significant weight loss in Phase II and III trials.", "aliases": [], "kind": "medication-hormone", "categories": [ "fat-loss" ], "research": [ { "id": "catalog:medication:tesofensine", "title": "Tesofensine", "summary": "A neurotransmitter reuptake inhibitor showing significant weight loss in Phase II and III trials.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "medication", "evidenceTier": "clinical-study", "evidenceSummary": "Tesofensine is an inhibitor of presynaptic serotonin, noradrenaline, and dopamine reuptake, acting as an appetite suppressant with effects on fat oxidation and energy expenditure. In Phase II trials, tesofensine produced mean weight loss of 4.5-10.6% at 24 weeks depending on dose, with placebo-subtracted weight loss of 4.5-10.6 kg. Phase III trials confirmed compelling efficacy and favorable safety profile. The most frequently reported adverse effects were gastrointestinal, similar to other weight-loss medications. Tesofensine was not approved in the United States but development continued in other contexts. Results suggest weight loss approximately twice that of some existing approved medications.", "verdict": { "benefits": [ "Demonstrated significant weight loss in Phase II and III randomized trials", "Safety profile favorable compared to placebo" ], "risks": [ "Gastrointestinal adverse events most common, similar to other weight-loss medications", "Not approved in United States", "Long-term safety and efficacy beyond trials not established" ], "bottomLine": "Tesofensine produced substantial weight loss in clinical trials but was not approved in major markets and development appears to have stalled.", "approvalStatus": "Not approved in the United States or other major markets." }, "originalLinks": [ { "title": "Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial", "url": "https://www.sciencedirect.com/science/article/abs/pii/S0140673608615251" }, { "title": "Tesofensine - Saniona", "url": "https://saniona.com/pipeline/tesofensine/" }, { "title": "Tesofensine Anti-Obesity Medication - Clinical Trials Arena", "url": "https://www.clinicaltrialsarena.com/projects/tesofensine/" } ], "links": [ { "title": "Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial", "url": "https://www.sciencedirect.com/science/article/abs/pii/S0140673608615251" }, { "title": "Tesofensine - Saniona", "url": "https://saniona.com/pipeline/tesofensine/" }, { "title": "Tesofensine Anti-Obesity Medication - Clinical Trials Arena", "url": "https://www.clinicaltrialsarena.com/projects/tesofensine/" } ], "protocols": [ { "population": "203 obese patients in Phase II trial (TIPO-1)", "regimen": "Tesofensine once-daily oral doses combined with diet", "duration": "24 weeks", "outcome": "Mean weight loss 4.5-10.6% depending on dose; placebo-subtracted loss 4.5-10.6 kg", "source": { "title": "Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial", "url": "https://www.sciencedirect.com/science/article/abs/pii/S0140673608615251" }, "origins": [ "evidence.json#/catalog:medication:tesofensine/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3055463/", "outcome": "trial-only", "reason": "The inspected PMC paper reports rat experiments. Animal interventions and mechanistic findings were not repurposed as human community practice." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 234, "source": "Lehr et al. 2007, Br J Clin Pharmacol, PMID 17324246 — human PK study; active metabolite M1 half-life is even longer, about 374 hours" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.sciencedirect.com/science/article/abs/pii/S0140673608615251", "https://saniona.com/pipeline/tesofensine/", "https://www.clinicaltrialsarena.com/projects/tesofensine/" ] }, "library:peptide-cjc-ipamorelin-blend": { "id": "library:peptide-cjc-ipamorelin-blend", "path": "/library/peptide-cjc-ipamorelin-blend.html", "title": "CJC-1295 / Ipamorelin blend", "summary": "Common combination vial pairing a GHRH analogue with a GH secretagogue. Sold premixed.", "aliases": [], "kind": "peptide", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:peptide:cjc-ipamorelin-blend", "title": "CJC-1295 / Ipamorelin blend", "summary": "Common combination vial pairing a GHRH analogue with a GH secretagogue. Sold premixed.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Human data covers the separate parts, not the blends sold today. A randomised placebo-controlled trial of CJC-1295 in healthy adults found dose-dependent rises in growth hormone and IGF-1, with no serious adverse reactions reported, and a second study found growth hormone pulses were preserved. Ipamorelin's own evidence is preclinical. Neither compound is approved for any use, and a 2026 review of peptide use in sport warns that supply is largely unregulated, with mislabelled or contaminated products and risks including cardiovascular strain and insulin resistance.", "verdict": { "benefits": [ "A placebo-controlled trial of CJC-1295 raised growth hormone and IGF-1 in healthy adults", "No serious adverse reactions were reported in that trial, and growth hormone pulses persisted" ], "risks": [ "Human data covers the separate parts, not the blends sold today; ipamorelin's data is preclinical", "Neither compound is approved for any use", "A review warns supply is unregulated, with mislabelled or contaminated products and heart strain" ], "bottomLine": "Human data exists for CJC-1295 alone, not the blend; neither part is approved and supply is unregulated." }, "originalLinks": [ { "title": "PubMed: growth hormone secretagogues", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=growth+hormone+secretagogue" } ], "links": [ { "title": "Peptide Wiki: CJC-1295 / Ipamorelin blend", "url": "https://vespassassina.github.io/peptide-wiki/peptides/cjc-1295.html" }, { "title": "Peptide Wiki: CJC-1295 / Ipamorelin blend", "url": "https://vespassassina.github.io/peptide-wiki/peptides/ipamorelin.html" }, { "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults (Teichman et al. 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/" }, { "title": "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog (Ionescu 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/17018654/" }, { "title": "A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review (Coutinho et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41880199/" }, { "title": "Ipamorelin, the first selective growth hormone secretagogue (Raun et al. 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" } ], "protocols": [ { "population": "healthy adults aged 21-61 in two randomised, placebo-controlled, double-blind ascending-dose trials", "regimen": "CJC-1295 subcutaneously, as single ascending doses in one trial and as two or three weekly or biweekly doses in the other", "duration": "28 days and 49 days", "outcome": "Mean plasma GH rose 2- to 10-fold for 6 days or more and IGF-1 1.5- to 3-fold for 9-11 days; no serious adverse reactions were reported.", "source": { "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults (Teichman et al. 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-ipamorelin-blend/protocols/0" ] }, { "population": "healthy men aged 20-40 years", "regimen": "a single injection of 60 or 90 micrograms per kg of CJC-1295, with 20-minute blood sampling over 12 h before and 1 week after", "duration": "single dose", "outcome": "Trough GH rose 7.5-fold, mean GH 46% and IGF-1 45%, with pulse frequency and magnitude unchanged; the two doses did not differ.", "source": { "title": "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog (Ionescu 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/17018654/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-ipamorelin-blend/protocols/1" ] }, { "population": "rat pituitary cells, pentobarbital-anaesthetised rats and conscious swine", "regimen": "single doses of ipamorelin; ED50 80 nmol/kg in rats and 2.3 nmol/kg in swine", "duration": "single dose", "outcome": "Ipamorelin released GH with potency and efficacy similar to GHRP-6 and, unlike GHRP-6 and GHRP-2, did not raise ACTH or cortisol.", "source": { "title": "Ipamorelin, the first selective growth hormone secretagogue (Raun et al. 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-ipamorelin-blend/protocols/2" ] } ], "community": [ { "description": "A protocol documented on fitness forums describes starting CJC-1295/ipamorelin blend at 0.3 mg daily before bedtime, escalating by 0.1 mg weekly for 8 weeks until reaching 1.0 mg daily maintenance, administered 5 days per week with 2 rest days.", "source": { "title": "CJC-1295/Ipamorelin Dosage Protocol: The Complete Clinical Guide", "url": "https://www.perfectb.com/cjc-1295-ipamorelin-dosage-protocol/" }, "origins": [ "evidence.json#/catalog:peptide:cjc-ipamorelin-blend/community/0" ] }, { "description": "CJC-1295 (with DAC) athletic recovery protocols described in dosing guides suggest 1-2 mg administered once or twice per week in the evening.", "source": { "title": "CJC-1295 & Sermorelin: Complete Dosing, Administration & Safety Guide", "url": "https://cjc-1295.com/article/cjc-1295-sermorelin-dosing-administration-safety" }, "origins": [ "evidence.json#/catalog:peptide:cjc-ipamorelin-blend/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [ "The attached trials concern individual components, not a clinical trial of this premixed blend. A community account about CJC-1295 with DAC does not establish a regimen for a CJC/ipamorelin blend or for no-DAC CJC." ], "community": [ { "origin": "evidence.json#/catalog:peptide:cjc-ipamorelin-blend/community/0", "url": "https://www.perfectb.com/cjc-1295-ipamorelin-dosage-protocol/", "claimMatch": "The attached trials concern individual components, not a clinical trial of this premixed blend. A community account about CJC-1295 with DAC does not establish a regimen for a CJC/ipamorelin blend or for no-DAC CJC. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "formulation-context-limited" }, { "origin": "evidence.json#/catalog:peptide:cjc-ipamorelin-blend/community/1", "url": "https://cjc-1295.com/article/cjc-1295-sermorelin-dosing-administration-safety", "claimMatch": "The attached trials concern individual components, not a clinical trial of this premixed blend. A community account about CJC-1295 with DAC does not establish a regimen for a CJC/ipamorelin blend or for no-DAC CJC. The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "formulation-context-limited" } ] } } ], "related": [ "peptide:cjc-1295", "peptide:ipamorelin" ], "conflicts": [], "sourceRefs": [ "https://vespassassina.github.io/peptide-wiki/peptides/cjc-1295.html", "https://vespassassina.github.io/peptide-wiki/peptides/ipamorelin.html", "pmid:16352683", "pmid:17018654", "pmid:41880199", "pmid:9849822", "https://pubmed.ncbi.nlm.nih.gov/?term=growth+hormone+secretagogue", "https://www.perfectb.com/cjc-1295-ipamorelin-dosage-protocol/", "https://cjc-1295.com/article/cjc-1295-sermorelin-dosing-administration-safety" ] }, "library:peptide-dihexa": { "id": "library:peptide-dihexa", "path": "/library/peptide-dihexa.html", "title": "Dihexa", "summary": "A neuropeptide showing regenerative effects in animal models of Alzheimer's and neurological injury, with no human trials.", "aliases": [], "kind": "peptide", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:peptide:dihexa", "title": "Dihexa", "summary": "A neuropeptide showing regenerative effects in animal models of Alzheimer's and neurological injury, with no human trials.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "Dihexa is a peptide with neuroregenerative properties being investigated for neurological disorders including stroke and traumatic brain injury. In preclinical models, dihexa promotes neuronal regeneration, increases dendritic spines and synaptic connections, and improves cognition. In one rat model of Alzheimer's disease, dihexa restored cognitive performance, reportedly outperforming donepezil (Aricept), a standard dementia medication. Despite these promising preclinical findings, dihexa has never been advanced into formal human clinical trials. No long-term safety studies in any species have been published.", "verdict": { "benefits": [ "Promotes neuronal regeneration and synaptic development in preclinical models", "Improved cognitive performance in rat models of Alzheimer's disease" ], "risks": [ "No human clinical trials have been conducted", "Not FDA-approved and has not been formally developed as a therapeutic", "Long-term safety in any species has not been studied", "Preclinical effects may not translate to human benefit" ], "bottomLine": "Dihexa shows neuroprotective and regenerative effects in animal research, but has never been tested in humans and is not an approved therapeutic." }, "originalLinks": [ { "title": "Dihexa", "url": "https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf" }, { "title": "Dihexa Peptide: Unlocking Brain Repair, Focus, and Memory", "url": "https://revolutionhealth.org/blogs/news/peptide-therapy-dihexa" }, { "title": "Hepatocyte growth factor mimics as therapeutic agents", "url": "https://image-ppubs.julius.com/dirsearch-public/print/downloadPdf/9051351" } ], "links": [ { "title": "Dihexa", "url": "https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf" }, { "title": "Dihexa Peptide: Unlocking Brain Repair, Focus, and Memory", "url": "https://revolutionhealth.org/blogs/news/peptide-therapy-dihexa" }, { "title": "Hepatocyte growth factor mimics as therapeutic agents", "url": "https://image-ppubs.julius.com/dirsearch-public/print/downloadPdf/9051351" } ], "protocols": [], "community": [ { "description": "A neuropeptide protocol guide describes oral dihexa dosing at 10–20 mg initiated once weekly, with titration to 50–100 mg weekly as tolerated.", "source": { "title": "Dihexa Protocol Guide — Dosing, Reconstitution & Administration - Path To Peptides", "url": "https://www.pathtopeptides.com/dihexa-protocol.html" }, "origins": [ "evidence.json#/catalog:peptide:dihexa/community/0" ] }, { "description": "The same guide recommends structuring dihexa use as 4–8 weeks on followed by 4 weeks off due to the compound's extended duration of action and potential for accumulation.", "source": { "title": "Dihexa Protocol Guide — Dosing, Reconstitution & Administration - Path To Peptides", "url": "https://www.pathtopeptides.com/dihexa-protocol.html" }, "origins": [ "evidence.json#/catalog:peptide:dihexa/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:dihexa/community/0", "url": "https://www.pathtopeptides.com/dihexa-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:dihexa/community/1", "url": "https://www.pathtopeptides.com/dihexa-protocol.html", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf", "https://revolutionhealth.org/blogs/news/peptide-therapy-dihexa", "https://image-ppubs.julius.com/dirsearch-public/print/downloadPdf/9051351", "https://www.pathtopeptides.com/dihexa-protocol.html" ] }, "library:peptide-kisspeptin-10": { "id": "library:peptide-kisspeptin-10", "path": "/library/peptide-kisspeptin-10.html", "title": "Kisspeptin-10", "summary": "Upstream regulator of GnRH release, studied in reproductive endocrinology.", "aliases": [], "kind": "peptide", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:peptide:kisspeptin-10", "title": "Kisspeptin-10", "summary": "Upstream regulator of GnRH release, studied in reproductive endocrinology.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "clinical-study", "evidenceSummary": "Kisspeptin sits upstream of the reproductive hormone axis and has been studied in real academic trials, more than most research peptides. The linked human work uses kisspeptin-54 as a trigger for egg maturation in IVF: a phase 2 trial in 60 women at high risk of ovarian hyperstimulation, and a phase 2 randomised trial in 62 women. A further clinical study looked at its effects on ovarian granulosa cells. The wiki also records brain imaging studies reporting effects on sexual and romantic brain processing in men. It is not approved for any indication.", "verdict": { "benefits": [ "Studied in real academic phase 2 trials, more than most research peptides", "As an IVF trigger, kisspeptin-54 matured eggs in most women with no moderate or severe hyperstimulation", "A second dose raised egg yield without more ovarian over-response" ], "risks": [ "The human trials used kisspeptin-54 in IVF, not this form for other purposes", "Brain imaging findings on sexual processing come from the wiki, not from outcome trials" ], "bottomLine": "Kisspeptin has genuine phase 2 IVF trial data under a related form, but is approved for nothing.", "approvalStatus": "Not FDA-approved." }, "originalLinks": [ { "title": "PubMed: kisspeptin-10", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=kisspeptin+10" } ], "links": [ { "title": "Peptide Wiki: Kisspeptin-10", "url": "https://vespassassina.github.io/peptide-wiki/peptides/kisspeptin.html" }, { "title": "Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy (Abbara et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26192876/" }, { "title": "A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial (Abbara et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28854728/" }, { "title": "The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function (Owens et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29206944/" } ], "protocols": [ { "population": "60 women at high risk of ovarian hyperstimulation syndrome during IVF", "regimen": "a single injection of kisspeptin-54 at 3.2, 6.4, 9.6 or 12.8 nmol/kg to trigger oocyte maturation, with retrieval 36 hours later", "duration": "single dose", "outcome": "Oocyte maturation occurred in 95% of women, oocyte yield was highest at 12.8 nmol/kg, and no woman developed moderate, severe or critical OHSS.", "source": { "title": "Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy (Abbara et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26192876/" }, "origins": [ "evidence.json#/catalog:peptide:kisspeptin-10/protocols/0" ] }, { "population": "62 women aged 18-34 at high risk of ovarian hyperstimulation syndrome during IVF", "regimen": "kisspeptin-54 9.6 nmol/kg subcutaneously 36 hours before retrieval, then a second identical dose or saline 10 hours later", "duration": "one or two doses within a single cycle", "outcome": "71% of women given a second dose reached an oocyte yield of at least 60% against 45% with one dose, without more ovarian over-response or moderate OHSS.", "source": { "title": "A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial (Abbara et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28854728/" }, "origins": [ "evidence.json#/catalog:peptide:kisspeptin-10/protocols/1" ] }, { "population": "48 women having IVF: 12 given hCG, 12 a GnRH agonist and 24 kisspeptin-54, most with PCOS", "regimen": "kisspeptin-54 9.6 nmol/kg as the oocyte maturation trigger, as one injection or two given 10 hours apart", "duration": "single treatment cycle", "outcome": "Granulosa lutein cells from kisspeptin-triggered women expressed more steroidogenic genes than after hCG or GnRH agonist; markers of OHSS were unchanged.", "source": { "title": "The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function (Owens et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29206944/" }, "origins": [ "evidence.json#/catalog:peptide:kisspeptin-10/protocols/2" ] } ], "community": [], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 0.5, "lowerHours": 0.3, "source": "Human infusion studies", "upperHours": 0.7 } } ], "related": [ "peptide:kisspeptin" ], "conflicts": [ { "status": "identity-uncertain", "text": "The source catalogue identifies KP-10 specifically; the legacy article covers KP-10 and related KISS1 fragments. Preserve the narrower identity separately rather than extrapolating findings across fragments.", "origins": [ "catalogue-authored.json#catalog:peptide:kisspeptin-10", "research/mapping.json" ] } ], "sourceRefs": [ "https://vespassassina.github.io/peptide-wiki/peptides/kisspeptin.html", "pmid:26192876", "pmid:28854728", "pmid:29206944", "https://pubmed.ncbi.nlm.nih.gov/?term=kisspeptin+10" ] }, "library:peptide-tb-500": { "id": "library:peptide-tb-500", "path": "/library/peptide-tb-500.html", "title": "TB-500 (thymosin beta-4 fragment)", "summary": "Synthetic fragment of thymosin beta-4 studied preclinically for tissue repair.", "aliases": [], "kind": "peptide", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:peptide:tb-500", "title": "TB-500 (thymosin beta-4 fragment)", "summary": "Synthetic fragment of thymosin beta-4 studied preclinically for tissue repair.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "peptide", "evidenceTier": "preclinical", "evidenceSummary": "TB-500 is sold as thymosin beta-4 or a fragment of it; the owner's wiki warns that products may contain either. The wiki records it as a research chemical: the parent molecule reached late-stage trials as eye drops and earlier phases in other forms, but none of these are approved or marketed. The linked studies are animal and laboratory work, including a rat Achilles tendon study where TB-500 improved failure load and histology, and a mouse corneal wound study of an engineered variant. A scoping review of emerging sports peptides found most publications used animal models and noted missing efficacy and safety data in people.", "verdict": { "benefits": [ "In a rat Achilles study it improved failure load and tendon histology against controls" ], "risks": [ "A research chemical; the parent molecule reached trials but nothing is approved or marketed", "Products may contain thymosin beta-4 or only a fragment of it", "A scoping review found mostly animal work and missing efficacy and safety data in people" ], "bottomLine": "An unapproved healing peptide with rat tendon results and no human efficacy or safety data." }, "originalLinks": [ { "title": "PubMed: thymosin beta-4", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=thymosin+beta+4" } ], "links": [ { "title": "Peptide Wiki: TB-500 (thymosin beta-4 fragment)", "url": "https://vespassassina.github.io/peptide-wiki/peptides/tb-500.html" }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine (Tewari et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/" }, { "title": "Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing (Nguyen et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41235866/" }, { "title": "Thymosin β4 and Actin: Binding Modes, Biological Functions and Clinical Applications (Ying et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36464872/" } ], "protocols": [ { "population": "32 male Sprague-Dawley rats after Achilles tendon transection and repair, 8 per group", "regimen": "TB-500 (synthetic thymosin beta-4) 60 µg/kg a day intraperitoneally, against control, BPC-157 and the two combined", "duration": "four weeks after surgery", "outcome": "The TB-500 group had significantly higher maximum load to failure and lower Bonar and Movin scores than controls; adding BPC-157 gave no further benefit.", "source": { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/" }, "origins": [ "evidence.json#/catalog:peptide:tb-500/protocols/0" ] } ], "community": [ { "description": "Swolverine's TB-500 dosage guide documents a loading phase of 4-8 mg per week split into 2 injections for weeks 1-4, followed by a maintenance phase of 2-6 mg per month (one injection every 1-2 weeks) for weeks 5-8 and beyond, with protocols varying by injury type from acute injuries at 6-8 mg weekly to chronic joint pain at 4-6 mg weekly.", "source": { "title": "TB‑500 Dosage Guide: How Much Should You Take for Recovery and Injury", "url": "https://swolverine.com/blogs/blog/tb-500-dosage-guide-how-much-should-you-take-for-recovery-and-injury-repair" }, "origins": [ "evidence.json#/catalog:peptide:tb-500/community/0" ] }, { "description": "Community discussions on TB-500 for injury recovery report typical loading protocols of 2.0-2.5 mg administered twice per week (4-5 mg weekly total) for 4-6 weeks, followed by maintenance doses of 2 mg every 1-2 weeks as needed, with administration via subcutaneous injection noted as systemic regardless of injection site.", "source": { "title": "The Wolverine Stack: Your Complete Guide to BPC-157 & TB-500 for Injury Healing", "url": "https://www.innerbody.com/thymosin-beta-4-and-tb-500" }, "origins": [ "evidence.json#/catalog:peptide:tb-500/community/1" ] } ], "communityFinding": null, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:peptide:tb-500/community/0", "url": "https://swolverine.com/blogs/blog/tb-500-dosage-guide-how-much-should-you-take-for-recovery-and-injury-repair", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" }, { "origin": "evidence.json#/catalog:peptide:tb-500/community/1", "url": "https://www.innerbody.com/thymosin-beta-4-and-tb-500", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 48, "source": "Thymosin beta-4 fragment; preclinical" } } ], "related": [ "peptide:tb-500" ], "conflicts": [ { "status": "identity-uncertain", "text": "The source catalogue names the thymosin beta-4 fragment specifically. The legacy page covers ambiguous products sold as TB-500, including full thymosin beta-4. Keep a distinct fragment page; do not transfer full-molecule trial or PK findings to the fragment.", "origins": [ "catalogue-authored.json#catalog:peptide:tb-500", "research/mapping.json" ] } ], "sourceRefs": [ "https://vespassassina.github.io/peptide-wiki/peptides/tb-500.html", "pmid:42542926", "pmid:42578445", "pmid:41235866", "pmid:36464872", "https://pubmed.ncbi.nlm.nih.gov/?term=thymosin+beta+4", "https://swolverine.com/blogs/blog/tb-500-dosage-guide-how-much-should-you-take-for-recovery-and-injury-repair", "https://www.innerbody.com/thymosin-beta-4-and-tb-500" ] }, "library:recovery-acupuncture": { "id": "library:recovery-acupuncture", "path": "/library/recovery-acupuncture.html", "title": "Acupuncture", "summary": "Needling therapy delivered by a practitioner.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:recovery:acupuncture", "title": "Acupuncture", "summary": "Needling therapy delivered by a practitioner.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "An individual patient data meta-analysis pooled results from 39 randomised trials and over 20,000 patients to compare acupuncture against sham or no-acupuncture control for chronic musculoskeletal pain, osteoarthritis, headache, and shoulder pain. Acupuncture outperformed both comparators, with treatment effects persisting a year later.", "verdict": { "benefits": [ "Acupuncture outperformed both sham and no-acupuncture control for musculoskeletal pain, osteoarthritis, headache, and shoulder pain across the pooled patient data.", "Treatment effects persisted with only a small decline at one year in the pooled analysis.", "The meta-analysis drew on individual patient data from 39 trials, a stronger design than pooling only summary statistics." ], "risks": [ "Effect sizes versus sham control were smaller than effect sizes versus no-treatment control, indicating part of the benefit may reflect nonspecific or placebo-related mechanisms.", "Effect sizes varied by trial and were sensitive to the intensity of the control-arm intervention.", "The review covered a limited set of pain conditions and cannot be generalized to other complaints." ], "bottomLine": "An individual patient data meta-analysis of 39 trials found acupuncture more effective than sham or no-acupuncture control for several chronic pain conditions, with effects persisting a year after treatment." }, "originalLinks": [ { "title": "Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/29198932/" } ], "links": [ { "title": "Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/29198932/" } ], "protocols": [ { "population": "20,827 patients with chronic musculoskeletal pain, osteoarthritis, chronic headache, or shoulder pain, pooled across 39 randomised trials", "regimen": "Acupuncture needling compared against sham acupuncture or against no-acupuncture control across the pooled trials", "duration": "Trials published through December 2015, with outcomes measured up to one year after treatment", "outcome": "Acupuncture reduced pain and improved function relative to both sham and no-acupuncture control across all four pain conditions, with only a small decline in effect size at one year", "source": { "title": "Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/29198932/" }, "origins": [ "evidence.json#/catalog:recovery:acupuncture/protocols/0" ] } ], "community": [ { "description": "A Kaiser Permanente patient guide describes an acupuncture appointment with dimmed lights, quiet music and the practitioner checking on the person's comfort.", "source": { "title": "Acupuncture 101 - Kaiser Permanente", "url": "https://healthy.kaiserpermanente.org/health-wellness/healtharticle.acupuncture-101" }, "origins": [ "evidence.json#/catalog:recovery:acupuncture/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://healthy.kaiserpermanente.org/health-wellness/healtharticle.acupuncture-101", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Kaiser Permanente patient guide describes an acupuncture appointment with dimmed lights, quiet music and the practitioner checking on the person's comfort." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:acupuncture/community/0", "url": "https://healthy.kaiserpermanente.org/health-wellness/healtharticle.acupuncture-101", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:29198932", "https://healthy.kaiserpermanente.org/health-wellness/healtharticle.acupuncture-101" ] }, "library:recovery-breathwork": { "id": "library:recovery-breathwork", "path": "/library/recovery-breathwork.html", "title": "Breathwork", "summary": "Structured breathing practice, recorded by protocol and duration.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:breathwork", "title": "Breathwork", "summary": "Structured breathing practice, recorded by protocol and duration.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 12 randomised controlled trials with 785 adults found breathwork lowered self-reported stress compared with controls, with a small-to-medium effect; anxiety and depression showed similar effects. A systematic review of 58 studies found most breathing interventions worked, and linked effectiveness to human-guided training and repeated practice rather than to fast-paced breathing alone. A 2026 randomised trial in 98 paramedicine students reported lower stress, anxiety and depression after a structured breathing programme. Most trials carried a moderate risk of bias.", "verdict": { "benefits": [ "Pooled randomised trials in 785 adults found lower self-reported stress, anxiety and depression", "A review of 58 studies found most breathing interventions worked", "A randomised trial in students reported lower stress, anxiety and depression and higher resilience" ], "risks": [ "Most trials carried a moderate risk of bias and outcomes are self-reported", "Effects tracked with guided training and repeated practice, not with breathing fast", "Insomnia and general wellbeing did not improve significantly in the student trial" ], "bottomLine": "Breathwork lowered self-reported stress and anxiety in randomised trials with moderate risk of bias." }, "originalLinks": [ { "title": "PubMed: breathwork", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=breathing+exercises+stress" } ], "links": [ { "title": "Effect of breathwork on stress and mental health: A meta-analysis of randomised-controlled trials (Fincham et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36624160/" }, { "title": "Breathing Practices for Stress and Anxiety Reduction: Conceptual Framework of Implementation Guidelines Based on a Systematic Review of the Published Literature (Bentley et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/38137060/" }, { "title": "Examining the Effectiveness of Breathwork to Improve Resilience and Psychological Wellbeing While Reducing Anxiety, Depression, Stress, and Insomnia in Paramedicine Students (Little et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41787752/" } ], "protocols": [ { "population": "adults in 58 clinical trials of isolated breathing interventions, covering 72 interventions", "regimen": "the effective interventions avoided fast-only breath paces and sessions under 5 minutes, and used human-guided training, multiple sessions and long-term practice", "duration": "not stated", "outcome": "54 of the 72 interventions reduced stress or anxiety; effectiveness tracked with guided training and repeated practice rather than breath pace.", "source": { "title": "Breathing Practices for Stress and Anxiety Reduction: Conceptual Framework of Implementation Guidelines Based on a Systematic Review of the Published Literature (Bentley et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/38137060/" }, "origins": [ "evidence.json#/catalog:recovery:breathwork/protocols/0" ] }, { "population": "98 paramedicine students at two Australian universities, randomised to breathwork or control", "regimen": "twice-daily slow diaphragmatic breathing, 5-second inhale, 5-second exhale, 2-second hold, with video and guided audio instruction", "duration": "12 weeks", "outcome": "Stress, anxiety and depression were lower and resilience higher than control; insomnia and psychological wellbeing did not change significantly.", "source": { "title": "Examining the Effectiveness of Breathwork to Improve Resilience and Psychological Wellbeing While Reducing Anxiety, Depression, Stress, and Insomnia in Paramedicine Students (Little et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41787752/" }, "origins": [ "evidence.json#/catalog:recovery:breathwork/protocols/1" ] } ], "community": [ { "description": "One NHS breathing practice uses a comfortable seated, standing or lying position, with gentle breaths in through the nose and out through the mouth and an optional count during each breath.", "source": { "title": "Breathing exercises for stress - NHS", "url": "https://www.nhs.uk/mental-health/self-help/guides-tools-and-activities/breathing-exercises-for-stress/" }, "origins": [ "evidence.json#/catalog:recovery:breathwork/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live NHS practice contains seated, standing and lying options, nasal inhalation, oral exhalation and optional counting. Its suggested duration is not repeated.", "checks": [ { "url": "https://www.nhs.uk/mental-health/self-help/guides-tools-and-activities/breathing-exercises-for-stress/", "outcome": "verified-description", "reason": "The live NHS practice contains seated, standing and lying options, nasal inhalation, oral exhalation and optional counting. Its suggested duration is not repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:breathwork/community/0", "url": "https://www.nhs.uk/mental-health/self-help/guides-tools-and-activities/breathing-exercises-for-stress/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:36624160", "pmid:38137060", "pmid:41787752", "https://pubmed.ncbi.nlm.nih.gov/?term=breathing+exercises+stress", "https://www.nhs.uk/mental-health/self-help/guides-tools-and-activities/breathing-exercises-for-stress/" ] }, "library:recovery-cold-exposure": { "id": "library:recovery-cold-exposure", "path": "/library/recovery-cold-exposure.html", "title": "Cold exposure", "summary": "Cold water immersion or shower, recorded by temperature and duration.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:recovery:cold-exposure", "title": "Cold exposure", "summary": "Cold water immersion or shower, recorded by temperature and duration.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 11 randomised studies with 3,177 healthy adults found cold-water immersion raised inflammation markers immediately and an hour afterwards, and lowered stress 12 hours later, with no significant effect on stress at other time points. A meta-analysis of 30 randomised trials found cold-water immersion lowered creatine kinase and muscle soreness after exercise, but did not improve maximal strength, and partial immersion reduced explosive power immediately afterwards. Whole-body and partial immersion did not differ overall. Evidence is pooled human trials of mixed quality.", "verdict": { "benefits": [ "Pooled randomised trials show lower creatine kinase and less muscle soreness after exercise.", "One meta-analysis found stress lower 12 hours after immersion." ], "risks": [ "The same trials show no gain in maximal strength, and partial immersion cut jump power.", "Inflammation markers rose immediately and an hour after; immune measures did not change.", "Stress was unchanged at every other time point, and pooled trials are of mixed quality." ], "bottomLine": "Cold-water immersion eases post-exercise soreness and muscle damage markers, without improving strength." }, "originalLinks": [ { "title": "PubMed: cold water immersion", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=cold+water+immersion" } ], "links": [ { "title": "Effects of cold-water immersion on health and wellbeing: A systematic review and meta-analysis (Cain et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39879231/" }, { "title": "Effects of cold-water immersion at different body regions on post-exercise muscle damage recovery: a systematic review and meta-analysis (Zhu et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41716304/" } ], "protocols": [ { "population": "3,177 healthy adults across 11 randomised studies", "regimen": "Cold-water immersion in baths or a shower at 7-15 C, lasting 30 seconds to 2 hours, acute or repeated", "duration": "Not stated", "outcome": "Inflammation rose immediately and 1 hour after; stress fell 12 hours after but not at other time points; immune function showed no significant change.", "source": { "title": "Effects of cold-water immersion on health and wellbeing: A systematic review and meta-analysis (Cain et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39879231/" }, "origins": [ "evidence.json#/catalog:recovery:cold-exposure/protocols/0" ] }, { "population": "Adults after exercise, across 30 randomised controlled trials", "regimen": "A single acute cold-water immersion, whole-body or partial, compared with seated passive rest", "duration": "Single session, followed 0-72 hours", "outcome": "Creatine kinase and muscle soreness fell, mostly at 24 h; maximal voluntary contraction and jump height did not improve, and partial immersion cut jump power at 0 h.", "source": { "title": "Effects of cold-water immersion at different body regions on post-exercise muscle damage recovery: a systematic review and meta-analysis (Zhu et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41716304/" }, "origins": [ "evidence.json#/catalog:recovery:cold-exposure/protocols/1" ] } ], "community": [ { "description": "Cold plunges are taken in a bath of cold tap water or water cooled further with ice, sometimes as part of a workout or wellness routine.", "source": { "title": "Are 'Cold Plunge' Ice Baths Good for You? - Cleveland Clinic", "url": "https://health.clevelandclinic.org/what-to-know-about-cold-plunges" }, "origins": [ "evidence.json#/catalog:recovery:cold-exposure/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The web-fetch tool retrieved the live Cleveland Clinic article and its description of cold tap water or added ice in a workout/wellness context. Direct curl was blocked; no source access barrier was bypassed and no temperature or safety-duration advice is repeated.", "checks": [ { "url": "https://health.clevelandclinic.org/what-to-know-about-cold-plunges", "outcome": "verified-description", "reason": "The web-fetch tool retrieved the live Cleveland Clinic article and its description of cold tap water or added ice in a workout/wellness context. Direct curl was blocked; no source access barrier was bypassed and no temperature or safety-duration advice is repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:cold-exposure/community/0", "url": "https://health.clevelandclinic.org/what-to-know-about-cold-plunges", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:39879231", "pmid:41716304", "https://pubmed.ncbi.nlm.nih.gov/?term=cold+water+immersion", "https://health.clevelandclinic.org/what-to-know-about-cold-plunges" ] }, "library:recovery-compression": { "id": "library:recovery-compression", "path": "/library/recovery-compression.html", "title": "Compression / pneumatic boots", "summary": "Intermittent pneumatic compression for perceived recovery.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:recovery:compression", "title": "Compression / pneumatic boots", "summary": "Intermittent pneumatic compression for perceived recovery.", "uncertainty": "Consistently improves perceived soreness; effects on actual performance recovery are much weaker.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A systematic review and meta-analysis of 17 studies with 319 participants found lower-limb intermittent pneumatic compression gave trivial to small benefits for muscle function after exercise, trivial to moderate effects on pain and soreness, and highly variable effects on muscle damage markers. In surgical patients, a meta-analysis of 16 randomised trials found compression reduced deep vein thrombosis compared with no prophylaxis, but not compared with drug prophylaxis. A meta-analysis of 14 trials in breast cancer patients found it reduced the incidence of lymphedema. Sports recovery evidence is weaker than the clinical evidence.", "verdict": { "benefits": [ "Pooled surgical trials found compression cut deep vein thrombosis versus no prophylaxis.", "Pooled trials in breast cancer patients found less lymphedema and better limb extension.", "For sports recovery, effects on pain and soreness ranged from trivial to moderate." ], "risks": [ "It was no better than drug prophylaxis for clots, and the overall comparison was null.", "Effects on muscle damage markers were highly variable, and on muscle function trivial to small.", "Sports recovery evidence is weaker than the clinical evidence." ], "bottomLine": "Compression devices prevent clots and lymphedema in clinical settings; sports recovery effects are small and variable." }, "originalLinks": [ { "title": "PubMed: intermittent pneumatic compression recovery", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=intermittent+pneumatic+compression+recovery" } ], "links": [ { "title": "Effects of lower-limb intermittent pneumatic compression on sports recovery: A systematic review and meta-analysis (Maia et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39416507/" }, { "title": "Effects of intermittent pneumatic compression devices interventions to prevent deep vein thrombosis in surgical patients: A systematic review and meta-analysis of randomized controlled trials (Sachdeva et al., 2022)", "url": "https://doi.org/10.1371/journal.pone.0307602" }, { "title": "Intermittent pneumatic compression devices for the prevention and treatment of breast cancer-related lymphedema (Su et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41272206/" } ], "protocols": [ { "population": "319 athletic and healthy participants across 17 studies", "regimen": "lower-limb intermittent pneumatic compression after exercise, most often about 20-30 minutes at around 80 mmHg", "duration": "not stated", "outcome": "Benefits were trivial to small for muscle function, trivial to moderate for pain and soreness, and highly variable for muscle damage markers.", "source": { "title": "Effects of lower-limb intermittent pneumatic compression on sports recovery: A systematic review and meta-analysis (Maia et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39416507/" }, "origins": [ "evidence.json#/catalog:recovery:compression/protocols/0" ] }, { "population": "2,828 adult surgical patients across 16 randomised trials", "regimen": "intermittent pneumatic compression, most often knee-length and in intermittent mode, started at anaesthesia in six trials, after surgery in five and before surgery in four", "duration": "not stated", "outcome": "Deep vein thrombosis fell against no prophylaxis (OR 0.41) but did not differ from drug prophylaxis (OR 1.32), and the overall comparison was null (OR 0.81).", "source": { "title": "Effects of intermittent pneumatic compression devices interventions to prevent deep vein thrombosis in surgical patients: A systematic review and meta-analysis of randomized controlled trials (Sachdeva et al., 2022)", "url": "https://doi.org/10.1371/journal.pone.0307602" }, "origins": [ "evidence.json#/catalog:recovery:compression/protocols/1" ] }, { "population": "1,397 breast cancer patients across 14 randomised trials", "regimen": "intermittent pneumatic compression of the affected limb; limb-volume outcomes were better at pressures of 40 mmHg or less", "duration": "treatment longer than two weeks in the subgroups with better limb-volume outcomes", "outcome": "Lymphedema after breast cancer surgery was less frequent (RR 0.36) and limb extension improved; other joint movements and subjective symptoms did not change.", "source": { "title": "Intermittent pneumatic compression devices for the prevention and treatment of breast cancer-related lymphedema (Su et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41272206/" }, "origins": [ "evidence.json#/catalog:recovery:compression/protocols/2" ] } ], "community": [ { "description": "The Conversation reports recovery boots used by athletes and wellness businesses, with inflatable sleeves applying pressure sequentially from the ends of the limbs towards the trunk.", "source": { "title": "Pneumatic compression therapy: can it really help Olympians (or you) recover after exercise? - The Conversation", "url": "https://theconversation.com/pneumatic-compression-therapy-can-it-really-help-olympians-or-you-recover-after-exercise-236228" }, "origins": [ "evidence.json#/catalog:recovery:compression/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://theconversation.com/pneumatic-compression-therapy-can-it-really-help-olympians-or-you-recover-after-exercise-236228", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: The Conversation reports recovery boots used by athletes and wellness businesses, with inflatable sleeves applying pressure sequentially from the ends of the limbs towards the trunk." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:compression/community/0", "url": "https://theconversation.com/pneumatic-compression-therapy-can-it-really-help-olympians-or-you-recover-after-exercise-236228", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:39416507", "doi:10.1371/journal.pone.0307602", "pmid:41272206", "https://pubmed.ncbi.nlm.nih.gov/?term=intermittent+pneumatic+compression+recovery", "https://theconversation.com/pneumatic-compression-therapy-can-it-really-help-olympians-or-you-recover-after-exercise-236228" ] }, "library:recovery-float-tank": { "id": "library:recovery-float-tank", "path": "/library/recovery-float-tank.html", "title": "Float tank", "summary": "Sensory reduction in a flotation tank.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:float-tank", "title": "Float tank", "summary": "Sensory reduction in a flotation tank.", "uncertainty": "Small trials, mostly on anxiety and stress. Not a well-replicated literature.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "Flotation-REST means floating in warm salt water with very little sensory input. A systematic review of the flotation literature reports relaxation and reductions in anxiety and pain across many small studies. A scoping review of eight studies with 401 participants in chronic pain found consistent short-term improvements in pain, anxiety and depression. A randomised trial in 99 patients with chronic pain found no lasting benefit over an indistinguishable placebo, with similar short-term gains in both groups. The evidence is small in scale and weakly controlled.", "verdict": { "benefits": [ "Reviews report short-term relaxation and lower anxiety and pain across many small studies" ], "risks": [ "A randomised trial in chronic pain found no lasting benefit over an indistinguishable placebo", "The short-term gains appeared just as much in the placebo group", "The evidence is small in scale and weakly controlled" ], "bottomLine": "Floating brings short-term relaxation, but a controlled trial found a placebo float worked just as well." }, "originalLinks": [ { "title": "PubMed: flotation REST", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=flotation+REST+anxiety" } ], "links": [ { "title": "A systematic review of flotation-restricted environmental stimulation therapy (REST) (Lashgari et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40611079/" }, { "title": "A Scoping Review of Flotation-REST (Restricted Environmental Stimulation Therapy) for Chronic Pain and Associated Comorbidities (Stuart et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41710285/" }, { "title": "Flotation Restricted Environmental Stimulation Therapy for Chronic Pain: A Randomized Clinical Trial (Loose et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33988708/" } ], "protocols": [ { "population": "99 patients with chronic pain disorder, mean age 51.7, 81% women", "regimen": "five flotation-REST sessions of 60 to 90 minutes, each separated by 4 days, against an indistinguishable placebo float and a wait-list control", "duration": "five sessions, with follow-up at 1, 12 and 24 weeks after the last one", "outcome": "No difference between groups in pain intensity at any follow-up; short-term gains in pain, anxiety and relaxation were matched in the placebo group.", "source": { "title": "Flotation Restricted Environmental Stimulation Therapy for Chronic Pain: A Randomized Clinical Trial (Loose et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33988708/" }, "origins": [ "evidence.json#/catalog:recovery:float-tank/protocols/0" ] } ], "community": [ { "description": "A Cleveland Clinic guide describes float therapy in a dark, quiet tank with a shallow pool of salt-saturated water.", "source": { "title": "The Benefits of Float Therapy - Cleveland Clinic", "url": "https://health.clevelandclinic.org/float-therapy-benefits" }, "origins": [ "evidence.json#/catalog:recovery:float-tank/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://health.clevelandclinic.org/float-therapy-benefits", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: A Cleveland Clinic guide describes float therapy in a dark, quiet tank with a shallow pool of salt-saturated water." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:float-tank/community/0", "url": "https://health.clevelandclinic.org/float-therapy-benefits", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:40611079", "pmid:41710285", "pmid:33988708", "https://pubmed.ncbi.nlm.nih.gov/?term=flotation+REST+anxiety", "https://health.clevelandclinic.org/float-therapy-benefits" ] }, "library:recovery-gratitude-therapy": { "id": "library:recovery-gratitude-therapy", "path": "/library/recovery-gratitude-therapy.html", "title": "Gratitude practice or therapy session", "summary": "A written gratitude practice or a talk-therapy session, logged as its own entry.", "aliases": [], "kind": "recovery-practice", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:gratitude-therapy", "title": "Gratitude practice or therapy session", "summary": "A written gratitude practice or a talk-therapy session, logged as its own entry.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "clinical-study", "evidenceSummary": "Three linked experiments randomly assigned adults to keep weekly or daily records focused on gratitude, hassles, or neutral life events. Participants in the gratitude condition consistently reported more positive affect and fewer physical symptoms than comparison groups, with a parallel benefit observed among people living with neuromuscular disease.", "verdict": { "benefits": [ "Participants in the gratitude condition reported more positive affect than comparison groups across three linked studies.", "A parallel benefit appeared among people living with neuromuscular disease, extending the finding beyond a general population.", "Effects appeared with sessions as brief as a weekly written record." ], "risks": [ "Effects were not uniform across every outcome measured; some measures showed no significant difference between conditions.", "The original studies relied on self-report measures of affect and physical symptoms.", "Study durations were short, ranging from two to ten weeks, so long-term persistence of the effect is not established." ], "bottomLine": "Randomized comparisons found a gratitude-focused writing practice linked with higher positive affect than comparison conditions across three linked studies, most robustly on measures of positive affect." }, "originalLinks": [ { "title": "Counting blessings versus burdens: an experimental investigation of gratitude and subjective well-being in daily life", "url": "https://pubmed.ncbi.nlm.nih.gov/12585811/" } ], "links": [ { "title": "Counting blessings versus burdens: an experimental investigation of gratitude and subjective well-being in daily life", "url": "https://pubmed.ncbi.nlm.nih.gov/12585811/" } ], "protocols": [ { "population": "Undergraduate and community adults across two studies, plus a group of adults living with neuromuscular disease in a third study", "regimen": "Weekly or daily written records focused on gratitude compared against records of hassles or neutral life events", "duration": "Study periods ranging from two to ten weeks, published 2003", "outcome": "The gratitude-focused groups showed higher positive affect and better self-reported physical health than comparison groups across the three studies", "source": { "title": "Counting blessings versus burdens: an experimental investigation of gratitude and subjective well-being in daily life", "url": "https://pubmed.ncbi.nlm.nih.gov/12585811/" }, "origins": [ "evidence.json#/catalog:recovery:gratitude-therapy/protocols/0" ] } ], "community": [ { "description": "In the Three Good Things writing practice, participants record three things that went well that day and explain why each happened, sometimes as a before-bed reflection.", "source": { "title": "Three Good Things - Greater Good in Action", "url": "https://ggia.berkeley.edu/practice/three-good-things" }, "origins": [ "evidence.json#/catalog:recovery:gratitude-therapy/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live Berkeley Three Good Things practice contains a written record of three good events and explanations of why they occurred. The source also discusses a before-bed reflection.", "checks": [ { "url": "https://ggia.berkeley.edu/practice/three-good-things", "outcome": "verified-description", "reason": "The live Berkeley Three Good Things practice contains a written record of three good events and explanations of why they occurred. The source also discusses a before-bed reflection." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:gratitude-therapy/community/0", "url": "https://ggia.berkeley.edu/practice/three-good-things", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:12585811", "https://ggia.berkeley.edu/practice/three-good-things" ] }, "library:recovery-hyperbaric-oxygen": { "id": "library:recovery-hyperbaric-oxygen", "path": "/library/recovery-hyperbaric-oxygen.html", "title": "Hyperbaric oxygen therapy", "summary": "Breathing supplemental oxygen at above-normal pressure in a chamber.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:recovery:hyperbaric-oxygen", "title": "Hyperbaric oxygen therapy", "summary": "Breathing supplemental oxygen at above-normal pressure in a chamber.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "clinical-study", "evidenceSummary": "A prospective crossover clinical trial tested hyperbaric oxygen therapy in sixty women diagnosed with fibromyalgia syndrome, pairing symptom and quality-of-life measures with brain imaging. The treated group showed improvement across fibromyalgia symptoms alongside measurable changes in brain activity patterns linked to pain processing.", "verdict": { "benefits": [ "Hyperbaric oxygen therapy was linked with significant improvement in fibromyalgia symptoms and quality-of-life measures in this crossover trial.", "Brain imaging in the treated group showed rectification of abnormal activity patterns linked to pain processing.", "The crossover design let each participant serve as their own control, strengthening the comparison." ], "risks": [ "The no-treatment control period showed no improvement, underscoring that benefits were specific to the oxygen therapy sessions rather than to time or attention alone.", "The trial enrolled only sixty female patients from a single center, limiting how broadly the findings generalize.", "Hyperbaric chambers carry known risks including barotrauma and oxygen toxicity that are not addressed by this trial's design." ], "bottomLine": "A prospective crossover trial found a forty-session hyperbaric oxygen protocol linked with improved fibromyalgia symptoms and altered brain activity patterns, based on a small single-center sample." }, "originalLinks": [ { "title": "Hyperbaric oxygen therapy can diminish fibromyalgia syndrome--prospective clinical trial", "url": "https://pubmed.ncbi.nlm.nih.gov/26010952/" } ], "links": [ { "title": "Hyperbaric oxygen therapy can diminish fibromyalgia syndrome--prospective clinical trial", "url": "https://pubmed.ncbi.nlm.nih.gov/26010952/" } ], "protocols": [ { "population": "60 female patients aged 21 to 67 diagnosed with fibromyalgia syndrome for at least two years", "regimen": "Forty hyperbaric oxygen sessions delivered five days a week, ninety minutes each, breathing pure oxygen at two atmospheres absolute, compared against a no-treatment control period", "duration": "Forty-session protocol delivered over eight weeks, with crossover-control comparison", "outcome": "Hyperbaric oxygen therapy was linked with significant improvement in fibromyalgia symptoms and quality of life, alongside rectification of abnormal brain activity patterns on imaging, while the no-treatment control period showed no improvement", "source": { "title": "Hyperbaric oxygen therapy can diminish fibromyalgia syndrome--prospective clinical trial", "url": "https://pubmed.ncbi.nlm.nih.gov/26010952/" }, "origins": [ "evidence.json#/catalog:recovery:hyperbaric-oxygen/protocols/0" ] } ], "community": [ { "description": "Harvard Health reports some treatment centres marketing hyperbaric oxygen for uses beyond FDA-cleared indications, distinguishing those claims from established medical uses.", "source": { "title": "Hyperbaric oxygen therapy: Evidence-based uses and unproven claims - Harvard Health", "url": "https://www.health.harvard.edu/healthy-aging-and-longevity/hyperbaric-oxygen-therapy-evidence-based-uses-and-unproven-claims" }, "origins": [ "evidence.json#/catalog:recovery:hyperbaric-oxygen/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.health.harvard.edu/healthy-aging-and-longevity/hyperbaric-oxygen-therapy-evidence-based-uses-and-unproven-claims", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: Harvard Health reports some treatment centres marketing hyperbaric oxygen for uses beyond FDA-cleared indications, distinguishing those claims from established medical uses." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:hyperbaric-oxygen/community/0", "url": "https://www.health.harvard.edu/healthy-aging-and-longevity/hyperbaric-oxygen-therapy-evidence-based-uses-and-unproven-claims", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:26010952", "https://www.health.harvard.edu/healthy-aging-and-longevity/hyperbaric-oxygen-therapy-evidence-based-uses-and-unproven-claims" ] }, "library:recovery-journaling": { "id": "library:recovery-journaling", "path": "/library/recovery-journaling.html", "title": "Journaling", "summary": "Written reflection. Distinct from the app's own check-in: this is the practice, the check-in is the measurement.", "aliases": [], "kind": "recovery-practice", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:journaling", "title": "Journaling", "summary": "Written reflection. Distinct from the app's own check-in: this is the practice, the check-in is the measurement.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 11 randomised trials with 1,178 breast cancer patients found expressive writing reduced negative physical symptoms within three months, with no significant effect on psychological outcomes at any time point. A randomised trial in 116 healthy adults found no overall effect on anxiety, depression or physical symptoms; anxiety fell only in people who normally express emotions and rose in those who do not. An online trial in people with mood disorders found all groups, including the control writing group, improved, with no difference between them. Overall the effects are small and inconsistent.", "verdict": { "benefits": [ "In breast cancer patients, pooled trials found negative physical symptoms fell in the first months" ], "risks": [ "No significant effect on mood, anxiety, depression or quality of life at any timepoint", "In healthy adults anxiety fell only in people who normally express emotions and rose in those who do not", "In mood disorders, plain control writing improved things just as much" ], "bottomLine": "Expressive writing showed small, inconsistent effects and no psychological benefit overall." }, "originalLinks": [ { "title": "PubMed: expressive writing", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=expressive+writing+health+outcomes" } ], "links": [ { "title": "Randomized controlled trial of expressive writing for psychological and physical health: the moderating role of emotional expressivity (Niles et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/23742666/" }, { "title": "Expressive writing and positive writing for participants with mood disorders: an online randomized controlled trial (Baikie et al. 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22209127/" }, { "title": "Effect of Expressive Writing Intervention on Health Outcomes in Breast Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (Zhou et al. 2015)", "url": "https://doi.org/10.1371/journal.pone.0131802" } ], "protocols": [ { "population": "116 healthy young adults", "regimen": "writing for 20 minutes on four occasions about deepest thoughts and feelings on a stressful event, or about a control topic", "duration": "four writing sessions, with follow-up at three months", "outcome": "No effect on anxiety, depressive symptoms or physical symptoms; anxiety fell in high-expressiveness writers and rose in low-expressiveness writers.", "source": { "title": "Randomized controlled trial of expressive writing for psychological and physical health: the moderating role of emotional expressivity (Niles et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/23742666/" }, "origins": [ "evidence.json#/catalog:recovery:journaling/protocols/0" ] }, { "population": "adults with mood disorders recruited online", "regimen": "writing for 20 minutes on four occasions, allocated to expressive writing, positive writing or time-management control writing", "duration": "four writing sessions, with follow-up to at least four months", "outcome": "All three groups, including the control writing group, improved on mental and physical symptoms, with no significant difference between groups.", "source": { "title": "Expressive writing and positive writing for participants with mood disorders: an online randomized controlled trial (Baikie et al. 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22209127/" }, "origins": [ "evidence.json#/catalog:recovery:journaling/protocols/1" ] }, { "population": "1,178 breast cancer patients across 11 randomised controlled trials", "regimen": "expressive writing on the Pennebaker and Beall paradigm, 1 to 6 sessions of at least 20 continuous minutes, most trials using more than 3 sessions", "duration": "varied by trial; results split at 3 months of follow-up", "outcome": "Negative somatic symptoms fell within 3 months but not after; mood, anxiety, depression and quality of life showed no significant effect at any timepoint.", "source": { "title": "Effect of Expressive Writing Intervention on Health Outcomes in Breast Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (Zhou et al. 2015)", "url": "https://doi.org/10.1371/journal.pone.0131802" }, "origins": [ "evidence.json#/catalog:recovery:journaling/protocols/2" ] } ], "community": [ { "description": "An expressive-writing practice describes writing freely about thoughts and feelings around an emotionally challenging experience for 20 minutes on four consecutive days, using a private notebook or digital document.", "source": { "title": "Expressive Writing - Greater Good in Action", "url": "https://ggia.berkeley.edu/practice/expressive_writing" }, "origins": [ "evidence.json#/catalog:recovery:journaling/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live Berkeley practice describes private expressive writing about a challenging emotional experience on four consecutive days. Its benefit claims are not repeated.", "checks": [ { "url": "https://ggia.berkeley.edu/practice/expressive_writing", "outcome": "verified-description", "reason": "The live Berkeley practice describes private expressive writing about a challenging emotional experience on four consecutive days. Its benefit claims are not repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:journaling/community/0", "url": "https://ggia.berkeley.edu/practice/expressive_writing", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:23742666", "pmid:22209127", "doi:10.1371/journal.pone.0131802", "https://pubmed.ncbi.nlm.nih.gov/?term=expressive+writing+health+outcomes", "https://ggia.berkeley.edu/practice/expressive_writing" ] }, "library:recovery-massage": { "id": "library:recovery-massage", "path": "/library/recovery-massage.html", "title": "Massage / soft tissue work", "summary": "Sports massage, foam rolling or manual therapy.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:recovery:massage", "title": "Massage / soft tissue work", "summary": "Sports massage, foam rolling or manual therapy.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A systematic review of 20 trials found low-quality evidence that soft tissue massage improves pain, function and range of motion in non-specific shoulder pain in the short term. A meta-analysis of nine randomised trials with 404 patients found massage continued over several weeks improved pain, anxiety and depression in fibromyalgia, but not sleep. A meta-analysis of 18 randomised trials with 1,989 people found Chinese massage added to usual physiotherapy improved motor function and reduced spasticity after stroke. Study sizes are small and protocols vary.", "verdict": { "benefits": [ "Pooled trials show better pain, anxiety and depression in fibromyalgia when massage continues.", "Pooled trials show better motor function and less spasticity after stroke, added to physiotherapy.", "Low-quality evidence of short-term gains in shoulder pain, function and range of motion." ], "risks": [ "The shoulder evidence was rated low quality and the gains were short-term.", "Massage did not improve sleep disturbance in fibromyalgia.", "Study sizes are small and protocols vary widely between trials." ], "bottomLine": "Massage shows modest pooled benefits for pain, mood and post-stroke motor function, on small varied trials." }, "originalLinks": [ { "title": "PubMed: massage and recovery", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=massage+muscle+recovery+meta-analysis" } ], "links": [ { "title": "Effectiveness of soft tissue massage and exercise for the treatment of non-specific shoulder pain: a systematic review with meta-analysis (van et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/22844035/" }, { "title": "Massage Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (Kalichman and Vulfsons, 2010)", "url": "https://doi.org/10.1371/journal.pone.0089304" }, { "title": "The Effectiveness of Massage Therapy for Improving Sequelae in Post-Stroke Survivors. A Systematic Review and Meta-Analysis (Cabanas-Valdés et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33919371/" } ], "protocols": [ { "population": "patients aged 18-80 with non-surgical, non-specific shoulder pain across 20 trials", "regimen": "hands-on soft tissue massage applied locally to the shoulder, alone or with exercise, against placebo, minimal or no treatment", "duration": "not stated", "outcome": "Low-quality evidence of moderate short-term gains in active flexion and abduction range, pain and function; exercise improved pain only slightly and not function.", "source": { "title": "Effectiveness of soft tissue massage and exercise for the treatment of non-specific shoulder pain: a systematic review with meta-analysis (van et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/22844035/" }, "origins": [ "evidence.json#/catalog:recovery:massage/protocols/0" ] }, { "population": "404 patients with fibromyalgia across 9 randomised trials", "regimen": "massage sessions of 25-90 minutes, 1-20 sessions in total, across trials running 1-24 weeks", "duration": "1 to 24 weeks; effects were significant only for massage lasting 5 weeks or more", "outcome": "Massage of 5 weeks or more improved pain, anxiety and depression immediately after treatment, but did not improve sleep disturbance.", "source": { "title": "Massage Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (Kalichman and Vulfsons, 2010)", "url": "https://doi.org/10.1371/journal.pone.0089304" }, "origins": [ "evidence.json#/catalog:recovery:massage/protocols/1" ] }, { "population": "1,989 stroke survivors across 18 randomised trials", "regimen": "Chinese massage (Tuina) added to conventional physiotherapy, against conventional physiotherapy alone", "duration": "not stated", "outcome": "Upper-limb motor function improved in the subacute stage (mean difference 2.75 on Fugl-Meyer) and upper- and lower-limb spasticity fell on the modified Ashworth scale.", "source": { "title": "The Effectiveness of Massage Therapy for Improving Sequelae in Post-Stroke Survivors. A Systematic Review and Meta-Analysis (Cabanas-Valdés et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33919371/" }, "origins": [ "evidence.json#/catalog:recovery:massage/protocols/2" ] } ], "community": [ { "description": "An American Massage Therapy Association account of post-event sports massage describes lighter strokes such as compression and effleurage with passive stretching, rather than deep massage.", "source": { "title": "Post-Event Sports Massage - Massage Therapy Journal (AMTA)", "url": "https://www.amtamassage.org/publications/massage-therapy-journal/post-event-sports-massage/" }, "origins": [ "evidence.json#/catalog:recovery:massage/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.amtamassage.org/publications/massage-therapy-journal/post-event-sports-massage/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: An American Massage Therapy Association account of post-event sports massage describes lighter strokes such as compression and effleurage with passive stretching, rather than deep massage." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:massage/community/0", "url": "https://www.amtamassage.org/publications/massage-therapy-journal/post-event-sports-massage/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:22844035", "doi:10.1371/journal.pone.0089304", "pmid:33919371", "https://pubmed.ncbi.nlm.nih.gov/?term=massage+muscle+recovery+meta-analysis", "https://www.amtamassage.org/publications/massage-therapy-journal/post-event-sports-massage/" ] }, "library:recovery-meditation": { "id": "library:recovery-meditation", "path": "/library/recovery-meditation.html", "title": "Meditation", "summary": "Seated or guided practice — mindfulness, transcendental, loving-kindness, body scan or open awareness. Recorded by duration and style, since they are not interchangeable.", "aliases": [], "kind": "recovery-practice", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:meditation", "title": "Meditation", "summary": "Seated or guided practice — mindfulness, transcendental, loving-kindness, body scan or open awareness. Recorded by duration and style, since they are not interchangeable.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A systematic review of 47 trials with 3,515 participants found moderate-strength evidence that mindfulness meditation programmes reduce anxiety, depression and pain, and low-strength evidence for stress and mental health-related quality of life, with no evidence of benefit for sleep, weight or substance use. A review of 38 randomised trials in chronic pain found low-quality evidence of a small reduction in pain, plus improvements in depression symptoms and quality of life. A meta-analysis of six trials in irritable bowel syndrome found better quality of life and less pain, while the symptom score was not significantly changed.", "verdict": { "benefits": [ "Moderate-strength evidence across 47 trials for less anxiety, depression and pain.", "In chronic pain, pooled trials found a small pain reduction plus better mood and quality of life.", "In irritable bowel syndrome, quality of life and pain improved." ], "risks": [ "No evidence of benefit for sleep, weight, attention, positive mood or substance use.", "The chronic pain evidence was rated low quality and the effect was small.", "The irritable bowel symptom score itself did not change significantly." ], "bottomLine": "Mindfulness meditation has moderate evidence for anxiety, depression and pain, and none for sleep, weight or substance use." }, "originalLinks": [ { "title": "PubMed: mindfulness meditation", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=mindfulness+meditation" } ], "links": [ { "title": "Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis (Hilton et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/27658913/" }, { "title": "Meditation programs for psychological stress and well-being: a systematic review and meta-analysis (Goyal et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24395196/" }, { "title": "Meditation and Irritable Bowel Syndrome, a Systematic Review and Meta-Analysis (Baboș et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/36362745/" } ], "protocols": [ { "population": "adults with chronic pain across 38 randomised trials", "regimen": "mindfulness programmes, MBSR in 21 trials and MBCT in 6, combining classroom instruction with home practice; 29 of 38 ran for 8 weeks", "duration": "3 to 12 weeks", "outcome": "Low-quality evidence of a small pain reduction (SMD 0.32) with improvements in depression symptoms and quality of life.", "source": { "title": "Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis (Hilton et al. 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/27658913/" }, "origins": [ "evidence.json#/catalog:recovery:meditation/protocols/0" ] }, { "population": "3,515 participants across 47 randomised trials with active controls", "regimen": "MBSR programmes of 20-27.5 hours over 8 weeks, other mindfulness programmes about half that, and transcendental meditation of 16-39 hours over 3-12 months", "duration": "3 to 15 weeks for mindfulness programmes; 3 to 12 months for mantra programmes", "outcome": "Moderate evidence of improved anxiety, depression and pain; no evidence of benefit for sleep, weight, attention, positive mood or substance use.", "source": { "title": "Meditation programs for psychological stress and well-being: a systematic review and meta-analysis (Goyal et al. 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24395196/" }, "origins": [ "evidence.json#/catalog:recovery:meditation/protocols/1" ] }, { "population": "adults with irritable bowel syndrome across six randomised trials", "regimen": "8-week programmes with weekly group sessions of 1.5 to 2.5 hours, MBSR in five trials and MBCT in one, two adding a 3-4 hour retreat", "duration": "8 weeks", "outcome": "Quality of life, mindful awareness and pain improved; the IBS symptom score change was not statistically significant (p = 0.054).", "source": { "title": "Meditation and Irritable Bowel Syndrome, a Systematic Review and Meta-Analysis (Baboș et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/36362745/" }, "origins": [ "evidence.json#/catalog:recovery:meditation/protocols/2" ] } ], "community": [ { "description": "A mindfulness practice guide describes a short seated session of five to ten minutes, with attention on the breath and a return to it when the mind wanders.", "source": { "title": "How to Meditate - Mindful", "url": "https://www.mindful.org/how-to-meditate/" }, "origins": [ "evidence.json#/catalog:recovery:meditation/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live Mindful guide describes a short seated practice with attention to breathing and returning attention when distracted. The text attributes the practice to this guide, not a measured population frequency.", "checks": [ { "url": "https://www.mindful.org/how-to-meditate/", "outcome": "verified-description", "reason": "The live Mindful guide describes a short seated practice with attention to breathing and returning attention when distracted. The text attributes the practice to this guide, not a measured population frequency." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:meditation/community/0", "url": "https://www.mindful.org/how-to-meditate/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:27658913", "pmid:24395196", "pmid:36362745", "https://pubmed.ncbi.nlm.nih.gov/?term=mindfulness+meditation", "https://www.mindful.org/how-to-meditate/" ] }, "library:recovery-nap": { "id": "library:recovery-nap", "path": "/library/recovery-nap.html", "title": "Nap", "summary": "Daytime sleep. Worth logging separately from night sleep — a long late nap explains a bad night that otherwise looks unprovoked.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:nap", "title": "Nap", "summary": "Daytime sleep. Worth logging separately from night sleep — a long late nap explains a bad night that otherwise looks unprovoked.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A nap is a short sleep taken during the day. A meta-analysis of 22 randomised trials in athletes and active adults found better cognitive and physical performance and less fatigue after napping, including after partial sleep loss. A second meta-analysis found improved running measures and less fatigue when naps followed a normal night's sleep. A meta-analysis of 11 studies found a small gain in cognitive performance, mainly alertness. An umbrella review of 16 meta-analyses links long naps with higher risk of coronary heart disease, diabetes and obesity.", "verdict": { "benefits": [ "Pooled randomised trials found better cognitive and physical performance and less fatigue", "Benefits held after partial sleep loss in athletes and active adults" ], "risks": [ "Muscle force, sprint and Wingate results did not change", "In one meta-analysis the cognitive gain was small and mainly about alertness", "An umbrella review links long naps with higher coronary heart disease, diabetes and obesity risk" ], "bottomLine": "Short naps consistently improve alertness and performance in trials, while long naps track higher disease risk." }, "originalLinks": [ { "title": "PubMed: napping and alertness", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=napping+cognitive+performance" } ], "links": [ { "title": "Is daytime napping an effective strategy to improve sport-related cognitive and physical performance and reduce fatigue? A systematic review and meta-analysis of randomised controlled trials (Mesas et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36690376/" }, { "title": "The Impact of Daytime Napping Following Normal Night-Time Sleep on Physical Performance: A Systematic Review, Meta-analysis and Meta-regression (Boukhris et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/37700141/" }, { "title": "Multiple Health Outcomes of Daytime Napping: A Comprehensive Umbrella Review (Du et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41710553/" }, { "title": "Effects of a Short Daytime Nap on the Cognitive Performance: A Systematic Review and Meta-Analysis (Dutheil et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34639511/" } ], "protocols": [ { "population": "291 male athletes and physically active adults aged 18-35 across 22 randomised trials", "regimen": "A daytime nap between 12:30 and 16:50, most often at 14:00; benefits were larger at 30 to under 60 minutes and over an hour before testing", "duration": "Single nap per trial condition", "outcome": "Cognitive performance rose (SMD 0.69), physical performance rose (SMD 0.99) and perceived fatigue fell (SMD -0.76), also after partial sleep loss.", "source": { "title": "Is daytime napping an effective strategy to improve sport-related cognitive and physical performance and reduce fatigue? A systematic review and meta-analysis of randomised controlled trials (Mesas et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36690376/" }, "origins": [ "evidence.json#/catalog:recovery:nap/protocols/0" ] }, { "population": "Physically active people and athletes in 18 studies, after a normal 7-9 hour night's sleep", "regimen": "A daytime nap compared with a no-nap condition", "duration": "Single nap per trial condition", "outcome": "Highest and total distance in the 5-m shuttle run improved and fatigue index fell; muscle force did not change (p = 0.267), nor did sprint or Wingate results.", "source": { "title": "The Impact of Daytime Napping Following Normal Night-Time Sleep on Physical Performance: A Systematic Review, Meta-analysis and Meta-regression (Boukhris et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/37700141/" }, "origins": [ "evidence.json#/catalog:recovery:nap/protocols/1" ] }, { "population": "16 meta-analyses covering 244 health-related outcomes", "regimen": "Daytime naps grouped as short (20-30 minutes), under 60 minutes, and over 60 minutes", "duration": "Not stated", "outcome": "Naps under 60 minutes tracked better cognition and less fatigue; naps over 60 minutes tracked 30% higher coronary heart disease and 20% higher diabetes risk.", "source": { "title": "Multiple Health Outcomes of Daytime Napping: A Comprehensive Umbrella Review (Du et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41710553/" }, "origins": [ "evidence.json#/catalog:recovery:nap/protocols/2" ] }, { "population": "381 working-aged adults across 11 studies, almost all in laboratory conditions", "regimen": "A single daytime nap averaging 55.4 plus or minus 29.4 minutes, mostly in the afternoon", "duration": "Single nap", "outcome": "Cognitive performance improved after the nap (effect size 0.18), mainly alertness (0.29); nap duration and time to testing made no difference.", "source": { "title": "Effects of a Short Daytime Nap on the Cognitive Performance: A Systematic Review and Meta-Analysis (Dutheil et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34639511/" }, "origins": [ "evidence.json#/catalog:recovery:nap/protocols/3" ] } ], "community": [ { "description": "An observational report describes midday siestas among adults in Spain, with regular nappers often reporting four days a week.", "source": { "title": "Researchers study how daytime naps may influence health - NHLBI", "url": "https://www.nhlbi.nih.gov/news/2023/researchers-study-how-daytime-naps-may-influence-health" }, "origins": [ "evidence.json#/catalog:recovery:nap/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "The original Sleep Foundation page returned HTTP 403 through both retrieval methods. The replacement describes observed siestas, not a recommended nap duration or an intervention.", "checks": [ { "url": "https://www.sleepfoundation.org/napping", "outcome": "blocked", "reason": "Direct retrieval and the web-fetch tool both returned HTTP 403; no claim was retained from this inaccessible page." }, { "url": "https://www.nhlbi.nih.gov/news/2023/researchers-study-how-daytime-naps-may-influence-health", "outcome": "verified-description", "reason": "The live NIH report explicitly describes observed regular midday siestas in a Spanish adult cohort, often four days a week. Its health-outcome associations are not repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:nap/community/0", "url": "https://www.nhlbi.nih.gov/news/2023/researchers-study-how-daytime-naps-may-influence-health", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:36690376", "pmid:37700141", "pmid:41710553", "pmid:34639511", "https://pubmed.ncbi.nlm.nih.gov/?term=napping+cognitive+performance", "https://www.nhlbi.nih.gov/news/2023/researchers-study-how-daytime-naps-may-influence-health" ] }, "library:recovery-red-light": { "id": "library:recovery-red-light", "path": "/library/recovery-red-light.html", "title": "Red light therapy", "summary": "Photobiomodulation. Wavelength, distance and duration determine the delivered dose.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "anti-aging" ], "research": [ { "id": "catalog:recovery:red-light", "title": "Red light therapy", "summary": "Photobiomodulation. Wavelength, distance and duration determine the delivered dose.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "Red and near-infrared photobiomodulation applies low-level light to tissue. A meta-analysis of 17 randomised trials in tendinopathy found light plus exercise beat sham plus exercise for pain and function, but no advantage over other treatments, at very low to moderate certainty. A systematic review of four trials in primary headache judged the evidence insufficient to support use. A broader review notes that results vary because devices, wavelengths and delivery are not standardised. The evidence is weak and condition-specific.", "verdict": { "benefits": [ "Added to exercise for tendinopathy, it beat sham plus exercise for pain and function in pooled trials" ], "risks": [ "It showed no advantage over other treatments, at very low to moderate certainty", "For primary headache, reviewers judged the evidence insufficient to support use", "Devices, wavelengths and delivery are not standardised, so results vary" ], "bottomLine": "Red and near-infrared light helped tendinopathy pain alongside exercise, on weak evidence." }, "originalLinks": [ { "title": "PubMed: photobiomodulation", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=photobiomodulation" } ], "links": [ { "title": "The effect of low-level red and near-infrared photobiomodulation on pain and function in tendinopathy: a systematic review and meta-analysis of randomized control trials (Tripodi et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34391447/" }, { "title": "From light to healing: photobiomodulation therapy in medical disciplines (Shivappa et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41466382/" }, { "title": "Photobiomodulation for the Treatment of Primary Headache: Systematic Review of Randomized Clinical Trials (Gomes et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35054491/" } ], "protocols": [ { "population": "835 participants with tendinopathy across 17 randomised trials, mostly elbow and rotator cuff", "regimen": "near-infrared photobiomodulation at 810-905 nm, 0.5-5 J/cm2, 7 to 24 sessions given 2-5 times a week, alone or added to exercise", "duration": "most trials measured at the end of 2 to 4 weeks of treatment, with follow-up at 3 months", "outcome": "Added to exercise it beat sham plus exercise for pain and function, but not other interventions; certainty was very low to moderate.", "source": { "title": "The effect of low-level red and near-infrared photobiomodulation on pain and function in tendinopathy: a systematic review and meta-analysis of randomized control trials (Tripodi et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34391447/" }, "origins": [ "evidence.json#/catalog:recovery:red-light/protocols/0" ] } ], "community": [ { "description": "Cleveland Clinic describes red light therapy promoted at beauty salons, gyms and wellness centres as well as in medical-office and at-home contexts.", "source": { "title": "Red Light Therapy: Benefits, Side Effects and Uses - Cleveland Clinic", "url": "https://my.clevelandclinic.org/health/articles/22114-red-light-therapy" }, "origins": [ "evidence.json#/catalog:recovery:red-light/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://my.clevelandclinic.org/health/articles/22114-red-light-therapy", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: Cleveland Clinic describes red light therapy promoted at beauty salons, gyms and wellness centres as well as in medical-office and at-home contexts." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:red-light/community/0", "url": "https://my.clevelandclinic.org/health/articles/22114-red-light-therapy", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:34391447", "pmid:41466382", "pmid:35054491", "https://pubmed.ncbi.nlm.nih.gov/?term=photobiomodulation", "https://my.clevelandclinic.org/health/articles/22114-red-light-therapy" ] }, "library:recovery-sauna": { "id": "library:recovery-sauna", "path": "/library/recovery-sauna.html", "title": "Sauna session", "summary": "Heat exposure recorded by temperature, duration and session count.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "longevity" ], "research": [ { "id": "catalog:recovery:sauna", "title": "Sauna session", "summary": "Heat exposure recorded by temperature, duration and session count.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A 2025 systematic review and meta-analysis of 20 randomised trials of passive heating, including sauna, found no significant pooled effect on most cardiometabolic and vascular measures. Its systolic blood pressure estimate was not statistically significant overall, with a reduction appearing only in whole-body heating subgroups. A meta-analysis of infrared sauna in heart failure found lower B-type natriuretic peptide and better left-ventricular ejection fraction, with evidence strength rated moderate to insufficient. A cohort of 2277 men found frequent sauna bathing together with higher fitness was associated with lower cardiovascular and all-cause mortality.", "verdict": { "benefits": [ "In heart failure, pooled infrared sauna trials showed lower BNP and better ejection fraction.", "A cohort of 2277 men linked frequent sauna bathing with lower cardiovascular and total mortality." ], "risks": [ "A meta-analysis of 20 randomised trials of passive heating found no significant effect on most measures.", "Its blood pressure reduction was not significant overall, appearing only in subgroups.", "The mortality finding is observational, and the heart-failure evidence was rated moderate to insufficient." ], "bottomLine": "Randomised sauna trials show little consistent cardiometabolic effect; the mortality link is observational." }, "originalLinks": [ { "title": "PubMed: sauna bathing", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=sauna+bathing" } ], "links": [ { "title": "Non-acute effects of passive heating interventions on cardiometabolic risk and vascular health: systematic review and meta-analysis of randomized controlled trials (Hamaya et al., 2025)", "url": "https://doi.org/10.1016/j.ajpc.2025.101082" }, { "title": "Effects of sauna bath on heart failure: A systematic review and meta-analysis (Källström et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30239008/" }, { "title": "Joint associations of sauna bathing and cardiorespiratory fitness on cardiovascular and all-cause mortality risk (Kunutsor et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/28972808/" } ], "protocols": [ { "population": "adults in 20 randomised trials of hot water bathing, saunas, hot yoga and local heating", "regimen": "passive heating interventions lasting at least one week", "duration": "2 to 15 weeks", "outcome": "No significant pooled effect on most outcomes; systolic blood pressure -2.46 mmHg was not significant overall, falling only in whole-body heating and coronary-risk subgroups.", "source": { "title": "Non-acute effects of passive heating interventions on cardiometabolic risk and vascular health: systematic review and meta-analysis of randomized controlled trials (Hamaya et al., 2025)", "url": "https://doi.org/10.1016/j.ajpc.2025.101082" }, "origins": [ "evidence.json#/catalog:recovery:sauna/protocols/0" ] }, { "population": "patients with heart failure, in 7 of the 9 included studies, all of them infrared sauna", "regimen": "infrared sauna at 60°C for 15 minutes followed by a 30-minute rest in a warm environment, five times a week", "duration": "2 to 4 weeks", "outcome": "B-type natriuretic peptide and cardiothoracic ratio fell and ejection fraction rose; no significant effect on blood pressure or chamber diameters.", "source": { "title": "Effects of sauna bath on heart failure: A systematic review and meta-analysis (Källström et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30239008/" }, "origins": [ "evidence.json#/catalog:recovery:sauna/protocols/1" ] }, { "population": "2,277 Finnish men with cardiorespiratory fitness measured by respiratory gas analysis at baseline", "regimen": "self-reported sauna bathing of 3-7 sessions a week, compared with 2 or fewer", "duration": "median 26.1 years of follow-up", "outcome": "Frequent sauna bathing was associated with lower cardiovascular (HR 0.74) and all-cause (HR 0.84) mortality, lowest when combined with high cardiorespiratory fitness.", "source": { "title": "Joint associations of sauna bathing and cardiorespiratory fitness on cardiovascular and all-cause mortality risk (Kunutsor et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/28972808/" }, "origins": [ "evidence.json#/catalog:recovery:sauna/protocols/2" ] } ], "community": [ { "description": "Finland's living-heritage register describes sauna bathing traditionally on Saturdays, with the practice now spread across other days too.", "source": { "title": "Sauna bathing - Elava perinto (Finnish national inventory of living heritage)", "url": "https://wiki.aineetonkulttuuriperinto.fi/wiki/Sauna_bathing" }, "origins": [ "evidence.json#/catalog:recovery:sauna/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://wiki.aineetonkulttuuriperinto.fi/wiki/Sauna_bathing", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: Finland's living-heritage register describes sauna bathing traditionally on Saturdays, with the practice now spread across other days too." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:sauna/community/0", "url": "https://wiki.aineetonkulttuuriperinto.fi/wiki/Sauna_bathing", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "doi:10.1016/j.ajpc.2025.101082", "pmid:30239008", "pmid:28972808", "https://pubmed.ncbi.nlm.nih.gov/?term=sauna+bathing", "https://wiki.aineetonkulttuuriperinto.fi/wiki/Sauna_bathing" ] }, "library:recovery-screen-curfew": { "id": "library:recovery-screen-curfew", "path": "/library/recovery-screen-curfew.html", "title": "Screen curfew", "summary": "A cutoff time for screens before bed, tracked by whether it held.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:screen-curfew", "title": "Screen curfew", "summary": "A cutoff time for screens before bed, tracked by whether it held.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A survey study separated the moment of going to bed from the later moment of attempting sleep, finding a measurable gap between the two driven mainly by electronic media use before bedtime. A separate systematic review of screen-limiting interventions in children found that reducing screen time before bed was linked with modestly longer and earlier sleep.", "verdict": { "benefits": [ "Interventions that reduced children's screen use before bedtime were linked with modestly longer sleep duration and earlier bedtimes in the pooled trials.", "Separating bedtime from the later moment of falling asleep let researchers isolate a thirty-nine-minute gap driven mainly by pre-bedtime media use.", "Longer gaps between bedtime and sleep onset were linked with poorer self-rated sleep quality." ], "risks": [ "The pooled screen-time trials showed only modest average effects, with sleep duration increasing by about eleven minutes a day.", "It is not possible to determine from these studies whether reduced screen time directly improved sleep or reflected other changes made alongside it.", "Most of the underlying evidence comes from self-report and observational designs rather than large randomized trials." ], "bottomLine": "A systematic review of controlled interventions found reduced screen time before bed linked with modest gains in sleep duration and earlier bedtimes in children, while survey data in young adults linked pre-bedtime media use with a longer gap before falling asleep." }, "originalLinks": [ { "title": "Bedtime, shuteye time and electronic media: sleep displacement is a two-step process", "url": "https://pubmed.ncbi.nlm.nih.gov/28271575/" }, { "title": "Interventions to control children's screen use and their effect on sleep: A systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/32567219/" } ], "links": [ { "title": "Bedtime, shuteye time and electronic media: sleep displacement is a two-step process", "url": "https://pubmed.ncbi.nlm.nih.gov/28271575/" }, { "title": "Interventions to control children's screen use and their effect on sleep: A systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/32567219/" } ], "protocols": [ { "population": "338 adults aged 18 to 25 completing an online survey, 67.6 percent women", "regimen": "Self-reported bedtime, shuteye time, and electronic media use before and after getting into bed", "duration": "Cross-sectional survey study, published 2017", "outcome": "A thirty-nine-minute average gap between bedtime and shuteye time was found, driven almost entirely by pre-bedtime media use, and longer gaps were linked with poorer sleep ratings", "source": { "title": "Bedtime, shuteye time and electronic media: sleep displacement is a two-step process", "url": "https://pubmed.ncbi.nlm.nih.gov/28271575/" }, "origins": [ "evidence.json#/catalog:recovery:screen-curfew/protocols/0" ] }, { "population": "4,656 children aged 2 to 13 across eleven controlled intervention studies", "regimen": "Interventions that limited or restructured children's screen use before bedtime, compared with usual-care control groups", "duration": "Intervention periods reviewed ranged from under three months to longer programs, meta-analysis published 2020", "outcome": "Interventions that reduced screen use were linked with modest increases in sleep duration and earlier bedtimes compared with control groups", "source": { "title": "Interventions to control children's screen use and their effect on sleep: A systematic review and meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/32567219/" }, "origins": [ "evidence.json#/catalog:recovery:screen-curfew/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The quoted timing is a CDC expert recommendation, not a report of an observed community routine.", "checks": [ { "url": "https://www.cdc.gov/sleep/about/index.html", "outcome": "no-practice-description", "reason": "The quoted timing is a CDC expert recommendation, not a report of an observed community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:28271575", "pmid:32567219" ] }, "library:recovery-stretching": { "id": "library:recovery-stretching", "path": "/library/recovery-stretching.html", "title": "Stretching / mobility", "summary": "Targeted mobility work, usually short and frequent rather than long and occasional.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "fitness-muscle" ], "research": [ { "id": "catalog:recovery:stretching", "title": "Stretching / mobility", "summary": "Targeted mobility work, usually short and frequent rather than long and occasional.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 11 randomised trials with 452 people found strength training and stretching improved range of motion about equally. A larger systematic review of 65 studies with 1542 adults examined why range of motion improves, looking at stretch tolerance, passive stiffness and fascicle length. A third systematic review of randomised trials compared post-exercise stretching with other recovery methods for soreness, strength and range of motion, and rated the evidence as limited. Nothing here supports stretching on its own as injury prevention.", "verdict": { "benefits": [ "Pooled randomised trials found stretching improved range of motion about as much as strength training.", "Chronic stretching raised stretch tolerance, and stretching slightly reduced stiffness." ], "risks": [ "After exercise it did not reduce soreness at 24, 48 or 72 hours, nor speed strength recovery.", "That post-exercise evidence was rated very low quality and limited.", "Nothing here supports stretching on its own as injury prevention." ], "bottomLine": "Stretching improves range of motion much like strength training, but did not ease soreness or speed recovery." }, "originalLinks": [ { "title": "PubMed: stretching and range of motion", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=stretching+range+of+motion+meta-analysis" } ], "links": [ { "title": "Strength Training versus Stretching for Improving Range of Motion: A Systematic Review and Meta-Analysis (Afonso et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33917036/" }, { "title": "The Effectiveness of Post-exercise Stretching in Short-Term and Delayed Recovery of Strength, Range of Motion and Delayed Onset Muscle Soreness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (Eckert et al., 2021)", "url": "https://doi.org/10.3389/fphys.2021.677581" }, { "title": "Mechanisms Underlying Range of Motion Improvements Following Acute and Chronic Static Stretching: A Systematic Review, Meta-analysis and Multivariate Meta-regression (Ingram et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40180774/" } ], "protocols": [ { "population": "229 participants, mostly males aged 17-38, across 11 randomised controlled trials", "regimen": "post-exercise stretching of roughly 1 to 30 minutes: active static (4 studies), passive static (6) or PNF (2), mostly lower limb", "duration": "single post-exercise sessions, with outcomes at 24, 48 and 72 hours", "outcome": "No effect on muscle soreness at 24, 48 or 72 hours and none on strength recovery versus passive recovery; evidence quality rated very low.", "source": { "title": "The Effectiveness of Post-exercise Stretching in Short-Term and Delayed Recovery of Strength, Range of Motion and Delayed Onset Muscle Soreness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (Eckert et al., 2021)", "url": "https://doi.org/10.3389/fphys.2021.677581" }, "origins": [ "evidence.json#/catalog:recovery:stretching/protocols/0" ] }, { "population": "1,542 adults (71% male, mean age 26) across 65 studies", "regimen": "static stretching as a single acute session or chronically over two or more sessions, against non-stretching passive controls", "duration": "acute single sessions and chronic programmes of two or more sessions", "outcome": "Both acute and chronic stretching slightly reduced stiffness; only chronic stretching raised stretch tolerance, and neither changed fascicle length.", "source": { "title": "Mechanisms Underlying Range of Motion Improvements Following Acute and Chronic Static Stretching: A Systematic Review, Meta-analysis and Multivariate Meta-regression (Ingram et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40180774/" }, "origins": [ "evidence.json#/catalog:recovery:stretching/protocols/1" ] } ], "community": [ { "description": "An NHS post-exercise stretching routine includes buttock, hamstring, inner-thigh, calf and front-of-thigh stretches, with each side stretched in turn.", "source": { "title": "How to stretch after exercising - NHS", "url": "https://www.nhs.uk/live-well/exercise/how-to-stretch-after-exercising/" }, "origins": [ "evidence.json#/catalog:recovery:stretching/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live NHS routine contains the named lower-body stretches with sides repeated in turn. Stretch durations and benefit claims are not repeated.", "checks": [ { "url": "https://www.nhs.uk/live-well/exercise/how-to-stretch-after-exercising/", "outcome": "verified-description", "reason": "The live NHS routine contains the named lower-body stretches with sides repeated in turn. Stretch durations and benefit claims are not repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:stretching/community/0", "url": "https://www.nhs.uk/live-well/exercise/how-to-stretch-after-exercising/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:33917036", "doi:10.3389/fphys.2021.677581", "pmid:40180774", "https://pubmed.ncbi.nlm.nih.gov/?term=stretching+range+of+motion+meta-analysis", "https://www.nhs.uk/live-well/exercise/how-to-stretch-after-exercising/" ] }, "library:recovery-sunlight": { "id": "library:recovery-sunlight", "path": "/library/recovery-sunlight.html", "title": "Morning sunlight", "summary": "Outdoor light exposure early in the day, for circadian timing.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:sunlight", "title": "Morning sunlight", "summary": "Outdoor light exposure early in the day, for circadian timing.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "A systematic review of 128 studies found that light exposure, and its timing, shifts melatonin secretion and circadian rhythm in people. A trial in 50 adults showed that morning bright light combined with afternoon melatonin advanced circadian timing over three days, with more light giving a larger shift. Two cross-sectional studies link more morning outdoor light with earlier sleep timing and better reported sleep quality. The cross-sectional parts show association only, and the trial combined light with melatonin, so light alone cannot be separated out.", "verdict": { "benefits": [ "A review of 128 studies shows light, and its timing, shifts melatonin and circadian rhythm", "In a trial, morning light with afternoon melatonin advanced circadian timing, more light shifting more" ], "risks": [ "That trial combined light with melatonin, so light on its own cannot be separated out", "The link between morning outdoor light and sleep quality is cross-sectional, so association only", "Evening blue light suppressed melatonin, most strongly at the shortest wavelengths" ], "bottomLine": "Light exposure and its timing measurably shift circadian rhythm; the sleep-quality links are associations only." }, "originalLinks": [ { "title": "PubMed: light exposure and circadian rhythm", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=morning+light+exposure+circadian" } ], "links": [ { "title": "Systematic review of light exposure impact on human circadian rhythm (Tähkämö et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30311830/" }, { "title": "Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep (Crowley 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25620199/" }, { "title": "The role of sunlight in sleep regulation: analysis of morning, evening and late exposure (de et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41053799/" }, { "title": "Light exposure behaviors predict mood, memory and sleep quality (Siraji et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37528146/" } ], "protocols": [ { "population": "128 studies of light exposure, mostly in adults in their twenties and thirties", "regimen": "the review describes laboratory exposures such as two hours of blue light at 460 nm in the evening, and night-time levels of 5-10 lux", "duration": "not stated", "outcome": "Evening blue light suppressed melatonin, most strongly at the shortest wavelengths, and melatonin recovered within about 15 minutes of the exposure ending.", "source": { "title": "Systematic review of light exposure impact on human circadian rhythm (Tähkämö et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30311830/" }, "origins": [ "evidence.json#/catalog:recovery:sunlight/protocols/0" ] }, { "population": "50 adults (27 men), mean age 25.9 years", "regimen": "0.5 mg melatonin 5 h before bedtime plus morning bright light of about 5000 lux on waking, in 2-hour, 1-hour or single 30-minute patterns, sleep advanced 1 h/day", "duration": "3 treatment days", "outcome": "Melatonin onset advanced 2.4 h in the 2-hour group, 1.7 h in the 1-hour group and 1.8 h in the 30-minute group.", "source": { "title": "Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep (Crowley 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25620199/" }, "origins": [ "evidence.json#/catalog:recovery:sunlight/protocols/1" ] }, { "population": "1,762 adults in the Iron Quadrilateral region, Brazil", "regimen": "self-reported sunlight exposure before 10 a.m., between 10 a.m. and 3 p.m., and after 3 p.m., analysed per 30-minute increment", "duration": "single cross-sectional survey, October to December 2020", "outcome": "Each extra 30 minutes of morning sun was linked to a 23-minute earlier sleep midpoint and a lower PSQI score; no link to sleep time, latency or efficiency.", "source": { "title": "The role of sunlight in sleep regulation: analysis of morning, evening and late exposure (de et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41053799/" }, "origins": [ "evidence.json#/catalog:recovery:sunlight/protocols/2" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.bannerhealth.com/healthcareblog/teach-me/sun-gating-and-morning-light-for-better-sleep", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." }, { "url": "https://health.yahoo.com/wellness/articles/circadian-sunmaxxing-free-morning-habit-230000245.html", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://theeverygirl.com/getting-morning-sunlight-every-day/", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:30311830", "pmid:25620199", "pmid:41053799", "pmid:37528146", "https://pubmed.ncbi.nlm.nih.gov/?term=morning+light+exposure+circadian" ] }, "library:recovery-yoga": { "id": "library:recovery-yoga", "path": "/library/recovery-yoga.html", "title": "Yoga", "summary": "Movement and breath practice. Sits between training and recovery depending on the style, so log the intensity rather than assuming.", "aliases": [], "kind": "recovery-practice", "categories": [ "recovery-healing", "fitness-muscle", "nootropics-cognitive" ], "research": [ { "id": "catalog:recovery:yoga", "title": "Yoga", "summary": "Movement and breath practice. Sits between training and recovery depending on the style, so log the intensity rather than assuming.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "recovery", "evidenceTier": "systematic-review", "evidenceSummary": "Yoga combines postures, breathing and meditation. A meta-analysis of randomised trials in adults with overweight or obesity found reductions in systolic and diastolic blood pressure, with smaller effects on lipids and moderate-quality evidence. A meta-analysis of 53 trials found improvements in cholesterol and triglyceride measures, with high variation between studies. A systematic review of six randomised trials in women with gynaecological cancer reported less anxiety and depression and better quality of life, at low to moderate certainty, and a further review covers controlled trials in type 2 diabetes. Styles and durations differ widely, which limits comparison between studies.", "verdict": { "benefits": [ "Pooled randomised trials in adults with overweight or obesity found blood pressure fell modestly", "In women with gynaecological cancer, anxiety, depression and quality of life improved", "Pooled trials found improvements in cholesterol and triglyceride measures" ], "risks": [ "Lipid changes were below clinically important thresholds and glucose effects stayed uncertain", "Certainty was low to moderate and studies varied widely", "Styles and durations differ so much that trials are hard to compare" ], "bottomLine": "Yoga gave modest blood pressure and mood benefits in randomised trials, with wide variation." }, "originalLinks": [ { "title": "NCCIH: yoga", "url": "https://www.nccih.nih.gov/health/yoga-what-you-need-to-know" }, { "title": "PubMed: yoga", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=yoga+randomized+controlled+trial" } ], "links": [ { "title": "Effects of Yoga Interventions on Health Outcomes in Women With Gynecological Cancers: A Systematic Review of Randomised Controlled Trials (Giridharan et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41281133/" }, { "title": "Yoga for Adults with Type 2 Diabetes: A Systematic Review of Controlled Trials (Innes and Selfe, 2016)", "url": "https://doi.org/10.1155/2016/6979370" }, { "title": "Impact of yoga on cardiometabolic health in adults with overweight or obesity: A systematic review and meta-analysis of randomized controlled trials (Wasityastuti et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42018531/" }, { "title": "The Effect of Yoga on the Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (Ghazvineh et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35911119/" } ], "protocols": [ { "population": "320 adult women with gynaecological cancers across six randomised trials", "regimen": "yoga interventions of at least four weeks, including meditative forms such as yoga nidra and pranayama, and restorative styles", "duration": "at least 4 weeks", "outcome": "Anxiety, depression and stress fell and quality of life, fatigue and cognition improved at low to moderate certainty; no adverse events were observed.", "source": { "title": "Effects of Yoga Interventions on Health Outcomes in Women With Gynecological Cancers: A Systematic Review of Randomised Controlled Trials (Giridharan et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41281133/" }, "origins": [ "evidence.json#/catalog:recovery:yoga/protocols/0" ] }, { "population": "2,689 adults with overweight or obesity across 30 randomised trials, 2,313 of them in the meta-analyses", "regimen": "the trials with benefit used sessions of at least 60 minutes, at least three times a week, totalling at least 180 minutes a week", "duration": "at least 12 weeks in the trials that showed benefit", "outcome": "Systolic blood pressure fell 4.35 mmHg and diastolic 2.06 mmHg; lipid changes were below clinically important thresholds and glucose effects stayed uncertain.", "source": { "title": "Impact of yoga on cardiometabolic health in adults with overweight or obesity: A systematic review and meta-analysis of randomized controlled trials (Wasityastuti et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42018531/" }, "origins": [ "evidence.json#/catalog:recovery:yoga/protocols/1" ] } ], "community": [ { "description": "Yoga as practiced in the United States typically combines physical postures, breathing techniques and meditation; styles range from gentle to physically demanding.", "source": { "title": "Yoga: Effectiveness and Safety - NCCIH", "url": "https://www.nccih.nih.gov/health/yoga-effectiveness-and-safety" }, "origins": [ "evidence.json#/catalog:recovery:yoga/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live NCCIH page explicitly describes the postures, breathing and meditation emphasis of US practice and its range of styles. Trial results are not repeated.", "checks": [ { "url": "https://www.nccih.nih.gov/health/yoga-effectiveness-and-safety", "outcome": "verified-description", "reason": "The live NCCIH page explicitly describes the postures, breathing and meditation emphasis of US practice and its range of styles. Trial results are not repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:recovery:yoga/community/0", "url": "https://www.nccih.nih.gov/health/yoga-effectiveness-and-safety", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Described practice context only; no clinical benefit or safety outcome is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:41281133", "doi:10.1155/2016/6979370", "pmid:42018531", "pmid:35911119", "https://www.nccih.nih.gov/health/yoga-what-you-need-to-know", "https://pubmed.ncbi.nlm.nih.gov/?term=yoga+randomized+controlled+trial", "https://www.nccih.nih.gov/health/yoga-effectiveness-and-safety" ] }, "library:supplement-5-htp": { "id": "library:supplement-5-htp", "path": "/library/supplement-5-htp.html", "title": "5-HTP", "summary": "A serotonin precursor studied for mood, with a thin base of quality trial evidence.", "aliases": [], "kind": "supplement", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:5-htp", "title": "5-HTP", "summary": "A serotonin precursor studied for mood, with a thin base of quality trial evidence.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "5-HTP, or 5-hydroxytryptophan, is a naturally occurring amino acid derivative and an intermediate step in the body's conversion of tryptophan into serotonin. It has been studied mainly as a potential aid for mood and sleep, with most available trials being small, short, and methodologically limited. A Cochrane systematic review found that only a small fraction of identified studies met quality standards for inclusion, leaving the overall evidence base thin despite decades of interest.", "verdict": { "benefits": [ "Small clinical trials suggest possible short-term improvement in depressive symptoms compared with placebo", "As a direct serotonin precursor, its proposed mechanism of action is biologically plausible and well characterized" ], "risks": [ "Combining it with antidepressants or other serotonergic drugs raises the risk of serotonin syndrome", "Most supporting trials are small, old, and short in duration, so long-term safety and effectiveness are not established", "Nausea and other gastrointestinal upset are commonly reported side effects" ], "bottomLine": "Evidence for 5-HTP remains preliminary: early trials look promising but a formal Cochrane review found too few high-quality studies to support confident use, and it carries meaningful interaction risk with serotonergic medications." }, "originalLinks": [ { "title": "Tryptophan and 5-hydroxytryptophan for depression - PubMed (Cochrane review)", "url": "https://pubmed.ncbi.nlm.nih.gov/11869656/" }, { "title": "Tryptophan and 5-Hydroxytryptophan for depression | Cochrane", "url": "https://www.cochrane.org/evidence/CD003198_tryptophan-and-5-hydroxytryptophan-depression" } ], "links": [ { "title": "Tryptophan and 5-hydroxytryptophan for depression - PubMed (Cochrane review)", "url": "https://pubmed.ncbi.nlm.nih.gov/11869656/" }, { "title": "Tryptophan and 5-Hydroxytryptophan for depression | Cochrane", "url": "https://www.cochrane.org/evidence/CD003198_tryptophan-and-5-hydroxytryptophan-depression" } ], "protocols": [ { "source": { "title": "Tryptophan and 5-hydroxytryptophan for depression - PubMed (Cochrane review)", "url": "https://pubmed.ncbi.nlm.nih.gov/11869656/" }, "population": "64 patients with depression, drawn from the only 2 trials out of 108 identified studies that met Cochrane quality criteria", "regimen": "5-HTP or tryptophan preparations compared with placebo in short-term randomized trials", "outcome": "Both substances performed better than placebo at reducing depressive symptoms, but the reviewers concluded the evidence was insufficient in quantity and quality to support routine clinical use pending further study.", "duration": "Short-term, across the two trials meeting inclusion criteria", "origins": [ "evidence.json#/catalog:supplement:5-htp/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.webmd.com/vitamins-and-supplements/5-htp-hydroxytryptophan", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://www.examine.com/supplements/5-htp/", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 4.800000000000001, "lowerHours": 2.2, "source": "Neurotransmitter precursor pharmacokinetics reviewed in the Cochrane background; range spans dose and formulation differences across the small human PK literature", "upperHours": 7.4 } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:11869656", "https://www.cochrane.org/evidence/CD003198_tryptophan-and-5-hydroxytryptophan-depression" ] }, "library:supplement-alpha-gpc": { "id": "library:supplement-alpha-gpc", "path": "/library/supplement-alpha-gpc.html", "title": "Alpha-GPC", "summary": "A choline compound studied mainly in stroke and vascular-dementia recovery.", "aliases": [], "kind": "supplement", "categories": [ "recovery-healing", "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:alpha-gpc", "title": "Alpha-GPC", "summary": "A choline compound studied mainly in stroke and vascular-dementia recovery.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Alpha-GPC is a choline-containing compound found naturally in the brain and used clinically in several countries as a source of choline for acetylcholine synthesis. It has been studied mainly in older adults recovering from stroke or with vascular dementia, where multicenter Italian trials measured cognitive and functional recovery, as well as in smaller studies of healthy adults looking at short-term measures of alertness or power output. Evidence in medically supervised, cognitively impaired populations is more extensive than evidence in healthy, unimpaired adults.", "verdict": { "benefits": [ "In clinical trials of stroke and vascular dementia patients, alpha-GPC was linked to measurable improvement in cognitive and functional test scores", "Reported tolerability in these clinical populations was generally good" ], "risks": [ "Most supporting trials were conducted in patients with stroke or dementia rather than healthy adults, so applicability to a general population is uncertain", "Mild gastrointestinal complaints, insomnia, and headache have been reported in trial participants" ], "bottomLine": "Alpha-GPC has real clinical trial support in stroke and vascular dementia populations, but evidence specific to cognitive or athletic enhancement in healthy adults is thinner and more mixed, so its benefits outside a medical context are not well established." }, "originalLinks": [ { "title": "alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/8030842/" }, { "title": "A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/1916007/" } ], "links": [ { "title": "alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/8030842/" }, { "title": "A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/1916007/" } ], "protocols": [ { "source": { "title": "alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/8030842/" }, "population": "2044 patients with recent stroke or transient ischemic attack across an open multicenter Italian trial", "regimen": "Alpha-GPC given intramuscularly at 1000 mg per day for 28 days, followed by oral dosing of 400 mg three times daily for the following five months", "outcome": "Statistically significant improvement in mental recovery scores during both the intramuscular and oral phases, with adverse events reported in a small minority of patients and good overall tolerability", "duration": "Twenty-eight days of intramuscular dosing followed by five months of oral dosing", "origins": [ "evidence.json#/catalog:supplement:alpha-gpc/protocols/0" ] }, { "source": { "title": "A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/1916007/" }, "population": "120 patients with mild to moderate vascular dementia in an open multicentre trial", "regimen": "Alpha-GPC 1 g per day given intramuscularly for 90 days, compared against intramuscular cytosine diphosphocholine at the same dose", "outcome": "Both treatments produced symptomatic improvement on psychometric tests with good tolerability, and alpha-GPC showed statistically higher efficacy on most measures than the comparator", "duration": "Ninety days", "origins": [ "evidence.json#/catalog:supplement:alpha-gpc/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://nootropicsexpert.com/alpha-gpc/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:8030842", "pmid:1916007" ] }, "library:supplement-aniracetam": { "id": "library:supplement-aniracetam", "path": "/library/supplement-aniracetam.html", "title": "Aniracetam", "summary": "A nootropic compound showing cognitive improvements in Alzheimer's disease trials but not in healthy individuals.", "aliases": [], "kind": "supplement", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:aniracetam", "title": "Aniracetam", "summary": "A nootropic compound showing cognitive improvements in Alzheimer's disease trials but not in healthy individuals.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Aniracetam is a racetam-class nootropic that has been studied in human clinical trials for cognitive impairment and dementia. In a randomized, placebo-controlled trial of 109 patients with mild to moderate Alzheimer's disease, daily aniracetam produced double-digit percentage improvements on cognitive assessment scales at 4-6 months, while placebo recipients showed deterioration over the same period. Emotional state improved significantly at 3 months in treated patients. However, efficacy in healthy individuals without cognitive impairment remains limited; animal studies in healthy mice found no cognitive enhancement. Aniracetam is approved in some countries but not the United States.", "verdict": { "benefits": [ "Randomized trials show cognitive and emotional improvements in Alzheimer's disease patients", "Generally well-tolerated in studied populations" ], "risks": [ "No evidence of benefit in healthy individuals; animal studies in healthy mice showed no effect", "Long-term safety beyond 12 months not established in trials", "Regulatory status varies by country; not approved in United States" ], "bottomLine": "Aniracetam has shown cognitive benefits in Alzheimer's disease trials but lacks evidence for enhancement in healthy people." }, "originalLinks": [ { "title": "Clinical Efficacy of Aniracetam, Either as Monotherapy or Combined with Cholinesterase Inhibitors, in Patients with Cognitive Impairment: A Comparative Open Study", "url": "https://pubmed.ncbi.nlm.nih.gov/22070796/" }, { "title": "Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice", "url": "https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0104443" }, { "title": "Aniracetam | Drugs & Aging", "url": "https://link.springer.com/article/10.2165/00002512-199404030-00007" } ], "links": [ { "title": "Clinical Efficacy of Aniracetam, Either as Monotherapy or Combined with Cholinesterase Inhibitors, in Patients with Cognitive Impairment: A Comparative Open Study", "url": "https://pubmed.ncbi.nlm.nih.gov/22070796/" }, { "title": "Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice", "url": "https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0104443" }, { "title": "Aniracetam | Drugs & Aging", "url": "https://link.springer.com/article/10.2165/00002512-199404030-00007" } ], "protocols": [ { "population": "109 patients with mild to moderate Alzheimer's disease", "regimen": "Aniracetam oral treatment for cognitive impairment", "duration": "6 months assessment", "outcome": "12-35% improvement on cognitive scales vs. 9-19% deterioration in placebo; emotional state improved at 3 months", "source": { "title": "Clinical Efficacy of Aniracetam, Either as Monotherapy or Combined with Cholinesterase Inhibitors, in Patients with Cognitive Impairment: A Comparative Open Study", "url": "https://pubmed.ncbi.nlm.nih.gov/22070796/" }, "origins": [ "evidence.json#/catalog:supplement:aniracetam/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://nootropicsexpert.com/aniracetam/", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:22070796", "https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0104443", "https://link.springer.com/article/10.2165/00002512-199404030-00007" ] }, "library:supplement-ashwagandha": { "id": "library:supplement-ashwagandha", "path": "/library/supplement-ashwagandha.html", "title": "Ashwagandha (Withania somnifera)", "summary": "Adaptogenic herb studied for cortisol and stress. Standardised by withanolide content.", "aliases": [], "kind": "supplement", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:ashwagandha", "title": "Ashwagandha (Withania somnifera)", "summary": "Adaptogenic herb studied for cortisol and stress. Standardised by withanolide content.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Ashwagandha (Withania somnifera) is a herb studied for stress and anxiety. A meta-analysis of nine randomised controlled trials with 558 people found lower perceived stress scores, lower Hamilton anxiety scores and lower serum cortisol than placebo, with mild to moderate side effects in four trials. A second systematic review of nine trials found cortisol fell without significant harm, but no study looked at what lowering cortisol does to adrenal function or at long-term use. Trials are short and use different preparations.", "verdict": { "benefits": [ "A meta-analysis of nine randomised trials found lower perceived stress and anxiety scores than placebo.", "Pooled trials also found serum cortisol fell." ], "risks": [ "Four trials reported mild to moderate side effects.", "No study examined what the cortisol drop does to adrenal function, or what long-term use does.", "Trials are short and use different preparations, so results may not transfer between products." ], "bottomLine": "Ashwagandha lowered stress, anxiety scores and cortisol in pooled trials; long-term effects are unstudied." }, "originalLinks": [ { "title": "PubMed: ashwagandha cortisol", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=ashwagandha+cortisol" } ], "links": [ { "title": "Effects of Ashwagandha Supplements on Cortisol, Stress, and Anxiety Levels in Adults: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12242034/" }, { "title": "Effects of Ashwagandha (Withania somnifera) on stress and anxiety: a systematic review and meta-analysis (Arumugam et al. 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39348746/" }, { "title": "Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review (Della et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/38140274/" } ], "protocols": [ { "population": "Stressed adults across nine clinical trials", "regimen": "Withania somnifera preparations from 60 mg to 5,000 mg daily, most as extracts standardised to 5% withanolides", "duration": "30 to 112 days, most 56 to 90 days", "outcome": "Cortisol secretion fell with no significant adverse effects; no study examined what the cortisol drop does to adrenal function or what long-term use does.", "source": { "title": "Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review (Della et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/38140274/" }, "origins": [ "evidence.json#/catalog:supplement:ashwagandha/protocols/0" ] } ], "community": [ { "description": "NCCIH describes ashwagandha as a medicinal plant historically used in traditional Ayurvedic practice.", "source": { "title": "Ashwagandha: Usefulness and Safety - NCCIH", "url": "https://www.nccih.nih.gov/health/ashwagandha" }, "origins": [ "evidence.json#/catalog:supplement:ashwagandha/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "The independently retrieved full NIH page contains a traditional-use report, not just navigation. Like the berberine description, this records a historical medicinal tradition without repeating indications, recommendations or claimed benefits.", "checks": [ { "url": "https://www.nccih.nih.gov/health/ashwagandha", "outcome": "verified-description", "reason": "The background section explicitly records longstanding medicinal-plant use, especially in Ayurvedic medicine. Current promotional indications and trial results were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:ashwagandha/community/0", "url": "https://www.nccih.nih.gov/health/ashwagandha", "claimMatch": "The earlier live reading supports only the bounded diary/traditional-use description; it does not establish effectiveness or a medical regimen.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "bounded-description-supported" } ] }, "pk": { "hours": 6, "source": "Withanolide PK; limited data" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC12242034/", "pmid:39348746", "pmid:38140274", "https://pubmed.ncbi.nlm.nih.gov/?term=ashwagandha+cortisol", "https://www.nccih.nih.gov/health/ashwagandha" ] }, "library:supplement-bcaa": { "id": "library:supplement-bcaa", "path": "/library/supplement-bcaa.html", "title": "BCAAs", "summary": "Branched-chain amino acids. Largely redundant when total protein intake is adequate.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:supplement:bcaa", "title": "BCAAs", "summary": "Branched-chain amino acids. Largely redundant when total protein intake is adequate.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 18 randomised trials found branched-chain amino acids lowered creatine kinase at some time points and reduced muscle soreness over the days after damaging exercise, with no effect on lactate dehydrogenase. A systematic review of 22 trials with 511 healthy participants found soreness may fall, but effects on strength, endurance and body composition were inconsistent, and no meta-analysis was possible because of bias risk. In liver cirrhosis, a meta-analysis of five trials with 434 patients found a better frailty index, body mass index and quality of life, but no change in grip strength or muscle index.", "verdict": { "benefits": [ "Pooled randomised trials found less muscle soreness and lower creatine kinase after hard exercise.", "In liver cirrhosis, pooled trials found a better frailty index, body mass index and quality of life." ], "risks": [ "Effects on strength, endurance and body composition were inconsistent across trials.", "One review could not pool its studies at all because of bias risk.", "Grip strength and muscle index did not change in cirrhosis; lactate dehydrogenase was unchanged." ], "bottomLine": "BCAAs reduced post-exercise soreness in pooled trials, with inconsistent effects on strength, endurance and body shape." }, "originalLinks": [ { "title": "PubMed: BCAA supplementation", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=branched+chain+amino+acid+supplementation" } ], "links": [ { "title": "Attenuating Muscle Damage Biomarkers and Muscle Soreness After an Exercise-Induced Muscle Damage with Branched-Chain Amino Acid (BCAA) Supplementation: A Systematic Review and Meta-analysis with Meta-regression", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11021390/" }, { "title": "The Effect of Oral Pure Branched-Chain Amino Acid Supplementation on Exercise Performance and Body Composition: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12674588/" }, { "title": "Branched-Chain Amino Acid Supplements for Sarcopenia in Liver Cirrhosis: A Systematic Review and Meta-analysis (Abuelazm et al. 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39834601/" } ], "protocols": [ { "population": "participants undergoing exercise-induced muscle damage across 18 randomised trials", "regimen": "branched-chain amino acids 3.15-29.3 g a day (0.08-0.54 g/kg), given before, on the day of, or after the damaging exercise", "duration": "1 to 28 days", "outcome": "Creatine kinase fell immediately after exercise and at 72 h and soreness fell at 24, 48, 72 and 96 h; lactate dehydrogenase did not change at any point.", "source": { "title": "Attenuating Muscle Damage Biomarkers and Muscle Soreness After an Exercise-Induced Muscle Damage with Branched-Chain Amino Acid (BCAA) Supplementation: A Systematic Review and Meta-analysis with Meta-regression", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11021390/" }, "origins": [ "evidence.json#/catalog:supplement:bcaa/protocols/0" ] }, { "population": "511 healthy participants across 22 randomised trials, 11 of them in trained athletes", "regimen": "branched-chain amino acids 1.5-82 g a day, most often in a 2:1:1 leucine to isoleucine to valine ratio", "duration": "one day to six months", "outcome": "Soreness fell in 5 of 11 studies, strength improved in 8 of 16, endurance in 7 of 10, and body composition in only 1 of 5; no meta-analysis was possible.", "source": { "title": "The Effect of Oral Pure Branched-Chain Amino Acid Supplementation on Exercise Performance and Body Composition: A Systematic Review", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12674588/" }, "origins": [ "evidence.json#/catalog:supplement:bcaa/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://ods.od.nih.gov/factsheets/BranchedChainAminoAcids-HealthProfessional/", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC11021390/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12674588/", "pmid:39834601", "https://pubmed.ncbi.nlm.nih.gov/?term=branched+chain+amino+acid+supplementation" ] }, "library:supplement-beetroot": { "id": "library:supplement-beetroot", "path": "/library/supplement-beetroot.html", "title": "Beetroot / Dietary Nitrate", "summary": "A dietary nitrate source studied for blood pressure and exercise performance.", "aliases": [], "kind": "supplement", "categories": [ "longevity", "fitness-muscle" ], "research": [ { "id": "catalog:supplement:beetroot", "title": "Beetroot / Dietary Nitrate", "summary": "A dietary nitrate source studied for blood pressure and exercise performance.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Beetroot, and the concentrated juice made from it, is a natural source of inorganic dietary nitrate that the body converts into nitric oxide, a molecule involved in blood vessel dilation. It has been tested in numerous randomized trials for effects on blood pressure and exercise performance, particularly in endurance and interval-based activities. Meta-analyses show a consistent, modest blood-pressure-lowering effect, while findings on exercise performance are more mixed and depend heavily on exercise type and training status.", "verdict": { "benefits": [ "Randomized trials consistently show a modest reduction in blood pressure, particularly systolic pressure", "Some evidence supports improved intermittent running capacity in recreationally active people", "Whole-food source of nitrate with a well-understood mechanism through nitric oxide production" ], "risks": [ "Effects on high-intensity power output in trained or elite athletes are largely absent in pooled analyses", "Urine and stool can turn red or pink after consumption, which is harmless but can be mistaken for a medical problem", "Long-term cardiovascular outcome data beyond blood pressure changes are limited" ], "bottomLine": "Beetroot and dietary nitrate have some of the more consistent supplement evidence for blood pressure, but the exercise-performance story is uneven and depends heavily on the sport and the athlete's training level." }, "originalLinks": [ { "title": "Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/23596162/" }, { "title": "The Effect of Beetroot Ingestion on High-Intensity Interval Training: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8618171/" } ], "links": [ { "title": "Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/23596162/" }, { "title": "The Effect of Beetroot Ingestion on High-Intensity Interval Training: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8618171/" } ], "protocols": [ { "source": { "title": "Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/23596162/" }, "population": "254 participants pooled across 16 randomized controlled trials of inorganic nitrate or beetroot juice versus placebo", "regimen": "Inorganic nitrate or beetroot juice supplementation, from a single acute dose up to 15 days of daily dosing, compared with a nitrate-depleted placebo", "outcome": "Supplementation was associated with a significant reduction in systolic blood pressure of about 4.4 mmHg, with a smaller and less consistent reduction in diastolic blood pressure.", "duration": "Single acute dose up to fifteen days of daily dosing", "origins": [ "evidence.json#/catalog:supplement:beetroot/protocols/0" ] }, { "source": { "title": "The Effect of Beetroot Ingestion on High-Intensity Interval Training: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8618171/" }, "population": "319 participants, mostly recreationally active adults, pooled across 17 randomized trials of high-intensity interval or sprint training", "regimen": "Acute nitrate doses of about 4.8 to 12.9 mmol, or chronic daily doses of about 5.2 to 29.0 mmol for 3 to 28 days, most often given 2 to 3 hours before exercise", "outcome": "Beetroot supplementation produced no significant improvement in peak or mean power output during high-intensity interval or sprint training, though a small, significant improvement appeared on an intermittent running recovery test.", "duration": "Three to twenty-eight days", "origins": [ "evidence.json#/catalog:supplement:beetroot/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://mcpress.mayoclinic.org/nutrition-fitness/preworkout-supplements-whats-safe-what-should-you-avoid/", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." }, { "url": "https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1347242/full", "outcome": "trial-only", "reason": "The inspected review compares dietary nitrate interventions and exercise outcomes. Trial regimens were not repurposed as community practice." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:23596162", "https://pmc.ncbi.nlm.nih.gov/articles/PMC8618171/" ] }, "library:supplement-berberine": { "id": "library:supplement-berberine", "path": "/library/supplement-berberine.html", "title": "Berberine", "summary": "A plant alkaloid studied for blood sugar and lipid control in type 2 diabetes.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:berberine", "title": "Berberine", "summary": "A plant alkaloid studied for blood sugar and lipid control in type 2 diabetes.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Berberine is a plant alkaloid found in Berberis and related species with a long history of use in traditional Chinese and Ayurvedic medicine. It has been studied mainly in people with type 2 diabetes for effects on glucose and lipid metabolism, most often as an addition to standard diabetes therapy rather than in place of it.", "verdict": { "benefits": [ "Consistent reductions in blood glucose markers across pooled trials", "Improvements in lipid profile alongside glucose effects", "Appears effective as an addition to standard diabetes therapy in pooled analysis" ], "risks": [ "Most underlying trials were conducted in China with variable reporting quality", "Gastrointestinal side effects are commonly reported", "Long-term safety data outside trial settings are limited" ], "bottomLine": "Pooled trial evidence for glucose and lipid effects is consistent, but the geographic concentration and quality of underlying trials warrant a cautious reading pending independent replication." }, "originalLinks": [ { "title": "The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/34956436/" } ], "links": [ { "title": "The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/34956436/" } ], "protocols": [ { "source": { "title": "The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/34956436/" }, "population": "Adults with type 2 diabetes across forty-six randomized controlled trials, most conducted in China", "regimen": "Berberine administered alone or combined with standard glucose-lowering or lipid-lowering therapy, compared with control groups, across trials of varying dose and duration", "outcome": "Significant reductions in HbA1c, fasting and post-meal glucose, triglycerides, total cholesterol and LDL cholesterol, alongside an increase in HDL cholesterol, versus control", "duration": "Trials of varying duration, pooled across forty-six studies", "origins": [ "evidence.json#/catalog:supplement:berberine/protocols/0" ] } ], "community": [ { "description": "Memorial Sloan Kettering's reference describes berberine-containing plants used in traditional Chinese medicine and Ayurveda; this records traditional use, not established clinical benefit.", "source": { "title": "Berberine | Memorial Sloan Kettering Cancer Center - About Herbs", "url": "https://www.mskcc.org/cancer-care/integrative-medicine/herbs/berberine" }, "origins": [ "evidence.json#/catalog:supplement:berberine/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://www.mskcc.org/cancer-care/integrative-medicine/herbs/berberine", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: Memorial Sloan Kettering's reference describes berberine-containing plants used in traditional Chinese medicine and Ayurveda; this records traditional use, not established clinical benefit." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:berberine/community/0", "url": "https://www.mskcc.org/cancer-care/integrative-medicine/herbs/berberine", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:34956436", "https://www.mskcc.org/cancer-care/integrative-medicine/herbs/berberine" ] }, "library:supplement-beta-alanine": { "id": "library:supplement-beta-alanine", "path": "/library/supplement-beta-alanine.html", "title": "Beta-Alanine", "summary": "An amino acid studied for buffering fatigue during short, high-intensity exercise.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:supplement:beta-alanine", "title": "Beta-Alanine", "summary": "An amino acid studied for buffering fatigue during short, high-intensity exercise.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Beta-alanine is a non-essential amino acid that serves as the rate-limiting substrate for synthesis of carnosine, a muscle dipeptide that buffers hydrogen ions during high-intensity exercise. It is one of the more extensively studied sports supplements, with a substantial meta-analytic literature on muscle carnosine loading and exercise performance.", "verdict": { "benefits": [ "Consistent ergogenic effect for high-intensity exercise lasting one to four minutes", "Well-characterized mechanism through increased muscle carnosine concentration", "One of the more extensively replicated effects among sports supplements" ], "risks": [ "Little to no benefit shown for exercise shorter than sixty seconds", "Paresthesia (skin tingling) is a common transient side effect at higher single doses", "Effect size is more modest in elite athletes than in recreational populations" ], "bottomLine": "Meta-analytic evidence for a modest but real performance benefit in high-intensity exercise lasting one to four minutes is among the strongest in the sports-supplement category." }, "originalLinks": [ { "title": "Effects of β-alanine supplementation on exercise performance: a meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22270875/" } ], "links": [ { "title": "Effects of β-alanine supplementation on exercise performance: a meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22270875/" } ], "protocols": [ { "source": { "title": "Effects of β-alanine supplementation on exercise performance: a meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22270875/" }, "population": "360 trained and untrained participants across twenty-three exercise tests pooled from fifteen published studies", "regimen": "Eighteen different beta-alanine supplementation regimens, totaling a median of 179 g of beta-alanine across the supplementation period", "outcome": "Greater improvement in exercise measures than placebo, with the largest benefit for exercise capacity lasting 60 to 240 seconds; a median 2.85 percent improvement in exercise outcome overall", "duration": "Supplementation periods varied across the eighteen regimens pooled", "origins": [ "evidence.json#/catalog:supplement:beta-alanine/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.healthline.com/nutrition/beta-alanine-101", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:22270875" ] }, "library:supplement-boron": { "id": "library:supplement-boron", "path": "/library/supplement-boron.html", "title": "Boron", "summary": "Trace mineral studied for effects on SHBG and free testosterone at modest doses.", "aliases": [], "kind": "supplement", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:supplement:boron", "title": "Boron", "summary": "Trace mineral studied for effects on SHBG and free testosterone at modest doses.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Boron is a trace element promoted as raising testosterone. The evidence here is one small randomised trial in 19 male bodybuilders over seven weeks, reported in two papers. Boron raised blood boron in most who took it but had no effect on total or free testosterone, lean body mass or strength. Both groups gained testosterone, lean mass and strength from the training itself.", "verdict": { "benefits": [], "risks": [ "The one small trial found no effect on total or free testosterone, lean mass or strength", "Gains in both groups came from the training itself, not from the supplement", "The whole evidence base here is a single trial in 19 male bodybuilders, reported twice" ], "bottomLine": "One small trial found boron raised blood boron but changed nothing about testosterone, lean mass or strength." }, "originalLinks": [ { "title": "PubMed: boron testosterone", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=boron+testosterone" } ], "links": [ { "title": "The effect of boron supplementation on lean body mass, plasma testosterone levels, and strength in male bodybuilders (Ferrando 1993)", "url": "https://pubmed.ncbi.nlm.nih.gov/8508192/" }, { "title": "Plasma boron and the effects of boron supplementation in males (Green 1994)", "url": "https://pubmed.ncbi.nlm.nih.gov/7889885/" } ], "protocols": [ { "population": "19 male bodybuilders aged 20-27 (10 on boron, 9 on placebo)", "regimen": "a 2.5 mg boron supplement or placebo every day, alongside their bodybuilding training", "duration": "7 weeks", "outcome": "Boron had no effect on total or free testosterone, lean body mass or strength; both groups gained testosterone, lean mass and strength from the training itself.", "source": { "title": "The effect of boron supplementation on lean body mass, plasma testosterone levels, and strength in male bodybuilders (Ferrando 1993)", "url": "https://pubmed.ncbi.nlm.nih.gov/8508192/" }, "origins": [ "evidence.json#/catalog:supplement:boron/protocols/0" ] }, { "population": "19 male bodybuilders aged 20-27 (10 on boron, 9 on placebo)", "regimen": "a 2.5 mg boron supplement or placebo daily, with plasma boron measured by inductively coupled argon plasma spectroscopy", "duration": "7 weeks", "outcome": "Plasma boron rose in 6 of the 10 supplemented men; boron affected testosterone, lean body mass, 1-RM squat and 1-RM bench press not at all.", "source": { "title": "Plasma boron and the effects of boron supplementation in males (Green 1994)", "url": "https://pubmed.ncbi.nlm.nih.gov/7889885/" }, "origins": [ "evidence.json#/catalog:supplement:boron/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://ods.od.nih.gov/factsheets/Boron-HealthProfessional/", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:8508192", "pmid:7889885", "https://pubmed.ncbi.nlm.nih.gov/?term=boron+testosterone" ] }, "library:supplement-caffeine": { "id": "library:supplement-caffeine", "path": "/library/supplement-caffeine.html", "title": "Caffeine", "summary": "A widely studied stimulant taken for alertness and physical performance.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle", "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:caffeine", "title": "Caffeine", "summary": "A widely studied stimulant taken for alertness and physical performance.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Caffeine is a naturally occurring methylxanthine stimulant found in coffee, tea and cacao that works mainly by blocking adenosine receptors in the central nervous system. It is one of the most extensively studied psychoactive compounds, with decades of research examining effects on alertness, cognitive function and physical performance across military, occupational and athletic settings.", "verdict": { "benefits": [ "Improves alertness, vigilance and reaction time at low to moderate intake", "Improves endurance, time-trial and high-intensity sprint performance in athletes", "Effects are consistent across a large and long-standing body of research" ], "risks": [ "Higher intake is linked with jitteriness, anxiety and sleep disruption", "Effects on memory and complex decision-making are inconsistent", "Tolerance develops with regular use, altering response over time" ], "bottomLine": "Evidence for alertness and physical performance benefits is strong and consistent across a large body of research, though effects on higher-order cognition remain mixed." }, "originalLinks": [ { "title": "A review of caffeine's effects on cognitive, physical and occupational performance - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/27612937/" } ], "links": [ { "title": "A review of caffeine's effects on cognitive, physical and occupational performance - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/27612937/" } ], "protocols": [ { "source": { "title": "A review of caffeine's effects on cognitive, physical and occupational performance - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/27612937/" }, "population": "Healthy adults across military, occupational and athletic contexts, synthesized from the trials reviewed", "regimen": "Doses of approximately 40 mg (about 0.5 mg/kg) up to 300 mg (about 4 mg/kg) evaluated for cognitive effects; doses exceeding roughly 200 mg (about 3 mg/kg) evaluated for physical performance effects", "outcome": "Low-to-moderate doses improved alertness, vigilance, attention and reaction time; higher doses improved time-to-exhaustion, time-trial performance, muscle strength and endurance, and high-intensity sprint performance", "duration": "Acute, single-dose administration in most trials reviewed", "origins": [ "evidence.json#/catalog:supplement:caffeine/protocols/0" ] } ], "community": [ { "description": "An exercise-nutrition guide describes regular caffeine intake through coffee, energy drinks and caffeinated soft drinks, alongside caffeine anhydrous supplements.", "source": { "title": "How Caffeine Improves Exercise Performance - Healthline", "url": "https://www.healthline.com/nutrition/caffeine-and-exercise" }, "origins": [ "evidence.json#/catalog:supplement:caffeine/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "The original numerical amounts were presented by the page as recommendations and study-based amounts. The revised description retains explicit consumption forms without implying an observed common dose.", "checks": [ { "url": "https://www.healthline.com/nutrition/caffeine-and-exercise", "outcome": "verified-description", "reason": "The live page names regular intake through coffee, energy drinks and caffeinated soda, and separately discusses caffeine anhydrous supplements. Dose and efficacy recommendations were excluded." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:caffeine/community/0", "url": "https://www.healthline.com/nutrition/caffeine-and-exercise", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 5, "source": "Kaplan et al. 1997, J Clin Pharmacol, PMID 9378841; Bonati et al. 1982, Clin Pharmacol Ther, PMID 7083737 — adult reference value, nonlinear/dose-dependent, ranges 3.5-10.5h depending on smoking, pregnancy and CYP1A2 genotype" } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:27612937", "https://www.healthline.com/nutrition/caffeine-and-exercise" ] }, "library:supplement-casein-protein": { "id": "library:supplement-casein-protein", "path": "/library/supplement-casein-protein.html", "title": "Casein protein", "summary": "Slow-digesting dairy protein, often taken before sleep for prolonged amino acid release.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:supplement:casein-protein", "title": "Casein protein", "summary": "Slow-digesting dairy protein, often taken before sleep for prolonged amino acid release.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Casein is a slow-digesting milk protein. Randomised crossover trials in small groups of healthy men show that how casein is processed changes how quickly amino acids appear in the blood, with cross-linked sodium caseinate fastest. In older men, casein taken in a milk matrix slowed digestion but did not change muscle protein synthesis afterwards. A trial comparing cow and goat casein found similar stomach emptying, with higher essential amino acids after cow casein. These are small mechanistic trials, not strength or body-composition studies.", "verdict": { "benefits": [ "Small crossover trials in healthy men show how processing changes the speed amino acids reach the blood", "Cow casein raised essential amino acids more than goat casein, at the same stomach emptying rate" ], "risks": [ "In older men a milk matrix slowed digestion without changing muscle protein synthesis", "These are small mechanistic trials; nothing here measures strength or body composition" ], "bottomLine": "Casein research here shows how fast its amino acids arrive, not whether it builds strength." }, "originalLinks": [ { "title": "PubMed: casein protein overnight", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=casein+protein+overnight+muscle" } ], "links": [ { "title": "Casein Protein Processing Strongly Modulates Post-Prandial Plasma Amino Acid Responses In Vivo in Humans", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468913/" }, { "title": "Ingestion of Casein in a Milk Matrix Modulates Dietary Protein Digestion and Absorption Kinetics but Does Not Modulate Postprandial Muscle Protein Synthesis in Older Men (Churchward-Venne et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26019248/" }, { "title": "Gastric digestion and changes in serum amino acid concentrations after consumption of casein from cow and goat milk: a randomized crossover trial in healthy men", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12799461/" } ], "protocols": [ { "population": "15 healthy young men (mean age 26)", "regimen": "40 g of micellar casein, calcium caseinate or cross-linked sodium caseinate dissolved in water, in a randomised crossover with about a week between trials", "duration": "single dose per session, blood sampled over the postprandial period", "outcome": "Cross-linked sodium caseinate raised plasma amino acids fastest, higher than the other two forms from 15 to 90 minutes after ingestion.", "source": { "title": "Casein Protein Processing Strongly Modulates Post-Prandial Plasma Amino Acid Responses In Vivo in Humans", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468913/" }, "origins": [ "evidence.json#/catalog:supplement:casein-protein/protocols/0" ] }, { "population": "32 healthy older men (mean age 71)", "regimen": "25 g labelled micellar casein dissolved in bovine milk serum or in water, with a tracer infusion", "duration": "single dose, measured over 300 minutes", "outcome": "The milk matrix slowed digestion and absorption but did not change myofibrillar protein synthesis rates at 0-120 or 120-300 minutes.", "source": { "title": "Ingestion of Casein in a Milk Matrix Modulates Dietary Protein Digestion and Absorption Kinetics but Does Not Modulate Postprandial Muscle Protein Synthesis in Older Men (Churchward-Venne et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26019248/" }, "origins": [ "evidence.json#/catalog:supplement:casein-protein/protocols/1" ] }, { "population": "18 healthy men (mean age 26)", "regimen": "300 mL of a drink with 30 g of protein from cow or goat milk casein concentrate, in a randomised crossover", "duration": "single dose per occasion", "outcome": "Gastric emptying half-time was the same (80 min goat, 85 min cow), while serum essential amino acids were higher over time after cow casein.", "source": { "title": "Gastric digestion and changes in serum amino acid concentrations after consumption of casein from cow and goat milk: a randomized crossover trial in healthy men", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12799461/" }, "origins": [ "evidence.json#/catalog:supplement:casein-protein/protocols/2" ] } ], "community": [ { "description": "A nutrition guide says most people supplementing with casein use it before bed, describing 1-2 scoops (25-50 g) mixed with water as an example.", "source": { "title": "Why Casein Is One of The Best Proteins You Can Take - Healthline", "url": "https://www.healthline.com/nutrition/casein-protein-is-highly-underrated" }, "origins": [ "evidence.json#/catalog:supplement:casein-protein/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide explicitly says most casein users consume it before bed and gives the water-mixed powder example. No efficacy statement is repeated.", "checks": [ { "url": "https://www.healthline.com/nutrition/casein-protein-is-highly-underrated", "outcome": "verified-description", "reason": "The live guide explicitly says most casein users consume it before bed and gives the water-mixed powder example. No efficacy statement is repeated." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:casein-protein/community/0", "url": "https://www.healthline.com/nutrition/casein-protein-is-highly-underrated", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468913/", "pmid:26019248", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12799461/", "https://pubmed.ncbi.nlm.nih.gov/?term=casein+protein+overnight+muscle", "https://www.healthline.com/nutrition/casein-protein-is-highly-underrated" ] }, "library:supplement-citrulline": { "id": "library:supplement-citrulline", "path": "/library/supplement-citrulline.html", "title": "L-Citrulline", "summary": "An amino acid studied for blood flow and exercise performance.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:supplement:citrulline", "title": "L-Citrulline", "summary": "An amino acid studied for blood flow and exercise performance.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "L-citrulline is a non-essential amino acid, naturally concentrated in watermelon, that the body converts to arginine and ultimately nitric oxide, a molecule involved in blood vessel dilation. It has been studied mainly as a pre-exercise ergogenic aid in athletes and recreationally active adults, with trials measuring aerobic performance, perceived exertion, and blood lactate. Findings across published trials remain inconsistent, with meta-analyses reporting no clear overall benefit for aerobic performance despite a possible trend favoring longer supplementation protocols.", "verdict": { "benefits": [ "May modestly support nitric-oxide-related blood flow in some individuals", "Chronic-use protocols in trials showed a non-significant trend toward improved endurance performance" ], "risks": [ "Gastrointestinal discomfort has been reported in some trial participants", "Evidence for a real performance benefit is inconsistent across independent meta-analyses" ], "bottomLine": "Trial evidence on aerobic performance is mixed, and the largest pooled meta-analysis found no significant overall benefit, so citrulline's ergogenic effect remains unproven despite its popularity as a pre-workout ingredient." }, "originalLinks": [ { "title": "Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36079738/" }, { "title": "Citrulline: Research Breakdown - Examine", "url": "https://examine.com/supplements/citrulline/research/" } ], "links": [ { "title": "Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36079738/" }, { "title": "Citrulline: Research Breakdown - Examine", "url": "https://examine.com/supplements/citrulline/research/" } ], "protocols": [ { "source": { "title": "Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36079738/" }, "population": "Ten randomized controlled trials in trained and recreationally active adults performing aerobic exercise tests", "regimen": "Pooled meta-analysis of acute and chronic citrulline supplementation protocols, most using 3 to 6 g given 40 to 60 minutes before exercise, compared against placebo across the included trials", "outcome": "No significant pooled effect on aerobic exercise performance, perceived exertion, oxygen-uptake kinetics, or blood lactate; a positive trend appeared only in chronic-use subgroups, and the authors called for further research", "duration": "Acute and chronic protocols pooled across the ten trials", "origins": [ "evidence.json#/catalog:supplement:citrulline/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt establishes an ingredient's presence in watermelon, not a community supplementation routine.", "checks": [ { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12566930/", "outcome": "no-practice-description", "reason": "The excerpt establishes an ingredient's presence in watermelon, not a community supplementation routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 0.895, "lowerHours": 0.65, "source": "Moinard et al. 2008, Br J Nutr, PMID 17953788 — dose-dependent (2-15 g oral); citrulline converts to arginine, but the authors could not compute a reliable arginine half-life from the resulting decay curves", "upperHours": 1.14 } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:36079738", "https://examine.com/supplements/citrulline/research/" ] }, "library:supplement-coenzyme-q10": { "id": "library:supplement-coenzyme-q10", "path": "/library/supplement-coenzyme-q10.html", "title": "Coenzyme Q10", "summary": "An antioxidant compound studied for heart failure and mitochondrial support.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:coenzyme-q10", "title": "Coenzyme Q10", "summary": "An antioxidant compound studied for heart failure and mitochondrial support.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Coenzyme Q10 is a fat-soluble compound made naturally by the body and present in every cell membrane, where it functions in mitochondrial energy production and as an antioxidant. Levels are reduced in some chronic conditions, and it has been studied as an adjunctive supplement mainly in heart failure, alongside smaller studies in migraine, statin-associated muscle symptoms and fibromyalgia.", "verdict": { "benefits": [ "Reduced major adverse cardiovascular events in a large randomized heart failure trial", "Generally well tolerated, with a low rate of reported side effects", "Some evidence also reported for statin-associated muscle symptoms and migraine prevention, though weaker" ], "risks": [ "Strong trial evidence exists mainly for heart failure and does not necessarily generalize to other claimed uses", "Product potency and formulation vary widely between manufacturers", "Long-term outcome data outside the heart failure trial setting are limited" ], "bottomLine": "The heart failure evidence is unusually robust for a supplement, but that same strength of evidence does not extend to most of the other uses it is marketed for." }, "originalLinks": [ { "title": "The Effect of Coenzyme Q10 on Morbidity and Mortality in Chronic Heart Failure: Results From Q-SYMBIO - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/25282031/" }, { "title": "Coenzyme Q10 - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK531491/" } ], "links": [ { "title": "The Effect of Coenzyme Q10 on Morbidity and Mortality in Chronic Heart Failure: Results From Q-SYMBIO - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/25282031/" }, { "title": "Coenzyme Q10 - StatPearls - NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK531491/" } ], "protocols": [ { "source": { "title": "The Effect of Coenzyme Q10 on Morbidity and Mortality in Chronic Heart Failure: Results From Q-SYMBIO - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/25282031/" }, "population": "Patients with moderate to severe chronic heart failure enrolled in the Q-SYMBIO randomized, double-blind, multicenter trial (420 participants)", "regimen": "Coenzyme Q10 100 mg three times daily added to standard heart failure therapy, compared with placebo, over a two-year prospective follow-up", "outcome": "Fewer major adverse cardiovascular events (15 percent versus 26 percent), lower cardiovascular and all-cause mortality, and fewer heart-failure hospitalizations compared with placebo", "duration": "Two-year prospective follow-up", "origins": [ "evidence.json#/catalog:supplement:coenzyme-q10/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nccih.nih.gov/health/coenzyme-q10", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://www.mayoclinic.org/drugs-supplements-coenzyme-q10/art-20362602", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 30.2, "source": "Mei et al. 2026, Clin Pharmacol Drug Dev, PMID 41789786 — single 240 mg oral dose, crossover; median 36.3h, range 6.8-52.6h, reflecting lipophilicity and enterohepatic recycling" } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:25282031", "https://www.ncbi.nlm.nih.gov/books/NBK531491/" ] }, "library:supplement-collagen": { "id": "library:supplement-collagen", "path": "/library/supplement-collagen.html", "title": "Collagen peptides", "summary": "Hydrolysed collagen studied for connective tissue and skin. Not a complete protein.", "aliases": [], "kind": "supplement", "categories": [ "recovery-healing", "anti-aging" ], "research": [ { "id": "catalog:supplement:collagen", "title": "Collagen peptides", "summary": "Hydrolysed collagen studied for connective tissue and skin. Not a complete protein.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Collagen peptides are hydrolysed collagen taken by mouth. A randomised, double-blind, placebo-controlled trial in 72 women reported better skin hydration and density with tuna collagen peptides. A second randomised trial in 99 women found more water in the outer skin layer and less water loss, but no change in elasticity or thickness. A third randomised trial tested a drink combining collagen with vitamins and other compounds, so its skin and joint results cannot be credited to collagen alone. The trials are small and short.", "verdict": { "benefits": [ "Two randomised placebo-controlled trials in women found better skin hydration and less water loss.", "One of those trials also reported higher skin density on ultrasound." ], "risks": [ "One trial found no change in skin elasticity or thickness.", "The trial reporting elasticity and joint gains mixed collagen with vitamins and other compounds.", "The trials are small and short, and all were in women." ], "bottomLine": "Small randomised trials link collagen peptides to better skin hydration; joint claims are weaker." }, "originalLinks": [ { "title": "PubMed: collagen peptides tendon", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=collagen+peptide+tendon" } ], "links": [ { "title": "The evidence from in vitro primary fibroblasts and a randomized, double-blind, placebo-controlled clinical trial of tuna collagen peptides intake on skin health", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11626298/" }, { "title": "Oral Supplementation of Collagen Peptides Improves Skin Hydration by Increasing the Natural Moisturizing Factor Content in the Stratum Corneum: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial (Miyanaga et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33774639/" }, { "title": "Daily oral supplementation with collagen peptides combined with vitamins and other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing (Czajka et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30122200/" } ], "protocols": [ { "population": "72 healthy women aged 40-60", "regimen": "5 g of tuna collagen peptides by mouth daily, against placebo", "duration": "8 weeks, with 2 weeks of follow-up after stopping", "outcome": "Skin hydration, viscoelasticity and ultrasound density rose and transepidermal water loss fell against placebo, with effects persisting through the follow-up.", "source": { "title": "The evidence from in vitro primary fibroblasts and a randomized, double-blind, placebo-controlled clinical trial of tuna collagen peptides intake on skin health", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11626298/" }, "origins": [ "evidence.json#/catalog:supplement:collagen/protocols/0" ] }, { "population": "99 healthy Japanese women aged 35-50, 33 per group", "regimen": "1 g or 5 g of collagen peptides by mouth once daily, against placebo", "duration": "12 weeks", "outcome": "Water content of the stratum corneum and epidermis rose and transepidermal water loss fell, while skin elasticity and skin thickness did not change.", "source": { "title": "Oral Supplementation of Collagen Peptides Improves Skin Hydration by Increasing the Natural Moisturizing Factor Content in the Stratum Corneum: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial (Miyanaga et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33774639/" }, "origins": [ "evidence.json#/catalog:supplement:collagen/protocols/1" ] }, { "population": "120 subjects", "regimen": "a daily liquid product combining hydrolysed fish collagen with chondroitin sulphate, glucosamine, L-carnitine, vitamins and minerals, against placebo", "duration": "90 days", "outcome": "Skin elasticity rose 40% against placebo with changes in skin architecture; self-reported joint pain fell 43% and joint mobility rose 39%.", "source": { "title": "Daily oral supplementation with collagen peptides combined with vitamins and other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing (Czajka et al. 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30122200/" }, "origins": [ "evidence.json#/catalog:supplement:collagen/protocols/2" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt describes product forms and absorption beliefs, not an observed or named community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/collagen/", "outcome": "no-practice-description", "reason": "The excerpt describes product forms and absorption beliefs, not an observed or named community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC11626298/", "pmid:33774639", "pmid:30122200", "https://pubmed.ncbi.nlm.nih.gov/?term=collagen+peptide+tendon" ] }, "library:supplement-creatine": { "id": "library:supplement-creatine", "path": "/library/supplement-creatine.html", "title": "Creatine monohydrate", "summary": "Among the most studied sports supplements. Daily consistency matters far more than timing.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:supplement:creatine", "title": "Creatine monohydrate", "summary": "Among the most studied sports supplements. Daily consistency matters far more than timing.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Evidence comes from several systematic reviews and meta-analyses of human trials. A meta-analysis of 23 studies found creatine lowered muscle-damage markers after a single hard exercise bout, but markers were higher after long-term use. A meta-analysis of 13 trials in trained people found no effect on endurance performance. A safety review covering 951 female participants reported no deaths or serious adverse outcomes and no rise in gastrointestinal, kidney or liver problems.", "verdict": { "benefits": [ "A safety review covering 951 female participants found no deaths or serious adverse outcomes.", "Pooled trials found lower muscle-damage markers after a single hard exercise bout." ], "risks": [ "After prolonged use, muscle-damage markers were higher than placebo at 24 hours.", "Pooled trials in trained people found no effect on endurance performance.", "Gastrointestinal events, creatinine, liver enzymes and weight did not differ from placebo there." ], "bottomLine": "Creatine looks safe across pooled human trials and blunts acute muscle damage, but does not improve endurance." }, "originalLinks": [ { "title": "ISSN position stand: creatine", "url": "https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0173-z" } ], "links": [ { "title": "The Paradoxical Effect of Creatine Monohydrate on Muscle Damage Markers: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9213373/" }, { "title": "Effects of Creatine Monohydrate on Endurance Performance in a Trained Population: A Systematic Review and Meta-analysis (Fernández-Landa et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36877404/" }, { "title": "Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353222/" } ], "protocols": [ { "population": "469 participants across 23 studies of exercise-induced muscle damage", "regimen": "loading of 20 g/day or 0.3 g/kg/day for 5-7 days, then maintenance of 5 g/day or 0.03-0.1 g/kg/day", "duration": "4 to 32 weeks", "outcome": "Muscle-damage markers were lower than placebo after a single hard bout but higher than placebo at 24 h after prolonged supplementation.", "source": { "title": "The Paradoxical Effect of Creatine Monohydrate on Muscle Damage Markers: A Systematic Review and Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9213373/" }, "origins": [ "evidence.json#/catalog:supplement:creatine/protocols/0" ] }, { "population": "951 female participants across 29 studies", "regimen": "loading alone at a median 20 g/day, loading 20 g/day for 5-7 days then 5 g/day, or 5 g/day maintenance alone; overall 1-30 g/day", "duration": "4 days to 365 days", "outcome": "No deaths or serious adverse outcomes; gastrointestinal events, serum creatinine, liver enzymes and body weight did not differ from placebo.", "source": { "title": "Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353222/" }, "origins": [ "evidence.json#/catalog:supplement:creatine/protocols/1" ] } ], "community": [ { "description": "A sports-nutrition guide describes a common creatine loading pattern of 20-25 g daily for 5-7 days, divided into four or five servings, followed by 3-5 g daily for maintenance.", "source": { "title": "What to Know About the Creatine Loading Phase - Healthline", "url": "https://www.healthline.com/nutrition/creatine-loading-phase" }, "origins": [ "evidence.json#/catalog:supplement:creatine/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide explicitly calls the loading sequence a common approach and distinguishes it from maintenance. The retained text attributes the sequence to the guide rather than prescribing it.", "checks": [ { "url": "https://www.healthline.com/nutrition/creatine-loading-phase", "outcome": "verified-description", "reason": "The live guide explicitly calls the loading sequence a common approach and distinguishes it from maintenance. The retained text attributes the sequence to the guide rather than prescribing it." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:creatine/community/0", "url": "https://www.healthline.com/nutrition/creatine-loading-phase", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC9213373/", "pmid:36877404", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353222/", "https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0173-z", "https://www.healthline.com/nutrition/creatine-loading-phase" ] }, "library:supplement-curcumin": { "id": "library:supplement-curcumin", "path": "/library/supplement-curcumin.html", "title": "Curcumin", "summary": "The main active compound in turmeric, studied for inflammation and metabolic markers.", "aliases": [], "kind": "supplement", "categories": [ "recovery-healing", "longevity" ], "research": [ { "id": "catalog:supplement:curcumin", "title": "Curcumin", "summary": "The main active compound in turmeric, studied for inflammation and metabolic markers.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Curcumin is the primary polyphenol compound in turmeric, studied for antioxidant and anti-inflammatory properties but limited by poor natural absorption from the gut. An umbrella review pooled a large number of randomized controlled trials examining bioavailability-enhanced and standard curcumin formulations for effects on body weight and related anthropometric measures.", "verdict": { "benefits": [ "Small reductions in body weight and waist circumference across pooled randomized trials", "Bioavailability-enhanced formulations show larger effects than standard curcumin", "Large research base also examines anti-inflammatory biomarkers alongside anthropometric outcomes" ], "risks": [ "Effect sizes on weight measures are small and of uncertain clinical relevance", "Natural absorption is poor, so formulation quality varies widely between products", "A substantial share of the pooled trials were rated at high risk of bias" ], "bottomLine": "Pooled randomized trial evidence shows a statistically real but modest effect on weight measures, with meaningful uncertainty from bias in the underlying trials." }, "originalLinks": [ { "title": "The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36898635/" } ], "links": [ { "title": "The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36898635/" } ], "protocols": [ { "source": { "title": "The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36898635/" }, "population": "Adults, including subgroups with obesity and type 2 diabetes, pooled across fifty randomized controlled trials", "regimen": "Standard and bioavailability-enhanced curcumin formulations (including piperine-combined and phospholipid forms) compared with placebo across trials of varying duration", "outcome": "Small but statistically significant reductions in body mass index, body weight and waist circumference, with larger reductions for bioavailability-enhanced formulations", "duration": "Trials of varying duration, pooled across fifty studies", "origins": [ "evidence.json#/catalog:supplement:curcumin/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt advises a piperine combination to increase absorption; this must not become a claim about observed common use or a benefit assertion.", "checks": [ { "url": "https://www.health.harvard.edu/healthy-aging-and-longevity/turmeric-benefits-a-look-at-the-evidence", "outcome": "no-practice-description", "reason": "The excerpt advises a piperine combination to increase absorption; this must not become a claim about observed common use or a benefit assertion." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 6.77, "source": "Vareed et al. 2008, Cancer Epidemiol Biomarkers Prev, PMID 18559556 — total-conjugate model at very high (10-12 g) doses; free curcumin was undetectable in 11 of 12 subjects, reflecting its famously poor oral bioavailability" } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:36898635" ] }, "library:supplement-fenugreek": { "id": "library:supplement-fenugreek", "path": "/library/supplement-fenugreek.html", "title": "Fenugreek", "summary": "Herbal extract studied for libido and testosterone markers. Results across trials are inconsistent.", "aliases": [], "kind": "supplement", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:supplement:fenugreek", "title": "Fenugreek", "summary": "Herbal extract studied for libido and testosterone markers. Results across trials are inconsistent.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Fenugreek is a plant whose extracts are sold for strength and testosterone support. A meta-analysis of seven trials with 449 participants found a small effect on total testosterone in male athletes, with effects on free testosterone, lean mass and leg press that were not clear. A newer systematic review and meta-analysis of randomised placebo-controlled trials in adult men reports that certainty about testosterone effects remains limited. A separate systematic review of six randomised trials found improved strength, muscle endurance and lean body mass in four of them. Effects are small and the trial base is thin.", "verdict": { "benefits": [ "A meta-analysis of seven trials found a small effect on total testosterone in male athletes", "Four of six randomised trials reported better strength, muscle endurance and lean body mass" ], "risks": [ "Effects on free testosterone, lean mass and leg press were not clear in that meta-analysis", "A newer meta-analysis reports certainty about testosterone effects remains limited", "Effects are small and the trial base is thin" ], "bottomLine": "Fenugreek shows a small testosterone signal and mixed strength results across a thin, low-certainty trial base." }, "originalLinks": [ { "title": "PubMed: fenugreek testosterone", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=fenugreek+testosterone" } ], "links": [ { "title": "The Anabolic Effect of Fenugreek: A Systematic Review with Meta-analysis (Isenmann et al. 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37253363/" }, { "title": "Effects of oral fenugreek-derived preparations on testosterone-related outcomes in adult men: a systematic review and meta-analysis of randomized placebo-controlled trials (Yang et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42688439/" }, { "title": "Fenugreek and Its Effects on Muscle Performance: A Systematic Review", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10054907/" } ], "protocols": [ { "population": "Mostly young men aged about 20-28, across six randomised trials", "regimen": "Trials used 300 mg a day of a glycoside fraction, 500 mg of powder or 900 mg of seed extract for 8 weeks, or single doses near 2 mg/kg", "duration": "Single doses up to 8 weeks", "outcome": "Four trials reported better 1RM bench and leg press, more repetitions to failure and improved lean body mass; glycogen resynthesis results were mixed.", "source": { "title": "Fenugreek and Its Effects on Muscle Performance: A Systematic Review", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10054907/" }, "origins": [ "evidence.json#/catalog:supplement:fenugreek/protocols/0" ] } ], "community": [ { "description": "NCCIH describes fenugreek seeds historically used as a culinary spice and in traditional medicine.", "source": { "title": "Fenugreek - NCCIH", "url": "https://www.nccih.nih.gov/health/fenugreek" }, "origins": [ "evidence.json#/catalog:supplement:fenugreek/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "The full public NIH page was independently retrieved and inspected. It reports historical culinary and medicinal use of the seeds; promoted indications, safety assertions and clinical results were not imported.", "checks": [ { "url": "https://www.nccih.nih.gov/health/fenugreek", "outcome": "verified-description", "reason": "The background section explicitly records seeds used as a spice and traditional medicine. The description does not turn the page's promoted uses into verified benefits." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:fenugreek/community/0", "url": "https://www.nccih.nih.gov/health/fenugreek", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:37253363", "pmid:42688439", "https://pmc.ncbi.nlm.nih.gov/articles/PMC10054907/", "https://pubmed.ncbi.nlm.nih.gov/?term=fenugreek+testosterone", "https://www.nccih.nih.gov/health/fenugreek" ] }, "library:supplement-glycine": { "id": "library:supplement-glycine", "path": "/library/supplement-glycine.html", "title": "Glycine", "summary": "Amino acid studied for sleep quality and as a glutathione precursor.", "aliases": [], "kind": "supplement", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:glycine", "title": "Glycine", "summary": "Amino acid studied for sleep quality and as a glutathione precursor.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Glycine is an amino acid studied for sleep. Small human trials from one research group report better subjective sleep quality in people who sleep poorly, and less fatigue with better psychomotor vigilance after nights of restricted sleep. Rat experiments point to a fall in core body temperature through NMDA receptors in the suprachiasmatic nucleus as the mechanism. The human evidence is limited to a few small studies; nothing here covers athletic use.", "verdict": { "benefits": [ "Small human trials report better subjective sleep quality in people who sleep poorly", "After restricted sleep, fatigue fell and psychomotor vigilance improved" ], "risks": [ "The human evidence is a few small studies from one research group", "Melatonin and clock-gene expression were unchanged, and sleepiness only tended to fall", "The cooling mechanism comes from rat work; nothing here covers athletic use" ], "bottomLine": "Glycine improved reported sleep and next-day alertness in a few small trials from one group." }, "originalLinks": [ { "title": "PubMed: glycine sleep", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=glycine+sleep" } ], "links": [ { "title": "New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep (Bannai 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22293292/" }, { "title": "The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus (Kawai et al. 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25533534/" }, { "title": "The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers (Bannai et al. 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22529837/" } ], "protocols": [ { "population": "healthy volunteers whose sleep was cut to 25% less than usual for three consecutive nights", "regimen": "3 g of glycine before bedtime, against placebo", "duration": "three consecutive nights", "outcome": "Fatigue fell significantly and psychomotor vigilance improved, sleepiness only tended to fall, and plasma melatonin and clock-gene expression were unchanged.", "source": { "title": "The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers (Bannai et al. 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22529837/" }, "origins": [ "evidence.json#/catalog:supplement:glycine/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4397399/", "outcome": "trial-only", "reason": "The inspected PMC paper reports rat sleep experiments. Its interventions and findings were not repurposed as community practice." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:22293292", "pmid:25533534", "pmid:22529837", "https://pubmed.ncbi.nlm.nih.gov/?term=glycine+sleep" ] }, "library:supplement-inositol": { "id": "library:supplement-inositol", "path": "/library/supplement-inositol.html", "title": "Inositol", "summary": "A sugar alcohol studied mainly for metabolic and reproductive outcomes in PCOS.", "aliases": [], "kind": "supplement", "categories": [ "longevity", "sexual-health" ], "research": [ { "id": "catalog:supplement:inositol", "title": "Inositol", "summary": "A sugar alcohol studied mainly for metabolic and reproductive outcomes in PCOS.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Inositol is a naturally occurring sugar alcohol involved in cell signaling, available in dietary and supplement forms as myo-inositol and D-chiro-inositol. It has been most studied in women with polycystic ovary syndrome, where randomized trials have examined effects on insulin sensitivity, hormone levels, and ovulation. A systematic review commissioned for international PCOS treatment guidelines found some metabolic and reproductive signals but concluded the overall evidence base remains limited and inconclusive.", "verdict": { "benefits": [ "Some randomized trials suggest inositol may improve insulin-related metabolic markers in women with polycystic ovary syndrome", "Appears better tolerated on the digestive system than metformin in head-to-head trials" ], "risks": [ "The evidence-review panel behind the 2023 international PCOS guidelines rated the overall evidence as limited and inconclusive", "Most research is in women with polycystic ovary syndrome, so benefits in other populations are not established" ], "bottomLine": "Inositol shows some promising signals for metabolic and reproductive outcomes in polycystic ovary syndrome, but the guideline-informing systematic review found the evidence too limited to draw firm conclusions." }, "originalLinks": [ { "title": "Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38163998/" }, { "title": "Inositol: Benefits, Dosage, and Side Effects - Examine", "url": "https://examine.com/supplements/inositol/" } ], "links": [ { "title": "Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38163998/" }, { "title": "Inositol: Benefits, Dosage, and Side Effects - Examine", "url": "https://examine.com/supplements/inositol/" } ], "protocols": [ { "source": { "title": "Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38163998/" }, "population": "Thirty randomized controlled trials, 2230 women with polycystic ovary syndrome, with nineteen trials pooled in meta-analyses", "regimen": "Trials of myo-inositol or D-chiro-inositol, alone or combined with other therapies, compared against placebo, metformin, or each other, across the pooled evidence base", "outcome": "Some evidence of benefit for select metabolic measures and for D-chiro-inositol on ovulation, but the authors judged evidence for most outcomes limited and inconclusive, with myo-inositol causing fewer gastrointestinal side effects than metformin", "duration": "Duration varied across the thirty pooled trials", "origins": [ "evidence.json#/catalog:supplement:inositol/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://my.clevelandclinic.org/health/drugs/25173-inositol", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:38163998", "https://examine.com/supplements/inositol/" ] }, "library:supplement-l-carnitine": { "id": "library:supplement-l-carnitine", "path": "/library/supplement-l-carnitine.html", "title": "L-Carnitine", "summary": "An amino-acid derivative studied for body composition and exercise recovery.", "aliases": [], "kind": "supplement", "categories": [ "recovery-healing", "fitness-muscle" ], "research": [ { "id": "catalog:supplement:l-carnitine", "title": "L-Carnitine", "summary": "An amino-acid derivative studied for body composition and exercise recovery.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "L-carnitine is a naturally occurring amino-acid derivative that shuttles fatty acids into cell mitochondria for energy production, and the body can synthesize it or obtain it from animal foods. It has been investigated in randomized trials for weight management, exercise recovery, and metabolic markers such as blood lipids and glycemic control. Meta-analyses report small but statistically significant reductions in body weight and markers of exercise-induced muscle damage, alongside more limited data on lipid and glucose outcomes.", "verdict": { "benefits": [ "Pooled trial data show a small but significant reduction in body weight and fat mass compared with placebo", "May reduce muscle soreness and blood markers of exercise-induced muscle damage in the day after exercise" ], "risks": [ "Effect sizes for weight loss are modest and mainly seen in people with overweight or obesity", "Gastrointestinal upset and a fishy body odor have been reported at higher intakes in some trials" ], "bottomLine": "Randomized trial evidence supports small benefits for body composition and post-exercise muscle soreness, but effect sizes are modest and most robust in specific populations such as adults with obesity or untrained exercisers." }, "originalLinks": [ { "title": "Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/32359762/" }, { "title": "The Effect of L-Carnitine Supplementation on Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/32154768/" }, { "title": "L-Carnitine: Research Breakdown - Examine", "url": "https://examine.com/supplements/carnitine/research/" } ], "links": [ { "title": "Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/32359762/" }, { "title": "The Effect of L-Carnitine Supplementation on Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/32154768/" }, { "title": "L-Carnitine: Research Breakdown - Examine", "url": "https://examine.com/supplements/carnitine/research/" } ], "protocols": [ { "source": { "title": "Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/32359762/" }, "population": "Thirty-seven randomized controlled trials, 2292 adult participants, mostly with overweight or obesity", "regimen": "Pooled dose-response analysis of oral L-carnitine trials ranging from 500 mg to 4 g per day for durations from 4 weeks up to a year", "outcome": "Significant reductions in body weight, body mass index, and fat mass compared with placebo, with a non-linear dose-response curve suggesting a plateau near 2000 mg per day and no significant effect on waist circumference", "duration": "Four weeks up to one year", "origins": [ "evidence.json#/catalog:supplement:l-carnitine/protocols/0" ] }, { "source": { "title": "The Effect of L-Carnitine Supplementation on Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/32154768/" }, "population": "Seven randomized controlled trials in resistance-trained and untrained adults performing damaging exercise bouts", "regimen": "Pooled analysis of oral L-carnitine supplementation trials, most using 1 to 3 g per day taken before or after exercise for one to three weeks", "outcome": "Significant reductions in muscle soreness and in creatine kinase, myoglobin, and lactate dehydrogenase measured one day post-exercise compared with placebo, with effects most consistent in untrained participants", "duration": "One to three weeks around the exercise bout", "origins": [ "evidence.json#/catalog:supplement:l-carnitine/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.mayoclinic.org/drugs-supplements-l-carnitine/art-20364833", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 5.2, "lowerHours": 3.9, "source": "Harper et al. 1988, Eur J Clin Pharmacol, PMID 3234464 — oral, dose-dependent (2-6 g). The FDA's IV label (Carnitor) quotes 17.4 hours, but that figure is uncorrected for endogenous carnitine background and reflects the IV route", "upperHours": 6.5 } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:32359762", "pmid:32154768", "https://examine.com/supplements/carnitine/research/" ] }, "library:supplement-l-theanine": { "id": "library:supplement-l-theanine", "path": "/library/supplement-l-theanine.html", "title": "L-Theanine", "summary": "A green-tea amino acid studied for stress and relaxation.", "aliases": [], "kind": "supplement", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:l-theanine", "title": "L-Theanine", "summary": "A green-tea amino acid studied for stress and relaxation.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "L-theanine is an amino acid found naturally in green tea leaves that crosses the blood-brain barrier and has been studied for effects on relaxation, attention and the stress response. A systematic review of randomized controlled trials examined its effect on stress and anxiety measures in adults exposed to stressful conditions.", "verdict": { "benefits": [ "Reduces self-reported stress in adults under stressful conditions in most trials", "Well tolerated, with a low rate of reported side effects", "Effects appear rapidly, within a single dose in some trials" ], "risks": [ "Anxiety-specific effects are inconsistent across trials", "Most trials are short-term and small, limiting confidence for long-term use", "Evidence is not yet sufficient to establish a role as a stand-alone therapy for anxiety disorders" ], "bottomLine": "Randomized trial evidence supports a modest, short-term stress-reduction effect, but larger and longer trials are needed to confirm a role in anxiety management." }, "originalLinks": [ { "title": "The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/31758301/" } ], "links": [ { "title": "The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/31758301/" } ], "protocols": [ { "source": { "title": "The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/31758301/" }, "population": "Adults exposed to acute or chronic stressful conditions across nine randomized controlled trials", "regimen": "200 to 400 mg per day of L-theanine as an oral supplement, with trial durations ranging from a single dose to several weeks", "outcome": "Reduced self-reported stress and anxiety measures compared with control in most trials reviewed, though anxiety-specific effects were inconsistent", "duration": "Single dose to several weeks across the nine trials reviewed", "origins": [ "evidence.json#/catalog:supplement:l-theanine/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.mskcc.org/cancer-care/integrative-medicine/herbs/l-theanine", "outcome": "no-practice-description", "reason": "The inspected reference discusses food sources, purported uses, research and clinical cautions. No trial or expert suggestion was recast as community practice." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:31758301" ] }, "library:supplement-magnesium": { "id": "library:supplement-magnesium", "path": "/library/supplement-magnesium.html", "title": "Magnesium", "summary": "Mineral supplement. Glycinate and citrate are the commonly used forms; oxide is poorly absorbed.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:magnesium", "title": "Magnesium", "summary": "Mineral supplement. Glycinate and citrate are the commonly used forms; oxide is poorly absorbed.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Magnesium is an essential mineral; the NIH Office of Dietary Supplements fact sheet is a general reference on intake, status and tolerance. A 24-week randomised, double-blind, placebo-controlled trial in 164 adults found that magnesium citrate, oxide and sulfate did not change arterial stiffness or blood pressure, although citrate raised blood and urine magnesium most. A rat study found that different organic forms reach different tissues, with behaviour changes in animals. No human trial here shows an anxiety or blood-pressure benefit.", "verdict": { "benefits": [ "Magnesium is an essential mineral, with the NIH fact sheet as a general reference.", "In a randomised trial, citrate raised blood and urine magnesium more than the other forms." ], "risks": [ "No human trial here shows an anxiety or blood-pressure benefit.", "A randomised trial in 164 adults found no change in arterial stiffness or blood pressure.", "Differences between forms were shown only in rats, where vascular relaxation was diminished." ], "bottomLine": "Magnesium is an essential mineral; the human trial here found no blood pressure or arterial stiffness effect." }, "originalLinks": [ { "title": "NIH ODS: Magnesium", "url": "https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/" } ], "links": [ { "title": "Office of Dietary Supplements - Magnesium (Health Professional Fact Sheet)", "url": "https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/" }, { "title": "Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial (Schutten et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35253448/" }, { "title": "Chronic Organic Magnesium Supplementation Enhances Tissue-Specific Bioavailability and Functional Capacity in Rats: A Focus on Brain, Muscle, and Vascular Health", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847085/" } ], "protocols": [ { "population": "164 overweight and slightly obese adults, mean age 63.2, 63% women", "regimen": "450 mg of magnesium a day as citrate, oxide or sulfate, or placebo, randomised and double-blind", "duration": "24 weeks", "outcome": "No change in carotid-to-femoral pulse wave velocity or blood pressure for any formulation; citrate raised plasma and 24-hour urinary magnesium most.", "source": { "title": "Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial (Schutten et al. 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35253448/" }, "origins": [ "evidence.json#/catalog:supplement:magnesium/protocols/0" ] }, { "population": "38 adult Sprague Dawley rats in four groups (control, citrate, glycinate, malate)", "regimen": "35.4 mg/kg/day of elemental magnesium as citrate, glycinate or malate by oral gavage once daily; controls got tap water the same way", "duration": "8 weeks", "outcome": "Citrate and glycinate shortened water-maze escape latency, malate improved grip strength; the elevated plus maze showed no difference and vascular relaxation was diminished.", "source": { "title": "Chronic Organic Magnesium Supplementation Enhances Tissue-Specific Bioavailability and Functional Capacity in Rats: A Focus on Brain, Muscle, and Vascular Health", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847085/" }, "origins": [ "evidence.json#/catalog:supplement:magnesium/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt only lists food and medicinal product sources, not a community supplementation routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/magnesium/", "outcome": "no-practice-description", "reason": "The excerpt only lists food and medicinal product sources, not a community supplementation routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/", "pmid:35253448", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847085/" ] }, "library:supplement-melatonin": { "id": "library:supplement-melatonin", "path": "/library/supplement-melatonin.html", "title": "Melatonin", "summary": "A circadian-clock hormone taken most often for jet lag and sleep timing.", "aliases": [], "kind": "supplement", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:melatonin", "title": "Melatonin", "summary": "A circadian-clock hormone taken most often for jet lag and sleep timing.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Melatonin is a hormone produced by the pineal gland that helps regulate the body's internal circadian clock in response to darkness. Synthetic melatonin is sold as an over-the-counter dietary supplement in the United States, while several other countries regulate it as a prescription medicine, and it has been studied most extensively for jet lag and circadian sleep-timing disorders.", "verdict": { "benefits": [ "Reduces jet lag symptoms after long eastward flights in the majority of trials reviewed", "Shortens time to sleep onset in circadian sleep-timing disorders", "Short-term use shows a low rate of side effects across trial populations" ], "risks": [ "Long-term safety data are limited", "Independent testing has found product content varying from label claims", "Case reports describe interactions in people with epilepsy or on warfarin" ], "bottomLine": "Evidence for jet lag is unusually strong for a supplement, resting on multiple randomized trials, while evidence for chronic insomnia remains weak by comparison." }, "originalLinks": [ { "title": "Melatonin for preventing and treating jet lag - Cochrane Database of Systematic Reviews (PubMed)", "url": "https://pubmed.ncbi.nlm.nih.gov/11279722/" }, { "title": "Melatonin: What You Need To Know - NCCIH", "url": "https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know" } ], "links": [ { "title": "Melatonin for preventing and treating jet lag - Cochrane Database of Systematic Reviews (PubMed)", "url": "https://pubmed.ncbi.nlm.nih.gov/11279722/" }, { "title": "Melatonin: What You Need To Know - NCCIH", "url": "https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know" } ], "protocols": [ { "source": { "title": "Melatonin for preventing and treating jet lag - Cochrane Database of Systematic Reviews (PubMed)", "url": "https://pubmed.ncbi.nlm.nih.gov/11279722/" }, "population": "Airline passengers, airline staff and military personnel crossing five or more time zones, pooled across ten randomized trials", "regimen": "Oral melatonin doses between 0.5 mg and 5 mg administered close to target bedtime at the destination (22:00 to midnight); doses above 5 mg showed no added benefit and a 2 mg slow-release formulation was less effective", "outcome": "Nine of ten trials found reduced jet lag symptoms after flights crossing five or more time zones, with a calculated number needed to treat of two; side effects were infrequent", "duration": "Single doses taken near destination bedtime, pooled across ten trials", "origins": [ "evidence.json#/catalog:supplement:melatonin/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.nccih.nih.gov/health/melatonin", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." }, { "url": "https://www.cdc.gov/yellow-book/hcp/preparing-international-travelers/complementary-and-integrative-health-approaches.html", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 0.9, "source": "Andersen et al. 2016, BMC Pharmacol Toxicol, PMID 26893170 — immediate-release oral, 10 mg dose; ranges 40-104 min depending on formulation and physiological state" } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:11279722", "https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know" ] }, "library:supplement-methylene-blue": { "id": "library:supplement-methylene-blue", "path": "/library/supplement-methylene-blue.html", "title": "Methylene Blue", "summary": "A redox compound showing acute memory effects in healthy volunteers, but unclear benefit in dementia trials.", "aliases": [], "kind": "supplement", "categories": [ "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:methylene-blue", "title": "Methylene Blue", "summary": "A redox compound showing acute memory effects in healthy volunteers, but unclear benefit in dementia trials.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Methylene blue is a redox-active compound with effects on mitochondrial function and reactive oxygen species. In double-blind, randomized, placebo-controlled trials in healthy volunteers, a single oral dose of methylene blue showed effects on working memory and sustained attention during functional MRI studies, with no negative adverse events reported. A phase II trial examined the same single-dose regimen for effects on cerebral blood flow, functional connectivity, and cognition in healthy aging, mild cognitive impairment, and mild Alzheimer's disease. In Alzheimer's disease trials, oral methylene blue was tested but large studies failed to find clear benefit, partly because blinding was difficult. Phase II malaria trials in children with falciparum malaria showed no drug-related serious adverse events or deaths.", "verdict": { "benefits": [ "Shows effects on memory and attention in healthy volunteers during functional MRI testing", "Generally well-tolerated with no serious adverse events in studies" ], "risks": [ "Large Phase III trials in Alzheimer's disease failed to show clear benefit", "Blinding difficulties in dementia trials complicate interpretation", "Long-term safety and efficacy in chronic use not established" ], "bottomLine": "Methylene blue shows acute cognitive effects in healthy volunteers but failed to demonstrate clear benefit in Alzheimer's disease trials." }, "originalLinks": [ { "title": "Methylene Blue Shows Promise for Improving Short-Term Memory", "url": "https://www.rsna.org/media/press/i/1888" }, { "title": "Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease", "url": "https://cdn.clinicaltrials.gov/large-docs/73/NCT02380573/Prot_SAP_000.pdf" }, { "title": "Clinical effectiveness and prospects of methylene blue", "url": "https://www.pfmjournal.org/m/journal/view.php?number=132" } ], "links": [ { "title": "Methylene Blue Shows Promise for Improving Short-Term Memory", "url": "https://www.rsna.org/media/press/i/1888" }, { "title": "Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease", "url": "https://cdn.clinicaltrials.gov/large-docs/73/NCT02380573/Prot_SAP_000.pdf" }, { "title": "Clinical effectiveness and prospects of methylene blue", "url": "https://www.pfmjournal.org/m/journal/view.php?number=132" } ], "protocols": [ { "population": "26 healthy volunteers aged 22-62 years", "regimen": "Oral methylene blue 280 mg single-dose or placebo", "duration": "Single dose with working memory and attention assessment", "outcome": "Methylene blue showed effects on working memory and sustained attention; no adverse events reported", "source": { "title": "Methylene Blue Shows Promise for Improving Short-Term Memory", "url": "https://www.rsna.org/media/press/i/1888" }, "origins": [ "evidence.json#/catalog:supplement:methylene-blue/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://nootropicsexpert.com/methylene-blue/", "outcome": "no-practice-description", "reason": "The inspected commercial nootropic guide includes product promotion, benefit claims and dosing advice. No protocol was imported from it." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 5.25, "source": "Peter, Hongwan, Kupfer & Lauterburg 2000, Eur J Clin Pharmacol, PMID 11214785 — oral/IV crossover in healthy volunteers; the IV and oral arms gave consistent results, unusual for this compound's other pharmacokinetic parameters" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.rsna.org/media/press/i/1888", "https://cdn.clinicaltrials.gov/large-docs/73/NCT02380573/Prot_SAP_000.pdf", "https://www.pfmjournal.org/m/journal/view.php?number=132" ] }, "library:supplement-nac": { "id": "library:supplement-nac", "path": "/library/supplement-nac.html", "title": "N-Acetylcysteine (NAC)", "summary": "An amino-acid derivative and glutathione precursor studied for exercise and antioxidant effects.", "aliases": [], "kind": "supplement", "categories": [ "longevity", "fitness-muscle" ], "research": [ { "id": "catalog:supplement:nac", "title": "N-Acetylcysteine (NAC)", "summary": "An amino-acid derivative and glutathione precursor studied for exercise and antioxidant effects.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "N-Acetylcysteine is a modified form of the amino acid cysteine and a precursor to glutathione, the body's primary intracellular antioxidant. It is used medically as a mucolytic and as an antidote, and has been studied separately as an oral supplement for antioxidant support, exercise recovery and cognitive effects, with results across these uses remaining mixed.", "verdict": { "benefits": [ "Some trials report reduced muscle soreness and lactate levels after exercise", "Well-characterized antioxidant and glutathione-precursor mechanism", "Long history of medical use as a mucolytic supports a known safety profile at studied doses" ], "risks": [ "Pooled evidence shows no significant net benefit for exercise performance", "Higher doses are linked with a higher rate of gastrointestinal and other side effects", "Reporting quality is inconsistent across trials, limiting confidence in the pooled results" ], "bottomLine": "The performance-enhancing case for NAC is weak and inconsistent in pooled analysis, and review authors found insufficient evidence to support its use as an ergogenic aid." }, "originalLinks": [ { "title": "Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/28102488/" } ], "links": [ { "title": "Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/28102488/" } ], "protocols": [ { "source": { "title": "Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/28102488/" }, "population": "Trained and recreationally active adults across seven trials included in the sport-performance meta-analysis", "regimen": "Daily oral NAC doses reported across trials ranged from 1.2 g to 20.0 g, with a typical reported dose around 5.8 g per day", "outcome": "Pooled analysis found a mean performance increase of 0.29 percent that was not statistically significant, and higher doses were associated with more frequent side effects", "duration": "Trial durations varied across the seven pooled studies", "origins": [ "evidence.json#/catalog:supplement:nac/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.fda.gov/food/hfp-constituent-updates/fda-releases-final-guidance-enforcement-discretion-certain-nac-products", "outcome": "no-practice-description", "reason": "The inspected FDA page explains a regulatory enforcement policy for products, not a reported community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 2.27, "source": "Borgstrom et al. 1986, Eur J Clin Pharmacol, PMID 3803419 — oral/IV crossover; oral bioavailability only 6-10%. The FDA's IV label (Acetadote) quotes 5.6 hours over a longer total-acetylcysteine sampling window" } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:28102488" ] }, "library:supplement-nmn": { "id": "library:supplement-nmn", "path": "/library/supplement-nmn.html", "title": "NMN (Nicotinamide Mononucleotide)", "summary": "An NAD+ precursor studied in an early human dose-finding trial.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:nmn", "title": "NMN (Nicotinamide Mononucleotide)", "summary": "An NAD+ precursor studied in an early human dose-finding trial.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "NMN, or nicotinamide mononucleotide, is a naturally occurring compound and a direct precursor in the body's production of NAD+, a molecule central to cellular energy metabolism. Interest in NMN grew out of animal aging research, and it has since moved into a small but growing number of human trials examining safety and its effects on NAD+ levels, metabolism, and physical performance. Long-term human outcome data, including any effect on aging itself or chronic disease risk, remain limited.", "verdict": { "benefits": [ "Well-designed randomized trials show NMN reliably raises blood NAD+ levels in healthy adults", "Short-term trials report good tolerability with no serious adverse events", "Early data point to possible benefits for physical endurance measures" ], "risks": [ "Long-term safety and effectiveness beyond a few months of use have not been studied in humans", "Much of the foundational evidence for anti-aging effects comes from animal models and has not been confirmed in people", "Regulatory status is unsettled and commercial product purity varies widely" ], "bottomLine": "NMN reliably raises NAD+ levels in short human trials and appears well tolerated, but the leap from that biomarker change to a meaningful long-term health benefit remains unproven in people." }, "originalLinks": [ { "title": "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36482258/" } ], "links": [ { "title": "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36482258/" } ], "protocols": [ { "source": { "title": "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36482258/" }, "population": "80 healthy middle-aged adults in a randomized, multicenter, double-blind, placebo-controlled, dose-dependent trial", "regimen": "Oral NMN once daily at 300 mg, 600 mg, or 900 mg, or a matching placebo, for 60 days", "outcome": "Blood NAD+ concentrations rose significantly in all treated groups in a dose-related manner, physical performance measures improved, and the compound was reported safe and well tolerated at every dose tested.", "duration": "Sixty days", "origins": [ "evidence.json#/catalog:supplement:nmn/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.mtangelvitamins.com/pages/nmn-forms-sublingual-vs-capsule-vs-powder", "outcome": "no-practice-description", "reason": "The inspected vendor page compares and recommends its supplement product forms. Product marketing was not accepted as a community usage report." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:36482258" ] }, "library:supplement-omega-3": { "id": "library:supplement-omega-3", "path": "/library/supplement-omega-3.html", "title": "Omega-3 (EPA/DHA)", "summary": "Marine fatty acids. Label totals and actual EPA/DHA content frequently differ.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:omega-3", "title": "Omega-3 (EPA/DHA)", "summary": "Marine fatty acids. Label totals and actual EPA/DHA content frequently differ.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 38 randomised trials with 149,051 participants found omega-3 supplements lowered cardiovascular death (RR 0.93), non-fatal heart attack, coronary heart disease events and revascularisation. Reductions were larger with EPA alone than with EPA plus DHA, but EPA alone also raised bleeding and atrial fibrillation, and omega-3 overall raised atrial fibrillation. A separate meta-analysis of 26 trials with 2,160 participants found a small overall benefit for depression symptoms, mainly with EPA-predominant formulas. Evidence is large pooled trial data.", "verdict": { "benefits": [ "Pooled data from 38 trials and 149,051 people found lower cardiovascular death and heart attack.", "Coronary heart disease events and revascularisation also fell.", "Pooled trials found a modest gain for depression symptoms, mainly with EPA-predominant formulas." ], "risks": [ "Omega-3 raised atrial fibrillation, and EPA alone also raised bleeding.", "DHA-pure and DHA-major formulations showed no benefit for depression." ], "bottomLine": "Large pooled trials show omega-3 lowers heart events and helps depression modestly, while raising atrial fibrillation." }, "originalLinks": [ { "title": "NIH ODS: Omega-3", "url": "https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/" } ], "links": [ { "title": "Effect of omega-3 fatty acids on cardiovascular outcomes: a systematic review and meta-analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8413259/" }, { "title": "Efficacy of omega-3 PUFAs in depression: a meta-analysis (Liao et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31383846/" } ], "protocols": [ { "population": "149,051 patients across 38 randomised trials", "regimen": "omega-3 of 0.4 to 5.5 g daily across the trials; EPA alone 1.8 to 4.0 g daily, EPA plus DHA 0.4 to 5.5 g daily", "duration": "median follow-up 2.0 years (IQR 1-4.2)", "outcome": "Cardiovascular death fell (RR 0.93), as did non-fatal myocardial infarction, while atrial fibrillation rose (RR 1.26) and EPA alone raised bleeding (RR 1.49).", "source": { "title": "Effect of omega-3 fatty acids on cardiovascular outcomes: a systematic review and meta-analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8413259/" }, "origins": [ "evidence.json#/catalog:supplement:omega-3/protocols/0" ] }, { "population": "2,160 participants across 26 double-blind randomised placebo-controlled trials of depression", "regimen": "omega-3 PUFA supplements; benefit seen with EPA-pure or EPA-major (60% or more EPA) formulas at an EPA dose of 1 g a day or less", "duration": "not stated", "outcome": "Depression symptoms improved modestly overall (SMD -0.28); DHA-pure and DHA-major formulations showed no such benefit.", "source": { "title": "Efficacy of omega-3 PUFAs in depression: a meta-analysis (Liao et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31383846/" }, "origins": [ "evidence.json#/catalog:supplement:omega-3/protocols/1" ] } ], "community": [ { "description": "The Harvard Nutrition Source describes algal oil as a vegan alternative to fish oil for omega-3 supplementation.", "source": { "title": "Omega-3 Fats - The Nutrition Source, Harvard T.H. Chan School of Public Health", "url": "https://nutritionsource.hsph.harvard.edu/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/" }, "origins": [ "evidence.json#/catalog:supplement:omega-3/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "An attributed practice description was verified without importing the source's benefit claims, recommendations or assumptions about prevalence.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/", "outcome": "verified-description", "reason": "Independently read the live source and checked this limited, attributed description: The Harvard Nutrition Source describes algal oil as a vegan alternative to fish oil for omega-3 supplementation." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:omega-3/community/0", "url": "https://nutritionsource.hsph.harvard.edu/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] }, "pk": { "hours": 48, "source": "EPA/DHA plasma; tissue incorporation is slower" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC8413259/", "pmid:31383846", "https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/", "https://nutritionsource.hsph.harvard.edu/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/" ] }, "library:supplement-plant-protein": { "id": "library:supplement-plant-protein", "path": "/library/supplement-plant-protein.html", "title": "Plant protein blend", "summary": "Pea, rice or soy protein blend. Blending improves the amino acid profile over single sources.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:supplement:plant-protein", "title": "Plant protein blend", "summary": "Pea, rice or soy protein blend. Blending improves the amino acid profile over single sources.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "In a randomised crossover trial in ten healthy young adults, a pea-rice blend did not raise blood essential amino acids above pea protein alone, and whey was higher than both. A double-blind crossover trial in 14 older adults found a dairy-plant blend gave amino acid availability similar to casein and whey and higher than soy or pea alone. A dataset analysis of protein quality scores found most single plant proteins score below animal proteins, while mixtures can raise the score. Evidence is small human trials plus composition data.", "verdict": { "benefits": [ "A dairy-plant blend matched casein and whey for amino acid availability in older adults", "Mixing plant proteins can raise protein quality scores above single plant sources" ], "risks": [ "Most single plant proteins score below animal proteins on protein quality", "A pea-rice blend was no better than pea alone, and whey beat both on blood amino acids", "Evidence is small human trials plus composition data" ], "bottomLine": "Single plant proteins rank below animal proteins, while blends can match dairy on amino acid availability." }, "originalLinks": [ { "title": "PubMed: plant protein muscle", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=plant+protein+muscle+protein+synthesis" } ], "links": [ { "title": "Postprandial plasma aminoacidemia and indices of appetite regulation following pea-rice blend, pea isolate and whey protein ingestion in healthy young adults", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11557286/" }, { "title": "Comprehensive overview of the quality of plant- and animal-sourced proteins based on the digestible indispensable amino acid score (Herreman et al. 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/33133540/" }, { "title": "Amino Acid Availability of a Dairy and Vegetable Protein Blend Compared to Single Casein, Whey, Soy, and Pea Proteins: A Double-Blind, Cross-Over Trial", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893549/" } ], "protocols": [ { "population": "10 healthy young adults (4 men, 6 women), mean age 22", "regimen": "a single bolus of 0.3 g protein per kg body mass in 400 ml water, as a pea-rice blend, pea isolate or whey, in randomised crossover order", "duration": "single dose, trials at least 5 days apart", "outcome": "Plasma essential amino acid area under the curve was greater after whey than after pea or the blend, with no difference between pea and the pea-rice blend.", "source": { "title": "Postprandial plasma aminoacidemia and indices of appetite regulation following pea-rice blend, pea isolate and whey protein ingestion in healthy young adults", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11557286/" }, "origins": [ "evidence.json#/catalog:supplement:plant-protein/protocols/0" ] }, { "population": "14 healthy elderly subjects, mean age 67.4 years", "regimen": "a single 18 g bolus in 360 ml, as a blend of 35% whey, 25% casein, 20% soy and 20% pea, or casein, whey, soy or pea alone, on visits about a week apart", "duration": "single dose per visit", "outcome": "Total amino acid availability from the blend matched casein and whey and exceeded soy and pea alone, with leucine and methionine well above the vegetable proteins.", "source": { "title": "Amino Acid Availability of a Dairy and Vegetable Protein Blend Compared to Single Casein, Whey, Soy, and Pea Proteins: A Double-Blind, Cross-Over Trial", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893549/" }, "origins": [ "evidence.json#/catalog:supplement:plant-protein/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The food-protein excerpt about quinoa and chia does not document a routine for the catalogue's plant-protein supplement.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/what-should-you-eat/protein/", "outcome": "no-practice-description", "reason": "The food-protein excerpt about quinoa and chia does not document a routine for the catalogue's plant-protein supplement." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC11557286/", "pmid:33133540", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893549/", "https://pubmed.ncbi.nlm.nih.gov/?term=plant+protein+muscle+protein+synthesis" ] }, "library:supplement-potassium": { "id": "library:supplement-potassium", "path": "/library/supplement-potassium.html", "title": "Potassium", "summary": "An essential mineral studied for blood pressure, requiring caution with kidney disease or certain medications.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:potassium", "title": "Potassium", "summary": "An essential mineral studied for blood pressure, requiring caution with kidney disease or certain medications.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "reference", "evidenceSummary": "Potassium is an essential mineral and electrolyte required for nerve signaling, muscle contraction, and fluid balance, and it is naturally abundant in fruits, vegetables, legumes, and dairy. It is classified as an essential nutrient with a well-established adequate intake, and decades of research have examined its role in blood pressure regulation and cardiovascular health. Most healthy adults meet their needs through diet alone, and supplementation is generally reserved for documented deficiency under medical supervision.", "verdict": { "benefits": [ "Supports normal nerve and muscle function as an essential electrolyte the body cannot do without", "Blood pressure reductions have been observed in supplementation trials in hypertensive populations", "Adequate dietary intake is associated with lower stroke risk in large observational cohorts" ], "risks": [ "Impaired kidney function or medications that reduce potassium excretion, such as ACE inhibitors, ARBs, or potassium-sparing diuretics, sharply raise the danger of hyperkalemia from added potassium", "Severe hyperkalemia can cause muscle weakness, paralysis, and life-threatening cardiac arrhythmias", "No tolerable upper intake level has been set for potassium because the harm reported in case studies came from rapid, concentrated exposure rather than food-level intake, which argues for caution rather than reassurance with concentrated supplements" ], "bottomLine": "Potassium is essential and well studied for cardiovascular health, but it is also a rare case where supplementation carries real danger for people with kidney disease or interacting medications, making it a nutrient best supplemented only under clinical monitoring of blood levels." }, "originalLinks": [ { "title": "Potassium - Health Professional Fact Sheet (NIH Office of Dietary Supplements)", "url": "https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/" }, { "title": "Potassium - Consumer Fact Sheet (NIH Office of Dietary Supplements)", "url": "https://ods.od.nih.gov/factsheets/Potassium-Consumer/" } ], "links": [ { "title": "Potassium - Health Professional Fact Sheet (NIH Office of Dietary Supplements)", "url": "https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/" }, { "title": "Potassium - Consumer Fact Sheet (NIH Office of Dietary Supplements)", "url": "https://ods.od.nih.gov/factsheets/Potassium-Consumer/" } ], "protocols": [ { "source": { "title": "Potassium - Health Professional Fact Sheet (NIH Office of Dietary Supplements)", "url": "https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/" }, "population": "Adults with hypertension, pooled across randomized controlled trials summarized by the NIH Office of Dietary Supplements", "regimen": "Potassium supplements, mostly potassium chloride, at 20 to 120 mmol per day for 1 to 36 months, compared with placebo", "outcome": "Systolic and diastolic blood pressure decreased significantly compared with placebo, with larger effects in people with higher baseline blood pressure and lower baseline potassium intake.", "duration": "One to thirty-six months", "origins": [ "evidence.json#/catalog:supplement:potassium/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt only establishes mineral and supplement identity, not a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/potassium/", "outcome": "no-practice-description", "reason": "The excerpt only establishes mineral and supplement identity, not a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/", "https://ods.od.nih.gov/factsheets/Potassium-Consumer/" ] }, "library:supplement-probiotic": { "id": "library:supplement-probiotic", "path": "/library/supplement-probiotic.html", "title": "Probiotic (Multi-Strain)", "summary": "Live microorganisms studied for gut and digestive outcomes, effects varying by strain.", "aliases": [], "kind": "supplement", "categories": [ "recovery-healing" ], "research": [ { "id": "catalog:supplement:probiotic", "title": "Probiotic (Multi-Strain)", "summary": "Live microorganisms studied for gut and digestive outcomes, effects varying by strain.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Probiotics are live microorganisms, most often lactobacillus and bifidobacterium species, marketed in single-strain and multi-strain blends for digestive and general health. Because different genera, species, and strains behave differently, research findings for one product cannot be assumed to apply to another, and study quality varies widely across the field. Systematic reviews consistently find that effects, when present, are specific to the exact strain combination and condition studied rather than a general property of probiotics as a category.", "verdict": { "benefits": [ "Certain multi-strain combinations have improved eradication rates and reduced side effects when added to antibiotic regimens in trials", "Some strain-specific formulations have trial support for irritable bowel symptom relief" ], "risks": [ "Benefits are strain- and condition-specific, so a positive finding for one product does not transfer to a different blend", "Many published probiotic trials are small or of variable methodological quality" ], "bottomLine": "Multi-strain probiotics can help with specific, well-studied conditions when the exact strain combination matches the trial evidence, but as a broad category the evidence does not support a single generic effect across all products." }, "originalLinks": [ { "title": "Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/27536365/" }, { "title": "Probiotics: Benefits, Dosage, and Side Effects - Examine", "url": "https://examine.com/supplements/probiotics/" } ], "links": [ { "title": "Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/27536365/" }, { "title": "Probiotics: Benefits, Dosage, and Side Effects - Examine", "url": "https://examine.com/supplements/probiotics/" } ], "protocols": [ { "source": { "title": "Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/27536365/" }, "population": "Nineteen randomized controlled trials, 2730 participants with Helicobacter pylori infection, testing twenty treatment arms across six multi-strain probiotic mixtures", "regimen": "Multi-strain probiotic mixtures given alongside standard antibiotic eradication therapy, compared against eradication therapy plus placebo or no adjunct, across the pooled trials", "outcome": "Four of the six probiotic mixtures significantly improved Helicobacter pylori eradication rates, five reduced any adverse reaction, and three reduced antibiotic-associated diarrhea, with effects specific to which strains were combined", "duration": "Given for the duration of standard antibiotic eradication therapy, varying by trial", "origins": [ "evidence.json#/catalog:supplement:probiotic/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt lists food and product sources without documenting a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/probiotics/", "outcome": "no-practice-description", "reason": "The excerpt lists food and product sources without documenting a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:27536365", "https://examine.com/supplements/probiotics/" ] }, "library:supplement-psyllium": { "id": "library:supplement-psyllium", "path": "/library/supplement-psyllium.html", "title": "Psyllium Husk", "summary": "A soluble fiber studied for cholesterol and digestive regularity.", "aliases": [], "kind": "supplement", "categories": [ "recovery-healing", "longevity" ], "research": [ { "id": "catalog:supplement:psyllium", "title": "Psyllium Husk", "summary": "A soluble fiber studied for cholesterol and digestive regularity.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Psyllium is a soluble, viscous fiber derived from the husk of Plantago ovata seeds, commonly used as a bulk-forming laxative and fiber supplement. Randomized controlled trials have examined its effects on chronic constipation and on blood lipid levels including LDL cholesterol. Pooled meta-analyses of these trials report consistent improvements in stool frequency for constipation and reductions in LDL and non-HDL cholesterol compared with placebo.", "verdict": { "benefits": [ "Randomized trials consistently show reductions in LDL and non-HDL cholesterol compared with control diets", "Well-supported as a bulk-forming fiber for relieving chronic constipation" ], "risks": [ "Mild gastrointestinal effects such as bloating and gas are commonly reported, especially when starting", "Product adulteration with cheaper fillers such as amaranth or wheat bran has been documented in the psyllium supplement market" ], "bottomLine": "Trial evidence solidly supports psyllium for improving cholesterol markers and relieving constipation, making it one of the better-evidenced fiber supplements on the market." }, "originalLinks": [ { "title": "Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/30239559/" }, { "title": "Psyllium: Benefits, Dosage, and Side Effects - Examine", "url": "https://examine.com/supplements/psyllium/" } ], "links": [ { "title": "Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/30239559/" }, { "title": "Psyllium: Benefits, Dosage, and Side Effects - Examine", "url": "https://examine.com/supplements/psyllium/" } ], "protocols": [ { "source": { "title": "Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/30239559/" }, "population": "Twenty-eight randomized controlled trials, 1924 participants with or without hypercholesterolemia", "regimen": "Oral psyllium fiber supplementation at a median dose of about 10 grams per day for at least three weeks, compared against control diets or placebo fiber", "outcome": "Significant reductions in LDL cholesterol, non-HDL cholesterol, and apolipoprotein B compared with control, graded as moderate to high quality evidence by the review authors", "duration": "At least three weeks across the twenty-eight pooled trials", "origins": [ "evidence.json#/catalog:supplement:psyllium/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://my.clevelandclinic.org/health/drugs/19079-psyllium", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:30239559", "https://examine.com/supplements/psyllium/" ] }, "library:supplement-resveratrol": { "id": "library:supplement-resveratrol", "path": "/library/supplement-resveratrol.html", "title": "Resveratrol", "summary": "A plant polyphenol studied widely, with evidence still short of a clinical recommendation.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:resveratrol", "title": "Resveratrol", "summary": "A plant polyphenol studied widely, with evidence still short of a clinical recommendation.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Resveratrol is a polyphenol compound found in red grape skins, red wine, and certain berries, first studied for its antioxidant and anti-inflammatory properties. It has since been tested in a large number of human clinical trials across many conditions, including metabolic syndrome, cardiovascular risk factors, and polycystic ovary syndrome. A systematic review of the accumulated trials concluded that despite two decades of research, poor oral absorption and inconsistent study design have kept the evidence too weak to support any specific clinical recommendation.", "verdict": { "benefits": [ "Trials consistently show reductions in inflammatory markers across many study populations", "Some evidence points to improved blood vessel function and metabolic markers in specific conditions", "Generally well tolerated in trials, with mostly mild gastrointestinal side effects reported" ], "risks": [ "Natural oral absorption is very poor, and different formulations have shown widely variable blood levels", "No consensus exists on which condition, dose, or duration produces reliable benefit", "Evidence quality across the field is inconsistent, dominated by small, short, early-phase trials" ], "bottomLine": "Resveratrol has one of the largest human trial bases of any dietary supplement, yet after two decades of research the evidence still falls short of supporting a specific clinical use." }, "originalLinks": [ { "title": "Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10815776/" }, { "title": "Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/35833325/" } ], "links": [ { "title": "Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10815776/" }, { "title": "Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/35833325/" } ], "protocols": [ { "source": { "title": "Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10815776/" }, "population": "Nearly 6,200 participants across 31 countries, pooled from 194 clinical trials, including 155 randomized controlled trials, published since 2004", "regimen": "Oral resveratrol supplementation across trials, generally well tolerated at doses up to 1 g per day, with no consensus regimen established for any single condition", "outcome": "Resveratrol consistently reduced inflammatory markers and improved aspects of dysregulated metabolism across studies, but the authors concluded the evidence remains insufficient for a formal clinical recommendation and called for larger, higher-quality trials.", "duration": "Duration varied across the 194 pooled trials", "origins": [ "evidence.json#/catalog:supplement:resveratrol/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.health.harvard.edu/blog/diet-rich-resveratrol-offers-health-boost-201405157153", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 3, "lowerHours": 1, "source": "Walle et al. 2004, Drug Metab Dispos, PMID 14977870 — human oral PK; rapid and extensive metabolism to glucuronide/sulfate conjugates limits free resveratrol exposure", "upperHours": 5 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC10815776/", "pmid:35833325" ] }, "library:supplement-saw-palmetto": { "id": "library:supplement-saw-palmetto", "path": "/library/supplement-saw-palmetto.html", "title": "Saw Palmetto", "summary": "A plant extract studied for urinary symptoms of benign prostatic hyperplasia.", "aliases": [], "kind": "supplement", "categories": [ "sexual-health" ], "research": [ { "id": "catalog:supplement:saw-palmetto", "title": "Saw Palmetto", "summary": "A plant extract studied for urinary symptoms of benign prostatic hyperplasia.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Saw palmetto is an extract from the berries of the Serenoa repens palm, widely marketed for lower urinary tract symptoms associated with an enlarged prostate. It is one of the most extensively studied botanical supplements, with dozens of randomized trials conducted over several decades. A Cochrane systematic review pooling this trial evidence found the extract, taken alone, provides little to no benefit over placebo for urinary symptoms or quality of life.", "verdict": { "benefits": [ "Extensively studied in dozens of randomized trials over several decades, giving unusually mature safety data for a botanical supplement", "Adverse event rates in trials were similar to placebo, indicating good tolerability" ], "risks": [ "The largest pooled analysis available, a Cochrane systematic review, found no meaningful benefit over placebo for urinary symptoms", "Relying on it in place of evaluated medical treatment for an enlarged prostate risks delaying effective care", "Mild gastrointestinal upset has been reported in a minority of users" ], "bottomLine": "Saw palmetto is among the best-studied herbal supplements for prostate symptoms, and that scrutiny is exactly what undermines it: the highest-quality pooled evidence finds no real benefit over placebo." }, "originalLinks": [ { "title": "Serenoa repens for benign prostatic hyperplasia | Cochrane", "url": "https://www.cochrane.org/evidence/CD001423_serenoa-repens-benign-prostatic-hyperplasia" }, { "title": "Saw Palmetto for the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38804752/" } ], "links": [ { "title": "Serenoa repens for benign prostatic hyperplasia | Cochrane", "url": "https://www.cochrane.org/evidence/CD001423_serenoa-repens-benign-prostatic-hyperplasia" }, { "title": "Saw Palmetto for the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38804752/" } ], "protocols": [ { "source": { "title": "Serenoa repens for benign prostatic hyperplasia | Cochrane", "url": "https://www.cochrane.org/evidence/CD001423_serenoa-repens-benign-prostatic-hyperplasia" }, "population": "4,656 men, mean age 52 to 68, with moderate lower urinary tract symptoms from benign prostatic hyperplasia, pooled across 27 randomized controlled trials", "regimen": "Saw palmetto extract, most commonly 320 mg per day, alone or combined with other plant extracts, compared with placebo for 3 to 17 months", "outcome": "Saw palmetto alone showed little to no difference from placebo in urinary symptoms or quality of life at both short-term (3 to 6 months) and long-term (12 to 17 months) follow-up, with no significant increase in adverse events.", "duration": "Three to seventeen months across the pooled trials", "origins": [ "evidence.json#/catalog:supplement:saw-palmetto/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://my.clevelandclinic.org/health/drugs/19423-saw-palmetto", "outcome": "blocked", "reason": "Independent direct retrieval returned HTTP 403. No description was verified from this inaccessible response." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.cochrane.org/evidence/CD001423_serenoa-repens-benign-prostatic-hyperplasia", "pmid:38804752" ] }, "library:supplement-selenium": { "id": "library:supplement-selenium", "path": "/library/supplement-selenium.html", "title": "Selenium", "summary": "An essential trace mineral studied for thyroid antibody levels.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:selenium", "title": "Selenium", "summary": "An essential trace mineral studied for thyroid antibody levels.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Selenium is an essential trace mineral obtained from diet, such as Brazil nuts, seafood, and organ meats, and required for antioxidant enzymes and thyroid hormone metabolism. It has an established recommended dietary allowance and has been studied both for general adequacy and in randomized trials of people with autoimmune thyroid conditions such as Hashimoto thyroiditis. Meta-analyses of these trials report reductions in thyroid-stimulating hormone and thyroid antibody levels among people without thyroid hormone replacement, alongside long-established data defining safe upper intake levels.", "verdict": { "benefits": [ "An essential nutrient with a well-established dietary allowance target set by national nutrition authorities", "Trials in people with Hashimoto thyroiditis found reductions in thyroid-stimulating hormone and thyroid antibody levels" ], "risks": [ "Chronic excess intake can cause selenosis, with hair and nail brittleness as characteristic signs", "Benefit for thyroid antibodies has mainly been shown in people with diagnosed autoimmune thyroid disease, not the general population" ], "bottomLine": "Selenium is a well-characterized essential nutrient with a defined safe intake range, and randomized trial evidence supports a role in lowering thyroid antibody levels for people with Hashimoto thyroiditis specifically." }, "originalLinks": [ { "title": "Selenium - Health Professional Fact Sheet - NIH Office of Dietary Supplements", "url": "https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/" }, { "title": "Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38243784/" } ], "links": [ { "title": "Selenium - Health Professional Fact Sheet - NIH Office of Dietary Supplements", "url": "https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/" }, { "title": "Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38243784/" } ], "protocols": [ { "source": { "title": "Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/38243784/" }, "population": "Thirty-five randomized controlled trials pooled across cohorts of people with Hashimoto thyroiditis, with and without thyroid hormone replacement therapy", "regimen": "Oral selenium supplementation trials, commonly in the range of 80 to 200 micrograms per day for periods of three months to two years, compared against placebo", "outcome": "Selenium supplementation reduced thyroid-stimulating hormone and thyroid peroxidase antibody levels in patients not on hormone replacement, with comparable adverse-event rates between selenium and placebo groups and moderate overall certainty of evidence", "duration": "Three months to two years", "origins": [ "evidence.json#/catalog:supplement:selenium/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt describes product formulations and promotional claims rather than a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/selenium/", "outcome": "no-practice-description", "reason": "The excerpt describes product formulations and promotional claims rather than a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/", "pmid:38243784" ] }, "library:supplement-tart-cherry": { "id": "library:supplement-tart-cherry", "path": "/library/supplement-tart-cherry.html", "title": "Tart Cherry", "summary": "A fruit extract studied for exercise-induced muscle soreness.", "aliases": [], "kind": "supplement", "categories": [ "recovery-healing", "fitness-muscle" ], "research": [ { "id": "catalog:supplement:tart-cherry", "title": "Tart Cherry", "summary": "A fruit extract studied for exercise-induced muscle soreness.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Tart cherry, most often studied as Montmorency tart cherry juice or concentrate, is a fruit source of anthocyanins and other polyphenols with antioxidant and anti-inflammatory properties. It has been tested mainly in athletes and recreationally active adults for effects on muscle soreness, inflammation markers, and recovery after strenuous exercise. Trial results are mixed: some randomized studies report meaningful reductions in exercise-induced pain and strength loss, while others in different populations find no measurable benefit.", "verdict": { "benefits": [ "Several randomized trials in runners and other athletes report less muscle pain and faster strength recovery after strenuous exercise", "Meta-analyses link supplementation with reductions in inflammatory markers such as IL-6 after exercise", "Whole-fruit source with a well-characterized polyphenol and anthocyanin content" ], "risks": [ "Findings are inconsistent across studies, and some trials in non-resistance-trained populations found no measurable benefit", "Many trials are small, short, and funded or supplied by cherry industry groups, which can bias reported outcomes", "High sugar content in juice form is a factor for people managing blood glucose" ], "bottomLine": "Tart cherry has real randomized-trial support for easing exercise-induced soreness in some athletic populations, but the effect is inconsistent enough across studies that it cannot be called a reliable recovery aid across the board." }, "originalLinks": [ { "title": "Efficacy of tart cherry juice in reducing muscle pain during running: a randomized controlled trial", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874510/" }, { "title": "No Effect of Tart Cherry Juice or Pomegranate Juice on Recovery from Exercise-Induced Muscle Damage in Non-Resistance Trained Men", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683053/" } ], "links": [ { "title": "Efficacy of tart cherry juice in reducing muscle pain during running: a randomized controlled trial", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874510/" }, { "title": "No Effect of Tart Cherry Juice or Pomegranate Juice on Recovery from Exercise-Induced Muscle Damage in Non-Resistance Trained Men", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683053/" } ], "protocols": [ { "source": { "title": "Efficacy of tart cherry juice in reducing muscle pain during running: a randomized controlled trial", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874510/" }, "population": "54 healthy runners in a randomized, double-blind, placebo-controlled trial during the Hood to Coast relay race", "regimen": "355 mL of tart cherry juice or a placebo cherry drink twice daily for 7 days before the event and on race day, each bottle equivalent to roughly 45 to 50 cherries with at least 600 mg phenolic compounds and 40 mg anthocyanins", "outcome": "The cherry juice group reported a significantly smaller increase in post-race muscle pain (12 mm on a visual analog scale) than the placebo group (37 mm), a statistically significant difference.", "duration": "Seven days before the event and on race day", "origins": [ "evidence.json#/catalog:supplement:tart-cherry/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.health.harvard.edu/diseases-and-conditions/living-with-gout", "outcome": "no-practice-description", "reason": "The inspected gout guide gives clinical and lifestyle advice rather than an independently verified tart-cherry community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874510/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683053/" ] }, "library:supplement-taurine": { "id": "library:supplement-taurine", "path": "/library/supplement-taurine.html", "title": "Taurine", "summary": "Conditionally essential amino acid studied for cardiovascular and exercise outcomes.", "aliases": [], "kind": "supplement", "categories": [ "longevity", "fitness-muscle" ], "research": [ { "id": "catalog:supplement:taurine", "title": "Taurine", "summary": "Conditionally essential amino acid studied for cardiovascular and exercise outcomes.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Taurine is an amino acid present in food and sold as a supplement. A systematic review of human studies in dilated cardiomyopathy and heart failure found reported improvements but concluded the evidence base is small and of mixed quality. A small double-blind heart-failure trial that reported benefits has since been retracted, so it is not cited here. An older review describes possible cardiovascular effects and says long-term double-blind trials are still needed. Human evidence is limited and the studies are small.", "verdict": { "benefits": [ "Individual studies in heart failure reported higher ejection fraction and smaller left ventricular volumes" ], "risks": [ "Pooled ejection fraction and stroke volume showed no significant effect", "The human evidence base is small and of mixed quality, and one supportive trial was retracted", "Reviewers say long-term double-blind trials are still needed" ], "bottomLine": "Taurine's heart-failure evidence is small and mixed, with no significant pooled effect on heart function." }, "originalLinks": [ { "title": "PubMed: taurine supplementation", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=taurine+supplementation" } ], "links": [ { "title": "Effect of taurine administration on symptoms, severity, or clinical outcome of dilated cardiomyopathy and heart failure in humans: a systematic review", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9257265/" }, { "title": "The potential health benefits of taurine in cardiovascular disease (Xu et al. 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/19343117/" } ], "protocols": [ { "population": "people with heart failure across 11 studies; no study was specific to dilated cardiomyopathy", "regimen": "500 mg to 6 g of taurine a day, in supplements taken once to three times daily", "duration": "2 weeks to 12 months, median 6 weeks", "outcome": "Pooled ejection fraction and stroke volume showed no significant effect; individual studies reported higher LVEF and smaller left ventricular volumes.", "source": { "title": "Effect of taurine administration on symptoms, severity, or clinical outcome of dilated cardiomyopathy and heart failure in humans: a systematic review", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9257265/" }, "origins": [ "evidence.json#/catalog:supplement:taurine/protocols/0" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.fda.gov/food/gras-notice-inventory/agency-response-letter-gras-notice-no-grn-000586", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 1, "source": "Ghandforoush-Sattari et al. 2010, J Amino Acids, PMID 22331937 — oral 4g dose, healthy adults; rapid clearance reflects efficient renal handling and tissue uptake, not first-order elimination in the pharmacokinetic sense" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC9257265/", "pmid:19343117", "https://pubmed.ncbi.nlm.nih.gov/?term=taurine+supplementation" ] }, "library:supplement-tongkat-ali": { "id": "library:supplement-tongkat-ali", "path": "/library/supplement-tongkat-ali.html", "title": "Tongkat ali (Eurycoma longifolia)", "summary": "Herbal extract studied for testosterone and stress markers. Extract ratios vary widely between products.", "aliases": [], "kind": "supplement", "categories": [ "sexual-health", "nootropics-cognitive" ], "research": [ { "id": "catalog:supplement:tongkat-ali", "title": "Tongkat ali (Eurycoma longifolia)", "summary": "Herbal extract studied for testosterone and stress markers. Extract ratios vary widely between products.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "A systematic review screened nine studies and pooled five randomised trials, finding higher serum total testosterone in men taking Eurycoma longifolia (SMD 1.352, 95% CI 0.565 to 2.138). The effect also held in the subgroup of men with hypogonadism. The authors note that more research is needed before clinical use. A separate six-month randomised trial in 45 middle-aged men combined the extract with training and reported better erectile function and testosterone, so the extract's own effect cannot be separated.", "verdict": { "benefits": [ "A review pooling five randomised trials found higher serum total testosterone in men.", "The effect held in the subgroup of men with hypogonadism." ], "risks": [ "The effect did not hold in men with normal testosterone.", "The review's authors say more research is needed before clinical use.", "A trial combining the extract with training had no arm testing either alone." ], "bottomLine": "Pooled trials link this extract to higher total testosterone, mainly in men who were low to begin with." }, "originalLinks": [ { "title": "PubMed: Eurycoma longifolia", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=Eurycoma+longifolia" } ], "links": [ { "title": "Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9415500/" }, { "title": "A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM) (Leitão et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33541567/" } ], "protocols": [ { "population": "267 men across five randomised trials: healthy men and men with hypogonadism", "regimen": "Eurycoma longifolia 100-600 mg daily, most often a water extract standardised to 0.8-1.5% eurycomanone", "duration": "2 weeks to 6 months", "outcome": "Total testosterone rose (SMD 1.352, 95% CI 0.565 to 2.138); the effect held in the hypogonadal subgroup but not in men with normal testosterone.", "source": { "title": "Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9415500/" }, "origins": [ "evidence.json#/catalog:supplement:tongkat-ali/protocols/0" ] }, { "population": "45 men with androgen deficiency of the aging male, mean age 47", "regimen": "200 mg Eurycoma longifolia daily and/or concurrent training 3 times a week for 60 minutes at progressive intensity, in four groups", "duration": "6 months", "outcome": "Erectile function improved with both interventions and most in the combined group, and total testosterone rose; no arm tested the extract or training alone.", "source": { "title": "A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM) (Leitão et al. 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33541567/" }, "origins": [ "evidence.json#/catalog:supplement:tongkat-ali/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.healthline.com/nutrition/tongkat-ali-longjack-review", "outcome": "no-practice-description", "reason": "This retrieved source was checked, but no suitable community description was independently verified. Research regimens, expert advice, product identity and efficacy claims were not repurposed." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC9415500/", "pmid:33541567", "https://pubmed.ncbi.nlm.nih.gov/?term=Eurycoma+longifolia" ] }, "library:supplement-vitamin-a": { "id": "library:supplement-vitamin-a", "path": "/library/supplement-vitamin-a.html", "title": "Vitamin A (retinol)", "summary": "Fat-soluble vitamin. Has a genuine upper limit — accumulates rather than clearing.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:vitamin-a", "title": "Vitamin A (retinol)", "summary": "Fat-soluble vitamin. Has a genuine upper limit — accumulates rather than clearing.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "reference", "evidenceSummary": "A European Food Safety Authority opinion kept a tolerable upper intake level for preformed vitamin A, choosing birth defects as the critical harm, with liver damage and bone effects also reviewed. No upper level could be set for beta-carotene; the panel picked lung cancer risk as the critical effect of beta-carotene supplements, especially in smokers. A separate review describes laboratory evidence that excess vitamin A harms mitochondria. These are authority opinions and reviews, not trials of a supplement.", "verdict": { "benefits": [], "risks": [ "Birth defects were the critical harm behind the upper limit for preformed vitamin A.", "Liver damage and bone effects were also reviewed, and laboratory work shows harm to mitochondria.", "No upper level could be set for beta-carotene, whose critical effect is lung cancer risk in smokers.", "The linked sources set safe upper intake limits; they report no benefit from supplementation." ], "bottomLine": "These sources describe vitamin A's safe upper limits and harms, including birth defects, not benefits from supplements." }, "originalLinks": [ { "title": "NIH ODS: Vitamin A", "url": "https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/" } ], "links": [ { "title": "Office of Dietary Supplements - Vitamin A and Carotenoids (Consumer)", "url": "https://ods.od.nih.gov/factsheets/VitaminA-Consumer/" }, { "title": "Vitamin A and Retinoids as Mitochondrial Toxicants", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452429/" }, { "title": "Scientific opinion on the tolerable upper intake level for preformed vitamin A and β-carotene", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11154838/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt describes chemical forms and food sources, not a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/vitamin-a/", "outcome": "no-practice-description", "reason": "The excerpt describes chemical forms and food sources, not a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://ods.od.nih.gov/factsheets/VitaminA-Consumer/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452429/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11154838/", "https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/" ] }, "library:supplement-vitamin-b-complex": { "id": "library:supplement-vitamin-b-complex", "path": "/library/supplement-vitamin-b-complex.html", "title": "Vitamin B complex", "summary": "Combined B vitamins. High-dose biotin within these can interfere with some lab immunoassays.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:vitamin-b-complex", "title": "Vitamin B complex", "summary": "Combined B vitamins. High-dose biotin within these can interfere with some lab immunoassays.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "reference", "evidenceSummary": "Vitamin B complex products combine several B vitamins, often including biotin. Review articles explain that biotin from supplements interferes with laboratory immunoassays that rely on biotin-streptavidin binding. Depending on the assay design the result can be falsely high or falsely low, most often in thyroid and cardiac tests. Laboratories manage this by asking about supplement use and by handling affected samples differently. The sources are reviews of laboratory methods, not trials of B-complex supplements.", "verdict": { "benefits": [], "risks": [ "Biotin in these products interferes with lab immunoassays, most often thyroid and cardiac tests", "Results can read falsely high or falsely low depending on how the assay is built", "Laboratories rely on being told about supplement use to handle affected samples", "No evidence of benefit in the sources here, which are reviews of laboratory methods" ], "bottomLine": "The sources here cover one thing only: biotin in B-complex products can distort common laboratory blood tests." }, "originalLinks": [ { "title": "NIH ODS: B vitamins", "url": "https://ods.od.nih.gov/factsheets/list-VitaminsMinerals/" } ], "links": [ { "title": "Immunoassay design and biotin interference (Dasgupta 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35953126/" }, { "title": "Biotin Supplementation—The Cause of Hypersensitivity and Significant Interference in Allergy Diagnostics", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12348524/" }, { "title": "Strategies for mitigating risk posed by biotin interference on clinical immunoassays (Gifford et al. 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30582902/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere.", "checks": [ { "url": "https://www.fda.gov/medical-devices/safety-communications/fda-warns-biotin-may-interfere-lab-tests-fda-safety-communication", "outcome": "not-found", "reason": "Independent direct retrieval returned HTTP 404. No description was verified at this attempted address." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "pmid:35953126", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12348524/", "pmid:30582902", "https://ods.od.nih.gov/factsheets/list-VitaminsMinerals/" ] }, "library:supplement-vitamin-b12": { "id": "library:supplement-vitamin-b12", "path": "/library/supplement-vitamin-b12.html", "title": "Vitamin B12 (cobalamin)", "summary": "Water-soluble vitamin. Methylcobalamin and cyanocobalamin are the common forms.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:vitamin-b12", "title": "Vitamin B12 (cobalamin)", "summary": "Water-soluble vitamin. Methylcobalamin and cyanocobalamin are the common forms.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "reference", "evidenceSummary": "Vitamin B12 (cobalamin) is an essential water-soluble vitamin, and the NIH fact sheets are general references on its forms, absorption and deficiency. Absorption of food-bound B12 depends on intrinsic factor in the stomach. A short journal commentary argues that methylcobalamin alone is incomplete because adenosylcobalamin has separate metabolic roles, and reports that oral treatment corrects deficiency as well as intramuscular injection. No trial data is linked, so this is reference-level material.", "verdict": { "benefits": [ "An essential vitamin; NIH fact sheets cover its forms, absorption and deficiency", "A commentary reports oral treatment corrects deficiency as well as injection" ], "risks": [ "No trial data is linked here, so this is reference-level material only", "Absorption of food-bound B12 depends on intrinsic factor in the stomach", "One commentary argues methylcobalamin alone is incomplete, since adenosylcobalamin has separate roles" ], "bottomLine": "An essential vitamin described here from reference sources; oral treatment reportedly matches injection." }, "originalLinks": [ { "title": "NIH ODS: Vitamin B12", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" } ], "links": [ { "title": "Vitamin B12 - Consumer (Office of Dietary Supplements)", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-Consumer/" }, { "title": "Vitamin B12 - Health Professional Fact Sheet", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" }, { "title": "Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion (Thakkar 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25117994/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt lists dosage forms and disputed absorption claims, not a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/vitamin-b12/", "outcome": "no-practice-description", "reason": "The excerpt lists dosage forms and disputed absorption claims, not a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://ods.od.nih.gov/factsheets/VitaminB12-Consumer/", "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/", "pmid:25117994" ] }, "library:supplement-vitamin-c": { "id": "library:supplement-vitamin-c", "path": "/library/supplement-vitamin-c.html", "title": "Vitamin C (ascorbic acid)", "summary": "Water-soluble antioxidant vitamin. Absorption saturates, so split dosing beats one large dose.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:vitamin-c", "title": "Vitamin C (ascorbic acid)", "summary": "Water-soluble antioxidant vitamin. Absorption saturates, so split dosing beats one large dose.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "clinical-study", "evidenceSummary": "Small human studies show that vitamin C absorption in the gut saturates: beyond a point, taking more does not raise absorption in proportion. In an intestinal perfusion study in volunteers, absorption followed saturation kinetics, and the authors suggested very large single doses are absorbed less efficiently than smaller ones taken separately. In a four-person comparison of oral forms, about 30% of a large oral dose was recovered in urine against about 85% after injection, with a timed-release capsule lower still, and absorption varied widely between people. The NIH fact sheet is a general reference.", "verdict": { "benefits": [ "Small human studies show gut absorption saturates, so spread intake is absorbed more efficiently.", "The NIH fact sheet serves as a general reference on the vitamin." ], "risks": [ "The absorption studies are tiny, one with four people, and absorption varied widely.", "Much of a large oral amount ends up in urine, and a timed-release capsule fared worst.", "The sources here test absorption only, not any health outcome." ], "bottomLine": "The evidence here covers absorption only: uptake saturates and varies between people, with no outcomes tested." }, "originalLinks": [ { "title": "NIH ODS: Vitamin C", "url": "https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/" } ], "links": [ { "title": "Vitamin C - Health Professional Fact Sheet", "url": "https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/" }, { "title": "Demonstration of saturation kinetics in the intestinal absorption of vitamin C in man and the guinea pig (Nelson et al. 1978)", "url": "https://pubmed.ncbi.nlm.nih.gov/209065/" }, { "title": "Ascorbic acid absorption in humans: a comparison among several dosage forms (Yung et al. 1982)", "url": "https://pubmed.ncbi.nlm.nih.gov/7069582/" } ], "protocols": [ { "population": "7 human volunteers, alongside guinea pig intestinal segments", "regimen": "triple-lumen intestinal perfusion with vitamin C concentrations from 0.85 to 11.36 mM", "duration": "single perfusion", "outcome": "Absorption followed saturation kinetics (Km 5.44 mM), and net water secretion appeared in three of seven subjects at the highest concentration.", "source": { "title": "Demonstration of saturation kinetics in the intestinal absorption of vitamin C in man and the guinea pig (Nelson et al. 1978)", "url": "https://pubmed.ncbi.nlm.nih.gov/209065/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-c/protocols/0" ] }, { "population": "4 human subjects", "regimen": "1 g of ascorbic acid by mouth as a solution, tablet, chewable tablet or timed-release capsule, against an intravenous dose", "duration": "single dose per form", "outcome": "About 85% of the intravenous dose was recovered in urine, against about 30% from solution and tablet and about 14% from the timed-release capsule.", "source": { "title": "Ascorbic acid absorption in humans: a comparison among several dosage forms (Yung et al. 1982)", "url": "https://pubmed.ncbi.nlm.nih.gov/7069582/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-c/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The proposed onset-of-cold timing is unsupported by the quote, and megadose promotion is not suitable practice content.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/vitamin-c/", "outcome": "no-practice-description", "reason": "The proposed onset-of-cold timing is unsupported by the quote, and megadose promotion is not suitable practice content." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 2, "source": "Dhotre et al. 2025, Pharmaceutics, PMID 41304796 — acute plasma disappearance; the separate, slower body-pool depletion kinetics relevant to scurvy risk operate over weeks and are a different process" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/", "pmid:209065", "pmid:7069582" ] }, "library:supplement-vitamin-d3": { "id": "library:supplement-vitamin-d3", "path": "/library/supplement-vitamin-d3.html", "title": "Vitamin D3 (cholecalciferol)", "summary": "Fat-soluble vitamin dosed in international units. Frequently paired with K2.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:vitamin-d3", "title": "Vitamin D3 (cholecalciferol)", "summary": "Fat-soluble vitamin dosed in international units. Frequently paired with K2.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "reference", "evidenceSummary": "Vitamin D3 (cholecalciferol) is made in skin from sunlight and also comes from food. The single linked source is a narrative review describing how it is converted in the liver and kidneys to the active form, calcitriol. The review reports benefits in specific groups, including bone density, immune balance and glucose control, and describes preclinical work on other organs. It is a review of mixed evidence, not a trial, and it does not cover the vitamin K2 combination.", "verdict": { "benefits": [ "A narrative review reports gains in bone density, immune balance and glucose control in some groups.", "The review reports slower femoral neck bone density decline than placebo.", "It also reports less fatigue and better cognition in the groups it covers." ], "risks": [ "The single source is a narrative review of mixed evidence, not a trial.", "It reports no improvement in beta-cell function and no fall in major cardiovascular events.", "It does not cover the vitamin K2 combination." ], "bottomLine": "One review links vitamin D3 to better bone, immune and glucose measures, with no effect on heart events or beta cells." }, "originalLinks": [ { "title": "NIH ODS: Vitamin D", "url": "https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/" } ], "links": [ { "title": "Cholecalciferol (vitamin D3): efficacy, safety, and implications in public health", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183072/" } ], "protocols": [ { "population": "1,774 participants with prediabetes, in a trial the review cites", "regimen": "4,000 IU of vitamin D3 daily", "duration": "24 months", "outcome": "The review reports no improvement in beta-cell function.", "source": { "title": "Cholecalciferol (vitamin D3): efficacy, safety, and implications in public health", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183072/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-d3/protocols/0" ] }, { "population": "general-population adults in the VITAL trial, as the review describes it", "regimen": "2,000 IU of vitamin D3 daily", "duration": "not stated", "outcome": "The review reports no significant reduction in major cardiovascular events.", "source": { "title": "Cholecalciferol (vitamin D3): efficacy, safety, and implications in public health", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183072/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-d3/protocols/1" ] }, { "population": "adults given weekly cholecalciferol against placebo, in a trial the review cites", "regimen": "20,000 IU of cholecalciferol weekly", "duration": "not stated", "outcome": "The review reports a slower decline in femoral neck bone mineral density than placebo.", "source": { "title": "Cholecalciferol (vitamin D3): efficacy, safety, and implications in public health", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183072/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-d3/protocols/2" ] }, { "population": "people recovering from COVID-19, in a study the review cites", "regimen": "50,000 IU of cholecalciferol a week", "duration": "8 weeks", "outcome": "The review reports a 42% reduction in fatigue and 35% improvement in cognition.", "source": { "title": "Cholecalciferol (vitamin D3): efficacy, safety, and implications in public health", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183072/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-d3/protocols/3" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt distinguishes chemical forms and origins, not a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/vitamin-d/", "outcome": "no-practice-description", "reason": "The excerpt distinguishes chemical forms and origins, not a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 360, "source": "25-OH-D circulating half-life" } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183072/", "https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/" ] }, "library:supplement-vitamin-e": { "id": "library:supplement-vitamin-e", "path": "/library/supplement-vitamin-e.html", "title": "Vitamin E (tocopherol)", "summary": "Fat-soluble antioxidant. Mixed tocopherols are closer to the dietary form than alpha alone.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:vitamin-e", "title": "Vitamin E (tocopherol)", "summary": "Fat-soluble antioxidant. Mixed tocopherols are closer to the dietary form than alpha alone.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "reference", "evidenceSummary": "Vitamin E is a fat-soluble antioxidant; alpha-tocopherol is the only form counted as essential. A Nordic Nutrition Recommendations scoping review reports that dietary vitamin E may help prevent some chronic disease, but that there is no clear benefit from alpha-tocopherol supplements in generally healthy people, and that deficiency is rare and usually has other causes. An EFSA scientific opinion keeps the existing tolerable upper intake levels, with impaired blood clotting and bleeding as the critical effect of excess. Both are reviews and guidance, not trials.", "verdict": { "benefits": [ "A Nordic scoping review reports dietary vitamin E may help prevent some chronic disease" ], "risks": [ "No clear benefit from alpha-tocopherol supplements in generally healthy people", "Deficiency is rare and usually has another underlying cause", "EFSA names impaired blood clotting and bleeding as the critical effect of excess intake" ], "bottomLine": "Vitamin E from food may help, while supplements show no clear benefit in healthy people and excess risks bleeding." }, "originalLinks": [ { "title": "NIH ODS: Vitamin E", "url": "https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/" } ], "links": [ { "title": "Vitamin E – A scoping review for Nordic Nutrition Recommendations 2023", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770650/" }, { "title": "Scientific opinion on the tolerable upper intake level for vitamin E", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294871/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt concerns a chemical form's physiological identity, not a documented supplementation routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/vitamin-e/", "outcome": "no-practice-description", "reason": "The excerpt concerns a chemical form's physiological identity, not a documented supplementation routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] }, "pk": { "hours": 45, "lowerHours": 42, "source": "Traber, Ramakrishnan & Kayden 1994, Proc Natl Acad Sci, PMID 7937827 — natural RRR-alpha-tocopherol; the synthetic SRR stereoisomer clears far faster (about 14 hours) due to selective hepatic retention of the natural form", "upperHours": 48 } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770650/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294871/", "https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/" ] }, "library:supplement-vitamin-k2": { "id": "library:supplement-vitamin-k2", "path": "/library/supplement-vitamin-k2.html", "title": "Vitamin K2 (MK-7)", "summary": "Fat-soluble vitamin involved in calcium handling. Often paired with vitamin D3.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:vitamin-k2", "title": "Vitamin K2 (MK-7)", "summary": "Fat-soluble vitamin involved in calcium handling. Often paired with vitamin D3.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "A meta-analysis of 16 randomised trials with 6,425 participants found vitamin K2 (MK-7) improved lumbar spine bone mineral density in postmenopausal women and lowered undercarboxylated osteocalcin. Fracture rates did not differ overall, though they were lower once one very different study was excluded. Reported adverse effects were no more common than in control groups. One randomised trial in 148 women with osteopenia found preserved trabecular bone structure at the tibia but no difference in bone density.", "verdict": { "benefits": [ "Pooled randomised trials in 6,425 people found better lumbar spine bone density in postmenopausal women", "Undercarboxylated osteocalcin fell, and reported adverse effects were no more common than in controls" ], "risks": [ "Fracture rates did not differ overall, and hip and femoral neck density did not change", "The lumbar gain appeared with combined therapy rather than K2 alone", "One trial preserved trabecular structure at the tibia but found no bone density difference" ], "bottomLine": "Vitamin K2 improved some bone density and markers in postmenopausal women without reducing fractures." }, "originalLinks": [ { "title": "NIH ODS: Vitamin K", "url": "https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/" } ], "links": [ { "title": "Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: a systematic review and meta-analysis of randomized controlled trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9403798/" }, { "title": "Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237441/" }, { "title": "Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women (Rønn et al. 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27625301/" } ], "protocols": [ { "population": "6,425 participants across 16 randomised trials, mostly postmenopausal women aged 50-80", "regimen": "vitamin K2 as MK-4 or menatetrenone 45 mg a day, or MK-7 180-375 µg a day, alone or with other bone treatment", "duration": "6 to 48 months", "outcome": "Undercarboxylated osteocalcin fell and lumbar spine density improved with combined therapy but not K2 alone; hip and femoral neck density and adverse events did not differ.", "source": { "title": "Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: a systematic review and meta-analysis of randomized controlled trials", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9403798/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-k2/protocols/0" ] }, { "population": "148 postmenopausal women with osteopenia", "regimen": "MK-7 375 µg a day against placebo, with calcium and vitamin D given to both groups", "duration": "12 months", "outcome": "Trabecular number, spacing and thickness at the tibia were preserved against age-related deterioration, but bone mineral density did not differ at any site.", "source": { "title": "Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women (Rønn et al. 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27625301/" }, "origins": [ "evidence.json#/catalog:supplement:vitamin-k2/protocols/1" ] } ], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt concerns food and bacterial origins of menaquinones, not a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/vitamin-k/", "outcome": "no-practice-description", "reason": "The excerpt concerns food and bacterial origins of menaquinones, not a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC9403798/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237441/", "pmid:27625301", "https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/" ] }, "library:supplement-whey-protein": { "id": "library:supplement-whey-protein", "path": "/library/supplement-whey-protein.html", "title": "Whey protein", "summary": "Fast-absorbing complete dairy protein with a high leucine content.", "aliases": [], "kind": "supplement", "categories": [ "fitness-muscle" ], "research": [ { "id": "catalog:supplement:whey-protein", "title": "Whey protein", "summary": "Fast-absorbing complete dairy protein with a high leucine content.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "systematic-review", "evidenceSummary": "Whey protein is a milk protein taken as a supplement. A systematic review with meta-analysis of 25 trials in older adults examined body composition, strength and cardiometabolic markers, usually alongside resistance training. A meta-analysis in postmenopausal women found benefits for strength and lean mass mainly where resistance training was part of the programme. A third meta-analysis looked at recovery of muscle function after resistance exercise. Evidence comes from several meta-analyses of randomised trials, and results depend heavily on training.", "verdict": { "benefits": [ "Pooled randomised trials in older adults show a small gain in lower-body strength.", "In postmenopausal women, strength and leg lean mass improved where resistance training was included.", "Small to medium effects on recovery of muscle function after resistance exercise." ], "risks": [ "No change in fat mass, lean mass, waist or blood lipids in older adults; fasting insulin rose.", "Only half the recovery studies found any benefit; the rest found none against control.", "Results depend heavily on resistance training happening alongside it." ], "bottomLine": "Whey protein adds small strength and recovery gains mostly when paired with resistance training, not alone." }, "originalLinks": [ { "title": "ISSN position stand: protein and exercise", "url": "https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0177-8" } ], "links": [ { "title": "Effects of Whey Protein Supplementation on Body Composition, Muscular Strength, and Cardiometabolic Health in Older Adults: A Systematic Review with Pairwise Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12610255/" }, { "title": "The Effect of Whey Protein Supplementation on the Temporal Recovery of Muscle Function Following Resistance Training: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852797/" }, { "title": "Effect of Whey Protein Supplementation in Postmenopausal Women: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9572824/" } ], "protocols": [ { "population": "1,454 older adults aged 64-84 across 25 randomised controlled trials", "regimen": "15 to 35 g of whey protein a day, with or without leucine enrichment, against maltodextrin or non-protein controls; 15 trials paired it with resistance training", "duration": "8 weeks to 2 years, most commonly 12-16 weeks", "outcome": "Lower-body strength rose slightly (SMD 0.16); no change in fat mass, lean mass, waist or blood lipids and glucose, while fasting insulin and HOMA-IR rose.", "source": { "title": "Effects of Whey Protein Supplementation on Body Composition, Muscular Strength, and Cardiometabolic Health in Older Adults: A Systematic Review with Pairwise Meta-Analysis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12610255/" }, "origins": [ "evidence.json#/catalog:supplement:whey-protein/protocols/0" ] }, { "population": "152 subjects, 92% male and mostly young untrained men, across 13 randomised trials in 8 studies", "regimen": "a median 25 g bolus of whey protein (range 20-120 g in total), given after exercise in 62% of trials, before in 23% and both in 15%, usually repeated through recovery", "duration": "the recovery window after a bout of damaging eccentric resistance exercise", "outcome": "Small to medium effects on recovery of muscle function (0.4-0.7), but only half the studies reported any benefit and the rest found none against control.", "source": { "title": "The Effect of Whey Protein Supplementation on the Temporal Recovery of Muscle Function Following Resistance Training: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852797/" }, "origins": [ "evidence.json#/catalog:supplement:whey-protein/protocols/1" ] }, { "population": "776 postmenopausal women aged 57-74 across the included trials", "regimen": "20 to 40 g of protein supplement daily; 11 studies combined it with resistance training and 4 gave it alone", "duration": "10 to 72 weeks, most commonly 12 weeks", "outcome": "Biceps curl strength and lower-limb lean mass improved with resistance training; no effect on grip strength, knee strength, gait speed, fat mass or weight.", "source": { "title": "Effect of Whey Protein Supplementation in Postmenopausal Women: A Systematic Review and Meta-Analysis", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9572824/" }, "origins": [ "evidence.json#/catalog:supplement:whey-protein/protocols/2" ] } ], "community": [ { "description": "A nutrition guide describes protein shakes as commonly used after workouts and lists whey as a powder used before or after training; powders typically contain 20-30 g of protein per scoop.", "source": { "title": "Should You Have a Protein Shake Before or After Your Workout? - Healthline", "url": "https://www.healthline.com/nutrition/protein-shake-before-or-after-workout" }, "origins": [ "evidence.json#/catalog:supplement:whey-protein/community/0" ] } ], "communityFinding": { "checkedOn": "2026-10-06", "status": "verified-description", "notes": "Rechecked the previously published description against live source content. The live guide describes shakes between meals or around workouts and specifies the powder's usual protein content per scoop. The description does not assert a superior training time.", "checks": [ { "url": "https://www.healthline.com/nutrition/protein-shake-before-or-after-workout", "outcome": "verified-description", "reason": "The live guide describes shakes between meals or around workouts and specifies the powder's usual protein content per scoop. The description does not assert a superior training time." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [ { "origin": "evidence.json#/catalog:supplement:whey-protein/community/0", "url": "https://www.healthline.com/nutrition/protein-shake-before-or-after-workout", "claimMatch": "The imported wording is preserved for attribution; its full clinical, dosing, efficacy or consensus claims have not been independently established.", "population": "Unvalidated source account; no validated human dosing population or animal-to-human equivalence is inferred.", "suitability": "historical-reference-only", "result": "unverified-historical-account" } ] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://pmc.ncbi.nlm.nih.gov/articles/PMC12610255/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852797/", "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9572824/", "https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0177-8", "https://www.healthline.com/nutrition/protein-shake-before-or-after-workout" ] }, "library:supplement-zinc": { "id": "library:supplement-zinc", "path": "/library/supplement-zinc.html", "title": "Zinc", "summary": "Essential mineral. Long-term high doses induce copper deficiency.", "aliases": [], "kind": "supplement", "categories": [ "longevity" ], "research": [ { "id": "catalog:supplement:zinc", "title": "Zinc", "summary": "Essential mineral. Long-term high doses induce copper deficiency.", "uncertainty": "Reference information only. Not medical advice.", "namespace": "supplement", "evidenceTier": "reference", "evidenceSummary": "Zinc is an essential trace mineral involved in hundreds of enzyme reactions. A review of zinc toxicity explains that excess intake can cause anaemia, low white cell counts and copper deficiency, and compares the upper limits set by EFSA and the FDA. It notes that non-oral exposure, such as inhalation, can also cause harm. The NIH Office of Dietary Supplements fact sheet is a general professional reference on zinc. Both sources are reference material rather than trials.", "verdict": { "benefits": [ "An essential trace mineral involved in hundreds of enzyme reactions." ], "risks": [ "Excess intake can cause anaemia, low white cell counts and copper deficiency.", "EFSA and the FDA set different upper limits; non-oral exposure such as inhalation can also harm.", "Both sources are reference material rather than trials.", "The linked sources are general reference material and report no trial of supplement benefit." ], "bottomLine": "Zinc is essential for enzyme function, and the linked sources mainly describe the harms of excess intake." }, "originalLinks": [ { "title": "NIH ODS: Zinc", "url": "https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/" } ], "links": [ { "title": "Zinc Toxicity: Understanding the Limits", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11243279/" }, { "title": "Office of Dietary Supplements - Zinc Health Professional Fact Sheet", "url": "https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/" } ], "protocols": [], "community": [], "communityFinding": { "checkedOn": "2026-10-06", "status": "no-verified-description", "notes": "No suitable community description was independently verified in these checks. The entry remains empty; this does not establish that no practice exists elsewhere. The excerpt lists product forms, not a community routine.", "checks": [ { "url": "https://nutritionsource.hsph.harvard.edu/zinc/", "outcome": "no-practice-description", "reason": "The excerpt lists product forms, not a community routine." } ] }, "reviewState": "historical-not-reverified", "sourceCommit": "adc7684614f9439b41d91a3312b62e7982c7e20e", "publicationReview": { "checkedOn": "2026-10-15", "status": "historical-reference-only", "clinicalVerification": "not-performed", "notices": [], "community": [] } } ], "related": [], "conflicts": [], "sourceRefs": [ "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11243279/", "https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/" ] } }, "sources": { "pmid:42542926": { "id": "pmid:42542926", "occurrences": [ { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/", "authorsYear": "Biçer et al. 2026", "origin": "peptides.json#/bpc-157/citations/0", "circular": false }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/", "origin": "catalog:peptide:bpc-157/links/1", "circular": false }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/", "origin": "evidence.json#/catalog:peptide:bpc-157/protocols/0/source", "circular": false }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/", "authorsYear": "Biçer et al. 2026", "origin": "peptides.json#/tb-500/citations/0", "circular": false }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/", "origin": "catalog:peptide:tb-500/links/1", "circular": false }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study (Biçer et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/", "origin": "evidence.json#/catalog:peptide:tb-500/protocols/0/source", "circular": false }, { "title": "Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study", "url": "https://pubmed.ncbi.nlm.nih.gov/42542926/", "authorsYear": "Biçer et al. 2026", "origin": "stacks.json#/bpc-157-tb-500/citations/0", "circular": false } ] }, "pmid:42578445": { "id": "pmid:42578445", "occurrences": [ { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/", "authorsYear": "Tewari et al. 2026", "origin": "peptides.json#/bpc-157/citations/1", "circular": false }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine (Tewari et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/", "origin": "catalog:peptide:bpc-157/links/2", "circular": false }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/", "authorsYear": "Tewari et al. 2026", "origin": "peptides.json#/tb-500/citations/1", "circular": false }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/", "authorsYear": "Tewari et al. 2026", "origin": "peptides.json#/ghk-cu/citations/0", "circular": false }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine (Tewari et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/", "origin": "catalog:peptide:ghk-cu/links/1", "circular": false }, { "title": "Peptide Supplements and Their Therapeutic Applications in Sports Medicine (Tewari et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42578445/", "origin": "catalog:peptide:tb-500/links/2", "circular": false } ] }, "pmid:41898733": { "id": "pmid:41898733", "occurrences": [ { "title": "From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management", "url": "https://pubmed.ncbi.nlm.nih.gov/41898733/", "authorsYear": "Yuan et al. 2026", "origin": "peptides.json#/bpc-157/citations/2", "circular": false }, { "title": "From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management (Yuan et al. 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41898733/", "origin": "catalog:peptide:bpc-157/links/3", "circular": false } ] }, "pmid:40789979": { "id": "pmid:40789979", "occurrences": [ { "title": "Regeneration or Risk? 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