{ "version": 2, "built": "2026-10-02", "method": "Counted human evidence per supplement and outcome. Counted: human randomized trials and meta-analyses or systematic reviews, each with an exact phrase from its PubMed abstract; uncontrolled human pilots are listed but do not decide a verdict; animal, cell, observational and review papers are context only.", "verdicts": { "supported": { "label": "Supported", "short": "Supported", "rule": "At least one positive meta-analysis or positive large trial (1,000+ participants), and no counted negative results." }, "mixed": { "label": "Mixed", "short": "Mixed", "rule": "Counted evidence points both ways." }, "not-supported": { "label": "Not supported in trials", "short": "Not supported", "rule": "Only null results among counted studies." }, "harm-signal": { "label": "Possible harm in trials", "short": "Possible harm", "rule": "Counted studies show only null or harmful results, including at least one harmful result." }, "early": { "label": "Early or small trials", "short": "Early evidence", "rule": "Only small randomized trials or uncontrolled pilots, all positive." }, "no-human-trials": { "label": "No human trials", "short": "No human trials", "rule": "No counted human trial evidence for this outcome." } }, "supplements": [ { "id": "nmn", "name": "NMN", "aka": "Nicotinamide mononucleotide", "kind": "supplement", "category": "NAD+ precursors", "glossary": [ "nmn-nicotinamide-mononucleotide" ], "outcomes": [ { "id": "nad", "outcome": "Blood NAD+ levels", "evidence": [ { "pmid": "36482258", "design": "rct", "direction": "benefit", "finding": "In a dose-finding trial, NMN raised blood NAD+, with the effect peaking at 600 mg a day.", "quotes": [ "Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Yi 2023, Geroscience", "title": "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "insulin", "outcome": "Insulin sensitivity", "evidence": [ { "pmid": "33888596", "design": "rct", "direction": "benefit", "finding": "In women with prediabetes, NMN improved muscle insulin sensitivity.", "quotes": [ "NMN increases muscle insulin sensitivity", "prediabetic women" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Yoshino 2021, Science", "title": "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "aerobic", "outcome": "Aerobic capacity", "evidence": [ { "pmid": "34238308", "design": "rct", "direction": "benefit", "finding": "In amateur runners in training, NMN improved aerobic capacity.", "quotes": [ "NMN increases the aerobic capacity of humans during exercise training", "amateur runners" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Liao 2021, J Int Soc Sports Nutr", "title": "Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [], "pubmed_counts": { "rct": 17, "meta": 7, "rct_query": "\"nicotinamide mononucleotide\"[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "\"nicotinamide mononucleotide\"[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "nad" }, { "id": "nr", "name": "NR", "aka": "Nicotinamide riboside", "kind": "supplement", "category": "NAD+ precursors", "glossary": [ "nr-nicotinamide-riboside" ], "outcomes": [ { "id": "nad", "outcome": "Blood NAD+ levels", "evidence": [ { "pmid": "29599478", "design": "rct", "direction": "benefit", "finding": "In healthy middle-aged and older adults, NR was well tolerated and raised NAD+ levels.", "quotes": [ "is well tolerated and effectively", "healthy middle-aged and older adults" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Martens 2018, Nat Commun", "title": "Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults." }, { "pmid": "29184669", "design": "rct", "direction": "benefit", "finding": "A combination of NR and pterostilbene safely raised NAD+ levels over repeated dosing.", "quotes": [ "a repeat dose of NRPT is a safe and effective way to increase NAD+ levels sustainably" ], "n": null, "n_quote": null, "basis": "abstract", "citation": "Dellinger 2017, NPJ Aging Mech Dis", "title": "Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 2, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "27721479", "kind": "pharmacokinetic study", "note": "First human pharmacokinetic study of NR (single doses), alongside mouse experiments.", "citation": "Trammell 2016, Nat Commun", "title": "Nicotinamide riboside is uniquely and orally bioavailable in mice and humans." } ], "pubmed_counts": { "rct": 31, "meta": 2, "rct_query": "\"nicotinamide riboside\"[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "\"nicotinamide riboside\"[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "nad" }, { "id": "niacin", "name": "Niacin (vitamin B3)", "aka": "Nicotinic acid", "kind": "supplement", "category": "Heart and metabolism", "glossary": [], "outcomes": [ { "id": "cv", "outcome": "Heart attacks and strokes, added to statins", "evidence": [ { "pmid": "22085343", "design": "rct", "direction": "null", "finding": "In 3,414 patients with cardiovascular disease and low LDL on statins, adding niacin gave no additional benefit (AIM-HIGH).", "quotes": [ "there was no incremental clinical benefit from the addition of niacin to statin therapy" ], "n": 3414, "n_quote": "A total of 3414 patients were randomly assigned", "basis": "pubmed", "citation": "Boden 2011, N Engl J Med", "title": "Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy." }, { "pmid": "25014686", "design": "rct", "direction": "null", "finding": "In 25,673 adults with vascular disease, extended-release niacin with laropiprant did not reduce major vascular events and increased serious adverse events (HPS2-THRIVE).", "quotes": [ "did not significantly reduce the risk of major vascular events", "but did increase the risk of serious adverse events" ], "n": 25673, "n_quote": "we randomly assigned 25,673 adults with vascular disease", "basis": "pubmed", "citation": "Landray 2014, N Engl J Med", "title": "Effects of extended-release niacin with laropiprant in high-risk patients." } ], "verdict": "not-supported", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 2, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "1088963", "kind": "historical trial", "note": "Coronary Drug Project (1975), an early niacin trial; PubMed has no abstract, so it is not counted here.", "citation": " 1975, JAMA", "title": "Clofibrate and niacin in coronary heart disease." } ], "pubmed_counts": { "rct": 497, "meta": 79, "rct_query": "(niacin[tiab] OR \"nicotinic acid\"[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(niacin[tiab] OR \"nicotinic acid\"[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "cv" }, { "id": "metformin", "name": "Metformin", "aka": "Prescription diabetes drug", "kind": "drug", "category": "Prescription drugs", "glossary": [ "metformin", "tame-trial-targeting-aging-with-metformin" ], "outcomes": [ { "id": "muscle", "outcome": "Muscle growth with strength training (older adults)", "evidence": [ { "pmid": "31557380", "design": "rct", "direction": "harm", "finding": "In healthy older adults doing resistance training, metformin blunted the gain in muscle size (MASTERS trial).", "quotes": [ "metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Walton 2019, Aging Cell", "title": "Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial." } ], "verdict": "harm-signal", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 1, "pilot": 0 } }, { "id": "aging", "outcome": "Slowing ageing in people", "evidence": [], "verdict": "no-human-trials", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "23900241", "kind": "animal", "note": "Extended healthspan and lifespan in mice.", "citation": "Martin-Montalvo 2013, Nat Commun", "title": "Metformin improves healthspan and lifespan in mice." }, { "pmid": "27304507", "kind": "review", "note": "The rationale for the TAME trial; effects on ageing in people are unproven.", "citation": "Barzilai 2016, Cell Metab", "title": "Metformin as a Tool to Target Aging." } ], "pubmed_counts": { "rct": 3450, "meta": 1010, "rct_query": "metformin[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "metformin[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "aging" }, { "id": "rapamycin", "name": "Rapamycin and rapalogs", "aka": "Sirolimus, everolimus (prescription mTOR inhibitors)", "kind": "drug", "category": "Prescription drugs", "glossary": [ "rapamycin", "rapalogs", "mtor-mechanistic-target-of-rapamycin" ], "outcomes": [ { "id": "immune", "outcome": "Immune function in older adults", "evidence": [ { "pmid": "25540326", "design": "rct", "direction": "benefit", "finding": "In older volunteers, the rapalog RAD001 (everolimus) improved the response to flu vaccination by about 20%.", "quotes": [ "RAD001 enhanced the response to the influenza vaccine by about 20%" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Mannick 2014, Sci Transl Med", "title": "mTOR inhibition improves immune function in the elderly." }, { "pmid": "29997249", "design": "rct", "direction": "benefit", "finding": "In 264 older adults, six weeks of low-dose TORC1 inhibition was followed by fewer reported infections over the next year.", "quotes": [ "a significant (P = 0.001) decrease in the rate of infections reported by elderly subjects for a year after study drug initiation" ], "n": 264, "n_quote": "264 elderly subjects given the study drugs for 6 weeks", "basis": "pubmed", "citation": "Mannick 2018, Sci Transl Med", "title": "TORC1 inhibition enhances immune function and reduces infections in the elderly." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 2, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "aging", "outcome": "Slowing ageing in people", "evidence": [], "verdict": "no-human-trials", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "19587680", "kind": "animal", "note": "Extended lifespan in mice, even when started late in life.", "citation": "Harrison 2009, Nature", "title": "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice." }, { "pmid": "27143112", "kind": "review", "note": "The rationale for testing rapamycin in companion dogs.", "citation": "Kaeberlein 2016, Mamm Genome", "title": "The dog aging project: translational geroscience in companion animals." } ], "pubmed_counts": { "rct": 1969, "meta": 466, "rct_query": "(sirolimus[tiab] OR rapamycin[tiab] OR everolimus[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(sirolimus[tiab] OR rapamycin[tiab] OR everolimus[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "aging" }, { "id": "acarbose", "name": "Acarbose", "aka": "Prescription diabetes drug", "kind": "drug", "category": "Prescription drugs", "glossary": [ "acarbose" ], "outcomes": [ { "id": "aging", "outcome": "Slowing ageing in people", "evidence": [], "verdict": "no-human-trials", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "27312235", "kind": "animal", "note": "Extended lifespan in male mice in the Interventions Testing Program.", "citation": "Strong 2016, Aging Cell", "title": "Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer." }, { "pmid": "30688027", "kind": "animal", "note": "Improved health and lifespan in ageing mice.", "citation": "Harrison 2019, Aging Cell", "title": "Acarbose improves health and lifespan in aging HET3 mice." } ], "pubmed_counts": { "rct": 284, "meta": 36, "rct_query": "acarbose[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "acarbose[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "aging" }, { "id": "glp1", "name": "GLP-1 drugs", "aka": "Semaglutide, tirzepatide, orforglipron (prescription)", "kind": "drug", "category": "Prescription drugs", "glossary": [ "glp-1-glucagon-like-peptide-1", "semaglutide", "tirzepatide", "orforglipron" ], "outcomes": [ { "id": "cv", "outcome": "Heart attacks, strokes and cardiovascular death", "evidence": [ { "pmid": "27633186", "design": "rct", "direction": "benefit", "finding": "In 3,297 people with type 2 diabetes at high cardiovascular risk, semaglutide lowered cardiovascular death, heart attack or stroke (SUSTAIN-6).", "quotes": [ "was significantly lower among patients receiving semaglutide" ], "n": 3297, "n_quote": "We randomly assigned 3297 patients", "basis": "pubmed", "citation": "Marso 2016, N Engl J Med", "title": "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes." }, { "pmid": "37952131", "design": "rct", "direction": "benefit", "finding": "In 17,604 people with cardiovascular disease and overweight or obesity but no diabetes, semaglutide reduced major cardiovascular events (SELECT).", "quotes": [ "was superior to placebo in reducing the incidence of death from cardiovascular causes" ], "n": 17604, "n_quote": "A total of 17,604 patients were enrolled", "basis": "pubmed", "citation": "Lincoff 2023, N Engl J Med", "title": "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes." } ], "verdict": "supported", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 2, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "weight", "outcome": "Body weight", "evidence": [ { "pmid": "35658024", "design": "rct", "direction": "benefit", "finding": "In 2,539 adults with obesity, weekly tirzepatide produced substantial, sustained weight loss over 72 weeks (SURMOUNT-1).", "quotes": [ "provided substantial and sustained reductions in body weight" ], "n": 2539, "n_quote": "we assigned 2539 adults", "basis": "pubmed", "citation": "Jastreboff 2022, N Engl J Med", "title": "Tirzepatide Once Weekly for the Treatment of Obesity." }, { "pmid": "40960239", "design": "rct", "direction": "benefit", "finding": "In 3,127 adults with obesity, the daily pill orforglipron reduced weight by up to 11.2%, versus 2.1% with placebo, over 72 weeks.", "quotes": [ "-11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1%" ], "n": 3127, "n_quote": "A total of 3127 patients underwent randomization", "basis": "pubmed", "citation": "Wharton 2025, N Engl J Med", "title": "Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment." } ], "verdict": "supported", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 2, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [], "pubmed_counts": { "rct": 1255, "meta": 722, "rct_query": "(\"glucagon-like peptide-1 receptor agonist\"[tiab] OR \"GLP-1 receptor agonist\"[tiab] OR semaglutide[tiab] OR liraglutide[tiab] OR tirzepatide[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"glucagon-like peptide-1 receptor agonist\"[tiab] OR \"GLP-1 receptor agonist\"[tiab] OR semaglutide[tiab] OR liraglutide[tiab] OR tirzepatide[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "cv" }, { "id": "fisetin", "name": "Fisetin", "aka": "Flavonoid studied as a senolytic", "kind": "supplement", "category": "Senolytics", "glossary": [ "senolytics" ], "outcomes": [ { "id": "senescence", "outcome": "Clearing senescent cells and health in people", "evidence": [], "verdict": "no-human-trials", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "30279143", "kind": "animal", "note": "Extended health and lifespan in mice.", "citation": "Yousefzadeh 2018, EBioMedicine", "title": "Fisetin is a senotherapeutic that extends health and lifespan." }, { "pmid": "28869295", "kind": "review", "note": "Overview of senolytic drug candidates.", "citation": "Kirkland 2017, J Am Geriatr Soc", "title": "The Clinical Potential of Senolytic Drugs." }, { "pmid": "34375437", "kind": "trial design", "note": "Describes planned fisetin trials in nursing homes; reports no results.", "citation": "Verdoorn 2021, J Am Geriatr Soc", "title": "Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era." } ], "pubmed_counts": { "rct": 7, "meta": 0, "rct_query": "fisetin[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "fisetin[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "senescence" }, { "id": "quercetin", "name": "Quercetin (with dasatinib)", "aka": "Flavonoid; tested with the drug dasatinib", "kind": "supplement", "category": "Senolytics", "glossary": [ "dasatinib-plus-quercetin-dplusq", "senolytics" ], "outcomes": [ { "id": "function", "outcome": "Physical function in lung fibrosis (with dasatinib)", "evidence": [ { "pmid": "30616998", "design": "trial", "direction": "benefit", "finding": "In a small open-label pilot in idiopathic pulmonary fibrosis, dasatinib plus quercetin was linked to better physical function.", "quotes": [ "initial evidence that senolytics may alleviate physical dysfunction in IPF", "open-label" ], "n": null, "n_quote": null, "basis": "abstract", "citation": "Justice 2019, EBioMedicine", "title": "Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 1 } }, { "id": "senescence", "outcome": "Senescent cells in people (with dasatinib)", "evidence": [ { "pmid": "31542391", "design": "trial", "direction": "benefit", "finding": "In 9 people with diabetic kidney disease, three days of dasatinib plus quercetin reduced senescent cells in fat tissue.", "quotes": [ "D + Q reduced adipose tissue senescent cell burden within 11 days", "open label Phase 1 pilot" ], "n": 9, "n_quote": "N = 9", "basis": "abstract", "citation": "Hickson 2019, EBioMedicine", "title": "Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 1 } } ], "context": [ { "pmid": "32686219", "kind": "review", "note": "Review of senolytic trials under way.", "citation": "Kirkland 2020, J Intern Med", "title": "Senolytic drugs: from discovery to translation." } ], "pubmed_counts": { "rct": 232, "meta": 81, "rct_query": "quercetin[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "quercetin[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "senescence" }, { "id": "berberine", "name": "Berberine", "aka": "Plant alkaloid", "kind": "supplement", "category": "Heart and metabolism", "glossary": [ "berberine" ], "outcomes": [ { "id": "glucose", "outcome": "Blood sugar in type 2 diabetes", "caveat": "The trials are mostly small and of low methodological quality.", "evidence": [ { "pmid": "18442638", "design": "rct", "direction": "benefit", "finding": "In a small pilot trial in type 2 diabetes, berberine lowered blood sugar and improved blood lipids.", "quotes": [ "berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Yin 2008, Metabolism", "title": "Efficacy of berberine in patients with type 2 diabetes mellitus." }, { "pmid": "23118793", "design": "meta", "direction": "benefit", "finding": "A meta-analysis found berberine lowered blood sugar and blood lipids in type 2 diabetes, but the trials were small and of low quality.", "quotes": [ "Berberine appeared to be efficacious for treating hyperglycaemia and dyslipidemia in T2DM", "low methodological quality" ], "n": null, "n_quote": null, "basis": "title", "citation": "Dong 2012, Evid Based Complement Alternat Med", "title": "Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis." }, { "pmid": "25498346", "design": "meta", "direction": "benefit", "finding": "A second meta-analysis reported effects comparable to standard treatment on blood sugar, lipids and blood pressure, with no serious side effects.", "quotes": [ "berberine has comparable therapeutic effect on type 2 DM, hyperlipidemia and hypertension with no serious side effect" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Lan 2015, J Ethnopharmacol", "title": "Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension." } ], "verdict": "supported", "tally": { "meta_benefit": 2, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "lipids", "outcome": "Cholesterol and triglycerides", "caveat": "The trials are mostly small and of low methodological quality.", "evidence": [ { "pmid": "23118793", "design": "meta", "direction": "benefit", "finding": "The same meta-analysis found improvements in blood lipids.", "quotes": [ "Berberine appeared to be efficacious for treating hyperglycaemia and dyslipidemia in T2DM" ], "n": null, "n_quote": null, "basis": "title", "citation": "Dong 2012, Evid Based Complement Alternat Med", "title": "Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis." }, { "pmid": "25498346", "design": "meta", "direction": "benefit", "finding": "The second meta-analysis found effects on high cholesterol comparable to standard treatment.", "quotes": [ "berberine has comparable therapeutic effect on type 2 DM, hyperlipidemia and hypertension" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Lan 2015, J Ethnopharmacol", "title": "Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension." } ], "verdict": "supported", "tally": { "meta_benefit": 2, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [], "pubmed_counts": { "rct": 110, "meta": 49, "rct_query": "berberine[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "berberine[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "glucose" }, { "id": "taurine", "name": "Taurine", "aka": "Amino sulfonic acid", "kind": "supplement", "category": "Longevity candidates", "glossary": [], "outcomes": [ { "id": "aging", "outcome": "Healthy ageing in people", "evidence": [], "verdict": "no-human-trials", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "37289866", "kind": "animal", "note": "Taurine supplementation increased healthspan in worms, rodents and monkeys and lifespan in worms and rodents; the authors call for human trials.", "citation": "Singh 2023, Science", "title": "Taurine deficiency as a driver of aging." }, { "pmid": "25229346", "kind": "animal", "note": "Taurine depletion accelerated muscle ageing in mice.", "citation": "Ito 2014, PLoS One", "title": "Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice." } ], "pubmed_counts": { "rct": 227, "meta": 41, "rct_query": "taurine[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "taurine[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "aging" }, { "id": "alpha_lipoic", "name": "Alpha-lipoic acid", "aka": "ALA, thioctic acid", "kind": "supplement", "category": "Heart and metabolism", "glossary": [], "outcomes": [ { "id": "neuropathy", "outcome": "Diabetic nerve pain", "evidence": [ { "pmid": "17065669", "design": "rct", "direction": "benefit", "finding": "In people with diabetic nerve damage, five weeks of oral ALA improved symptoms; 600 mg a day gave the best balance of benefit and side effects.", "quotes": [ "Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP", "600 mg once daily appears to provide the optimum risk-to-benefit ratio" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Ziegler 2006, Diabetes Care", "title": "Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "glucose", "outcome": "Blood sugar in type 2 diabetes", "evidence": [ { "pmid": "21666939", "design": "rct", "direction": "benefit", "finding": "In 57 people with type 2 diabetes, eight weeks of ALA lowered fasting and after-meal blood sugar.", "quotes": [ "showed a significant decrease in FBG and PPG levels", "followed-up for 8 weeks" ], "n": 57, "n_quote": "(n=57)", "basis": "pubmed", "citation": "Ansar 2011, Saudi Med J", "title": "Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "22001972", "kind": "review", "note": "Review of lipoic acid biology and proposed uses.", "citation": "Gorąca 2011, Pharmacol Rep", "title": "Lipoic acid - biological activity and therapeutic potential." } ], "pubmed_counts": { "rct": 287, "meta": 58, "rct_query": "(\"alpha-lipoic acid\"[tiab] OR \"lipoic acid\"[tiab] OR \"thioctic acid\"[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"alpha-lipoic acid\"[tiab] OR \"lipoic acid\"[tiab] OR \"thioctic acid\"[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "neuropathy" }, { "id": "omega3", "name": "Omega-3 (fish oil)", "aka": "EPA and DHA", "kind": "supplement", "category": "Heart and metabolism", "glossary": [ "omega-3-index", "epa-eicosapentaenoic-acid", "icosapent-ethyl" ], "outcomes": [ { "id": "cv", "outcome": "Heart attacks and cardiovascular events (fish-oil supplements)", "evidence": [ { "pmid": "30146932", "design": "rct", "direction": "null", "finding": "In 15,480 people with diabetes but no cardiovascular disease, 1 g of fish oil a day did not reduce serious vascular events (ASCEND).", "quotes": [ "there was no significant difference in the risk of serious vascular events" ], "n": 15480, "n_quote": "We randomly assigned 15,480 patients with diabetes", "basis": "pubmed", "citation": "Bowman 2018, N Engl J Med", "title": "Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus." }, { "pmid": "30415637", "design": "rct", "direction": "null", "finding": "In 25,871 generally healthy adults, fish oil did not reduce major cardiovascular events or cancer (VITAL).", "quotes": [ "did not result in a lower incidence of major cardiovascular events or cancer than placebo" ], "n": 25871, "n_quote": "A total of 25,871 participants", "basis": "pubmed", "citation": "Manson 2019, N Engl J Med", "title": "Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer." }, { "pmid": "31567003", "design": "meta", "direction": "benefit", "finding": "A meta-analysis of 13 trials with 127,477 people found small reductions in heart attacks (rate ratio 0.92) and cardiovascular death (0.93).", "quotes": [ "Marine omega-3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD", "0.92 [0.86, 0.99]", "127 477 Participants" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Hu 2019, J Am Heart Assoc", "title": "Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants." } ], "verdict": "mixed", "tally": { "meta_benefit": 1, "meta_null": 0, "rct_benefit": 0, "rct_null": 2, "rct_harm": 0, "pilot": 0 } }, { "id": "epa", "outcome": "Cardiovascular events with prescription EPA (high-risk patients)", "evidence": [ { "pmid": "30415628", "design": "rct", "direction": "benefit", "finding": "In 8,179 statin-treated patients with raised triglycerides, prescription EPA (icosapent ethyl, 4 g a day) reduced ischaemic events, including cardiovascular death (REDUCE-IT).", "quotes": [ "the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily" ], "n": 8179, "n_quote": "A total of 8179 patients were enrolled", "basis": "pubmed", "citation": "Bhatt 2019, N Engl J Med", "title": "Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia." } ], "verdict": "supported", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [], "pubmed_counts": { "rct": 3417, "meta": 864, "rct_query": "(\"omega-3\"[tiab] OR \"n-3 fatty acid\"[tiab] OR \"fish oil\"[tiab] OR \"n-3 fatty acids\"[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"omega-3\"[tiab] OR \"n-3 fatty acid\"[tiab] OR \"fish oil\"[tiab] OR \"n-3 fatty acids\"[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "cv" }, { "id": "coq10", "name": "Coenzyme Q10", "aka": "CoQ10, ubiquinone, ubiquinol", "kind": "supplement", "category": "Heart and metabolism", "glossary": [], "outcomes": [ { "id": "bp", "outcome": "Blood pressure", "evidence": [ { "pmid": "17287847", "design": "meta", "direction": "benefit", "finding": "A 2007 meta-analysis of older trials reported blood-pressure reductions in people with hypertension.", "quotes": [ "coenzyme Q10 has the potential in hypertensive patients to lower" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Rosenfeldt 2007, J Hum Hypertens", "title": "Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials." }, { "pmid": "26935713", "design": "meta", "direction": "null", "finding": "A 2016 Cochrane review, pooling the two trials at acceptable risk of bias, found no clinically significant effect on blood pressure.", "quotes": [ "coenzyme Q10 does not have a clinically significant effect on blood pressure", "moderate-quality evidence" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Ho 2016, Cochrane Database Syst Rev", "title": "Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension." } ], "verdict": "mixed", "tally": { "meta_benefit": 1, "meta_null": 1, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "hf", "outcome": "Heart failure outcomes", "evidence": [ { "pmid": "25282031", "design": "rct", "direction": "benefit", "finding": "In 420 people with chronic heart failure, CoQ10 reduced major adverse cardiovascular events (Q-SYMBIO).", "quotes": [ "Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events" ], "n": 420, "n_quote": "A total of 420 patients were enrolled", "basis": "pubmed", "citation": "Mortensen 2014, JACC Heart Fail", "title": "The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "statin", "outcome": "Muscle symptoms on statins", "evidence": [ { "pmid": "25440725", "design": "meta", "direction": "null", "finding": "A 2015 meta-analysis found no significant benefit for statin-related muscle problems.", "quotes": [ "do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced myopathy" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Banach 2015, Mayo Clin Proc", "title": "Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials." }, { "pmid": "30371340", "design": "meta", "direction": "benefit", "finding": "A 2018 meta-analysis of 12 trials (575 patients) found less muscle pain, weakness, cramps and tiredness.", "quotes": [ "CoQ10 supplementation ameliorated statin-associated muscle symptoms", "Twelve randomized controlled trials with a total of 575 patients" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Qu 2018, J Am Heart Assoc", "title": "Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials." } ], "verdict": "mixed", "tally": { "meta_benefit": 1, "meta_null": 1, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [], "pubmed_counts": { "rct": 426, "meta": 116, "rct_query": "(\"coenzyme Q10\"[tiab] OR ubiquinone[tiab] OR ubiquinol[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"coenzyme Q10\"[tiab] OR ubiquinone[tiab] OR ubiquinol[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "statin" }, { "id": "magnesium", "name": "Magnesium", "aka": "Essential mineral", "kind": "supplement", "category": "Vitamins and minerals", "glossary": [], "outcomes": [ { "id": "bp", "outcome": "Blood pressure", "evidence": [ { "pmid": "27402922", "design": "meta", "direction": "benefit", "finding": "A meta-analysis of 34 trials (2,028 people) found magnesium lowered blood pressure slightly, by about 2 mm Hg.", "quotes": [ "34 trials involving 2028 participants", "significantly reduced systolic BP by 2.00 mm Hg", "diastolic BP by 1.78 mm Hg" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Zhang 2016, Hypertension", "title": "Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials." } ], "verdict": "supported", "tally": { "meta_benefit": 1, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "27927203", "kind": "observational", "note": "Meta-analysis of cohort studies: higher dietary magnesium was linked to lower risk of stroke, heart failure and diabetes (an association, not trial evidence).", "citation": "Fang 2016, BMC Med", "title": "Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies." }, { "pmid": "22364157", "kind": "review", "note": "Review of magnesium status in the United States.", "citation": "Rosanoff 2012, Nutr Rev", "title": "Suboptimal magnesium status in the United States: are the health consequences underestimated?" } ], "pubmed_counts": { "rct": 359, "meta": 75, "rct_query": "(magnesium[ti] AND supplement*[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(magnesium[ti] AND supplement*[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "bp" }, { "id": "lion_mane", "name": "Lion's mane", "aka": "Hericium erinaceus mushroom", "kind": "supplement", "category": "Brain", "glossary": [], "outcomes": [ { "id": "cognition", "outcome": "Memory and thinking", "evidence": [ { "pmid": "18844328", "design": "rct", "direction": "benefit", "finding": "In a small trial in older adults with mild cognitive impairment, lion's mane improved cognitive scores.", "quotes": [ "Yamabushitake is effective in improving mild cognitive impairment" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Mori 2009, Phytother Res", "title": "Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial." }, { "pmid": "31413233", "design": "rct", "direction": "benefit", "finding": "A small trial reported improved cognitive function with lion's mane.", "quotes": [ "Improvement of cognitive functions by oral intake of Hericium erinaceus" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Saitsu 2019, Biomed Res", "title": "Improvement of cognitive functions by oral intake of Hericium erinaceus." }, { "pmid": "32581767", "design": "rct", "direction": "benefit", "finding": "In people with mild Alzheimer's disease, an erinacine A-enriched extract was linked to higher cognitive and daily-function scores than placebo over 49 weeks.", "quotes": [ "demonstrated higher CASI, MMSE, and IADL scores", "for 49 weeks" ], "n": null, "n_quote": null, "basis": "abstract", "citation": "Li 2020, Front Aging Neurosci", "title": "Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 3, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [], "pubmed_counts": { "rct": 5, "meta": 0, "rct_query": "(\"Hericium erinaceus\"[tiab] OR \"lion's mane\"[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"Hericium erinaceus\"[tiab] OR \"lion's mane\"[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "cognition" }, { "id": "creatine", "name": "Creatine", "aka": "Creatine monohydrate", "kind": "supplement", "category": "Muscle and mitochondria", "glossary": [], "outcomes": [ { "id": "strength", "outcome": "Muscle strength and lean mass, with strength training (older adults)", "evidence": [ { "pmid": "29138605", "design": "meta", "direction": "benefit", "finding": "In older adults doing resistance training, creatine added about 1.37 kg of lean mass and improved upper- and lower-body strength.", "quotes": [ "creatine supplementation increases lean tissue mass and upper and lower body muscular strength during resistance training of older adults", "mean difference =1.37 kg" ], "n": null, "n_quote": null, "basis": "title", "citation": "Chilibeck 2017, Open Access J Sports Med", "title": "Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis." } ], "verdict": "supported", "tally": { "meta_benefit": 1, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } }, { "id": "memory", "outcome": "Memory", "caveat": "The benefit was concentrated in older adults (66 to 76), and results varied between trials.", "evidence": [ { "pmid": "35984306", "design": "meta", "direction": "benefit", "finding": "A 2023 meta-analysis found creatine improved memory, mainly in adults aged 66 to 76.", "quotes": [ "Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults", "[SMD] = 0.29" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Prokopidis 2023, Nutr Rev", "title": "Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials." } ], "verdict": "supported", "tally": { "meta_benefit": 1, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "28615996", "kind": "review", "note": "International Society of Sports Nutrition position stand on creatine safety and efficacy.", "citation": "Kreider 2017, J Int Soc Sports Nutr", "title": "International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine." }, { "pmid": "27108136", "kind": "review", "note": "Review of creatine in ageing.", "citation": "Gualano 2016, Amino Acids", "title": "Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain." }, { "pmid": "33800439", "kind": "review", "note": "Review of creatine in women's health.", "citation": "Smith-Ryan 2021, Nutrients", "title": "Creatine Supplementation in Women's Health: A Lifespan Perspective." } ], "pubmed_counts": { "rct": 408, "meta": 42, "rct_query": "(creatine[ti] AND supplement*[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(creatine[ti] AND supplement*[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "strength" }, { "id": "bacopa", "name": "Bacopa", "aka": "Bacopa monnieri", "kind": "supplement", "category": "Brain", "glossary": [], "outcomes": [ { "id": "memory", "outcome": "Memory and attention", "caveat": "Effects are small, and the meta-analysis calls for a large head-to-head trial.", "evidence": [ { "pmid": "18611150", "design": "rct", "direction": "benefit", "finding": "A trial in older adults found bacopa improved cognitive performance.", "quotes": [ "B. monnieri has potential for safely enhancing cognitive performance in the aging" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Calabrese 2008, J Altern Complement Med", "title": "Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial." }, { "pmid": "20590480", "design": "rct", "direction": "benefit", "finding": "In healthy older Australians, bacopa improved memory, with digestive side effects such as cramps and nausea.", "quotes": [ "Bacopa significantly improved memory acquisition and retention in healthy older Australians", "Bacopa caused GIT side-effects" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Morgan 2010, J Altern Complement Med", "title": "Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial." }, { "pmid": "24252493", "design": "meta", "direction": "benefit", "finding": "A meta-analysis found bacopa may improve cognition, especially speed of attention, but called for larger trials.", "quotes": [ "has the potential to improve cognition, particularly speed of attention", "only a large well designed 'head-to-head' trial" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Kongkeaw 2014, J Ethnopharmacol", "title": "Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract." } ], "verdict": "supported", "tally": { "meta_benefit": 1, "meta_null": 0, "rct_benefit": 2, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [], "pubmed_counts": { "rct": 27, "meta": 2, "rct_query": "(\"Bacopa monnieri\"[tiab] OR bacopa[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"Bacopa monnieri\"[tiab] OR bacopa[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "memory" }, { "id": "vitd3", "name": "Vitamin D3", "aka": "Cholecalciferol", "kind": "supplement", "category": "Vitamins and minerals", "glossary": [], "outcomes": [ { "id": "prevention", "outcome": "Preventing cancer and heart disease (generally healthy adults)", "evidence": [ { "pmid": "30415629", "design": "rct", "direction": "null", "finding": "In 25,871 generally healthy adults, vitamin D did not lower cancer or cardiovascular events (VITAL).", "quotes": [ "did not result in a lower incidence of invasive cancer or cardiovascular events than placebo" ], "n": 25871, "n_quote": "A total of 25,871 participants", "basis": "pubmed", "citation": "Manson 2019, N Engl J Med", "title": "Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease." }, { "pmid": "30027269", "design": "rct", "direction": "null", "finding": "In 5,110 adults, monthly high-dose vitamin D for up to four years did not prevent cancer (ViDA, post hoc analysis).", "quotes": [ "may not prevent cancer" ], "n": 5110, "n_quote": "5110 participants were randomized", "basis": "pubmed", "citation": "Scragg 2018, JAMA Oncol", "title": "Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial." } ], "verdict": "not-supported", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 2, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "38828931", "kind": "guideline", "note": "2024 Endocrine Society guideline: suggests vitamin D for specific groups (ages 1-18, over 75, pregnancy, high-risk prediabetes), not routine testing.", "citation": "Demay 2024, J Clin Endocrinol Metab", "title": "Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline." } ], "pubmed_counts": { "rct": 1892, "meta": 726, "rct_query": "(\"vitamin D\"[ti] AND supplement*[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"vitamin D\"[ti] AND supplement*[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "prevention" }, { "id": "resveratrol", "name": "Resveratrol", "aka": "Polyphenol in grapes and red wine", "kind": "supplement", "category": "Longevity candidates", "glossary": [ "resveratrol" ], "outcomes": [ { "id": "exercise", "outcome": "Exercise benefits (older men)", "evidence": [ { "pmid": "23878368", "design": "rct", "direction": "harm", "finding": "In older men doing exercise training, resveratrol blunted the cardiovascular benefits of exercise.", "quotes": [ "Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Gliemann 2013, J Physiol", "title": "Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men." } ], "verdict": "harm-signal", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 1, "pilot": 0 } } ], "context": [ { "pmid": "15684413", "kind": "biochemical", "note": "Found that resveratrol's apparent activation of sirtuins depended on the test substrate, with no effect on Sir2 activity in yeast.", "citation": "Kaeberlein 2005, J Biol Chem", "title": "Substrate-specific activation of sirtuins by resveratrol." }, { "pmid": "17086191", "kind": "animal", "note": "Improved health and survival of mice on a high-calorie diet.", "citation": "Baur 2006, Nature", "title": "Resveratrol improves health and survival of mice on a high-calorie diet." } ], "pubmed_counts": { "rct": 263, "meta": 115, "rct_query": "resveratrol[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "resveratrol[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "exercise" }, { "id": "spermidine", "name": "Spermidine", "aka": "Polyamine found in food", "kind": "supplement", "category": "Longevity candidates", "glossary": [ "spermidine" ], "outcomes": [ { "id": "memory", "outcome": "Memory in older adults", "evidence": [ { "pmid": "35616942", "design": "rct", "direction": "null", "finding": "In 100 older adults with subjective memory decline, longer-term spermidine did not improve memory or biomarkers (SmartAge).", "quotes": [ "did not modify memory and biomarkers compared with placebo" ], "n": 100, "n_quote": "A total of 100 participants", "basis": "pubmed", "citation": "Schwarz 2022, JAMA Netw Open", "title": "Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial." } ], "verdict": "not-supported", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 1, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "27841876", "kind": "animal", "note": "Extended lifespan and protected the heart in mice; in people, higher dietary spermidine was linked to lower blood pressure and heart disease (an association).", "citation": "Eisenberg 2016, Nat Med", "title": "Cardioprotection and lifespan extension by the natural polyamine spermidine." }, { "pmid": "30306826", "kind": "review", "note": "Review of spermidine as an autophagy inducer.", "citation": "Madeo 2019, Autophagy", "title": "Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?" } ], "pubmed_counts": { "rct": 41, "meta": 2, "rct_query": "spermidine[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "spermidine[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "memory" }, { "id": "ashwagandha", "name": "Ashwagandha", "aka": "Withania somnifera", "kind": "supplement", "category": "Brain", "glossary": [], "outcomes": [ { "id": "stress", "outcome": "Stress and anxiety", "caveat": "Rare but serious liver injury has been reported.", "evidence": [ { "pmid": "23439798", "design": "rct", "direction": "benefit", "finding": "In 64 adults with chronic stress, a root extract improved stress resistance and self-rated quality of life.", "quotes": [ "safely and effectively improves an individual" ], "n": 64, "n_quote": "A total of 64 subjects with a history of chronic stress", "basis": "abstract", "citation": "Chandrasekhar 2012, Indian J Psychol Med", "title": "A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults." }, { "pmid": "32021735", "design": "rct", "direction": "benefit", "finding": "In a small trial in healthy adults, an aqueous root extract reduced stress and anxiety and improved sleep quality.", "quotes": [ "Ashwagandha root aqueous extract was beneficial in reducing stress and anxiety", "significant improvement in sleep quality" ], "n": null, "n_quote": null, "basis": "abstract", "citation": "Salve 2019, Cureus", "title": "Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 2, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "37756041", "kind": "case series", "note": "Liver-injury case series: ashwagandha can cause cholestatic hepatitis, which can be dangerous in people with existing liver disease.", "citation": "Philips 2023, Hepatol Commun", "title": "Ashwagandha-induced liver injury-A case series from India and literature review." } ], "pubmed_counts": { "rct": 59, "meta": 17, "rct_query": "(ashwagandha[tiab] OR \"Withania somnifera\"[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(ashwagandha[tiab] OR \"Withania somnifera\"[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "stress" }, { "id": "zinc", "name": "Zinc", "aka": "Essential mineral", "kind": "supplement", "category": "Vitamins and minerals", "glossary": [], "outcomes": [ { "id": "infection", "outcome": "Infections in older adults", "evidence": [ { "pmid": "17344507", "design": "rct", "direction": "benefit", "finding": "In a small trial in older adults, zinc lowered the rate of infections.", "quotes": [ "the incidence of infections was significantly lower" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Prasad 2007, Am J Clin Nutr", "title": "Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 1, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "18054190", "kind": "review", "note": "Review of zinc in immunity and inflammation.", "citation": "Prasad 2008, Exp Gerontol", "title": "Clinical, immunological, anti-inflammatory and antioxidant roles of zinc." }, { "pmid": "23493534", "kind": "review", "note": "Review of human zinc deficiency.", "citation": "Prasad 2013, Adv Nutr", "title": "Discovery of human zinc deficiency: its impact on human health and disease." } ], "pubmed_counts": { "rct": 724, "meta": 147, "rct_query": "(zinc[ti] AND supplement*[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(zinc[ti] AND supplement*[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "infection" }, { "id": "egcg", "name": "Green tea extract (EGCG)", "aka": "Epigallocatechin gallate", "kind": "supplement", "category": "Heart and metabolism", "glossary": [], "outcomes": [ { "id": "chol", "outcome": "Cholesterol", "caveat": "Very few long-term trials exist.", "evidence": [ { "pmid": "21715508", "design": "meta", "direction": "benefit", "finding": "A meta-analysis found green tea drinks or extracts modestly lowered total and LDL cholesterol, with no effect on HDL.", "quotes": [ "resulted in significant reductions in serum TC and LDL-cholesterol concentrations", "no effect on HDL cholesterol was observed" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Zheng 2011, Am J Clin Nutr", "title": "Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials." }, { "pmid": "23780706", "design": "meta", "direction": "benefit", "finding": "A Cochrane review found favourable effects on cardiovascular risk factors but very few long-term trials.", "quotes": [ "tea has favourable effects on CVD risk factors", "There are very few long-term studies" ], "n": null, "n_quote": null, "basis": "pubmed", "citation": "Hartley 2013, Cochrane Database Syst Rev", "title": "Green and black tea for the primary prevention of cardiovascular disease." } ], "verdict": "supported", "tally": { "meta_benefit": 2, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 0 } } ], "context": [ { "pmid": "16968850", "kind": "observational", "note": "Japanese cohort: green tea drinking was linked to lower all-cause and cardiovascular death (an association).", "citation": "Kuriyama 2006, JAMA", "title": "Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study." }, { "pmid": "29580974", "kind": "safety review", "note": "Derived a safe intake of 338 mg EGCG a day for tea preparations taken as a solid bolus dose.", "citation": "Hu 2018, Regul Toxicol Pharmacol", "title": "The safety of green tea and green tea extract consumption in adults - Results of a systematic review." } ], "pubmed_counts": { "rct": 543, "meta": 171, "rct_query": "(\"green tea\"[tiab] OR \"epigallocatechin gallate\"[tiab] OR EGCG[tiab]) AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "(\"green tea\"[tiab] OR \"epigallocatechin gallate\"[tiab] OR EGCG[tiab]) AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "chol" }, { "id": "urolithin_a", "name": "Urolithin A", "aka": "Gut-microbe metabolite of ellagitannins", "kind": "supplement", "category": "Muscle and mitochondria", "glossary": [ "urolithin-a" ], "outcomes": [ { "id": "muscle", "outcome": "Muscle endurance", "evidence": [ { "pmid": "35050355", "design": "rct", "direction": "null", "finding": "In 66 older adults, urolithin A was safe, but its primary endpoints (walking distance and hand-muscle energy production) did not significantly improve.", "quotes": [ "the improvements in the 6-minute walk distance and maximal ATP production in the hand muscle were not" ], "n": 66, "n_quote": "A total of 66 participants were randomized", "basis": "pubmed", "citation": "Liu 2022, JAMA Netw Open", "title": "Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial." } ], "verdict": "not-supported", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 1, "rct_harm": 0, "pilot": 0 } }, { "id": "mito", "outcome": "Markers of mitochondrial health", "evidence": [ { "pmid": "32694802", "design": "trial", "direction": "benefit", "finding": "In a first-in-human trial in older adults, urolithin A was safe and changed blood and muscle markers of mitochondrial health over four weeks.", "quotes": [ "modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression", "first-in-human clinical trial" ], "n": null, "n_quote": null, "basis": "abstract", "citation": "Andreux 2019, Nat Metab", "title": "The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans." } ], "verdict": "early", "tally": { "meta_benefit": 0, "meta_null": 0, "rct_benefit": 0, "rct_null": 0, "rct_harm": 0, "pilot": 1 } } ], "context": [ { "pmid": "27400265", "kind": "animal", "note": "Induced mitophagy and extended lifespan in worms; improved exercise capacity in rodents.", "citation": "Ryu 2016, Nat Med", "title": "Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents." } ], "pubmed_counts": { "rct": 25, "meta": 0, "rct_query": "\"urolithin A\"[tiab] AND randomized controlled trial[pt] AND humans[mh]", "meta_query": "\"urolithin A\"[tiab] AND meta-analysis[pt]", "counted": "2026-10-02", "note": "All uses, not only ageing; volume is not quality." }, "headline": "muscle" } ] }