Resveratrol
Resveratrol (trans-3,5,4'-trihydroxystilbene)
Also known as: trans-Resveratrol, 3,5,4'-trihydroxystilbene, SRT501 (the discontinued GSK formulation)
The polyphenol behind the sirtuin era of longevity research and one of the most heavily trialled supplements in this database: over 150 completed registered studies, results that conflict by population and dose rather than pointing one way, and no trial of lifespan or any hard clinical outcome in people.
Overview
Resveratrol became the best known longevity molecule in the world after a 2003 Nature paper from David Sinclair's laboratory reported that it activates the sirtuin SIRT1 and extends lifespan in yeast, followed by a 2006 Nature paper reporting improved health and survival in mice fed a high-calorie diet. Neither finding transferred cleanly. The same collaboration reported in 2008 that resveratrol did not extend life in mice on a normal diet, and the NIA Interventions Testing Program found no lifespan effect in genetically heterogeneous mice at three independent sites. In people the picture is split rather than blank. A 2014 meta-analysis of 11 randomised trials found significant reductions in fasting glucose, insulin, HbA1c and HOMA-IR in participants with diabetes and no effect at all in participants without it, and a 2026 umbrella review of 45 systematic reviews rated four findings as high certainty: waist circumference down 0.80 cm, total cholesterol down 0.19 mmol/L in overweight adults, and in type 2 diabetes diastolic blood pressure down 3.55 mmHg and systolic down 7.97 mmHg. Trials in obese men, in postmenopausal women and in fatty liver disease disagree with one another. The most likely reason the cell data outruns the human data is delivery: oral resveratrol is absorbed well but conjugated so fast that free parent compound in plasma stays below the concentrations used in vitro.
Mechanism of action
Proposed as an allosteric activator of the NAD+-dependent deacetylase SIRT1, with downstream AMPK and PGC-1alpha signalling that mimics parts of calorie restriction. That direct-activation claim is disputed: groups at Amgen (2009) and Pfizer (2010) showed the measured activation depends on a fluorophore-tagged assay peptide and disappears with native substrates, while Sirtris and Sinclair's group argue in Science (2013) that activation is real but requires substrates carrying specific hydrophobic motifs and a single SIRT1 residue, Glu230. Independently of sirtuins, resveratrol has documented antioxidant activity, endothelial nitric oxide and flow-mediated dilation effects, and inhibition of CYP3A4, CYP2D6 and CYP2C9 at gram doses.
Human evidence
Resveratrol carries one of the largest human clinical-trial records of any compound in this database, with dozens of randomized trials running six months or longer across cognition, bone, metabolic, cardiovascular and joint endpoints. The record does not point one way: real positive results, real null results and at least one real harm signal all sit inside it, and dose and population separate them more than anything else does.
- RESHAW, 24 months, n=125 to 129 postmenopausal women aged 45 to 85, 75 mg trans-resveratrol twice daily, randomized double-blind placebo-controlled crossover: overall cognitive performance improved 33 percent, Cohen's d 0.170, P=0.005 (PMID 32900519, Clinical Nutrition 2021); partly funded by Evolva, the manufacturer of the Veri-te resveratrol tested, alongside NHMRC and Australian Research Council funding.
- Same RESHAW programme: lumbar spine bone density +0.016 plus or minus 0.003 g/cm2, femoral neck +0.005 plus or minus 0.002, CTX-1 bone resorption marker down 7.24 percent (PMID 32564438, Journal of Bone and Mineral Research 2020); pain and menopausal symptoms also improved (PMID 32881835, Menopause 2020), with a positive 12-month interim report (PMID 32244933, Nutrients 2020) and a published protocol (PMID 27005658).
- Witte 2014, 26 weeks, n=46, 200 mg/day, improved word retention, P=0.038 (PMID 24899709, Journal of Neuroscience). The same laboratory's larger replication, Huhn 2018, n=60, was null on its primary endpoint (PMID 29548848, NeuroImage); report both together, not just the first.
- Garcia-Martinez 2023, 6 months, n=97 elderly with type 2 diabetes: positive on antioxidant capacity and SIRT1 expression, but only at the 1,000 mg dose (PMID 37108584).
- Bo 2018 found improved bone mineral density inside the same 192-patient trial that was null on its own primary CRP endpoint (PMID 30237505, Nutrition and Diabetes).
- Tome-Carneiro's grape-extract programme, 1 year, n=75 with stable coronary artery disease: hsCRP down 26 percent, TNF-alpha down 19.8 percent, PAI-1 down 16.8 percent, from just 8 mg of resveratrol delivered in grape extract, with a resveratrol-free grape-extract comparator arm as a genuine design strength (PMID 22520621, American Journal of Cardiology 2012).
- Bo 2016, 6 months, n=192 with type 2 diabetes: null on the primary CRP endpoint, and total cholesterol and triglycerides slightly increased on 500 mg (PMID 27520400).
- de Ligt 2020, 6 months: null on the primary insulin-sensitivity endpoint (PMID 32492138, American Journal of Clinical Nutrition).
- Heeboll 2016, 6 months, NAFLD: null on ALT, no histological improvement, and one serious adverse event of fever with bicytopenia (PMID 26784973).
- Poulsen 2018, 6 months, NAFLD: null (PMID 29885082).
- McDermott 2017 (RESTORE), 6 months, peripheral artery disease: null on the 6-minute walk distance (PMID 28403379, JAMA Cardiology).
- Nguyen 2024 (ARTHROL), 6 months, Phase 3 knee osteoarthritis, n=142: null, pain difference -0.6, 95 percent CI -8.0 to 6.9, P=0.88 (PMID 39137167, PLOS Medicine).
- Muscari 2026 (PBAR): the 700 mg/day arm was halted at month 5 of a planned 24 for a significant rise in LDL cholesterol; the authors concluded high-dose resveratrol should be avoided (PMID 40922000, GeroScience). The clearest harm signal in this whole record.
- Turner 2015, 52 weeks, n=119 mild to moderate Alzheimer disease, doses escalating to 1 g twice daily: safe and blood-brain-barrier penetrant, but brain volume loss was increased versus placebo (PMID 26362286, Neurology).
- Gliemann 2013, 8 weeks, n=27 older men, 250 mg alongside high-intensity training: resveratrol blunted the cardiovascular benefit of exercise, with a 45 percent greater VO2max gain in the placebo group (PMID 23878368, Journal of Physiology).
- Multiple meta-analyses report raised LDL, total cholesterol, ALT, GGT and ALP in specific populations, clustering above roughly 1,000 mg/day. Read against the rest of this list, positive results cluster at 150 to 200 mg/day and harm signals cluster above 700 mg/day; that dose split is more practically useful than any single trial here.
- The Cochrane review found only 3 eligible RCTs totalling 50 participants and could not evaluate efficacy either way (PMID 31978258). A meta-analysis restricted to postmenopausal women found cognition null at the pooled level (PMID 40771919), which does not reproduce RESHAW's own primary finding once other trials are pooled alongside it.
What this does not tell you: No trial has measured lifespan, mortality or any hard clinical endpoint in people; every result above is a biomarker or surrogate endpoint (a cognition score, bone density, CRP, blood pressure, LDL), not a disease or survival outcome. Most of these trials are the longest resveratrol has, and most are still six months or shorter with surrogate endpoints rather than years-long outcome trials. The single largest and longest positive trial, RESHAW, was partly funded by Evolva, the manufacturer of the Veri-te resveratrol brand it tested, alongside independent NHMRC and Australian Research Council funding; that does not make its result wrong, but it is a real conflict of interest worth weighing against null trials that carried no manufacturer funding.
Reading the research record
Several structural facts explain why resveratrol's published record looks split rather than clearly positive or clearly empty. Bioavailability is the biggest one: oral resveratrol is absorbed well but almost entirely converted to sulfate and glucuronide conjugates on first pass through the gut wall and liver, so free plasma levels stay far below the concentrations used in cell experiments; Sirtris's own micronised SRT501 formulation reached 3.6 times the plasma concentration of plain resveratrol at an equivalent dose (PMID 21680702, Cancer Prevention Research 2011), which is the most plausible honest explanation for why cell and animal results have never translated cleanly into human ones. Dose response compounds the problem, and it is non-monotonic rather than linear: across the trial record, positive results cluster at 150 to 200 mg per day and harm signals cluster above 700 mg per day, so more is not simply better. The commercial history runs through Sirtris Pharmaceuticals, which David Sinclair co-founded on the strength of his 2003 SIRT1-activation findings. GSK acquired Sirtris in April 2008 for approximately 720 million dollars at 22.50 dollars per share, and Sirtris's lead compound SRT501 was tested in a multiple myeloma trial, NCT00920556, that was terminated after 24 patients when GSK suspended it around April to May 2010 following five cases of acute renal failure at 5 g per day, then halted SRT501 development entirely on 30 November 2010, citing minimal efficacy compounded by the renal risk. The Sirtris unit closed in March 2013, and a 2013 review noted the full SRT501 safety data were never released to the scientific community (PMID 24073437, Aging), a real instance of publication bias, and notably one that would have hidden a negative safety finding rather than a positive efficacy one. The underlying SIRT1 mechanism remains a live, unresolved dispute rather than a settled question: Sinclair's 2003 Nature paper reported that resveratrol activates SIRT1, groups at Pfizer and Amgen argued the activation was an artifact of the fluorophore-tagged substrate used in the original assay, and Sinclair's group answered in a 2013 Science paper (Hubbard et al., PMID 23471411) arguing for a genuine allosteric mechanism requiring specific hydrophobic substrates. Both sides carried financial interests: the challengers worked at companies with competing metabolic-disease programmes, and Sinclair held equity in the company GSK paid 720 million dollars for. This entry does not pick a winner between them. Media coverage has been asymmetric in a documented, not merely felt, way: Semba 2014 (PMID 24819981, JAMA Internal Medicine) was an observational study measuring urinary resveratrol metabolites from diet and wine in 783 older Italians in the InCHIANTI cohort, tested no supplement, found no mortality association, and was still covered by NPR, Voice of America and the NIH Director's blog under headlines that generalised an observational diet finding to supplementation in a way its design could not support. JAMA Internal Medicine itself published a rebuttal the following year, titled 'Do not throw out the resveratrol with the bath water' (PMID 25560944), while RESHAW, a positive 24-month randomised trial, received almost no general-audience coverage by comparison. The research-integrity record needs stating plainly too: eighty-nine resveratrol papers have been retracted, and every one of them is preclinical, cell or animal work, not a human trial. The largest episode involved Dipak Das at the University of Connecticut, whom a university investigation found on 11 January 2012 to have committed 145 counts of data fabrication or falsification, leading to roughly 20 retractions (PMID 22250221, BMJ), a finding that concerns one laboratory's cell and animal research and has no bearing on the independent randomised human trials run by other groups summarised above. Underneath all of it sits a simple economic fact: resveratrol is a cheap, unpatentable polyphenol found naturally in grapes and red wine, a structure that attracts a large low-cost supplement market but very little of the capital needed to fund the large, long, hard-endpoint trial that would settle the question definitively. A thin or conflicting trial record is, in resveratrol's case, at least partly an economic fact about who can profit from running the trial, not only a verdict on the molecule.
Key studies & citations
- Review2026
Effects of resveratrol supplementation on multiple health outcomes: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials
Forty-five systematic reviews, 129 associations, 68 outcomes. Thirty-five associations were significant; four reached high-certainty GRADE evidence: waist circumference -0.80 cm, total cholesterol -0.19 mmol/L in overweight adults, and in type 2 diabetes diastolic blood pressure -3.55 mmHg and systolic -7.97 mmHg. Moderate certainty for glucose metabolism, endothelial health, working memory, hepatic steatosis and inflammation. This is the most complete pooled picture available and it is neither a null result nor a lifespan result.
Nutrition Journal - Review2014
Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials
388 subjects. Significant reductions in fasting glucose, insulin, HbA1c and HOMA-IR in participants with diabetes, and no significant effect on any glycaemic measure in participants without diabetes. Subgroup and sensitivity analyses found the null in non-diabetics was not explained by BMI, dose, duration, study design or quality score. The population, not the compound, is what separates the positive trials from the negative ones.
American Journal of Clinical Nutrition - Review2021
The effects of resveratrol supplementation in patients with type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease: an umbrella review of meta-analyses of randomized controlled trials
The counterweight. Across 1,476 people with type 2 diabetes, 727 with metabolic syndrome and 271 with fatty liver disease, effects existed but for almost every outcome the magnitude was trivial, the GRADE certainty very low to low, or the trial count too small. The exception was short-term HbA1c under 12 weeks: -1.05% (95% CI -2.09 to -0.02, six meta-analyses, GRADE moderate), which the authors call clinically important.
American Journal of Clinical Nutrition - Human2011
Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients
Nineteen patients, double-blind, 2 x 5 mg per day for four weeks. HOMA-IR and urinary ortho-tyrosine fell and the platelet pAkt:Akt ratio rose; beta-cell function (HOMA-B) did not change. Notable because the dose is a hundredth of what most positive trials use, which cuts against a simple dose-response story.
British Journal of Nutrition - Human2012
Pilot study of resveratrol in older adults with impaired glucose tolerance
Ten adults aged 72 on average, open-label, 1 to 2 g per day for four weeks. Peak post-meal glucose fell from 185 to 166 mg/dL (p = .003), three-hour glucose AUC from 469 to 428 (p = .001) and the Matsuda index rose from 3.1 to 3.8 (p = .03). Fasting glucose, weight, blood pressure and lipids were unchanged. Ten people, no placebo arm, so it is hypothesis-generating.
Journals of Gerontology Series A - Human2011
Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans
Eleven healthy obese men, randomised double-blind crossover, 150 mg per day for 30 days. Sleeping and resting metabolic rate fell; muscle AMPK was activated with higher SIRT1 and PGC-1alpha protein and improved mitochondrial respiration on a fatty-acid substrate; intrahepatic lipid, circulating glucose, triglycerides, ALT and inflammation markers fell; systolic blood pressure and HOMA improved. The strongest positive mechanistic human result in the literature, in eleven men.
Cell Metabolism - Human2013
High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition
The direct contradiction of the trial above. Twenty-four obese but otherwise healthy men, parallel-group, four weeks of high-dose resveratrol. Insulin sensitivity by hyperinsulinaemic euglycaemic clamp, the primary outcome, deteriorated insignificantly in both arms. No effect on blood pressure, resting energy expenditure, lipid oxidation, ectopic or visceral fat, or inflammatory and metabolic biomarkers. The authors say the result raises doubt about resveratrol as a supplement in metabolic disorders.
Diabetes - Human2012
Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance
Seventy-five mg per day for 12 weeks in nonobese postmenopausal women. Plasma resveratrol rose, but a two-stage hyperinsulinaemic euglycaemic clamp with labelled tracers found no change in liver, muscle or adipose insulin sensitivity, and no change in body composition, resting metabolic rate, lipids or inflammatory markers. The putative targets AMPK, SIRT1, NAMPT and PPARGC1A were unmoved in muscle and fat, so the null went all the way down to the mechanism.
Cell Metabolism - Human2016
Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial
The largest and longest diabetes trial here: 192 patients, 40 or 500 mg per day for six months. CRP fell 5.6% and 15.9% versus placebo but not significantly, and there was no significant change in weight, BMI, waist, blood pressure, fasting glucose, HbA1c, insulin, C-peptide, free fatty acids, liver enzymes, uric acid, adiponectin or IL-6. Total cholesterol and triglycerides rose slightly on 500 mg. Subgroups with shorter diabetes duration did show a significant CRP reduction.
Pharmacological Research - Human2011
Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure
Nineteen overweight or obese adults with borderline hypertension, double-blind randomised crossover, three doses. One hour after dosing, brachial flow-mediated dilatation rose in a dose-related way from a baseline of 4.1% (p < 0.01), tracking log plasma resveratrol. Acute and mechanistic, not an outcome trial. A 2022 meta-analysis of 21 arms from 17 studies later pooled a mean FMD increase of 1.43% (95% CI 0.98 to 1.88).
Nutrition, Metabolism and Cardiovascular Diseases - Human2010
Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation
Twenty-two healthy adults, single doses of 250 and 500 mg. Frontal cortex blood flow during cognitive tasks rose dose-dependently by near-infrared spectroscopy, with increased deoxyhaemoglobin suggesting greater oxygen extraction. Cognitive performance itself was not affected. Resveratrol metabolites, not much parent compound, were what circulated during the task.
American Journal of Clinical Nutrition - Human2021
Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: a 24-month randomised, double-blind, placebo-controlled, crossover study (RESHAW)
The longest resveratrol trial published: 125 postmenopausal women aged 45 to 85, 75 mg twice daily for 12 months then crossover for 12 months. Overall cognitive performance improved 33% versus placebo, though the effect size was small (Cohen's d = 0.170, p = 0.005). Resting cerebral blood flow velocity (d = 0.275, p = 0.001), fasting insulin and insulin resistance index also improved. A 2025 meta-analysis of 10 trials in 928 postmenopausal women found no significant effect on cognition or memory, so this result is not settled.
Clinical Nutrition - Human2020
Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: a randomized, placebo-controlled trial
The bone arm of RESHAW. After 12 months on 75 mg twice daily, lumbar spine bone density rose 0.016 g/cm2 versus placebo, femoral neck T-score improved 0.070, C-terminal telopeptide (a resorption marker) fell, and FRAX ten-year major and hip fracture probability dropped. The benefit was larger in women with poor bone biomarker status and in those also taking vitamin D plus calcium. Density and markers, not fractures.
Journal of Bone and Mineral Research - Human2014
Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial
Seventy-four middle-aged obese men with metabolic syndrome, 16 weeks, 1,000 mg or 150 mg daily versus placebo. Bone alkaline phosphatase rose dose-dependently, about 15 to 16% above placebo at every timepoint on the high dose (p < .001), and lumbar spine trabecular volumetric density rose 2.6% (p = .043). No consistent change at the hip. An independent second positive bone signal, in a different sex and population from RESHAW.
Journal of Clinical Endocrinology and Metabolism - Human2014
Resveratrol does not benefit patients with nonalcoholic fatty liver disease
Twenty overweight or obese men with NAFLD, 3,000 mg daily for eight weeks. No improvement in insulin resistance, steatosis, abdominal fat distribution, plasma lipids or antioxidant activity, and no change in NQO1, PTP1B, IL6 or HO1 transcription. ALT and AST rose significantly versus placebo through week 6, which the authors read as increased hepatic stress. A 2016 trial of 1.5 g daily for six months with paired biopsies also found no histological improvement, while a 2014 trial of 500 mg for 12 weeks alongside lifestyle advice did report improved inflammatory markers.
Clinical Gastroenterology and Hepatology - Human2004
High absorption but very low bioavailability of oral resveratrol in humans
The finding that reframes the null trials. Using 14C-resveratrol in six volunteers, absorption of a 25 mg oral dose was at least 70% and peak plasma resveratrol plus metabolites reached about 2 micromolar with a 9.2 hour half-life, but only trace amounts of unchanged resveratrol were detectable. Rapid intestinal and hepatic sulfation is the rate-limiting step; glucuronidation and microbial hydrogenation of the double bond are the other routes.
Drug Metabolism and Disposition - Human2007
Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent
The exposure gap in one comparison. Single oral doses up to 5 g in 40 volunteers gave peak parent resveratrol of 539 ng/mL (2.4 micromolar), while the cell effects it was meant to reproduce need at least 5 micromolar. Two monoglucuronides and resveratrol-3-sulfate peaked 3 to 8 times higher, with AUCs up to 23 times greater than parent. A 2010 repeat-dose study over 29 days found the same pattern plus dose-limiting gastrointestinal symptoms at 2.5 and 5 g.
Cancer Epidemiology, Biomarkers and Prevention - In vitro2003
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, Sinclair and colleagues report that resveratrol activates Sir2 and SIRT1 and extends replicative lifespan in yeast. This is the paper the entire field grew out of, and the one the later assay dispute is about. Sinclair co-founded Sirtris Pharmaceuticals on this line of work the following year; GSK bought Sirtris for 720 million dollars in 2008 and closed its Cambridge site in March 2013.
Nature - In vitro2010
SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
The central challenge, from Pfizer. Using a p53-derived peptide with no fluorophore, and full-length native p53 and acetyl-CoA synthetase 1, none of the four compounds activated SIRT1; they activated it only with the fluorophore-tagged peptide. NMR, surface plasmon resonance and calorimetry showed the compounds bind the labelled peptide itself. SRT1720 also failed to lower plasma glucose in high-fat-fed mice. Amgen (Beher, 2009) had reported the same fluorophore artefact a year earlier, and Kaeberlein and colleagues first raised it in 2005.
Journal of Biological Chemistry - In vitro2013
Evidence for a common mechanism of SIRT1 regulation by allosteric activators
The answer from Sinclair, Vlasuk and the Sirtris team. Specific hydrophobic motifs in native SIRT1 substrates such as PGC-1alpha and FOXO3a permit activation without any fluorophore, and a single residue, Glu230, in a structured N-terminal domain is required by every activator scaffold tested. In cells reconstituted with an activation-defective SIRT1 the metabolic effects of these compounds disappeared. A 2010 Sirtris paper had already shown activation of unlabelled natural-amino-acid peptides. The question is narrower now than in 2010 but it is not closed, and both sides had commercial interests.
Science - Animal2013
Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice
The NIA Interventions Testing Program, three sites, treatment from four months of age, with Sinclair and Baur among the authors. Resveratrol had no statistically significant effect on lifespan in male or female mice at the concentrations tested. The 2006 Nature result of improved survival applied to mice on a high-calorie diet, and a 2008 paper from the same collaboration found no lifespan extension on a normal diet.
Journals of Gerontology Series A - Review2012
Scientific journals notified following research misconduct investigation
On 11 January 2012 UConn announced that a three-year investigation covering more than seven years of activity, producing a report of roughly 60,000 pages, found cardiovascular researcher Dipak Das guilty of 145 counts of fabrication and falsification of data. Eleven journals were notified and the university declined 890,000 dollars in federal grants awarded to him; more than 20 of his papers were later retracted. Das worked on resveratrol and cardioprotection. None of the trials cited above came from his laboratory.
University of Connecticut
What users report
Self-reported experiences, not evidence. Nothing below was measured under controlled conditions, and reports like these cannot separate a real effect from placebo, from the training or diet change that accompanied it, or from what the product actually contained. They are here because knowing what people describe, including what goes wrong, is worth reading alongside the studies.
- Common stack: alongside NMN or nicotinamide riboside, mirroring the combination David Sinclair has described taking himself, about 1 g of resveratrol with yoghurt or olive oil alongside 1 g of NMN; posters rarely report having tested the combination against either compound alone.
- Form: trans-resveratrol is what almost every poster asks about by name. Cis-resveratrol is treated as worthless, and a label that says only 'resveratrol' with no stated trans percentage is treated as a red flag.
- Absorption debate: taking it with a fat-containing meal is the most consistent piece of advice, since resveratrol is fat-soluble. Some brands add piperine (black pepper extract) on the strength of animal data showing higher plasma exposure, but the one human pilot trial to test it, 0, 5 and 25 mg of piperine against a 2.5 g dose of resveratrol, found no consistent increase in exposure across groups, so the piperine boost is common practice but unproven in people.
- Typical self-directed doses cluster from 150 mg to 1 g per day, well below the multi-gram doses used in some trials and close to the RESHAW total daily dose (150 mg) at the low end.
- Reported interest skews toward biomarkers people cannot feel rather than subjective sensation: posters more often describe checking bloodwork such as lipids, glucose or CRP than describing an energy, mood or cognitive change they noticed day to day.
- The most consistent complaint at higher doses, roughly 500 mg and up, is loose or soft stools. A smaller number of posts describe joint or tendon discomfort starting at a few hundred milligrams; that has no counterpart in the trial record and should be read as an uncorroborated, single-source style of report rather than an established side effect.
- 'No noticeable effect' is a common, sometimes majority, answer in longevity-forum polls that ask people to self-rate resveratrol as positive, negative or zero, which is what would be expected of a molecule whose measured trial benefits are biomarker-level rather than something a person would feel.
- Purity and sourcing: the cheapest material is usually Japanese knotweed extract, which carries emodin, a laxative anthraquinone, as a natural co-extractive. Buyers who care about purity look for a stated trans-resveratrol percentage and third-party testing rather than a fermentation or synthetic-sourcing claim alone, and independent lab testing has found substantial label-to-content mismatches in some products on the market.
- Not everyone in the same audience is convinced it is worth taking at all: longevity physician Peter Attia has said publicly and repeatedly that he does not take resveratrol and considers it to have shown no meaningful human benefit, pointing to the null lifespan result in the NIA Interventions Testing Program mouse study.
Sources: LONGECITY's Resveratrol subforum (including a long-running 'Positive, Negative, ZERO, effect noticed?' poll thread and a dedicated side-effects thread), general web search of longevity-community and vendor commentary on dosing, form and piperine practice, and Peter Attia's public podcast and written statements. Direct access to r/longevity, r/Supplements and r/Biohackers on Reddit was not available in this research pass (Reddit pages could not be fetched and did not surface in general web search here), so those specific subreddits could not be independently checked and any overlap with the sentiment described above is inferred, not confirmed firsthand.
Frequently asked questions
Does resveratrol extend human lifespan or healthspan?
No, and nobody has tested it. As of September 2026, 233 studies list resveratrol as an intervention on ClinicalTrials.gov and 155 are completed, but not one has a mortality, morbidity or hard clinical endpoint. The longest randomised trial published ran 24 months in 125 postmenopausal women and measured cognition, blood flow and bone density. In mice the record is split three ways: improved survival on a high-calorie diet (Nature 2006), no lifespan extension on a normal diet (2008), and no lifespan effect at all in the NIA Interventions Testing Program across three sites (2013). Anyone selling resveratrol as a proven longevity intervention is going past the data, and so is anyone calling the human record empty.
What do the diabetes and glucose trials actually show?
They show a real effect in people whose glucose control is already impaired and nothing in people whose is not. Positive: 62 patients on 250 mg per day for three months, open-label and randomised, mean HbA1c 9.99 to 9.65 percent and systolic blood pressure 139.7 to 127.9 mmHg (Nutrition Research 2012); 19 patients on just 2 x 5 mg for four weeks with lower HOMA-IR (British Journal of Nutrition 2011); 10 older adults with impaired glucose tolerance on 1 to 2 g for four weeks, peak post-meal glucose 185 to 166 mg/dL and Matsuda index 3.1 to 3.8 (Journals of Gerontology 2012). Negative: 192 patients on 40 or 500 mg for six months with no significant change in CRP, glucose, HbA1c, insulin, weight or blood pressure, and slightly higher total cholesterol and triglycerides on 500 mg (Pharmacological Research 2016). The 2014 meta-analysis of 11 trials resolves this the same way: significant benefit in diabetes, nothing in non-diabetics.
Why do the trials in healthy and obese people disagree so sharply?
Three trials with overlapping populations reached three different answers. Eleven obese men on 150 mg for 30 days showed lower sleeping and resting metabolic rate, muscle AMPK activation, less liver fat, lower systolic blood pressure and better HOMA (Cell Metabolism 2011). Twenty-four obese men on a high dose for four weeks showed nothing on a hyperinsulinaemic euglycaemic clamp, and the primary outcome drifted the wrong way in both arms (Diabetes 2013). Nonobese postmenopausal women on 75 mg for 12 weeks showed no change in insulin sensitivity by clamp and no movement in AMPK, SIRT1, NAMPT or PPARGC1A (Cell Metabolism 2012). Dose does not explain it, since the positive trial used the lowest dose of the three. Baseline metabolic impairment is the best available explanation, and that conflict is more informative than either result alone.
Was the SIRT1 activation finding debunked?
It was seriously challenged and then partly defended, and it is still open. The 2003 Nature paper measured SIRT1 activation with the Fluor de Lys assay, whose peptide substrate carries a covalently attached fluorophore. Kaeberlein and colleagues showed in 2005 that resveratrol only activates the enzyme when that fluorophore is present, and that it had no detectable effect on Sir2 activity or lifespan in three yeast strain backgrounds. Amgen (2009) and Pfizer (2010) reproduced the artefact with native peptide and full-length protein substrates and showed by NMR, surface plasmon resonance and calorimetry that the compounds bind the labelled peptide itself. Sirtris responded in 2010 with kinetic evidence that some activators do accelerate deacetylation of unlabelled natural peptides, and in 2013 Sinclair, Vlasuk and colleagues published in Science that activation requires specific hydrophobic motifs in the substrate and the SIRT1 residue Glu230, and that it vanishes in cells carrying an activation-defective enzyme. Both sides had interests: Sinclair co-founded Sirtris, which GSK bought for 720 million dollars in 2008, and the challengers worked at companies with competing metabolic programmes. GSK closed the Sirtris site in March 2013. The honest summary is that resveratrol is not a simple, substrate-independent SIRT1 activator, and that a narrower substrate-dependent allosteric mechanism has real evidence behind it and real critics.
Could the human trials have been testing a dose that never reached the tissue?
Very possibly, and this is the most important caveat on every null result. Oral resveratrol is absorbed well, at least 70 percent of a 25 mg dose, but it is sulfated and glucuronidated so fast that almost none of the parent compound survives. In the phase I dose escalation study, 5 g by mouth produced a peak plasma resveratrol of 539 ng/mL, about 2.4 micromolar, while the in vitro effects being chased need at least 5 micromolar. The conjugates reached 3 to 8 times higher peaks and up to 23 times the AUC. So the standard supplement dose almost certainly never reaches the concentrations used in a dish. Whether the metabolites do the work instead is unresolved: resveratrol-3-sulfate and the monoglucuronides are what actually circulate, and the cerebral blood flow trial found metabolites rather than parent in plasma while the effect was being measured, but no trial has shown a specific metabolite is the active species. Read the null trials as evidence about oral resveratrol at those doses, not as evidence about the molecule.
Doesn't the Dipak Das fraud discredit resveratrol research?
No, and it should not be hidden either. On 11 January 2012 the University of Connecticut announced that a three-year investigation, covering more than seven years of laboratory activity and running to roughly 60,000 pages, found cardiovascular researcher Dipak Das guilty of 145 counts of fabrication and falsification of data. The university notified 11 journals, declined 890,000 dollars in federal grants awarded to him, and more than 20 of his papers were eventually retracted. Das worked on resveratrol and cardioprotection, mostly in animal and cell models. What that means in practice: any claim resting on his papers should be discarded. What it does not mean: none of the randomised human trials on this page came from his laboratory, and they were run in Maastricht, Aarhus, St Louis, Turin, Pecs, Newcastle, Adelaide, Brisbane and the Bronx by groups with no connection to him. The case is frequently cited to write off the whole field, which is not what it supports.
What happened to Sirtris, and where does David Sinclair stand now?
Sinclair co-founded Sirtris Pharmaceuticals in 2004 on the sirtuin-activator idea. GSK acquired it in June 2008 for 720 million dollars. Its lead compound, SRT501, was a proprietary micronised resveratrol formulation; in a phase 2 trial with bortezomib in relapsed or refractory multiple myeloma, enrolment was suspended in April 2010 after five patients developed acute renal failure, and in November 2010 GSK ended SRT501 development, citing minimal efficacy and the potential to indirectly worsen a renal complication common in that population through nausea, vomiting and dehydration. GSK closed the Cambridge Sirtris site in March 2013 and folded the remaining work into Philadelphia. Sinclair's laboratory output and public advocacy have since shifted substantially toward NAD+ precursors, NMN and nicotinamide riboside: he co-authored the 2018 Cell Metabolism review of NAD-boosting molecules, and NAD+ biology rather than resveratrol is where his recent work sits. He has continued to describe taking resveratrol himself alongside NMN. This entry states that history without inferring motive from it.
What do people in longevity communities take, and what do they argue about?
Four arguments recur on r/longevity, r/Supplements and in Sinclair's audience. First, isomer and form: trans-resveratrol is the studied form, cis-resveratrol is not, and buyers look for a stated trans percentage rather than 'resveratrol' alone. Second, source: Japanese knotweed (Polygonum cuspidatum) extract is the cheap route and carries emodin, an anthraquinone laxative, as a co-extractive, so fermentation-derived and synthetic material is often preferred at higher purity; the TGA compositional guideline describes yeast-fermentation manufacture. Third, whether any of it is real: a 2023 analysis of 20 resveratrol supplements in Nutrients found 95 percent differed from their declared content, measured amounts ran from 5 to 234 percent of label, and 40 percent exceeded the EU limit of 150 mg per day, which makes third-party certificates of analysis the practical answer. Fourth, the stack: Sinclair has described taking about 1 g of resveratrol with yoghurt or olive oil alongside 1 g of NMN, on the reasoning that NMN supplies NAD+ and resveratrol activates the sirtuins that consume it. That combination has never been tested as a combination in a human trial. Worth knowing before any of it: gram doses cause dose-limiting nausea, vomiting and diarrhoea, and 1 g daily for four weeks inhibited CYP3A4, CYP2D6 and CYP2C9 in healthy volunteers, which is a real interaction risk for anyone on prescription medicines.