Resveratrol dosage and evidence

What is Resveratrol?

How does Resveratrol work?

The main idea is that resveratrol switches on SIRT1, an enzyme that needs NAD+ to work. That in turn sets off signals, AMPK and PGC-1alpha, that copy parts of eating less. That claim is disputed. Teams at Amgen (2009) and Pfizer (2010) showed the switch-on only happened with a glowing tag stuck to the test protein. It vanished with natural proteins. Sirtris and Sinclair's group answered in Science (2013). They argued the switch-on is real, but only with target proteins that carry certain water-avoiding patches, plus one spot on SIRT1, Glu230. Apart from sirtuins, resveratrol is a known antioxidant. It helps blood vessels widen through nitric oxide. And at gram doses it blocks the liver enzymes CYP3A4, CYP2D6 and CYP2C9, which break down many prescription drugs.

What have studies in people found about Resveratrol?

Resveratrol has one of the biggest human trial records of anything on this site. There are dozens of trials running six months or longer, on thinking, bone, metabolism, the heart and joints. The record does not point one way. It holds real good results, real no-effect results, and at least one real harm signal. Dose and who took it separate them more than anything else.

• Bo 2016, six months, 192 people with type 2 diabetes on 40 or 500 mg a day: no real change in the inflammation marker CRP, the main thing measured. Total cholesterol and triglycerides rose slightly on 500 mg (PMID 27520400).
• Bo 2018, from inside that same 192-person trial: bone density improved, even though the trial's main measure came up empty (PMID 30237505).
• Nguyen 2024 (ARTHROL), six months, a large final-stage trial in 142 people with knee arthritis: no effect. Pain scores came out almost exactly the same as on the dummy pill (PMID 39137167).
• RESHAW, 24 months, 125 to 129 women past menopause aged 45 to 85, 75 mg twice a day. Each woman spent a year on resveratrol and a year on a dummy pill. Overall thinking scores improved 33 percent, though the effect was small (PMID 32900519). It was partly paid for by Evolva, which makes the Veri-te resveratrol tested, along with Australian government research funds.
• Same RESHAW program: bone density in the lower spine rose 0.016 g/cm2, the top of the thigh bone rose 0.005, and a blood marker of bone breakdown fell 7.24 percent (PMID 32564438). Pain and menopause symptoms also improved (PMID 32881835). A 12-month interim report was positive (PMID 32244933), and the plan was published in advance (PMID 27005658).
• Turner 2015, 52 weeks, 119 people with mild to moderate Alzheimer disease, doses rising to 1 g twice a day: it was safe and got into the brain, but brains shrank more than on the dummy pill (PMID 26362286).
• Garcia-Martinez 2023, six months, 97 older people with type 2 diabetes: antioxidant levels and SIRT1 went up, but only at the 1,000 mg dose (PMID 37108584).
• Tome-Carneiro, one year, 75 people with stable heart disease: the inflammation marker hsCRP fell 26 percent, TNF-alpha fell 19.8 percent and PAI-1 fell 16.8 percent. That came from just 8 mg of resveratrol in grape extract. One group got grape extract without resveratrol, which makes the comparison stronger (PMID 22520621).
• Witte 2014, 26 weeks, 46 people on 200 mg a day: better at remembering words (PMID 24899709). The same lab's bigger repeat, Huhn 2018 in 60 people, found nothing on its main measure (PMID 29548848). Read both together, not just the first.
• Gliemann 2013, 8 weeks, 27 older men on 250 mg alongside hard interval training: resveratrol blunted the heart and lung benefit of exercise. The dummy pill group gained 45 percent more in VO2max, a measure of fitness (PMID 23878368).
• de Ligt 2020, six months: no effect on insulin sensitivity, the main thing measured (PMID 32492138).
• Heeboll 2016, six months, fatty liver disease: no effect on the liver enzyme ALT and no improvement in liver tissue. One person had a serious side effect, fever with low blood cell counts (PMID 26784973).
• Poulsen 2018, six months, fatty liver disease: no effect (PMID 29885082).
• McDermott 2017 (RESTORE), six months, poor blood flow to the legs: no effect on how far people could walk in 6 minutes (PMID 28403379).
• Muscari 2026 (PBAR): the 700 mg a day group was stopped at month 5 of a planned 24, because LDL cholesterol rose clearly. The authors said high-dose resveratrol should be avoided (PMID 40922000). This is the clearest harm signal in the whole record.
• Several reviews that pooled trials report raised LDL, total cholesterol and liver enzymes (ALT, GGT and ALP) in some groups, mostly above about 1,000 mg a day. Read against the rest of this list, good results cluster at 150 to 200 mg a day and harm signals cluster above 700 mg a day. That dose split is more useful than any single trial here.
• The Cochrane review found only 3 trials it could use, with 50 people in total, and could not judge whether it works either way (PMID 31978258). A review of trials in women past menopause found no effect on thinking once the trials were pooled (PMID 40771919). That does not match RESHAW's own main result.

What this does not tell you: No trial has measured lifespan, death or any hard health result in people. Every result above is a marker, like a thinking score, bone density, CRP, blood pressure or LDL, not a disease or survival result. These are the longest trials resveratrol has, and most still ran six months or less. The biggest and longest good trial, RESHAW, was partly paid for by Evolva, the maker of the Veri-te resveratrol it tested. It also had independent Australian government funding. That does not make its result wrong. It is a real conflict of interest, worth weighing against the no-effect trials that had no maker funding.

What do people who took Resveratrol report?

This is what real people say happened to them, good and bad. Nobody measured it. A report cannot tell a real effect from the lift people get just from expecting it to work, from a diet or training change made at the same time, or from what was really in the vial. We still put it near the top. It is the next best thing to a study in people: what happens when real people use it, including what goes wrong.

• Common stack: with NMN or nicotinamide riboside, copying what David Sinclair has said he takes himself, about 1 g of resveratrol with yoghurt or olive oil plus 1 g of NMN. Posters rarely say they tested the combination against either one alone.
• Form: trans-resveratrol is what almost every poster asks for by name. Cis-resveratrol is seen as worthless. A label that just says resveratrol, with no trans percentage, is treated as a red flag.
• Absorption: taking it with a meal that has fat in it is the most common advice, since resveratrol dissolves in fat. Some brands add piperine, a black pepper extract, based on animal data showing higher blood levels. The one human pilot trial to test it used 0, 5 and 25 mg of piperine with 2.5 g of resveratrol, and found no steady rise in blood levels. So the pepper boost is common but unproven in people.
• Self-chosen doses mostly run from 150 mg to 1 g a day. That is well below the multi-gram doses in some trials, and close to RESHAW's 150 mg a day total at the low end.
• Interest leans toward blood test numbers people cannot feel. Posters more often talk about checking cholesterol, blood sugar or CRP than about any change in energy, mood or thinking they noticed day to day.
• The most common complaint at higher doses, about 500 mg and up, is loose or soft stools. A smaller number of posts describe joint or tendon aches starting at a few hundred milligrams. Nothing like that shows up in the trials, so read it as an unconfirmed, single-source kind of report, not a known side effect.
• No noticeable effect is a common answer, sometimes the most common, in longevity forum polls that ask people to rate it as positive, negative or zero. That is what you would expect when the trial benefits are blood markers, not something a person would feel.
• Purity and sourcing: the cheapest material is usually Japanese knotweed extract, which naturally carries emodin, a laxative. Buyers who care look for a stated trans-resveratrol percentage and third-party testing, not just a claim about how it was made. Independent lab tests have found big gaps between label and contents in some products.
• Not everyone in the same crowd thinks it is worth taking. Longevity doctor Peter Attia has said many times in public that he does not take resveratrol and that it has shown no meaningful human benefit. He points to the no-effect lifespan result in the US government's mouse testing program.

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.

The state of the research

The evidence, in charts

The studies we cite

• Study in people2011
  Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients

  A tiny dose improved insulin resistance in nineteen patients over four weeks. A marker of oxidative damage in the urine fell, and a signalling protein in the blood platelets rose. The insulin-making cells did not change. The odd thing here is the dose. It is a hundredth of what most good trials use, which is hard to square with the idea that more does more.

  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.

  PMID 21385509 British Journal of Nutrition
• Study in people2012
  Pilot study of resveratrol in older adults with impaired glucose tolerance

  Ten older adults took resveratrol for a month and their blood sugar after meals came down. The peak reading fell by about a tenth, the total sugar load over three hours fell, and their response to insulin improved. Fasting sugar, weight, blood pressure and cholesterol did not move. There was no comparison group, and everyone knew what they were taking. So this raises a question rather than answering one.

  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.

  PMID 22219517 Journals of Gerontology Series A
• Study in people2011
  Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

  This is the strongest good human result resveratrol has, and it rests on eleven men. Obese but otherwise healthy men took 150 mg a day for a month, and also spent a month on a dummy pill. Their resting metabolism slowed the way it does when people eat less. Liver fat, blood sugar, triglycerides, a liver enzyme and inflammation markers all fell. Blood pressure improved. Muscle samples showed the cell's energy machinery switched on.

  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.

  PMID 22055504 Cell Metabolism
• Study in people2013
  High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition

  Run again at a high dose, the same idea produced nothing. Twenty-four obese but otherwise healthy men took high-dose resveratrol or a dummy pill for four weeks. The main measure was how well their bodies answered insulin, using the most exacting test there is. It drifted slightly worse in both groups. Blood pressure, energy burned at rest, fat burning, fat around the organs and inflammation markers did not move. The authors say this casts doubt on resveratrol for metabolic problems.

  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.

  PMID 23193181 Diabetes
• Study in people2012
  Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance

  Resveratrol did nothing in healthy postmenopausal women, right down to the mechanism. They took 75 mg daily for 12 weeks, and blood tests confirm it reached them. The most exacting test of insulin response found no change in liver, muscle or fat. Body composition, resting metabolism, blood fats and inflammation markers were unchanged. The proteins resveratrol is supposed to act on were unmoved in muscle and fat too. There is no hidden effect being missed here.

  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.

  PMID 23102619 Cell Metabolism
• Study in people2016
  Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial

  The longest and largest diabetes trial of resveratrol found nothing that counted. 192 patients took 40 mg, 500 mg or a dummy pill every day for six months. An inflammation marker fell further on resveratrol, but not by enough to call real. Weight, waist, blood pressure, blood sugar, insulin and a string of other markers did not change. Cholesterol and triglycerides rose slightly on the high dose. Patients earlier in their diabetes did show a real fall in inflammation.

  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.

  PMID 27520400 Pharmacological Research
• Study in people2011
  Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure

  A single dose opened up the arteries for an hour. Nineteen overweight adults with slightly raised blood pressure took three different doses on separate days. The bigger the dose, the more the artery in the arm widened, in step with how much reached the blood. This is an hour-long measurement, not a study of heart attacks. A later review that pooled 21 comparisons found the same effect, and it was small.

  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).

  PMID 20674311 Nutrition, Metabolism and Cardiovascular Diseases
• Study in people2010
  Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation

  Blood flow to the front of the brain went up, and thinking did not improve. Twenty-two healthy adults took one dose of 250 or 500 mg. The bigger the dose, the more blood flowed to the frontal cortex during mental tasks, and the tissue appeared to pull more oxygen out of it. Performance on those tasks did not change. What was circulating during the test was mostly broken-down resveratrol, not resveratrol itself.

  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.

  PMID 20357044 American Journal of Clinical Nutrition
• Study in people2021
  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 found a small gain in thinking that has not been confirmed since. 125 women past menopause, aged 45 to 85, took 75 mg twice a day for a year and a dummy pill for another year. Their overall thinking scores came out better on resveratrol, though the gain was small. Blood flow in the brain, fasting insulin and insulin resistance improved too. A 2025 review pooling ten trials in 928 women found no effect on thinking or memory.

  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.

  PMID 32900519 Clinical Nutrition
• Study in people2020
  Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: a randomized, placebo-controlled trial

  The same trial found a real gain in bone. After a year on 75 mg twice daily, bone density in the lower spine rose against the dummy, the hip score improved a little, and a marker of bone being broken down fell. Estimated ten year fracture risk came down. Women with the worst bone markers gained most, as did those also taking vitamin D and calcium. What was measured was density and blood markers. Nobody counted a single broken bone.

  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.

  PMID 32564438 Journal of Bone and Mineral Research
• Study in people2014
  Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial

  A second study, this time in men, points the same way on bone. 74 middle-aged obese men with metabolic syndrome took 1,000 mg, 150 mg or a dummy for 16 weeks. A blood marker of bone building rose around 15 percent above the dummy on the high dose at every check. Density in the spongy part of the lower spine rose about 2.6 percent. The hip did not change consistently. Different sex, different team, same direction.

  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.

  PMID 25322274 Journal of Clinical Endocrinology and Metabolism
• Study in people2014
  Resveratrol does not benefit patients with nonalcoholic fatty liver disease

  Resveratrol did not help fatty liver, and it may have irritated it. Twenty overweight men took 3,000 mg daily for eight weeks. Insulin resistance, liver fat, belly fat, blood fats and antioxidant activity were all unchanged, and so were the genes it was meant to act on. Two liver enzymes rose against the dummy, which the authors read as the liver being put under strain. A later six month trial with tissue samples also found no improvement.

  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.

  PMID 24582567 Clinical Gastroenterology and Hepatology
• Study in people2004
  High absorption but very low bioavailability of oral resveratrol in humans

  This is the study that explains why so many resveratrol trials come back empty. Six volunteers took a labelled dose, and their guts absorbed at least 70 percent of it. Almost none of it stayed as resveratrol. The gut wall and the liver tag it chemically almost immediately, so what ends up circulating is a set of breakdown products. You can swallow it, absorb it, and still have barely any of the actual compound in your blood.

  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.

  PMID 15333514 Drug Metabolism and Disposition
• Study in people2007
  Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent

  Even five grams does not get resveratrol to the level the laboratory work needs. 40 volunteers took single doses up to 5 g. The peak amount of true resveratrol in their blood reached about half the concentration the cell experiments required to do anything. Its breakdown products ran three to eight times higher. A repeat-dose study over 29 days found the same pattern, and doses of 2.5 g and above gave people stomach trouble.

  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.

  PMID 17548692 Cancer Epidemiology, Biomarkers and Prevention
• Review of studies2026
  Effects of resveratrol supplementation on multiple health outcomes: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials

  A 2026 review that pooled 45 earlier reviews. Four findings came out solid. Waist size fell 0.80 cm. Total cholesterol fell 0.19 mmol/L in overweight adults. In type 2 diabetes, the bottom blood pressure number fell 3.55 points and the top fell 7.97. It is the fullest pooled picture there is, and it is neither a no-effect result nor a lifespan result.

  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.

  PMID 41987155 Nutrition Journal
• Review of studies2014
  Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials

  A 2014 review that pooled 11 trials in 388 people. In people with diabetes, fasting blood sugar, insulin, average blood sugar and insulin resistance all fell. In people without diabetes, nothing changed. Who took it, not dose or trial length, separated the good results from the empty ones.

  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.

  PMID 24695890 American Journal of Clinical Nutrition
• Review of studies2021
  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

  A 2021 review of pooled reviews, and the counterweight. It covered 1,476 people with type 2 diabetes, 727 with metabolic syndrome and 271 with fatty liver. There were effects, but for almost every measure they were tiny, the evidence was weak, or there were too few trials. The exception was average blood sugar in trials shorter than 12 weeks. It fell 1.05 points, which the authors call a meaningful amount.

  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.

  PMID 34320173 American Journal of Clinical Nutrition
• Review of studies2012
  Scientific journals notified following research misconduct investigation

  A university announcement from 2012. A heart researcher who worked on resveratrol, Dipak Das, was found guilty of 145 counts of making up or altering data. More than 20 of his papers were later retracted. None of the human trials on this page came from his lab.

  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.

  Source University of Connecticut
• Animal study2013
  Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice

  In mice. The US government's mouse testing program, at three sites, found resveratrol did not make male or female mice live longer. The earlier good survival result was in mice on a high-calorie diet.

  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.

  PMID 22451473 Journals of Gerontology Series A
• Lab (cells in a dish)2003
  Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

  In yeast and in a dish. The 2003 paper that started it all. It reported that resveratrol switches on sirtuin enzymes and makes yeast live longer. Sinclair co-founded Sirtris on this work the next year. GSK bought Sirtris for 720 million dollars in 2008.

  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.

  PMID 12939617 Nature
• Lab (cells in a dish)2010
  SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1

  In a dish. The main challenge, from Pfizer. With natural test proteins that had no glowing tag, none of the four compounds switched SIRT1 on. They only worked with the tagged test protein, because they stick to the tag. One of them also failed to lower blood sugar in mice on a fatty diet.

  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.

  PMID 20061378 Journal of Biological Chemistry
• Lab (cells in a dish)2013
  Evidence for a common mechanism of SIRT1 regulation by allosteric activators

  In a dish. Sinclair's team answered back. They found that natural target proteins with certain water-avoiding patches let SIRT1 be switched on without any tag, using one key spot on the enzyme. The question is narrower now, but it is not closed, and both sides had money at stake.

  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.

  PMID 23471411 Science