Resveratrol

Resveratrol is a plant polyphenol found in grape skins, red wine, peanuts and some berries. Most supplements are made from the root of Japanese knotweed (Polygonum cuspidatum). It became famous in the 2000s as a possible “calorie restriction mimetic” (a compound that copies some effects of eating less) after lab studies linked it to the longevity enzyme SIRT1.

The excitement has not held up well. Whether resveratrol directly activates SIRT1 is still disputed, very little unchanged resveratrol reaches the blood after a pill, and the US National Institute on Aging’s mouse lifespan program found no lifespan extension in normal mice. Human trials show small, inconsistent effects on blood sugar, blood pressure and lipids. One trial in older men found it blunted the benefits of exercise training.

This page summarizes what clinical trials, meta-analyses and the primary lab studies report. It is for education only and is not medical advice.

Property	Detail
Class	Plant polyphenol (stilbene); trans-3,5,4′-trihydroxystilbene
Formula	C₁₄H₁₂O₃, 228.24 g/mol (PubChem)
Main supplement source	Japanese knotweed (Polygonum cuspidatum) root extract; also grape and red wine extracts
Food sources	Grape skins, red wine (global mean ≈1.9 mg/L, ≈0.3 mg per 5-oz glass), peanuts, cocoa, blueberries and cranberries
Route	Oral
Doses used in trials	75 mg/day to 5 g/day
Half-life	≈9 h for resveratrol plus its metabolites (radiolabel study, 25 mg dose); unchanged resveratrol is barely detectable
Mechanism	Disputed: direct SIRT1 activation was challenged as a test artifact; phosphodiesterase inhibition and indirect AMPK activation proposed in mice
US status	Sold as a dietary supplement; not an approved drug
WADA status	Not named on the 2026 Prohibited List

What it is

Resveratrol (PubChem name 5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol) is a small molecule with two phenol rings joined by a double bond (PubChem). It exists as trans and cis forms. Heat, light or ultraviolet radiation can convert the trans form, the one used in most supplements and studies, into the cis form (Shaito et al., Int J Mol Sci 2020).

Sources

In grapes, resveratrol is found only in the skins. Its content varies with grape variety, region and fungal infection, and white and rosé wines generally contain less than red because the skins are removed early in production (Linus Pauling Institute). The institute’s summary of red wine data:

Red wine	Mean trans-resveratrol (mg/L)	Per 5-oz glass (mg)
Pinot Noir	3.6	0.5
Merlot	2.8	0.4
Cabernet Sauvignon	1.7	0.2
Red wines, global	1.9	0.3

Supplements contain anywhere from under 1 mg to 500 mg per tablet or capsule (Linus Pauling Institute). Doses used in clinical trials are far higher than anything a normal diet or wine intake provides.

The sirtuin story and the SIRT1 controversy

Sirtuins are enzymes that remove acetyl groups from proteins and need NAD+ to work (see NAD+). In 2003 a screen reported that resveratrol activated human SIRT1 and extended yeast lifespan by 70% (Howitz et al., Nature 2003). In 2006 the same group reported that resveratrol improved health and survival of middle-aged mice on a high-calorie diet (Baur et al., Nature 2006).

The SIRT1 claim was soon challenged:

• 2005, two independent labs. The 2003 screen used a commercial test substrate with a fluorescent tag attached. Resveratrol activated SIRT1 only when this tag was present. With natural, untagged substrates it had no effect, and in yeast it did not change Sir2 activity or lifespan (Kaeberlein et al., J Biol Chem 2005; Borra et al., J Biol Chem 2005).
• 2010, Pfizer. Using native peptides and full-length proteins, researchers found that resveratrol and the synthetic “sirtuin activators” SRT1720, SRT2183 and SRT1460 did not activate SIRT1. The compounds bound the fluorescent substrate itself, and they hit many other receptors, enzymes and ion channels (Pacholec et al., J Biol Chem 2010).
• 2012, NIH. In cells and mice, resveratrol inhibited cAMP phosphodiesterases. This set off a signaling chain that activated AMPK and raised NAD+, which in turn raised SIRT1 activity indirectly. A different phosphodiesterase inhibitor, rolipram, reproduced its metabolic benefits in mice (Park et al., Cell 2012).
• 2013, rebuttal. The original group reported that certain hydrophobic features of natural SIRT1 substrates such as PGC-1α and FOXO3a can stand in for the fluorescent tag. A single amino acid in SIRT1 (Glu230) was needed for activation, which they took as evidence of a real allosteric (binding-site) mechanism (Hubbard et al., Science 2013).

So whether resveratrol activates SIRT1 directly, and whether that matters at the blood levels people actually reach, is not settled. In human muscle, a single 300 mg dose did not change SIRT1 activity or AMPK phosphorylation (Williams et al., PLoS One 2014).

Retracted research

Part of the cardiovascular literature on resveratrol came from the lab of Dipak K. Das at the University of Connecticut. Several of his resveratrol papers have since been retracted. One retraction notice states that a University of Connecticut Health Center misconduct investigation found fabricated data in a figure of a 2006 paper on resveratrol and heart protection (Free Radic Res retraction, 2012). PubMed also flags as retracted, for example, his 2008 paper on resveratrol and redox signaling in the heart (Das et al., Free Radic Biol Med 2008). Both of these were rat heart studies, so the retractions affect the preclinical heart literature rather than the human trials summarized below.

Pharmacokinetics

Resveratrol is well absorbed but very little of it survives as the parent compound. The gut wall and liver rapidly attach sulfate and glucuronide groups (conjugation), and gut bacteria reduce its double bond (Walle et al., Drug Metab Dispos 2004).

Study	Design	Key findings
Walle et al., 2004	6 volunteers, ¹⁴C-labeled 25 mg oral and IV doses	At least 70% absorbed. Resveratrol plus metabolites peaked at ≈491 ng/mL with a half-life of 9.2 h, but unchanged resveratrol was under 5 ng/mL. Rapid sulfate conjugation limits bioavailability.
Boocock et al., 2007	40 healthy volunteers, single doses of 0.5, 1, 2.5 or 5 g	At 5 g, parent resveratrol peaked at 539 ng/mL (2.4 µmol/L) 1.5 h after the dose. Exposure (AUC) to the sulfate and glucuronide metabolites was up to 23 times higher. 77% of urinary products were excreted within 4 h at the lowest dose.
Brown et al., 2010	40 healthy volunteers, 0.5–5 g/day for 29 days	Metabolite exposure exceeded parent exposure by up to 20.3-fold. Circulating IGF-1 and IGFBP-3 fell.

Boocock and colleagues noted that cell-culture anticancer effects need at least 5 µmol/L, a level not reached even with 5 g. Many lab effects were therefore seen at concentrations people do not achieve. Whether the conjugated metabolites are active in their own right is still being studied.

What the research shows

Blood sugar and insulin

Meta-analysis	Trials (people)	Main result
Liu et al., Am J Clin Nutr 2014	11 RCTs (388)	Lower fasting glucose, insulin, HbA1c and insulin resistance in people with diabetes; no effect in people without diabetes
Zhu et al., Nutr Metab 2017	9 RCTs (283), type 2 diabetes	Fasting glucose −0.29 mmol/L (≈−5 mg/dL; 95% CI −0.51 to −0.06); HbA1c change negligible
Zeraattalab-Motlagh et al., Am J Clin Nutr 2021	Umbrella review of 11 meta-analyses in type 2 diabetes (1,476)	Most effects trivial or very low to low certainty; HbA1c −1.05% (95% CI −2.09 to −0.02) in trials under 12 weeks, moderate certainty

The 2021 umbrella review concluded that current evidence does not support resveratrol for managing cardiometabolic risk in type 2 diabetes, metabolic syndrome or fatty liver disease. The one possible exception was a short-term HbA1c effect, based on small, short trials.

Two well-known single trials show how mixed the results are:

Trial	Population	Dose and duration	Result
Timmers et al., Cell Metab 2011	11 obese men, crossover	150 mg/day for 30 days	Lower resting metabolic rate, liver fat, glucose and systolic pressure; better HOMA insulin resistance index
Yoshino et al., Cell Metab 2012	Nonobese postmenopausal women with normal glucose tolerance	75 mg/day for 12 weeks	No change in insulin sensitivity (clamp), body composition, lipids, or muscle SIRT1/AMPK

Blood pressure

The largest standard meta-analysis pooled 17 trials. Overall, resveratrol did not significantly lower systolic pressure (−2.5 mmHg, 95% CI −5.5 to 0.6) or diastolic pressure (−0.5 mmHg, 95% CI −2.2 to 1.3). Significant drops appeared only in subgroups: trials using ≥300 mg/day and trials in people with diabetes (Fogacci et al., Crit Rev Food Sci Nutr 2019).

A 2026 umbrella review of 45 systematic reviews rated as high certainty a drop of 7.97 mmHg systolic (95% CI −10.63 to −5.31) and 3.55 mmHg diastolic (95% CI −5.18 to −1.93) in people with type 2 diabetes (Sun et al., Nutr J 2026). The benefit, if real, appears limited to people with metabolic disease.

Blood lipids

• No overall effect in early pooling. Seven RCTs (282 people) showed no significant change in total cholesterol, LDL, HDL or triglycerides (Sahebkar, Nutr Rev 2013).
• No effect in a larger update. Twenty-one trials showed no change in total cholesterol, LDL or HDL. A triglyceride effect disappeared after one study was removed, and heterogeneity was very high (Haghighatdoost & Hariri, Pharmacol Res 2018).
• A small signal in overweight adults. The 2026 umbrella review rated a total cholesterol reduction of 0.19 mmol/L (≈7 mg/dL; 95% CI −0.32 to −0.06 mmol/L) in overweight adults as high certainty (Sun et al., Nutr J 2026).

Exercise training and muscle

This is the most relevant evidence for people who train, and it points in different directions.

Gliemann 2013. Twenty-seven healthy, inactive men aged about 65 did 8 weeks of high-intensity training with either 250 mg/day trans-resveratrol (n = 14) or placebo (n = 13) (Gliemann et al., J Physiol 2013):

Outcome	Placebo + training	Resveratrol + training
Rise in maximal oxygen uptake (VO₂max)	45% greater than in the resveratrol group	Smaller rise
Mean arterial pressure	−4.8 mmHg	No significant drop
LDL, total/HDL cholesterol ratio, triglycerides	Improved	Improvements abolished
Muscle SIRT1 protein	Unchanged	Unchanged

A companion analysis of the same study found that training improved muscle mitochondrial markers and endurance with no added benefit from resveratrol. Resveratrol also blunted the training-induced drop in muscle oxidative damage and in the inflammatory marker TNF-α (Olesen et al., J Physiol 2014).

Alway 2017. In 30 adults aged 65–80 who did 12 weeks of aerobic and resistance exercise, 500 mg/day resveratrol did not lower cardiovascular risk more than placebo. However, mitochondrial density, fatigue resistance, knee-extensor peak torque (+8%) and power (+14%) and muscle fiber area improved more with resveratrol (Alway et al., J Gerontol A 2017).

Both trials were small and in older people, with different doses and training types. They do not show that resveratrol helps trained younger adults, and the Gliemann result is a real signal that it can interfere with some cardiovascular training gains.

Lifespan (mouse data)

The National Institute on Aging Interventions Testing Program (ITP) tests compounds in genetically mixed mice at three sites at once. All results below are in mice:

Study	Dose and start age	Lifespan result
Miller et al., J Gerontol A 2011	300 or 1,200 ppm in food from 12 months	No significant effect in either sex. In the same study, rapamycin extended median survival by 10% in males and 18% in females.
Strong et al., J Gerontol A 2013	300 ppm in food from 4 months	No significant effect in either sex
Pearson et al., Cell Metab 2008	Standard diet, from 12 months	Fewer signs of aging (better aortic elasticity, motor coordination, bone density, fewer cataracts), but no longer life

The only positive mouse survival result came from animals on a high-calorie diet (Baur et al., Nature 2006). No human study has measured lifespan.

Combination with NAD+ precursors

Resveratrol is often sold or taken with NAD+ precursors such as NMN and NR, on the theory that more NAD+ plus a sirtuin activator works better. The one randomized trial that tested this directly was NICE. In 90 people with peripheral artery disease, NR improved 6-minute walk distance compared with placebo, and adding resveratrol did not add benefit (McDermott et al., Nat Commun 2024).

Side effects and risks

Tolerability

In healthy volunteers, single doses up to 5 g caused no serious adverse events (Boocock et al., 2007). In 29-day dosing, 2.5 and 5 g/day caused mild to moderate gastrointestinal symptoms (Brown et al., 2010). A review lists diarrhea, nausea, hypersensitivity and anal itching at 2–5 g/day (Shaito et al., 2020).

Kidney failure in a myeloma trial

SRT501 was a micronized (finely milled) resveratrol formulation made to raise blood levels. In an open-label, non-randomized phase 2 trial in relapsed multiple myeloma, given with bortezomib, it was linked to serious adverse events including kidney failure, and the trial was stopped (Popat et al., Br J Haematol 2013). The dose was 5 g/day (Shaito et al., 2020). Kidney failure is common in myeloma itself, so how much was caused by SRT501 is unclear (Linus Pauling Institute).

Drug interactions

• Liver enzymes (CYP450). In 42 healthy volunteers, 1 g/day for 4 weeks inhibited CYP3A4, CYP2D6 and CYP2C9 activity and induced CYP1A2. The authors warned this could raise adverse drug reactions or change drug effects (Chow et al., Cancer Prev Res 2010). CYP3A4 handles a large share of prescription drugs.
• Bleeding risk. Resveratrol inhibits human platelet aggregation in the test tube, so high supplement intakes could in theory add to the effect of anticoagulants (warfarin, heparin), antiplatelet drugs (clopidogrel) and NSAIDs (Linus Pauling Institute). In a mouse model, trans-resveratrol increased warfarin’s anticoagulant effect (Shaito et al., 2020).

Who should be cautious

Based on the data above, extra caution is warranted for people taking blood thinners or drugs cleared by CYP3A4, CYP2D6 or CYP2C9, people with kidney disease or myeloma, and anyone exercising for cardiovascular fitness given the Gliemann result. Long-term safety data in humans are limited (Shaito et al., 2020).

Legal status and sport

Resveratrol is sold in the US as a dietary supplement (Linus Pauling Institute). It is not named on the WADA 2026 Prohibited List. The list does ban “activators of the AMP-activated protein kinase (AMPK)” as a class (S4.4.1), with AICAR, BAM15 and MOTS-c as named examples; resveratrol is not among them.

For other compounds marketed for healthy aging, see spermidine and fisetin.

Key takeaways

• The SIRT1 story is unresolved. Direct SIRT1 activation was first seen in an assay later shown to depend on a fluorescent tag; supporters later reported a real allosteric mechanism, while others point to phosphodiesterase inhibition.
• Very little reaches the blood intact. At least 70% of an oral dose is absorbed, but rapid sulfate and glucuronide conjugation leaves parent resveratrol below the concentrations used in many lab studies.
• Human metabolic effects are small and mixed. Meta-analyses show no meaningful change in people without diabetes and modest, low-certainty effects on glucose, blood pressure and cholesterol in people with metabolic disease.
• It may blunt some exercise benefits. In older men, 250 mg/day reduced training gains in VO₂max, blood pressure and lipids; a later trial with 500 mg/day found better muscle adaptations, so the picture is mixed.
• No lifespan extension in normal mice. Two NIA ITP studies found no effect on mouse lifespan; no human lifespan data exist.
• Interactions matter at high doses. 1 g/day changed several CYP450 enzymes in volunteers, and grams per day cause GI upset.

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