Resveratrol

Overview

Resveratrol is a plant polyphenol found in grape skins and red wine, and it is the compound behind the sirtuin claims that made the supplement famous. The sirtuin activation was first reported with a fluorescent tag on the test peptide. Without the tag, two papers from 2009 and 2010 found no activation, and human trials at 150 mg to 5 g a day show small, mixed effects.

What is Resveratrol?

Quick facts

Key Takeaways

• The sirtuin activation claim came from a fluorescent tag on the test peptide. Two papers from 2009 and 2010 found no SIRT1 activation with untagged substrates (Beher et al., 2009; Pacholec et al., 2010).
• Human trials used daily doses from 150 mg to 5 g. The 250 mg in one MAV serving sits inside that range, below the 1.5 g and 5 g doses used in other trials.
• One 26-week trial in 46 older adults (200 mg a day) reported better 30-minute word recall than placebo (p = 0.038) on a single memory measure.
• In 11 obese men, 30 days at 150 mg a day improved the HOMA index and lowered triglycerides (Timmers et al., 2011). A 4-week trial in 24 obese men at 1.5 g a day found no change in insulin sensitivity (Poulsen et al., 2013).
• After one 500 mg tablet, three volunteers reached roughly 300 to 400 ng per mL of resveratrol in plasma at 90 minutes. The 50 micromolar concentration used in many sirtuin assays is about 11,400 ng per mL (Poulsen et al., 2013).
• Plasma resveratrol is mostly in conjugated forms. After 29 days at 0.5 to 5 g a day, the main metabolites reached exposure up to 20.3 times that of the parent compound (Brown et al., 2010).
• A 2010 healthy-volunteer study reported lower activity indices for CYP3A4, CYP2D6 and CYP2C9 at 1 g a day for four weeks, as summarized by EFSA in 2016. Ask a clinician if you take medicines these enzymes clear.

What Is Resveratrol?

Resveratrol is a stilbene, a small plant molecule in the polyphenol family. Plants produce it as a defense against stress and infection, which is why it turns up in grape skins and wine. Red wine averages about 1.9 mg per liter, so a glass delivers a small amount at most (Poulsen et al., 2013).

The supplement market mostly uses two sources. The first is synthetic or purified trans-resveratrol, the form named in the 2014 crossover trial by Wightman et al. and in the EFSA safety opinion. The second is botanical extract from Polygonum cuspidatum (Japanese knotweed) root. The MAV serving uses the root extract. Its label gives 250 mg of resveratrol and does not state how much of that is the trans form.

How the body handles it

Absorption is fast. In a pilot with three volunteers, traceable resveratrol appeared in plasma within 15 minutes of a single 500 mg tablet, and concentrations peaked at about 90 minutes, at 300 to 400 ng per mL (Poulsen et al., 2013). Most of the material that follows is conjugated. In Brown et al. (2010), resveratrol-3-O-sulfate, resveratrol-4'-O-glucuronide and resveratrol-3-O-glucuronide were the major plasma forms. Their exposure reached up to 20.3 times the parent compound's exposure during the 29-day study. EFSA reports conjugate half-lives of 3.2 to 11.5 hours for the sulfate and 2.9 to 10.6 hours for the glucuronides (EFSA, 2016).

What the blood concentrations mean

Many lab studies run at micromolar concentrations. Brown et al. (2010) reported micromolar plasma levels of the parent compound at daily doses of 0.5 to 5 g. The abstracts checked for this page did not report plasma parent levels at 250 mg, the dose in one MAV serving. The gap between lab concentrations and what a supplement dose delivers is the first reason to read sirtuin claims with care.

Where the longevity idea came from

Much of resveratrol's longevity reputation comes from animal work. Baur et al. (2006) reported that mice on a high-calorie diet given resveratrol had health markers closer to those of mice on a standard diet, and significantly longer survival. Those were mice on one specific diet, not people. The human trials discussed below measured metabolic and cognitive markers, not survival.

Quercetin, another plant polyphenol, has its own monograph. The NAD+ precursors in the same MAV serving have monographs too: NMN and NR.

How it works

Sirtuins are protein deacetylases. They remove acetyl groups from target proteins and use NAD+ in each reaction, which ties their activity to the cell's energy state (Gertz et al., 2012). SIRT1 is the sirtuin most often linked to resveratrol. It acts on transcription factors that run energy metabolism, including PGC-1α and NF-κB (Poulsen et al., 2013). Mitochondria and NAD+ are covered in the mitochondrial health guide and the NAD+ and cellular energy guide.

The proposed chain runs like this. Resveratrol binds SIRT1 and makes it act more efficiently on its targets. The proposed chain then runs through those target proteins into mitochondrial energy metabolism. That chain is proposed, not proven in people. In one 11-person trial, muscle showed higher SIRT1 and PGC-1α protein, more AMPK activation and better mitochondrial respiration on a fatty-acid substrate after 30 days at 150 mg a day (Timmers et al., 2011). A larger-dose trial at 1.5 g a day found no change in AMPK activation (Poulsen et al., 2013).

The assay history

The assay work matters here. Pacholec et al. (2010) tested resveratrol and related compounds with native peptide and full-length protein substrates. They found no apparent SIRT1 activation. Activation appeared only with a peptide carrying a covalently attached fluorophore, and binding studies showed that the compounds contact that fluorophore directly. Beher et al. (2009) reached the same conclusion with a p53-derived peptide and with acetylated PGC-1α.

Gertz et al. (2012) complicated the picture. In their assays, resveratrol stimulated Sirt5 and inhibited Sirt3 on fluorophore-free peptides and proteins, and the effect depended on which sirtuin and which substrate were used. That paper did not test SIRT1 on fluorophore-free substrates, so it does not settle the SIRT1 question in people.

Evidence at a glance

For the wider blood-pressure evidence, see the heart and blood pressure guide. For the broader memory evidence, see brain health and focus.

What the evidence doesn't support yet

Four popular claims have outrun the data.

1. Resveratrol activates SIRT1 in people at supplement doses. None of the trials checked measured SIRT1 activity. The one trial that measured SIRT1 found more SIRT1 protein in muscle, which is not the same as activity (Timmers et al., 2011). A 4-week trial at 1.5 g a day measured total lysine acetylation in muscle and found no change (Poulsen et al., 2013).

2. Resveratrol extends human lifespan. The survival result comes from mice on one high-calorie diet (Baur et al., 2006). The studies checked here measured no human survival outcome.

3. Resveratrol sharpens memory in older adults in a clinically meaningful way. One 26-week trial in 46 people found better word retention than placebo at p = 0.038, on a single memory measure (Witte et al., 2014). That is a signal worth a larger trial, not a settled result.

4. Resveratrol raises blood NAD+. A PubMed search for randomized human trials of resveratrol and blood NAD+ returned no results on 20 October 2026. The combination of resveratrol with NAD+ precursors has not been tested in a human trial in the sources checked for this page.

Related reading

• Trimethylglycine (TMG): the methyl donor in the same stack

Clinical evidence

• Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans — Who and how many: 11 healthy obese men in a double-blind crossover against placebo. Duration and dose: 30 days at 150 mg a day of resveratrol (resVida, a DSM product). Measured: resting and sleeping metabolic rate, muscle signaling, blood lipids, glucose and blood pressure. Result: resting metabolic rate fell; HOMA index improved; systolic pressure dropped; muscle SIRT1 and PGC-1alpha protein rose. Limitation: 11 men and a crossover design; one author is affiliated with DSM Nutritional Products, the maker of the ingredient.
• High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition — Who and how many: 24 obese men, randomized and double-blind against placebo, with 12 per arm analyzed for most measures. Duration and dose: 4 weeks of 500 mg tablets three times daily, or 1.5 g a day. Measured: insulin sensitivity by clamp (primary outcome), energy expenditure, ectopic fat, 24-hour blood pressure, inflammatory markers and AMPK activation. Result: no significant change in insulin sensitivity or blood pressure; body composition and ectopic fat unchanged. Limitation: 4 weeks and a small sample. The authors suggest baseline differences may explain the gap with Timmers et al.
• Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults — Who and how many: 46 healthy overweight adults aged 50 to 75, placebo-controlled, with 23 per arm completing. Duration and dose: 26 weeks at 200 mg a day. Measured: memory tasks, hippocampal imaging, HbA1c, body fat and leptin. Result: word retention over 30 minutes beat placebo (p = 0.038); hippocampal connectivity rose; HbA1c and body fat fell. Limitation: one memory measure reached significance; small groups; completers were matched in pairs.
• Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation — Who and how many: 23 adults in a double-blind crossover on separate days. Dose: single doses of placebo, 250 mg trans-resveratrol, or 250 mg plus 20 mg piperine. Measured: frontal blood flow by near-infrared spectroscopy during cognitive tasks, cognition, mood, blood pressure, and plasma levels in a separate group of six. Result: blood flow rose during tasks only with the combination; cognition, mood and blood pressure were unchanged; plasma resveratrol did not differ between treatments. Limitation: single doses only, and the plasma group was six people.
• Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis — Who and how many: 40 healthy volunteers in four dose groups. Duration and dose: 0.5, 1.0, 2.5 or 5.0 g a day for 29 days. Measured: safety, plasma resveratrol and metabolites, IGF-I and IGFBP-3. Result: resveratrol was safe; 2.5 g and 5 g caused mild to moderate gastrointestinal symptoms; conjugate exposure reached up to 20.3 times that of the parent compound; IGF-I and IGFBP-3 fell. Limitation: doses far above a supplement serving, and no placebo arm is described in the abstract.
• Resveratrol improves health and survival of mice on a high-calorie diet — Who and how many: mice fed a high-calorie diet, with and without resveratrol. Duration: followed to survival. Measured: health markers and survival. Result: resveratrol moved health markers toward those of mice on a standard diet and significantly increased survival. Limitation: mice on one high-calorie diet; no human survival data.
• SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1 — Who and how many: enzyme assays with purified SIRT1, plus NMR, surface plasmon resonance and calorimetry on binding. Measured: SIRT1 deacetylation with native peptide and full-length protein substrates, compared with a fluorophore-labeled peptide. Result: resveratrol gave no apparent activation with native substrates and activated only the fluorophore-labeled peptide; the compounds bound the fluorophore directly. Limitation: test-tube systems; one mouse experiment with the related compound SRT1720 found no change in glucose or mitochondrial capacity.
• Resveratrol is not a direct activator of SIRT1 enzyme activity. — Who and how many: enzyme assays with purified SIRT1. Measured: deacetylation of a p53-derived peptide and of acetylated PGC-1alpha, with and without resveratrol, and the fluorophore-labeled peptide compared. Result: the fluorophore-labeled peptide is not a substrate without its label, and resveratrol did not activate SIRT1 with the other two substrates. Limitation: in vitro only; the authors conclude that effects in animal models are unlikely to come from direct SIRT1 activation.
• A molecular mechanism for direct sirtuin activation by resveratrol. — Who and how many: enzyme assays with human Sirt3 and Sirt5, plus crystal structures of each with a peptide and a modulator. Measured: deacetylation of fluorophore-labeled and fluorophore-free peptides and proteins. Result: resveratrol inhibited Sirt3 and stimulated Sirt5; with the fluorophore-free full-length Prx1 protein, Sirt5 deacetylation rose about 2.7-fold. The sirtuin and the substrate set the direction of the effect. Limitation: concentrations around 0.2 millimolar; SIRT1 was not tested on fluorophore-free substrates.

Dosage & forms

• Trans-resveratrol capsule or tablet (synthetic or purified):
• Botanical root extract (Polygonum cuspidatum, Japanese knotweed):
• Trans-resveratrol with piperine (black pepper extract):
• Food sources: grapes and red wine:

Safety & interactions

How much to take

The trials checked here used daily doses from 150 mg to 5 g. Timmers et al. (2011) used 150 mg a day for 30 days, and that dose produced the metabolic changes reported in that trial. Witte et al. (2014) used 200 mg a day for 26 weeks, and that dose produced the memory signal. Poulsen et al. (2013) used 1.5 g a day for 4 weeks and found no change in the primary outcome. Brown et al. (2010) tested 0.5, 1.0, 2.5 and 5.0 g a day for 29 days, mainly to measure safety and blood levels.

The MAV serving, NMN + NR with Resveratrol and TMG, contains 250 mg of resveratrol from Polygonum cuspidatum root in 2 capsules, and the label says to take 2 capsules daily. That daily dose is above the 150 mg and 200 mg doses that produced reported changes, and it matches the single 250 mg dose in Wightman et al. (2014). The comparison is about dose only. It is not evidence that the serving produces any outcome the trials measured, and the one 250 mg trial measured blood flow only when piperine was added.

No government body has set an upper intake level for resveratrol in the sources checked for this page. EFSA, the EU food safety agency, assessed synthetic trans-resveratrol as a novel food in 2016 and judged a daily intake of 150 mg safe for adults under the conditions the applicant proposed (EFSA, 2016). EFSA set no upper limit, and its opinion covers that synthetic product, not a root extract. The label serving is above the 150 mg figure, and the label does not say how much of the 250 mg is trans-resveratrol, the form EFSA assessed.

Timing and food were not compared in the sources checked here. The 2013 trial dosed tablets three times a day (Poulsen et al., 2013). The one trial that combined resveratrol with another ingredient used piperine (Wightman et al., 2014). No trial checked here tested other pairings.

Changes in the trials appeared after 30 days for the metabolic outcomes (150 mg) and after 26 weeks for memory (200 mg). A 4-week trial at 1.5 g did not show the same changes. The trials do not test a range of doses for one outcome, so this page cannot name a point of diminishing returns.

Safety profile

Resveratrol was generally well tolerated in the trials checked. In the 29-day study, the 2.5 g and 5 g doses caused mild to moderate gastrointestinal symptoms, and the lower doses were safe (Brown et al., 2010). In the 4-week trial at 1.5 g a day, placebo and resveratrol tablets were both generally well tolerated. One participant developed a generalized rash after a week and left the study. The paper does not say whether the tablets caused it (Poulsen et al., 2013).

Side effects by frequency: the common ones at high doses are diarrhea, nausea and abdominal discomfort. EFSA reports diarrhea or other gastrointestinal symptoms in four uncontrolled studies at 1 g a day or higher (EFSA, 2016). Less common: heartburn, which EFSA lists among events in the study data it examined (EFSA, 2016).

Signs of taking too much are the ones seen at the highest doses: stomach upset and loose stools (Brown et al., 2010; EFSA, 2016).

Interactions

Who should ask first

• People taking prescription medicines, especially medicines cleared by CYP2C9, CYP3A4 or CYP2D6, and anyone taking blood-thinning or antiplatelet medicine.
• People with a bleeding disorder. This page did not verify a specific bleeding mechanism for resveratrol in people, so this advice rests on caution, not a documented effect.
• Pregnant or breastfeeding people. EFSA's assessment targeted adults, and it reported a lower margin of exposure in pregnant rats (below 62) than in female rats (172) (EFSA, 2016).

If you take a prescription medicine, or you are pregnant or breastfeeding, ask a clinician or pharmacist before you start, and bring the label dose with you.

Buying guide

Use this checklist in the store aisle or on the product page. It takes about a minute.

The dose

The human trials checked for this page used 150 mg to 5 g a day. Check the resveratrol amount per serving and per day on the label, not the headline on the front of the bottle. A 250 mg serving sits inside that range. A product that lists 2 mg or 2 g per serving is far from anything the trials tested.

The form

Look for trans-resveratrol, or ask for the trans share in writing. The trials checked used trans-resveratrol or a named product (Wightman et al., 2014; Timmers et al., 2011). Botanical extracts can be sold with a total resveratrol figure and no trans figure, so the form question is the one to ask about.

Proof of testing

Mt. Angel Vitamins is a brand of Highland Laboratories, which makes its supplements in Mt. Angel, Oregon, in a cGMP facility. Every incoming lot is tested for identity, potency, heavy metals and microbes, and the product page says ISO 17025-accredited outside labs check the results. Certificates of analysis are published by lot at lab testing and certificates of analysis, and the MAV product page links a lot-specific certificate for this formula. Ask every brand for the same thing, including us.

Fillers and excipients

The MAV label lists a vegetarian capsule (hypromellose and water), organic brown rice and magnesium stearate as other ingredients, and each active has a stated amount. A proprietary blend that hides the resveratrol amount is the signal to avoid. For the full label checklist, see how to check an NMN or NR label.

Price per day

The MAV product lists at $59.99 for 60 capsules. The label gives 30 servings of 2 capsules, which works out to about $2.00 a day. Divide any price by its servings per container, then compare the resveratrol per day, not per bottle. Check the price on the day you buy, since prices change.

Red flags

• Proprietary blends that hide the dose.
• "Clinically proven" with no named study.
• Doses far outside the 150 mg to 5 g range the trials used.
• Any claim that resveratrol activates sirtuins in people. Two papers from 2009 and 2010 found no activation with untagged substrates (Beher et al., 2009; Pacholec et al., 2010).

Bottom line

Read the amount per serving and the form before you read any claim. The human trials cited here are small and short, and the largest had 46 people. This page can tell you the dose, the form and the testing to look for, but it cannot tell you that a supplement will produce a particular outcome. If you compare NMN and NR products too, the best NMN + NR supplements guide covers this category.

Related reading

• Zinc in a resveratrol and NAD+ formula
• Reishi history: ancient texts to modern trials
• the 1939 isolation and the trials that have not settled the question

Frequently Asked Questions

What is resveratrol and where does it come from?

Resveratrol is a plant polyphenol. Plants make it as a defense against stress and infection, so it appears in grape skins and red wine, which averages about 1.9 mg per liter (Poulsen et al., 2013). Most supplements use either synthetic or purified trans-resveratrol or an extract of Polygonum cuspidatum (Japanese knotweed) root. The form on a label matters, because the trials checked used trans-resveratrol or a named product.

Does resveratrol activate SIRT1 in the body?

Not in people, as far as the sources checked show. The SIRT1 activation reports used a peptide with a fluorescent tag, and two papers from 2009 and 2010 found no activation without the tag (Beher et al., 2009; Pacholec et al., 2010). Gertz et al. (2012) reported stimulation of Sirt5 and inhibition of Sirt3 with untagged substrates, but did not test SIRT1 that way. One 11-person trial measured higher SIRT1 protein in muscle, which is not the same as activity (Timmers et al., 2011).

What did the assay studies show about resveratrol and sirtuins?

Pacholec et al. (2010) found no SIRT1 activation with native peptide or full-length protein substrates, and activation only with a fluorophore-labeled peptide. Beher et al. (2009) found no activation with a p53-derived peptide or with acetylated PGC-1alpha. Gertz et al. (2012) found that resveratrol stimulated Sirt5 and inhibited Sirt3 on untagged substrates, at concentrations around 0.2 millimolar. The sirtuin and the substrate set the direction of the effect.

How much resveratrol do human trials use, and how does 250 mg compare?

The daily doses in the trials checked were 150 mg for 30 days (Timmers et al., 2011), 200 mg for 26 weeks (Witte et al., 2014) and 1.5 g for 4 weeks (Poulsen et al., 2013). Brown et al. (2010) tested 0.5 to 5 g a day for 29 days. The 2-capsule serving gives 250 mg a day. That sits inside the range the trials used, above the two doses that reported changes, and close to the single 250 mg dose in Wightman et al. (2014). That is a dose comparison. It does not show that the serving produces any outcome.

How well is resveratrol absorbed, and what happens to it after?

Absorption is fast, but the parent compound stays low in plasma. In a three-person pilot, one 500 mg tablet peaked at 300 to 400 ng per mL at about 90 minutes (Poulsen et al., 2013). Most of what follows is conjugated. The sulfate and glucuronide forms reached exposure up to 20.3 times that of the parent in the 29-day study (Brown et al., 2010). EFSA reports conjugate half-lives of about 3 to 11 hours (EFSA, 2016).

Who should ask a clinician before taking resveratrol?

People taking prescription medicines should ask a clinician first, especially for drugs cleared mainly by CYP2C9, CYP3A4 or CYP2D6. People taking blood-thinning or antiplatelet medicines should ask too. People with a bleeding disorder should ask a clinician before starting. Pregnant or breastfeeding people should ask as well, because EFSA's assessment targeted adults and reported a lower margin of exposure in pregnant rats (EFSA, 2016).

Are there documented drug interactions with resveratrol?

In people, one 2010 healthy-volunteer study reported lower activity indices for CYP3A4, CYP2D6 and CYP2C9 after resveratrol (PubMed 20716633). EFSA summarized that study at 1 g a day for four weeks (EFSA, 2016). In lab tests, the sulfate metabolite inhibited CYP2C9 at an IC50 near 9 micromolar (EFSA, 2016). No controlled human study of a clinically important interaction was found in the sources checked for this page.

Do I need resveratrol at all?

Not for any outcome the trials checked here show clearly. The memory result is one measure in one 26-week trial of 46 people (Witte et al., 2014), and it deserves a larger test. If you want resveratrol for a specific reason, check the trans share, the amount per serving and the price per day, and ask a clinician first if you take prescription medicine. Red wine delivers about 1.9 mg per liter, far less than any dose used in the trials (Poulsen et al., 2013).