Resveratrol
Evidence Fact Sheet
trans-resveratrol
Resveratrol (trans-resveratrol) is a polyphenol/stilbene studied for vascular, glycemic, and inflammatory research markers via SIRT1/eNOS/NF-kB pathways. Human RCT evidence concentrates in disease populations (T2DM, metabolic syndrome, CAD) and is mixed, with several honest null findings. US dietary-supplement ingredient; EU Novel Food (≤150 mg/day).
Also known as: trans-Resveratrol · 3,5,4'-trihydroxy-trans-stilbene · Polygonum cuspidatum extract (knotweed-derived)
Overview
Resveratrol is a naturally occurring polyphenol (stilbene; trans-resveratrol), typically derived from Japanese knotweed (Polygonum cuspidatum). In research models it is framed as a SIRT1 activator with reported effects on endothelial eNOS/nitric-oxide signaling, NF-kB-mediated inflammatory pathways, and Nrf2/AMPK antioxidant signaling, and is often described as a calorie-restriction mimetic — though SIRT1-specificity is contested and no human longevity endpoint has been demonstrated. Common RCT doses span roughly 150-1500 mg/day, with doses at or above ~2 g/day associated with gastrointestinal effects; oral bioavailability is very low. In the US it is a legal dietary-supplement ingredient permitting structure/function (not disease) claims, and in the EU trans-resveratrol is an authorised Novel Food for food supplements at up to 150 mg/day for adults. It is not approved as a China novel food/health-food raw material.
Mechanism of Action
SIRT1 activation reported (deacetylase activity → mitochondrial biogenesis / autophagy / epigenetic modulation); SIRT1-specificity is contested in the literature (specificity questioned by later pharmacology studies) · Endothelial eNOS activation → NO bioavailability (research-context mechanism) · NF-κB inhibition → CRP / IL-6 / TNF-α downregulation (research-context anti-inflammatory pathway) · Nrf2 / AMPK pathway activation → antioxidant defense (mechanistic) · Proposed calorie-restriction mimetic (preclinical framing · not demonstrated in human longevity endpoints)
Body systems: Cardiovascular · Endocrine & Metabolic · Immune System · Cellular Renewal · Mitochondrial & Cellular Energy · DNA & Epigenetic
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — Resveratrol is not characterized as a treatment for any disease.
Endothelial / Vascular Function
Meta-analysis supported- WMD 1.43%FMD · p<.001
- −7.09 ng/mlICAM-1 · p<.001
- 17 studies21 arms pooled
In a meta-analysis of randomized controlled trials, resveratrol supplementation significantly improved flow-mediated dilation (a marker of endothelial function) and lowered the adhesion molecule ICAM-1. The authors framed this as potentially important in cardiovascular-disease populations.
Reported effect: FMD WMD 1.43% (95% CI 0.98 to 1.88, p<.001); ICAM-1 WMD −7.09 ng/ml (95% CI −7.45 to −6.73, p<.001); 21 arms from 17 studies
“resveratrol significantly change the concentrations of FMD (WMD: 1.43%; 95% CI: 0.98 to 1.88, p < .001) ... ICAM-1 (WMD: -7.09 ng/ml, 95% CI: -7.45 to -6.73, p < .001)”
Source: PMID 35833325 · Mohammadipoor 2022 · Phytother Res
Glycemic Control (Type 2 Diabetes)
Meta-analysis supported- SMD −0.64HbA1c · p=0.01
- SMD −0.34HOMA-IR · p=0.01
A systematic review and meta-analysis found resveratrol supplementation was associated with statistically significant reductions in HbA1c and insulin resistance (HOMA-IR), with the fasting-glucose benefit significant only in individuals with diabetes. Heterogeneity was high (I2 up to 90%), so the pooled estimate is uncertain.
Reported effect: HbA1c SMD −0.64 (95% CI −1.22, −0.07; p=0.01; I2=90%); HOMA-IR SMD −0.34 (95% CI −0.64, −0.04; p=0.01; I2=70%); fasting glucose SMD −0.85 (diabetes subgroup; p=0.01)
“Glycated Hemoglobin (HbA1c): SMD: -0.64; CI 95%: -1.22, -0.07; p = 0.01; I2 = 90% ... Insulin Resistance (HOMA-IR): SMD: -0.34; CI 95%: -0.64, -0.04; p = 0.01; I2 = 70%”
Source: PMID 33480264 · Delpino 2022 · Crit Rev Food Sci Nutr
Inflammatory Markers
Meta-analysis supported- WMD −0.44TNF-α · p=0.002
- WMD −0.27hs-CRP · p=0.033
- 17 RCTs736 subjects
A meta-analysis of 17 RCTs reported significant reductions in TNF-α and hs-CRP with resveratrol supplementation, but no significant effect on IL-6 — a mixed inflammatory profile rather than a uniform anti-inflammatory effect.
Reported effect: TNF-α WMD −0.44 (95% CI −0.71 to −0.164; P=0.002); hs-CRP WMD −0.27 (95% CI −0.5 to −0.02; P=0.033); IL-6 WMD −0.16 (95% CI −0.53 to 0.20; P=0.38, non-significant); 17 RCTs, 736 subjects
“significant reductions in the level of TNF-α (WMD, -0.44; 95% CI, -0.71 to -0.164; P = 0.002 ... hs-CRP (WMD, -0.27; 95% CI, -0.5 to -0.02; P = 0.033 ... no significant effect on the level of IL-6 (WMD, -0.16; 95% CI, -0.53 to 0.20; P = 0.38”
Source: PMID 30017172 · Koushki 2018 · Clin Ther
Blood Pressure (Metabolic Syndrome)
Null / no benefit Meta-analysis supported- SMD −0.27systolic BP · p=0.07 (ns)
- SMD −0.21diastolic BP · p=0.19 (ns)
- 28 RCTspooled trials
In a meta-analysis of 28 RCTs in metabolic-syndrome patients, resveratrol significantly increased flow-mediated dilation but did NOT significantly change systolic or diastolic blood pressure — an honest null on blood pressure despite a vascular-function signal.
Reported effect: Systolic BP SMD −0.27 (95% CI −0.57, 0.03; P=0.07, non-significant); diastolic BP SMD −0.21 (95% CI −0.52, 0.11; P=0.19, non-significant); FMD SMD 1.77 (95% CI 0.25, 3.29; P=0.02); 28 RCTs
“resveratrol supplements did not affect systolic blood pressure (SBP) (SMD - 0.27; 95% CI - 0.57, 0.03; P = 0.07 ... diastolic blood pressure (DBP) (SMD - 0.21; 95% CI - 0.52, 0.11; P = 0.19”
Source: PMID 31264084 · Akbari 2019 · High Blood Press Cardiovasc Prev
Glucose Metabolism (Older Adults · Null RCT)
Null / no benefit RCT supported- 2.02 vs 1.76reactive hyperemia · p=.002
- 30 adultsglucose-intolerant
- 2-3 g/day6-week crossover
In a randomized double-blind crossover trial of glucose-intolerant older adults, resveratrol improved the fasting reactive hyperemia index (vascular function) but produced no changes in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipids — a clear dissociation between vascular benefit and metabolic null.
Reported effect: Fasting reactive hyperemia index 2.02 ± 0.2 vs 1.76 ± 0.02 (p=.002); NO changes in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipid profile; n=30, resveratrol 2-3 g/day for 6 weeks
“Fasting reactive hyperemia index improved with resveratrol (2.02 ± 0.2 vs 1.76 ± 0.02, p = .002) ... There were no changes in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipid profile following resveratrol treatment.”
Source: PMID 28329397 · Pollack 2017 · J Gerontol A Biol Sci Med Sci
Type 2 Diabetes (Cochrane · Insufficient Evidence)
Null / no benefit Meta-analysis supported- MD 0.1%HbA1c · p=0.09 (ns)
- MD 2 mg/dLfasting glucose · p=0.29 (ns)
- 2 studies31 participants
A Cochrane systematic review found neutral effects of resveratrol versus placebo on HbA1c, fasting glucose, and insulin resistance, but rated the evidence as very low-certainty from very few small studies, concluding the research is insufficient to evaluate safety or efficacy in adults with T2DM.
Reported effect: HbA1c MD 0.1% (95% CI −0.02 to 0.2; P=0.09; 2 studies, 31 participants; very low-certainty); fasting glucose MD 2 mg/dL (95% CI −2 to 7; P=0.29); insulin resistance MD −0.35 (95% CI −0.99 to 0.28; P=0.27)
“Resveratrol versus placebo showed neutral effects for glycosylated haemoglobin A1c (HbA1c) levels (mean difference (MD) 0.1%, 95% confidence interval (CI) -0.02 to 0.2; P = 0.09; 2 studies; 31 participants; very low-certainty evidence). ... Currently, research is insufficient for review authors to evaluate the safety and efficacy of resveratrol supplementation for treatment of adults with T2DM.”
Source: PMID 31978258 · Jeyaraman 2020 · Cochrane Database Syst Rev
Dosage (research context · not a recommendation)
150-1500 mg/day trans-resveratrol (common RCT range · educational reference) · ≥2 g/day associated with gastrointestinal effects
Regulatory Status · 4 Markets
- US · FDA
- Legal dietary supplement ingredient (trans-resveratrol) · multiple NDI notifications on file · structure/function claims permissible (antioxidant support / heart health support / healthy aging) with mandatory DSHEA disclaimer · NO disease claims
- EU · EFSA
- trans-Resveratrol is an authorised EU Novel Food (Commission Implementing Decision (EU) 2016/1190) for food supplements (<=150 mg/day, adults); EFSA did not authorise any Reg 432/2012 resveratrol health claim.
- CN · China
- Not approved as a China novel food ingredient or SAMR health-food raw material; cleared only for cosmetic use; sold domestically via cross-border e-commerce gray channel only.
- BR · ANVISA
- RDC 243/2018 dietary-supplement framework available · no resveratrol-specific Anexo V alegação funcional
Safety
Generally well tolerated at ≤500 mg/day in short-term trials; high doses (≥2-2.5 g/day) associated with gastrointestinal side effects. Inhibits multiple cytochrome P450 enzymes (incl. CYP3A4) → potential interaction with prescription medications and anticoagulants. Oral bioavailability is very low (<1%), so systemic exposure at marketed doses is uncertain. Pregnant individuals should avoid supplementation (preclinical placental-flow signal · Bourque/Roberts primate studies). Consult a healthcare provider before use if on prescription medication.
Related
Goals: longevity-stack · heart-health
Lifestyles: intermittent-fasting · senior-60-plus
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 35833325 · Mohammadipoor 2022 · Phytother Res — Endothelial / Vascular Function
- PMID 33480264 · Delpino 2022 · Crit Rev Food Sci Nutr — Glycemic Control (Type 2 Diabetes)
- PMID 30017172 · Koushki 2018 · Clin Ther — Inflammatory Markers
- PMID 31264084 · Akbari 2019 · High Blood Press Cardiovasc Prev — Blood Pressure (Metabolic Syndrome)
- PMID 28329397 · Pollack 2017 · J Gerontol A Biol Sci Med Sci — Glucose Metabolism (Older Adults · Null RCT)
- PMID 31978258 · Jeyaraman 2020 · Cochrane Database Syst Rev — Type 2 Diabetes (Cochrane · Insufficient Evidence)
Frequently Asked Questions
1. What does the strongest human evidence for resveratrol actually show?
The most consistent signal is on endothelial/vascular function: a meta-analysis of 17 studies (21 arms) found resveratrol significantly improved flow-mediated dilation (WMD 1.43%, p<.001). Glycemic and inflammatory findings are more mixed — pooled HbA1c reductions appear in some meta-analyses (SMD −0.64) but a Cochrane review rated T2DM evidence as very low-certainty and insufficient. Most evidence comes from disease populations (T2DM, metabolic syndrome), not healthy adults.
2. Are there honest negative or null findings?
Yes, several. A meta-analysis of 28 RCTs in metabolic-syndrome patients found resveratrol did NOT significantly change systolic (p=0.07) or diastolic (p=0.19) blood pressure. A randomized crossover trial in 30 glucose-intolerant older adults improved vascular function (reactive hyperemia) but showed no change in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipids. And the inflammatory meta-analysis found no significant effect on IL-6 (p=0.38) despite reductions in TNF-α and CRP.
3. Does resveratrol extend lifespan or activate SIRT1 in humans?
The SIRT1-activation and calorie-restriction-mimetic framing comes from preclinical (cell and animal) work, and SIRT1-specificity is contested in the pharmacology literature. There is no human RCT with an aging or lifespan endpoint demonstrating longevity benefit. This page reports measured research markers (vascular, glycemic, inflammatory) in studied populations, not anti-aging outcomes.
4. What doses and regulatory status apply?
Common RCT doses range roughly 150-1500 mg/day, with doses around 2 g/day or more linked to gastrointestinal effects (the older-adult RCT used 2-3 g/day). In the US, trans-resveratrol is a legal dietary-supplement ingredient permitting structure/function (not disease) claims; in the EU it is an authorised Novel Food for food supplements at up to 150 mg/day for adults. It is not approved as a China novel food or health-food raw material. This is evidence reporting, not dosing or clinical guidance — consult a healthcare provider, especially given low oral bioavailability and CYP enzyme interactions.
Last evidence review: 2026-06-13