Resveratrol
The polyphenol behind the 'French Paradox' — a SIRT1 activator with cardiovascular and longevity potential
Also known as: Trans-Resveratrol • Red Wine Extract • Japanese Knotweed Extract
Overview
Resveratrol is a polyphenol found in red wine, grapes, and Japanese knotweed that gained fame as the potential explanation for the 'French Paradox' — the observation that the French have low heart disease rates despite a high-fat diet. Resveratrol activates sirtuins (particularly SIRT1), a family of proteins involved in cellular stress response, DNA repair, and longevity pathways. It also activates AMPK (the cellular energy sensor) and inhibits NF-kB (a master inflammatory switch). While animal studies showed dramatic lifespan extension, human evidence is more modest but still promising for cardiovascular health, insulin sensitivity, and inflammation. The key challenge is bioavailability — resveratrol is rapidly metabolized, and most of the circulating forms are conjugated metabolites rather than free resveratrol.
Key Benefits
Cardiovascular Protection
Resveratrol improves endothelial function, reduces LDL oxidation, inhibits platelet aggregation, and has anti-inflammatory effects on blood vessels. Meta-analyses show improvements in systolic blood pressure and flow-mediated dilation (a measure of vascular health).
SIRT1 Activation & Longevity Pathways
Resveratrol is the most studied natural SIRT1 activator. SIRT1 regulates DNA repair, mitochondrial biogenesis, inflammation, and stress resistance. In animal models, resveratrol extended lifespan and improved healthspan markers, particularly in the context of metabolic stress.
Insulin Sensitivity
Clinical trials show resveratrol improves insulin sensitivity and reduces fasting glucose, particularly in people with type 2 diabetes or metabolic syndrome. It activates AMPK, the same pathway targeted by metformin.
Anti-Inflammatory
Resveratrol inhibits NF-kB, COX-2, and multiple inflammatory cytokines. Clinical studies show reductions in CRP, TNF-alpha, and IL-6 — key markers of chronic inflammation.
Dosage & How to Take
150-500mg trans-resveratrol daily. Higher doses (1,000-2,000mg) have been studied but may cause GI side effects. The sweet spot for most people is 250-500mg. Always choose trans-resveratrol (the active isomer) over cis-resveratrol.
| Purpose | Dose | Notes |
|---|---|---|
| Cardiovascular health | 150-250 mg/day | Lower doses may be optimal for vascular benefits |
| Metabolic health/insulin sensitivity | 250-500 mg/day | Based on clinical trials in metabolic syndrome |
| Anti-aging/SIRT1 activation | 250-500 mg/day | Optimal dose for sirtuin activation unclear in humans |
| Anti-inflammatory | 500 mg/day | Higher doses for inflammatory conditions |
Best Time to Take
Take with a fat-containing meal to improve absorption. Some evidence suggests morning dosing is better for metabolic effects.
With or Without Food
Always take with food containing fat. Bioavailability is significantly improved with dietary fat and other polyphenols.
Forms & Bioavailability
| Form | Absorption | Best For | Notes |
|---|---|---|---|
| Trans-Resveratrol (Japanese Knotweed) | Low-Moderate | Standard supplementation | Most common source. Standardized to 50-98% trans-resveratrol. |
| Micronized Trans-Resveratrol | Improved | Better absorption | Smaller particle size improves dissolution and absorption. |
| Resveratrol + Piperine | Enhanced | Maximum absorption | Piperine (black pepper extract) inhibits glucuronidation, increasing free resveratrol levels. |
Side Effects & Safety
Common
- GI upset (nausea, diarrhea) at high doses
- Headache
Rare
- Kidney issues at very high doses (>2.5g/day)
- Interaction with blood thinners
Contraindications
- Anticoagulant medications (resveratrol has mild antiplatelet effects)
- Estrogen-sensitive conditions (resveratrol has weak estrogenic activity)
- Surgery (stop 2 weeks before due to antiplatelet effects)
Interactions
Resveratrol has antiplatelet effects; may increase bleeding risk
Resveratrol inhibits CYP3A4 enzyme; may increase levels of many medications
Synergistic — quercetin inhibits resveratrol metabolism, increasing its bioavailability
Scientific Research
Resveratrol and Cardiovascular Health Meta-Analysis
Resveratrol supplementation significantly improved flow-mediated dilation and reduced systolic blood pressure
Resveratrol and Insulin Sensitivity
250mg/day resveratrol for 3 months improved insulin sensitivity and reduced HbA1c in type 2 diabetes patients
Resveratrol and SIRT1
Resveratrol activated SIRT1 and extended lifespan in mice on a high-fat diet, improving metabolic health markers
Food Sources
Frequently Asked Questions
Medical Disclaimer
This content is for educational and informational purposes only and is not intended as medical advice. Always consult with a qualified healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications. The statements on this page have not been evaluated by the Food and Drug Administration.