Resveratrol
A polyphenol found in red wine, grapes, and berries that activates SIRT1 sirtuins and AMPK, studied for cardiovascular protection, anti-aging, and metabolic health.
What is Resveratrol?
Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic stilbene produced by plants as a defense phytoalexin in response to stress, infection, and UV radiation. It is the compound most associated with the 'French Paradox' — the observation of low cardiovascular mortality despite high saturated fat intake in French populations consuming red wine.
Known Health Benefits
How It Works
Resveratrol activates SIRT1, the most studied mammalian sirtuin, through an allosteric mechanism that increases SIRT1's affinity for NAD+ and its protein substrates. Activated SIRT1 deacetylates PGC-1α (promoting mitochondrial biogenesis), FOXO transcription factors (enhancing stress resistance and autophagy), NF-κB p65 subunit (suppressing inflammation), and p53 (modulating cell survival). Resveratrol independently activates AMPK through upstream kinase CaMKKβ and LKB1, promoting glucose uptake, fatty acid oxidation, and mitochondrial function — effects that partially overlap with caloric restriction mimicry. Cardiovascular protection occurs through multiple mechanisms: eNOS upregulation increases nitric oxide-mediated vasodilation, NADPH oxidase inhibition reduces vascular oxidative stress, and anti-platelet effects reduce thrombosis risk. Resveratrol also activates Nrf2, upregulating Phase II detoxification enzymes. At high concentrations, resveratrol exhibits weak phytoestrogenic activity via ERβ binding, which may contribute to bone-protective effects.
What Research Says
A meta-analysis by Mousavi et al. (Clinical Nutrition, 2019) of 24 RCTs found resveratrol significantly reduced fasting glucose, insulin, HbA1c, and systolic blood pressure. Tomé-Carneiro et al. (American Journal of Cardiology, 2013) demonstrated that grape extract with resveratrol reduced oxidized LDL by 20% and increased anti-inflammatory IL-10 in stable coronary artery disease patients. Magyar et al. (American Journal of Cardiology, 2012) showed 10 mg/day trans-resveratrol improved left ventricular function and endothelial function in post-MI patients. Baur et al. (Nature, 2006) demonstrated resveratrol improved healthspan and survival in obese mice on a high-fat diet, mimicking caloric restriction gene expression patterns. Witte et al. (Journal of Neuroscience, 2014) found 200 mg/day resveratrol improved memory and hippocampal functional connectivity in healthy older adults. However, the REALIST trial (Goh et al., 2014) found no benefit in non-alcoholic fatty liver disease, highlighting the condition-specific nature of resveratrol's effects.
Active Compounds
Trans-resveratrol, cis-resveratrol, piceatannol, pterostilbene
Forms & Bioavailability
Oral resveratrol has very low bioavailability (~1–5%) due to rapid glucuronidation and sulfation in the intestine and liver. However, resveratrol metabolites (resveratrol-3-O-sulfate, resveratrol-3-O-glucuronide) may retain biological activity. Pterostilbene has 80% bioavailability. Micronization, lipid formulation, and piperine co-administration improve resveratrol absorption.
Dosage Guidance
| Use Case | Dosage |
|---|---|
| General cardiovascular and anti-aging | 100–250 mg trans-resveratrol/day |
| Metabolic support (blood sugar) | 250–500 mg/day |
| Cognitive support | 200 mg/day |
| Longevity protocol | 500 mg + 500 mg NMN |
Always consult a healthcare provider for personalized dosing.
Natural Food Sources
- Red grapes and red grape juice
- Red wine (1–3 mg per glass)
- Blueberries and cranberries
- Peanuts and pistachios
- Dark chocolate (cocoa)
- Japanese knotweed (Polygonum cuspidatum — supplement source)
Potential Side Effects
GI upset at high doses; potential estrogen-like effects at very high doses
Who Should Avoid It
- Estrogen-sensitive cancers (weak phytoestrogen activity at high doses)
- Blood-clotting disorders (anti-platelet effects)
- Scheduled surgery (discontinue 2 weeks prior)
- CYP3A4 substrate medications without dose review
Pregnancy & Lactation
Resveratrol's phytoestrogenic properties raise theoretical concerns during pregnancy. Animal studies show mixed results. Not recommended during pregnancy or lactation at supplemental doses. Dietary amounts from food are considered safe.
Known Drug Interactions
May interact with blood thinners, NSAIDs, and CYP3A4 substrates
Evidence Classification
Supported by cohort studies, case-control studies, or multiple observational studies with consistent findings.
Frequently Asked Questions
Can I get enough resveratrol from red wine?
No. Red wine contains only 1–3 mg resveratrol per glass. Therapeutic doses in studies range from 100–500 mg/day — equivalent to drinking 50–500 glasses of wine daily. Supplementation is needed for clinical effects.
What is the difference between resveratrol and pterostilbene?
Pterostilbene is a naturally methylated analog of resveratrol with 80% oral bioavailability versus resveratrol's 1–5%. It has a longer half-life and may be more biologically active. Some supplements combine both for complementary benefits.
Does resveratrol actually extend lifespan?
In yeast, worms, flies, and obese mice, resveratrol extends lifespan. In normal-weight mice and humans, the evidence is less clear. Resveratrol likely improves healthspan (quality of life during aging) more than raw lifespan extension. Long-term human longevity data does not yet exist.
Should I take resveratrol with NMN?
The theoretical synergy is compelling: resveratrol activates SIRT1 (the enzyme), while NMN provides the NAD+ substrate SIRT1 requires. Without NAD+, SIRT1 activation is limited. This combination is popular in longevity protocols but lacks dedicated human RCTs.
Does resveratrol affect exercise adaptations?
Some studies suggest high-dose resveratrol may blunt exercise-induced adaptations by reducing the hormetic stress response that drives mitochondrial biogenesis. If you exercise intensely, consider taking resveratrol on non-training days or at lower doses.
References
- Impact of resveratrol on glucose control, lipid profile and body composition: a meta-analysis. Mousavi SM, Milajerdi A, Sheikhi A, et al.. Clinical Nutrition (2019)View study
- Resveratrol improves health and survival of mice on a high-calorie diet. Baur JA, Pearson KJ, Price NL, et al.. Nature (2006)View study
- Resveratrol improves memory performance and hippocampal connectivity in healthy older adults. Witte AV, Kerti L, Margulies DS, Flöel A. Journal of Neuroscience (2014)View study
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This entry is for educational purposes only. It is not medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement regimen, especially if you take medications or have health conditions.