Resveratrol
A polyphenol from grapes and Japanese knotweed that launched the sirtuin-activation hypothesis of aging. Despite enormous animal and mechanistic literature and reasonable human trial numbers, results in people are inconsistent and often null, and poor oral bioavailability limits its effects.
01 Overview
Resveratrol (trans-3,5,4'-trihydroxystilbene) is a plant polyphenol proposed to activate SIRT1 and mimic aspects of caloric restriction. Early-2000s work showing lifespan extension in yeast, worms, flies, and obese mice made it the first mass-market longevity supplement, though the sirtuin-activation mechanism was later disputed as partly an assay artefact.
Human trials are numerous but mixed: some show improved glycaemic control, endothelial function, or inflammatory markers, particularly in people with metabolic disease, while others (including in healthy or athletic subjects) show no benefit and occasionally blunt exercise adaptations. Oral bioavailability is very low due to rapid glucuronidation and sulfation. No human evidence supports a lifespan effect.
02 Mechanism
Proposed to allosterically activate SIRT1 and to activate AMPK; also acts as an antioxidant and phytoestrogen. The relative contribution of each mechanism in vivo is debated.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Common | 150–500 mg/day | Oral | Typical supplement range; often taken with fat to aid absorption. |
| High trial dose | 1000–2000 mg/day | Oral | Higher doses studied for metabolic endpoints; more GI effects. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved glycaemic / metabolic markers (diabetics)Meta-analyses suggest small improvements in fasting glucose and insulin resistance in people with type 2 diabetes; less clear in healthy adults. | modest | Clinical | |
| Improved endothelial functionSome trials show improved flow-mediated dilation, especially post-meal or in metabolic disease. | small | Clinical | |
| May blunt exercise training adaptationHigh-dose resveratrol reduced training-induced gains in cardiovascular fitness in some studies of older men. | context-dependent | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| GI upset (higher doses)Nausea, cramping, and diarrhoea are common at gram-level doses. | Mild | Common at >1 g/day | Clinical | |
| Drug interactions (CYP inhibition, antiplatelet)Inhibits several CYP450 enzymes and has mild antiplatelet activity, with theoretical interaction risk with anticoagulants and other drugs. | Moderate | Uncommon | Preclinical |