Mechanism of Action
Resveratrol directly activates SIRT1 deacetylase, which deacetylates PGC-1α to drive mitochondrial biogenesis, and p53 to modulate apoptosis. It also activates AMPK, inhibits mTOR, and reduces NF-κB-mediated inflammation. Trans-resveratrol (the active isomer) is far more bioavailable than cis-resveratrol.
Human Trial Evidence
A 2012 British Journal of Nutrition RCT showed 500 mg/day improved insulin sensitivity and reduced oxidative stress in type 2 diabetics. Multiple trials show reductions in inflammatory markers (IL-6, TNF-α, CRP) at doses of 150–500 mg/day. Bioavailability is low (~1%) but significantly enhanced when taken with fat or combined with piperine.
Dosing Protocol
150–500 mg/day of trans-resveratrol. David Sinclair takes 1,000 mg/day with yogurt (fat enhances absorption). Best taken with a meal containing fat. Pterostilbene (a methylated analog) has ~4× better bioavailability.
Safety & Contraindications
Well-tolerated in trials up to 5,000 mg/day. At high doses (≥2.5 g/day), GI side effects are common. Resveratrol inhibits CYP3A4 — potential drug interactions with statins, blood thinners, and immunosuppressants. Avoid in pregnancy.
Key Papers
Resveratrol improves insulin sensitivity and reduces oxidative stress in type 2 diabetic patients
British Journal of Nutrition · 2012
Resveratrol improves health and survival of mice on a high-calorie diet
Nature · 2006
SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis
EMBO Journal · 2007