Also known as: trans-resveratrol, red wine polyphenol, sirtuin activator
The cautionary tale of the longevity field: a beautiful hypothesis, a retracted foundation, and a trial that found it made exercise work worse.
Human trials have consistently failed to reproduce the animal findings, an observational study found no mortality association, and one controlled trial found resveratrol blunted the cardiovascular benefits of exercise training. The sirtuin-activation mechanism it was built on has been substantially disputed.
Resveratrol deserves a place in this directory not because it works but because understanding why it does not is genuinely useful.
The story began beautifully. Red wine contains resveratrol; the French eat richly and have low heart disease; resveratrol was reported to activate SIRT1, the enzyme linked to the life-extending effects of caloric restriction; and in 2006 a paper in *Nature* showed it extended lifespan in obese mice. A biotech company was sold to GlaxoSmithKline for $720 million on the strength of the idea. It was, for a few years, the most exciting molecule in ageing research.
Then it came apart in stages. The SIRT1 activation turned out to depend heavily on the fluorescent tag used in the assay — with native substrates, the effect largely vanished, and the mechanism the whole field rested on was thrown into doubt. Separately, the University of Connecticut researcher who had produced a large body of resveratrol cardiac work was found to have fabricated data across more than a hundred instances, and papers were retracted. GSK discontinued its development programme.
The human data has been no kinder. A well-conducted observational study of older Italian adults, measuring resveratrol metabolites directly rather than relying on diet questionnaires, found no association with inflammation, cardiovascular disease, cancer, or mortality. And in the finding that should give any supplement user pause, a controlled trial in older men found that resveratrol *blunted* the cardiovascular improvements from exercise training — the placebo group improved more. High-dose antioxidant supplementation interfering with the adaptive signalling that makes exercise work is a recurring theme, and this was a clean demonstration of it.
No dose is listed in this entry because no defensible one exists. Bioavailability is poor and erratic, doses in trials have ranged wildly, and none has produced a reliable human benefit.
What remains is the lesson. A compelling mechanism, an enthusiastic press cycle, and enormous investment do not add up to a working intervention — and when the human trials arrive, sometimes the answer is worse than nothing.
Resveratrol was proposed to activate SIRT1, mimicking the effects of caloric restriction. That mechanism was later challenged: much of the original SIRT1 activation appeared to be an artefact of the fluorescent assay used to measure it. Oral bioavailability is also very poor, with rapid conjugation in the gut and liver leaving little free compound in circulation.
Generally well tolerated at low doses, with GI upset common above about 1 g/day. The more relevant concern is not toxicity but interference: it may blunt exercise adaptations, and it inhibits CYP enzymes and platelet aggregation. It also has oestrogenic activity, which matters for hormone-sensitive conditions.
This guide is educational, not medical advice. Talk to a physician or pharmacist before starting any supplement, especially alongside prescription medication or a medical condition.
Evidence review last updated