Resveratrol
Polyphenol from red wine and Japanese knotweed, preclinically prolific, clinically disappointing, but the most commonly-asked-about longevity compound.
Why
Resveratrol (trans-3,5,4'-trihydroxystilbene) is the polyphenol from red wine, grapes and Japanese knotweed that triggered the modern longevity-supplement field after Sinclair's sirtuin-activating publications in the 2000s. Despite extensive preclinical work, human RCTs have largely been disappointing, no consistent effect on lifespan biomarkers, modest and inconsistent effects on glycaemia and endothelial function, and a notable null in heart-failure (Magyar 2012). The Witte 2014 RCT in older adults reported memory improvement. Bioavailability is poor and a fundamental clinical limit.
How it works
Sirtuin-1 activation (originally proposed mechanism, contested). AMPK activation. Endothelial nitric oxide synthase modulation. PDE4 inhibition. The proposed 'caloric restriction mimetic' framing has not been confirmed in clinical trials.
Expected onset · Biomarker changes over weeks; clinical endpoints not consistently demonstrated
How to take
Dosage
150–500 mg/day. Trials use a wide range (75–1,500 mg/day). Higher doses do not consistently improve outcomes.
Timing
With meals containing fat for absorption
On the label
trans-resveratrol (the bioactive isomer) with stated mg per dose. Often from Japanese knotweed (Polygonum cuspidatum) rather than grape, chemically equivalent. Micronised or liposomal forms have marginally better absorption.
Ideal for
Adults exploring longevity-focused interventions with realistic expectations; people who would otherwise drink red wine and want a non-alcohol alternative source of trans-resveratrol.
Safety
Evidence
Witte 2014 J Neurosci RCT (n=46 healthy older adults): resveratrol 200 mg/day for 26 weeks improved memory performance and hippocampal connectivity. Multiple other RCTs in metabolic and cardiovascular endpoints have been null or mixed. Preliminary evidence, no Cochrane review, EMA HMPC monograph or EFSA-authorised health claim covers this indication; cited RCTs are small or in non-tier-1 journals. Useful as honest reference rather than evidence-grade recommendation. Among the most-asked-about longevity compounds; honest framing about gap between preclinical and clinical evidence matters here.
The gap between extensive preclinical promise and disappointing or inconsistent clinical results is the central honest framing for resveratrol. No Cochrane review, no EMA monograph, no EFSA-authorised claim. Bioavailability of oral resveratrol is the fundamental limit.
- Witte et al., J Neurosci 2014, effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults (RCT)
- Magyar et al., Clin Hemorheol Microcirc 2012, cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease (RCT)
- Smoliga et al., Nutr Res 2015, challenges of translating basic research into therapeutics: resveratrol as an example
Where to get it
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