Supplements
Evidence: moderate_human
Resveratrol activates SIRT1 (the longevity sirtuin) via allosteric binding, promoting deacetylation of PGC-1alpha (mitochondrial biogenesis), FOXO3 (stress resistance), and p53 (DNA repair). It inhibits NF-kB and COX-2, reducing chronic inflammation. Resveratrol also activates AMPK independently of SIRT1 and inhibits phosphodiesterases (PDEs), raising cAMP levels. It improves endothelial function via eNOS upregulation and NO production.
Standard: 250-500mg trans-resveratrol daily
Loading: 1000mg/day for first 2 weeks
Maintenance: 250mg/day
Administration: oralsublingual
Timing: Morning with a fat-containing meal. Often taken alongside NMN for synergistic sirtuin activation.
Duration: ongoing
Cornerstone of David Sinclair's protocol alongside NMN. Morning fat-soluble dosing is key — Sinclair takes with yogurt. Bioavailability is notoriously poor; micronized or liposomal formulas address this. Pterostilbene is the 'next-gen' alternative with better pharmacokinetics. The estrogen question means careful client screening for hormone-sensitive conditions. High doses (>1g) may paradoxically have pro-oxidant effects.
Trans-resveratrol is the bioactive isomer — ensure >98% trans form. Micronized or liposomal for improved bioavailability. Derived from Japanese knotweed (Polygonum cuspidatum) or grape skin. Brands: RevGenetics, Thorne ResveraCel, Nootropics Depot. Pterostilbene (methylated resveratrol) has 4x better bioavailability and may be preferred.
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