OnePin Peptide Library · Longevity
Resveratrol
trans-Resveratrol · Trans-Resveratrol
Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic stilbene compound found in red grape skins, red wine, peanuts, blueberries, and Japanese knotweed (Polygonum cuspidatum, the source of most commercial supplement-grade resveratrol). Discovered as a phytoalexin (plant defense compound) in 1939, resveratrol gained worldwide attention in the 1990s after media coverage of the 'French Paradox' - the observation that French populations have low cardiovascular disease rates despite high saturated fat intake, attributed in part to red wine consumption.,Resveratrol's primary research interest is as a sirtuin activator, particularly SIRT1 - the longevity-associated NAD+-dependent deacetylase. David Sinclair's laboratory at Harvard published foundational work in the early 2000s showing resveratrol extends lifespan in yeast, worms, flies, and short-lived fish, with the proposed mechanism being SIRT1 activation. This sparked a wave of pharmaceutical interest (GlaxoSmithKline acquired Sinclair's company Sirtris for $720M in 2008), though subsequent research has complicated the picture - resveratrol's direct SIRT1 activation is now debated, with effects more likely mediated through AMPK, autophagy induction, and indirect sirtuin modulation.,In humans, resveratrol has limited oral bioavailability (rapidly metabolized to sulfate and glucuronide conjugates with ~1% reaching systemic circulation as parent compound). Despite this, clinical trials have shown effects on insulin sensitivity, endothelial function, blood pressure, inflammatory markers, and exercise tolerance. The supplement is popular in longevity protocols, often paired with NAD+ precursors (NR/NMN) to leverage the SIRT1 substrate-activator combination. Trans-resveratrol (the bioactive isomer) at 250-500mg/day is the standard dose.
Take with a fatty meal to improve absorption (resveratrol is fat-soluble). Most clinical trials use 150-500mg/day. Pairs naturally with NR/NMN (substrate for SIRT1) and with quercetin (synergistic AMPK activation). Trans-resveratrol form (>98% trans isomer) is preferred over cis.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
Resveratrol's most-discussed mechanism is allosteric activation of SIRT1, the NAD+-dependent histone deacetylase that regulates gene expression, mitochondrial biogenesis (via PGC-1alpha deacetylation), and cellular stress responses. SIRT1 activation mimics caloric restriction effects and is associated with extended lifespan in lower organisms. However, direct SIRT1 activation by resveratrol is now debated - some studies show resveratrol's apparent SIRT1 activation is an artifact of fluorogenic substrate assays, with the real mechanism being indirect (via AMPK activation upstream).,The more robust mechanism is AMPK (AMP-activated protein kinase) activation, which orchestrates a metabolic shift toward catabolism (fatty acid oxidation, glucose uptake, mitochondrial biogenesis) and away from anabolism (lipogenesis, protein synthesis). AMPK activation by resveratrol is dose-dependent and reproducible. Downstream effects include PGC-1alpha activation, autophagy induction (mTOR inhibition), and reduced inflammatory cytokine production via NF-kB inhibition.,Additional mechanisms include: direct antioxidant activity (scavenging free radicals via the polyphenol structure), eNOS upregulation (improving endothelial NO production for vascular health), estrogen receptor modulation (resveratrol is a phytoestrogen with mixed agonist/antagonist activity depending on tissue), and modulation of multiple inflammatory pathways (COX-2, iNOS, NF-kB). The pleiotropic activity makes mechanism attribution difficult but explains the broad range of clinical effects observed.
Resveratrol's most-discussed mechanism is allosteric activation of SIRT1, the NAD+-dependent histone deacetylase that regulates gene expression, mitochondrial biogenesis (via PGC-1alpha deacetylation), and cellular stress responses. SIRT1 activation mimics caloric restriction effects and is associated with extended lifespan in lower organisms. However, direct SIRT1 activation by resveratrol is now debated - some studies show resveratrol's apparent SIRT1 activation is an artifact of fluorogenic substrate assays, with the real mechanism being indirect (via AMPK activation upstream).,The more robust mechanism is AMPK (AMP-activated protein kinase) activation, which orchestrates a metabolic shift toward catabolism (fatty acid oxidation, glucose uptake, mitochondrial biogenesis) and away from anabolism (lipogenesis, protein synthesis). AMPK activation by resveratrol is dose-dependent and reproducible. Downstream effects include PGC-1alpha activation, autophagy induction (mTOR inhibition), and reduced inflammatory cytokine production via NF-kB inhibition.,Additional mechanisms include: direct antioxidant activity (scavenging free radicals via the polyphenol structure), eNOS upregulation (improving endothelial NO production for vascular health), estrogen receptor modulation (resveratrol is a phytoestrogen with mixed agonist/antagonist activity depending on tissue), and modulation of multiple inflammatory pathways (COX-2, iNOS, NF-kB). The pleiotropic activity makes mechanism attribution difficult but explains the broad range of clinical effects observed.
What to expect
Days 1-14: Subclinical AMPK activation. No subjective change for most.
Evidence
Interactions & stacking
What's safe to combine, and what belongs in a separate pin.
Safe & synergistic
Keep separate
Pharmacokinetics
Storage. Store at room temperature (20-25C) in a cool, dry, dark place. Resveratrol is light-sensitive - keep in opaque containers. Capsules shelf-stable for 18-24 months. Trans-resveratrol can isomerize to less-active cis form with light/heat exposure - quality brands use light-protected packaging.
Regulatory status
Classified as a dietary supplement in the US (no FDA pre-approval). Available widely over the counter. EU permits resveratrol as food supplement up to 150mg/day from synthetic sources, higher from food/extract sources. Generally Recognized as Safe at typical supplement doses.
Put it to work
Calculate, log & track
Open Resveratrol straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
Open Resveratrol in the app →Go deeper
The guide & community
The complete Resveratrol walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
Join the community ↗