Trans-Resveratrol · 3,5,4'-trihydroxystilbene
The sirtuin activator from red wine — synergizes with NAD+ for longevity signaling.
FDA
Research Only
WADA
Not Listed
HALF-LIFE
~1–3 hours
ROUTE
Oral
SCHEDULE
Daily with fat-containing meal
In Plain English
The sirtuin activator from red wine — synergizes with NAD+ for longevity signaling.
Status & Legality
What do these mean?Sirtuin activation
Anti-aging signaling
Cardiovascular protection
Anti-inflammatory
Resveratrol is a polyphenol found in red wine, grapes, and berries that gained mainstream longevity attention through David Sinclair's research. It activates SIRT1 and other sirtuins — NAD+-dependent enzymes that regulate DNA repair, metabolism, and stress resistance. The longevity case for resveratrol is strongest when paired with NAD+ precursors (NMN/NR), which provide the substrate sirtuins consume. Bioavailability is poor alone; micronized or combined with fat significantly improves absorption.
GI discomfort at high doses
Mild estrogenic activity at high doses (theoretical concern)
Headache
Blood thinning effects at high doses — caution with anticoagulants
Buying supplements without verifying trans-resveratrol content — cis-resveratrol is inactive; verify the active isomer on the label
Not taking with fat — bioavailability without dietary fat is very poor (~20%); always take with a fat-containing meal or fish oil
Using resveratrol without an NAD+ precursor — resveratrol activates sirtuins that depend on NAD+ as their substrate; without NMN or NR, the pathway stalls
Anticoagulants (warfarin) — modest blood-thinning effect at high doses; monitor INR if on warfarin
CYP enzyme substrates — resveratrol inhibits multiple CYP isoforms; check medications metabolized by CYP2C9 and CYP3A4
Estrogen medications — mild estrogenic activity at high doses; relevant for hormone-sensitive conditions
The Sinclair longevity stack doesn't work without the NAD+ component — resveratrol activates SIRT1 but SIRT1 is catalytically inert without NAD+ as its substrate. NMN or NR is the required co-supplement. Trans-resveratrol 250–500 mg with a fat-containing meal + NMN 500 mg is the protocol most consistent with the published longevity research.
NMN
The most direct oral precursor to NAD+ — fast conversion, strong uptake.
NAD+
The master coenzyme of cellular energy — levels drop 50% by age 50.
QUERCETIN
Dual-action polyphenol and senolytic — clears aged cells while reducing inflammation.
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Stats
Sources & Studies
Baur JA, Sinclair DA., Nat Rev Drug Discov, 2006