Resveratrol

Polyphenolic stilbene that activates SIRT1 deacetylase through an allosteric mechanism, enhancing deacetylation of PGC-1alpha and FOXO transcription factors. Improves mitochondrial biogenesis and oxidative metabolism via AMPK activation. Functions as a caloric restriction mimetic, engaging nutrient-sensing pathways that promote cellular maintenance over growth. Anti-inflammatory through NF-kB suppression and COX-2 inhibition.

Half-life

1-3 hours (parent compound), 9.2 hours (metabolites)

Bioavailability

~20% (oral, extensive phase II conjugation; bioactive metabolites retain activity)

Route

oral

Evidence tier

T2 — Single-RCT or mechanistic

Optimization pillars

anti-aging · cellular-health

References

4 peer-reviewed

Dose ranges

Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.

conservative

150–250 mg/day with fat

SIRT1 activation threshold

moderate

250–500 mg/day with fat

Standard longevity dose

aggressive

1000–2000 mg/day

High-dose (exercise mimetic research)

Monitoring

fasting-glucose
hba1c
fasting-insulin
lipid-panel
alt
ast
hs-crp
estradiol

Contraindications

concurrent-anticoagulants
estrogen-sensitive-conditions
active-bleeding-disorder
pregnancy

References

PMID:17086191Resveratrol improves health and survival of mice on a high-calorie diet — Nature, 2006
PMID:22882400Resveratrol as a SIRT1-activating compound — Science, 2012
PMID:25090227Effects of resveratrol on glucose control and insulin sensitivity in humans: a systematic review — Ann N Y Acad Sci, 2013
PMID:29210129Resveratrol and cellular mechanisms of aging — Ageing Res Rev, 2018

Notes

Resveratrol is the longevity compound that launched an entire field and then became the poster child for translational disappointment. The 2006 Nature paper showed resveratrol could rescue mice on a high-fat diet from metabolic dysfunction. The SIRT1 activation mechanism was confirmed in 2012. Then the human data started landing and the effect sizes were modest at best. The bioavailability problem is real — 80% gets conjugated on first pass. The metabolites retain some activity but the parent compound barely survives the gut-liver axis. Take it with fat. Take it with quercetin if you want to inhibit the sulfotransferases that conjugate it. The caloric restriction mimicry angle is the most promising path forward.

This is not medical advice

Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.

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