RESEARCH MONOGRAPH · KDC-MN-097

Resveratrol

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

60/100

Iconic compound, mostly disappointing once you read past the Sinclair papers

Resveratrol is the molecule that built the modern longevity industry's marketing playbook, and honestly it's also the molecule that taught the field its hardest lesson about translating yeast and mouse data to humans. The original Howitz/Sinclair Nature paper showed SIRT1 activation, the Baur 2006 paper showed protection against high-fat-diet metabolic dysfunction in mice, the press cycle was enormous, and then the replication problems started.

The Pacholec 2010 paper from Pfizer (in JBC) showed that the in vitro SIRT1 activation by resveratrol was largely an artifact of the fluorescent substrate they were using, and that with native substrates the effect mostly went away. Subsequent human RCTs in metabolic and cognitive endpoints have been mixed, with the more rigorous trials showing small or null effects. Sirtris got acquired for $720M and the lead SIRT1 activator program quietly wound down.

Mechanistically resveratrol is a real polyphenol that does real things. It hits multiple targets (AMPK indirectly, NQO1, NRF2, COX), the bioavailability is genuinely bad (oral resveratrol has 1-2 hour half-life and most of it gets glucuronidated and sulfated in first pass), and the tissue concentrations you reach in humans are orders of magnitude below the in vitro EC50s for most of the proposed targets. Thats the elephant.

What we like is that it remains a useful research tool for studying polyphenol signaling, vascular endothelial responses, and combination work with metabolites like NAD+ precursors. The literature is huge, the compound is well-characterized, and HPLC purity is straightforward.

What we dont like is how often it still gets sold as a longevity miracle. The Sinclair-era story didnt survive contact with replication, and pretending otherwise is just selling vibes.

For sourcing: trans-resveratrol from reputable suppliers is fine, purity 98%+ HPLC is standard, but be aware that the trans isomer photoisomerizes and a lot of cheap material is heavily cis-contaminated. Stored cold and dark.

Worth studying? sure, for what it actually is. Worth treating as the headline longevity compound? not really, the field has moved on.

Evidence: 55
Mechanism: 58
Reliability: 45
Safety: 85
Sourcing: 80
Value: 60
Signal: 45
Staying power: 50

Plain-language summary Intrigue 60 / 100

Resveratrol is a natural compound found in red wine, grape skins, and Japanese knotweed. It activates sirtuins and other longevity-associated pathways and has been the subject of intense longevity research. Oral bioavailability is poor, limiting clinical efficacy. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Stilbenoid polyphenol / sirtuin modulator

A trans-stilbenoid polyphenol from grapes and other plants, characterized by SIRT1 activation and pleiotropic anti-aging effects with disputed clinical efficacy.

Abstract

Resveratrol (trans-3,4',5-trihydroxystilbene; CAS 501-36-0; molecular formula C14H12O3; molecular weight 228.25) is a stilbenoid polyphenol present in grapes, peanuts, berries, and several other plants. The compound has been extensively studied for anti-aging applications since David Sinclair's group at Harvard demonstrated SIRT1 activation in 2003. Mechanism includes SIRT1 sirtuin activation (allosteric activator at certain peptide substrates; the activity is substrate-dependent), AMPK activation, anti-inflammatory effects through NF-kB inhibition, and direct antioxidant activity. Resveratrol extends lifespan in obese mice and in some short-lived model organisms but does not extend lifespan in normally fed mice; the lifespan-extending effect appears to be selective for high-fat-diet stress conditions. Bioavailability is poor (high first-pass metabolism); plasma resveratrol concentrations after oral administration are typically 1 to 10 percent of those that produce in vitro effects. Reported research dose ranges in the literature are typically 250 to 1500 mg. The clinical evidence base in humans is mixed; many endpoints show no effect at achievable plasma concentrations.

Mechanism of action

SIRT1 allosteric activator (substrate-dependent). AMPK activation. Anti-inflammatory through NF-kB. Direct antioxidant.

Reported research dose ranges

250 to 1500 mg (reported research dose ranges in the literature); bioavailability is poor.

References

Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003.
Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, and a curated reference list. Available as a research-use-only PDF download.

KDC-MN-097

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Kodiac sells research compounds for investigative use only.

Resveratrol

Abstract

Mechanism of action

Reported research dose ranges

References

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Abstract

Mechanism of action

Reported research dose ranges

References

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