Remedy Routes
    ResveratroltoSirtuin Activation(moderate evidence)
    Outcome
    Moderate Evidence

    Resveratrol for Sirtuin Activation

    Resveratrol's sirtuin activation was an assay artefact, and human trials have been largely disappointing.

    Overview

    Resveratrol's sirtuin activation was an assay artefact, and human trials have been largely disappointing.

    Verdict

    Not supported

    How It Works

    Originally proposed as a direct SIRT1 activator; later work suggests indirect AMPK effects at best.

    Dosing & Protocol

    Typical dose

    Recommended dose
    Not recommended for sirtuin activation
    Expected timeframe
    n/a

    Protocol

    form
    Not applicable
    duration
    Not applicable
    co factor
    Evidence indicates no direct effect. Resveratrol was identified in 2003 as a SIRT1 activator, launching the sirtuin-activating compound field. The finding was subsequently challenged: Pacholec and colleagues at Pfizer, and independent groups, showed that resveratrol activated SIRT1 only in assays using a fluorophore-tagged peptide substrate, and had no effect on native substrates - the activation was an artefact of the assay design. Subsequent work suggested any in vivo sirtuin effect is indirect, via AMPK activation raising NAD+ availability rather than direct enzyme activation. Timmers found increased SIRT1 expression in human muscle at 150 mg/day, but expression is not activity, and no trial has measured sirtuin activity in humans.
    titration
    Not applicable
    starting dose
    Not applicable. No human trial has demonstrated sirtuin activation with resveratrol at any dose

    Evidence

    What the studies say

    The original activation findings did not replicate with native substrates. Human trials show poor bioavailability and inconsistent metabolic outcomes, with one trial finding it blunted exercise adaptations.

    Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

    Score: 7/10
    2011
    rct
    n=11

    Timmers S, Konings E, Bilet L +3 more

    Resveratrol activated AMPK and increased SIRT1 and mitochondrial protein levels

    View source

    Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial

    Score: 7/10
    2016
    rct
    n=17

    Timmers S, de Ligt M, Phielix E +6 more

    Resveratrol failed to improve insulin sensitivity, mitochondrial function or hepatic lipid content compared with placebo

    View source

    Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials

    Score: 7/10
    2014
    meta_analysis
    n=388

    Liu K, Zhou R, Wang B +1 more

    Resveratrol significantly improved glucose control and insulin sensitivity in people with diabetes but produced no significant effect in non-diabetic participants

    View source

    Safety

    Caveats

    Poorly absorbed. May blunt training adaptations and interact with anticoagulants.

    Less likely to help if

    Everyone - direct sirtuin activation by resveratrol was an assay artefact.

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