Resveratrol for AMPK Activation

Resveratrol drove much of the early AMPK and sirtuin excitement. Translation to human metabolic outcomes has been disappointing.

Overview

Resveratrol drove much of the early AMPK and sirtuin excitement. Translation to human metabolic outcomes has been disappointing.

Verdict

Mixed evidence

Resveratrol activates AMPK in cells, but human trials show small and inconsistent metabolic effects.

How It Works

Resveratrol activates SIRT1 and, indirectly, AMPK via mild mitochondrial stress; bioavailability after oral dosing is very low because of rapid glucuronidation.

Dosing & Protocol

Typical dose

Recommended dose: 150-500 mg/day; higher doses are not better
Expected timeframe: 8-12 weeks

Protocol

form: Trans-resveratrol; oral bioavailability is under 1% owing to rapid glucuronidation and sulfation
duration: Trials ran 4 weeks to 6 months
co factor: Evidence is mixed. AMPK is the cellular energy sensor, and resveratrol activates it robustly in cell culture and rodent muscle, largely indirectly through mild mitochondrial inhibition raising the AMP to ATP ratio - the same broad mechanism as metformin. Human muscle biopsy data are inconsistent: Timmers and colleagues found increased AMPK activation and SIRT1 expression in obese men at 150 mg/day over 30 days, while Gliemann and colleagues found resveratrol at 250 mg/day blunted the training-induced improvements in blood pressure and lipids in older men, and Scribbans found it impaired training adaptations in young men. Activating AMPK is also not a health outcome.
titration: Not applicable - no human dose-response for AMPK activation has been established
starting dose: Not established for this outcome. Human trials used 150-1,000 mg/day, with the muscle biopsy studies around 150 mg/day (Timmers) and 500 mg/day

Evidence

What the studies say

Meta-analyses of human trials report small fasting-glucose reductions in people with type 2 diabetes and essentially no change in healthy adults. One trial in trained men found resveratrol blunted exercise-induced training adaptations. Doses, formulations and populations vary widely across studies.

Resveratrol, AMPK activation and mTOR inhibition in humans: a randomized controlled trial

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

Safety

Caveats

Poor oral bioavailability. May inhibit CYP enzymes and interact with anticoagulants. High doses have caused GI upset and, in one trial, renal issues in myeloma patients.

Less likely to help if

Metabolically healthy adults should not expect measurable change.

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