4 weeks of high-dose resveratrol had no effect on insulin sensitivity, blood pressure, or body composition - directly contradicting the promising rodent data that drove the original hype.
| Evidence tier | B Direct human evidence |
| Study type | 2 - Human Clinical Trial |
| Model system | Humans, RCT, obese men (n=24) |
| Journal | Diabetes |
| Year | 2013 |
| Peer reviewed | Yes |
| Source | DOI 10.2337/db12-0975 · PMID 23193181 · Free full text (PMC3609591) |
Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.
| Intervention | Resveratrol (high-dose) |
| Target | SIRT1 (mTOR-adjacent) |
| Model | Human – RCT (obese men, n=24) |
| Effect | High-dose resveratrol did NOT improve insulin sensitivity, substrate metabolism or body composition in obese men (negative trial) |