title: High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition.
abstract: 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.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. mmp@ki.au.dk
authors.forename: Morten M
authors.initials: MM
authors.lastname: Poulsen
authors.forename: Poul F
authors.initials: PF
authors.lastname: Vestergaard
authors.forename: Berthil F
authors.initials: BF
authors.lastname: Clasen
authors.forename: Yulia
authors.initials: Y
authors.lastname: Radko
authors.forename: Lars P
authors.initials: LP
authors.lastname: Christensen
authors.forename: Hans
authors.initials: H
authors.lastname: Stødkilde-Jørgensen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010865:Pilot Projects; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol