High-Dose Resveratrol Supplementation in Obese Men: An Investigator-Initiated, Randomized, Placebo-Controlled Clinical Trial of Substrate Metabolism, Insulin Sensitivity, and Body Composition

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 4; pp. 1186 - 1195
• Main Authors: POULSEN, Morten M, VESTERGAARD, Poul F, CLASEN, Berthil F, RADKO, Yulia, CHRISTENSEN, Lars P, STØDKILDE-JØRGENSEN, Hans, MØLLER, Niels, JESSEN, Niels, PEDERSEN, Steen B, JØRGENSEN, Jens Otto L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2013
• Subjects: Adolescent; Adult; Aged; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Biological and medical sciences; Biomarkers; Biopsy; Blood pressure; Body Composition - drug effects; Body fat; Care and treatment; Catheters; Complications and side effects; Diabetes; Diabetes. Impaired glucose tolerance; Dietary Supplements; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Metabolism - drug effects; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene Expression Regulation; Genetic aspects; Glucose; Glucose metabolism; Human subjects; Humans; Insulin; Insulin Resistance - physiology; Investigations; Male; Medical sciences; Metabolic diseases; Metabolism; Middle Aged; Obesity; Obesity - drug therapy; Original Research; Oxidation; Physiological aspects; Pilot Projects; Resveratrol; Stilbenes - administration & dosage; Stilbenes - therapeutic use; Young Adult; Denmark; Endocrinopathy; Human; Obesity; Pancreatic hormone; Diabetes mellitus; Nutrition disorder; Metabolism; Insulin; Stilbene derivatives; Body composition; Polyphenol; Sensitivity; Resveratrol; Phenols; Clinical trial; Proanthocyanidin; Supplementation; High dose; Nutritional status
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db12-0975

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.