High-Dose Resveratrol Supplementation in Obese Men

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.

Chronic resveratrol administration improves diabetic cardiomyopathy in part by reducing oxidative stress

“…Moreover, Bhatt et al [20] have shown that 3 months' supplementation of resveratrol in type 2 diabetic patients improved glycemic control with no significant change in body weight. On the other hand, Poulsen et al [21] have proved that 4 weeks' treatment with resveratrol had no effect on resting energy expenditure and endogenous glucose turnover.…”

Dose response biology of resveratrol in obesity

“…Among these, PGC-1α, SIRT1, NF-kβ, AMPK, Forkhead Box O3 (FOXO3), and peroxisome proliferatoractivated receptor-γ (PPARγ) appear to be related to obesity pathophysiology and affected by specific hormetic mechanisms (Poulsen et al 2013b;Barrajón-Catalán et al 2014). For instance, SIRT1 is the primary molecular target of resveratrol and is an important regulator of many processes influencing obesity, including fatty acid oxidation, gluconeogenesis, adipogenesis, insulin secretion, and glucose and cholesterol homeostasis.…”

AMPK activation—protean potential for boosting healthspan

“…Unfortunately, in humans, it is conjugated rapidly and completely following absorption; despite reasonably efficient absorption, orally administered resveratrol does not appear to achieve sustained serum levels of free resveratrol sufficient to inhibit mitochondrial ATP synthase and thereby activate AMPK (Walle et al 2004;Boocock et al 2007). Consistent with this, several recent controlled clinical studies have failed to observe an impact of oral resveratrol on insulin sensitivity, blood pressure, body composition, or other clinical parameters; in addition, AMPK activity in skeletal muscle or adipocytes was not influenced (Yoshino et al 2012;Poulsen et al 2013). However, oral resveratrol might have the potential to transiently activate AMPK in the intestinal mucosa.…”