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.

译文

肥胖,糖尿病,高血压和高脂血症是发病率和过早死亡的危险因素。根据动物和体外研究,白藜芦醇通过刺激无声交配类型信息调节2同源物1(SIRT1)来逆转这些危险因素,但人类受试者的数据却很少。这项研究的目的是检查高剂量白藜芦醇在肥胖人类受试者中的代谢作用。在随机,安慰剂对照,双盲和平行组设计中,将24名肥胖但其他方面健康的男性随机分配到白藜芦醇或安慰剂治疗4周。在治疗之前和之后进行了广泛的代谢检查,包括评估葡萄糖更新和胰岛素敏感性(高胰岛素正常血糖钳夹)。两组的主要结果指标胰岛素敏感性均无显着性恶化。内源性葡萄糖的产生以及葡萄糖的周转率和氧化率保持不变。补充白藜芦醇对血压也没有影响。静息能量消耗;脂质的氧化速率;异位或内脏脂肪含量;或炎症和代谢生物标志物。缺乏效果与从啮齿动物模型获得的有说服力的数据不同,并引起人们对白藜芦醇作为代谢障碍中人类营养补充剂的合理性的怀疑。

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