Exploring the Promise of Resveratrol: Where Do We Go From Here?

Resveratrol (3,5,4’-trihydroxystilbene), a plant-derived polyphenol and activator of the mammalian sirtuin, SIRT1, has demonstrated promising effects on glucose metabolism in rodent models (1). However, despite the widespread use of resveratrol as a nutritional supplement and the many health claims made on its behalf, data from human studies are extremely limited. Here, we explore why, in contrast to many studies in mammalian models, the article by Poulsen et al. (2) in this issue of Diabetes reports that chronic high doses of resveratrol have no demonstrable metabolic effects. Interest in resveratrol has skyrocketed in recent years, initially from its association with the health benefits of red wine (the “French paradox”) and its in vitro anticancer activity (3). Subsequent reports demonstrated that it activates sirtuins and extends the life span of lower organisms (“calorie restriction mimetic”), including rodents (4). Studies in vitro show that resveratrol enhances insulin-stimulated glucose uptake in skeletal muscle, liver, and adipocytes (5,6) and stimulates insulin secretion via inhibition of β-cell KATP channels (7). These observations have been confirmed in vivo in several animal models, including aging, diet-induced obesity, and diabetic ( db / db ) mice (4,8–10). Importantly, key metabolic effects of resveratrol can be monitored in relevant tissues (muscle, fat, and liver), thus providing critical insight into mechanisms. These effects include increased mitochondrial biogenesis and oxidative …