Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans.

Timmers S, Konings E, Bilet L, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 2011;14:612-622.

Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.  PMID: 22055504

Commentary by Gregory Kelly, ND:

Calorie restriction has been extensively studied for its ability to extend the life span in a variety of organisms and animals. Unfortunately, intentionally eating significantly less – in calorie restriction studies the goal is usually about 25 percent less – than a person usually eats leads to large increases in hunger. Forcing animals to be chronically hungry when you control their access to food is one thing. Asking a person to live a lifetime with hunger when they are surrounded by food is another. Because of this, there has been a search for other ways to extend life span. Certain natural compounds appear to mimic at least some of the effects of calorie restriction on genes and life span. Resveratrol is one of these compounds, which has lead to it being considered as a potential calorie restriction mimetic. In this short-term human study – 30 days – supplementation of resveratrol to obese individuals induced many of the physiological and gene changes that occur when calories are restricted. Longer studies would be needed to verify whether these positive changes would be maintained over a longer period of supplementation. And much, much longer studies would be required before any longevity effect in humans could be established. Despite these limitations, this study adds to the growing evidence base demonstrating significant effects of this molecule.