Resveratrol appears to make fat men fitter

The first clinical trial to test the effects of resveratrol -- the plant compound plentiful in red wine and grapes -- on humans has found that a small daily dose of a purified resveratrol supplement lowered blood pressure and improved a wide range of human health measures in a small group of obese men.

The study, conducted in the Netherlands and published this week in the journal Cell Metabolism, found that men taking 150 milligrams of resveratrol daily for 30 days looked for all the world as if they were either dieting successfully or were engaged in endurance training. (That dose is about the equivalent of the resveratrol in 100 glasses of red wine, so don’t pull that cork just yet.)

Without changing their diet or exercise habits, the mens’ metabolic function improved, evidence of inflammation declined, fat deposits in their livers decreased and circulating triglyceride levels fell. While their bodies burned up the same amount of energy over a 24-hour period, their bodies’ resting and sleeping metabolic rate declined and their muscles’ use of fuel became more efficient -- signs that they were using and storing calories more like athletes in training than obese couch potatoes.

There was just one incongruity in the picture researchers gleaned from the clinical tests of the men taking resveratrol: although clearly healthier, they were not losing weight.

The first of roughly a dozen human clinical trials of resveratrol, the Dutch study suggested that the plant extract may provide obese people some protection from the health consequences of their extra poundage, including elevated risks of type-2 diabetes, high blood pressure, heart disease, certain cancers and dementia. Virtually all of those conditions are linked to factors that responded favorably to resveratrol in the current study, including inflammation, metabolic disturbance and high levels of circulating glucose and triglycerides.

Resveratrol has earned an almost mythic reputation as a life-extending agent, despite the fact its benefits have largely been demonstrated in animal and test-tube studies. Dietary supplement manufacturers aggressively market the plant extract in a wide range of doses (including some far higher than that used in the Dutch trial), although its long-term safety and effective dosages have not been established by human trials.

Still, the promise of resveratrol -- both as a nutritional supplement and a model for future disease-fighting medications -- has excited widespread interest among researchers. Currently, about 25 clinical trials are recruiting or already underway to test resveratrol’s effectiveness against diseases as diverse as colon cancer, diabetes, Alzheimer’s disease, cardiovascular disease, melanoma and multiple myeloma.

The 11 participants in the Dutch study were obese but otherwise healthy men, who served as their own control group. A participant who took a placebo supplement for 30 days would wait a month and then take a resveratrol supplement for 30 days. Another who took resveratrol first would get a placebo after a month’s “wash-out” period. The 150-milligram dose given to the men was actually much smaller, pound for pound, than doses routinely given to mice in past experiments, yet yielded similar blood concentrations of the plant extract.

The men were given a broad panel of routine clinical tests each week in an effort to detect adverse reactions. There were none, the researchers reported.

“Although most of the effects we observed were modest, they were very consistently pointing toward beneficial metabolic adaptations,” wrote the authors, whose study was underwritten by TI Nutrition, a public-private research partnership of food manufacturers, universities and the Dutch government. They added that future studies should test the long-term safety of resveratrol supplementation, as well as whether better results could safely be gained at lower or higher dosages than 150 milligrams.

Alzheimer’s disease researcher Philippe Marambaut of the Feinstein Institute for Medical Research in Long Island, N.Y., called the findings “very promising.” Marambaut, who was not involved in the current study, said the beneficial metabolic effects appeared “impressive,” and added that “they will certainly motivate additional clinical trials for other conditions associated with a deregulated metabolism, such as diabetes or some age-related neurodegenerative conditions like Alzheimer’s disease.”