Everyone's Health

Wine element lets fat mice live longer

Harvard Medical School researchers found that resveratrol offset the bad effects of a high-calorie diet in these mice, significantly extending their life span.

Nicholas Wade, November, 2006

Can you have your cake and eat it? Is there a free lunch after all, red wine included?

Researchers at the Harvard Medical School and the National Institute on Aging report that a natural substance found in red wine, known as resveratrol, offsets the bad effects of a high-calorie diet in mice and significantly extends their life span.

Their report, published electronically yesterday in the journal Nature, implies that very large daily doses of resveratrol could offset the unhealthy, high-calorie diet thought to underlie the rising toll of obesity in the United States and elsewhere, if people are found to respond to the drug as mice do.

Resveratrol is found in the skin of grapes and other plants and in red wine, and is conjectured to be a partial explanation for the “French paradox,” the puzzling fact that people in France enjoy a high-fat diet yet suffer less heart disease than Americans.

The researchers fed one group of mice a diet in which 60 percent of calories came from fat.

The diet started when the mice, all males, were 1 year old, which is middle-aged for a mouse. As expected, those mice soon developed signs of impending diabetes, with grossly enlarged livers, and started to die much sooner than mice fed a standard diet.

Another group was fed the identical high-fat diet but with a large daily dose of resveratrol (the equivalent of hundreds of bottles of wine per day).

The resveratrol did not stop them from putting on weight and growing as tubby as the other fat-eating mice. But it averted the high levels of glucose and insulin in the bloodstream, which are warning signs of diabetes, and it kept the mice's livers at normal size.

Even more striking, the substance sharply extended the mice's lifetimes. Those fed resveratrol along with the high-fat diet died many months later than the mice on high fat alone, and at the same rate as mice on a standard healthy diet.

They had all the pleasures of gluttony but paid none of the price.

Scientists have long known that a moderate intake of alcohol – red wine in particular – is associated with a lowered risk of heart disease and other benefits.

More recently, scientists began to suspect that resveratrol had particularly powerful effects and began investigating its role in longevity.

The researchers, led by David Sinclair and Joseph Baur at the Harvard Medical School and by Rafael de Cabo at the National Institute on Aging, also tried to estimate the effect of resveratrol on the mice's physical quality of life.

They gauged how well the mice could walk along a rotating rod before falling off, a test of their motor skills. The mice on resveratrol did better as they grew older, ending up with much the same staying power on the rod as mice fed a normal diet.

The study shows, the researchers conclude, that orally taken drugs “at doses achievable in humans, can safely reduce many of the negative consequences of excess caloric intake, with an overall improvement in health and survival.”

If the results seen in mice are replicated in humans, the study could someday prove to be a landmark, said Reuben J. Shaw, a researcher at the Salk Institute in La Jolla who contributed to the report.

“I think this could be looked back on as one of the first points where scientists proved that a naturally occurring compound of the diet can have a very specific health benefit,” Shaw said of potentially using resveratrol to prevent obesity-related diseases.

Several experts said that people who are wondering whether they should take resveratrol should wait until more results are in, particularly from safety tests in humans.

Another caution is that the theory about why resveratrol works is still unproved. “It's a pretty exciting area, but these are early days,” said Dr. Ronald Kahn, president of the Joslin Diabetes Center in Boston. Information about resveratrol's effects on human metabolism should be available in a year or so, he said, adding, “Have another glass of pinot noir – that's as far as I'd take it right now.”

The mice were fed a hefty dose of resveratrol, 24 milligrams per kilogram of body weight.

Red wine has about 1.5 to 3 milligrams of resveratrol per liter, so a 150-pound person would need to drink from 750 to 1,500 bottles of red wine a day to get such a dose.

Dr. Richard Hodes, director of the National Institute on Aging, which helped support the study, also said that people should wait for the results of safety testing.

Substances that are safe and beneficial in small doses, like vitamins, sometimes prove to be harmful when taken in high doses, he said.

One person who is not following this prudent advice, however, is Sinclair, the chief author of the study. He has long been taking resveratrol, though at a dose of only 5 milligrams per kilogram.

Mice given that amount in a second feeding trial have shown results similar to, but less dramatic than, those on the 24 milligram-a-day dose, he said.

Sinclair has had a physician check his metabolism, because many resveratrol preparations contain possibly hazardous impurities, but so far no ill effects have come to light. His wife, his parents and “half my lab” are also taking resveratrol, he said.

Sinclair declined to name his source of resveratrol. Many companies sell the substance, along with claims that rivals' preparations are inactive.

One such company, Longevinex, sells an extract of red wine and knotweed that contains an unspecified amount of resveratrol. But each capsule is equivalent to “5 to 15 5-ounce glasses of the best red wine,” the company's Web page asserts.

Sinclair has a financial stake in the research. He is the founder of a company, Sirtris Pharmaceuticals, that has developed several chemicals designed to mimic the role of resveratrol but at much lower doses.

Sirtris has begun clinical trials of one of these compounds, an improved version of resveratrol, with the aim of seeing if it helps control glucose levels in people with diabetes. “We believe you cannot reach therapeutic levels in man with ordinary resveratrol,” said Dr. Christoph Westphal, the company's chief executive.

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