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Resveratrol: nice for mice

October 08, 2007|Karen Ravn | Special to The Times

The pace of human clinical trials does seem to be picking up. Two groups of researchers are studying resveratrol's effects in prostate cancer patients, and several trials are currently in progress with a proprietary form of resveratrol, testing its usefulness in preventing and treating diabetes.

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An 'elixir' in rodents

If studies of resveratrol in people are few and far between, studies of resveratrol in mice and rats have been coming in right and left.

Perhaps the most famous is a study published in Nature last year that had some people calling resveratrol the "elixir of youth." Researchers at Harvard Medical School and the National Institute on Aging found that obese mice could eat high-fat, high-calorie diets and still live as long as mice fed a usual mouse diet if their pig-outs also included big doses of resveratrol.

And they lived months longer than fellow over-indulgers whose diets did not include resveratrol. (A month in the life of a mouse is equivalent to about three years in the life of a person.)

The mice who lived large also grew large regardless of whether they took resveratrol or not. But if they did take it, they didn't develop the pre-diabetes symptoms of oversized livers and high blood levels of glucose and insulin.

Researchers on this study -- led by David Sinclair and Joseph Baur at Harvard Medical School and Rafael de Cabo at the National Institute on Aging -- suspect that resveratrol works by activating the SIRT1 gene, which they believe is also switched on when mice are fed extremely low-calorie, or famine-level, diets.

Such extreme diets increase the life spans of mice and other animals, and many hypothesize the same is true in people.

Other scientists aren't convinced that resveratrol activates SIRT1, but believe it could work in other ways.

"It would be important to know whether resveratrol has an effect on mice on a normal diet," says Brian Kennedy, a professor of biochemistry at the University of Washington.

"If not, then it isn't mimicking caloric restriction," adds Matt Kaeberlein, a professor of pathology at the University of Washington.

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Seeking benefits

Some researchers are tackling age-related diseases one at a time. "Day by day a new property of resveratrol is being added," says Dr. Dipak Das, a professor of surgery at the University of Connecticut, referring to reports on new uses for resveratrol.

For example, in a study now in press in the journal ARS, Das and others report for the first time that resveratrol lessens the sensitivity of rats to pain.

Other recent resveratrol success stories include these findings: Resveratrol in combination with statins works better than either one alone in improving lipid levels in rats with high cholesterol and in improving their recovery after heart attacks (Journal of Molecular and Cellular Cardiology); resveratrol can greatly reduce the risk that mice will develop the most deadly kind of prostate tumors (August online edition of Carcinogenesis); fairly low doses of resveratrol are enough to increase the sensitivity of mice to insulin, which could lead to new therapies for type 2 diabetes (October issue of Cell Metabolism).

Of course, the scientists who are studying resveratrol to a fare-thee-well aren't simply interested in the welfare of rodents. They hope the benefits they're finding in animals will translate into benefits for humans, too.

But though resveratrol doesn't appear to be toxic to people, some research implies there could be problems if it's taken in excess or by people with particular sensitivities.

Resveratrol has been shown to mimic the action of estrogen in some situations and to block it in others. Similarly, in low concentrations, resveratrol has been shown to stimulate angiogenesis -- growth of new blood vessels -- while at high concentrations it can have the opposite effect. Sometimes angiogenesis is good -- e.g., in recovery from a heart attack. And sometimes it's not -- e.g., when trying to stop the growth of a tumor.

In short, many researchers believe, testing in people has been too limited to truly establish resveratrol's safety. (The supplement can be sold without FDA approval because it's a natural compound, not a drug.)

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Mystery of red wine

The theory that resveratrol explains the French paradox was the beginning of the resveratrol craze, and the theory is not unsupported. "There's evidence resveratrol can affect platelet aggregation and mediate the spasming of blood vessels," says Holcombe of UC Irvine.

But is there enough resveratrol in red wine to have such a major effect? There have always been plenty of naysayers.

And a study in Nature last year claimed the French do owe their healthy hearts to some miracle-working chemicals in red wine -- but they're called procyanidins, not resveratrol.

Of course, some researchers question whether red wine has anything to do with the paradox at all.

It's quite possible that the red-hot field of resveratrol research is based on some unfounded jumping to a conclusion.

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