Breaking news on Resveratrol

In a second clinical trial described this year by a team of researchers at UC Irvine, nine colon cancer patients took resveratrol for about two weeks between their diagnosis and their surgery. It was given either in pill form (20 milligrams a day) or as freeze-dried grape powder (mixed in water, either two or three times a day, at doses corresponding to either two-thirds or one pound of fresh grapes).

Part of the tissue from the patients' diagnostic biopsies was saved and later compared with tissue removed during surgery. The researchers were looking for changes in cellular metabolism that occur in more than 85% of patients with colon cancer. Earlier lab studies had indicated that resveratrol might inhibit these changes.

Preliminary results from six patients -- presented in a poster at the meeting of the American Assn. for Cancer Research in Los Angeles this April -- showed that the changes were indeed inhibited by about 50%, with more inhibition occurring in healthy tissue than in cancerous tissue.

"This doesn't prove that resveratrol definitely prevents colon cancer," says principal investigator Holcombe. "But it provides a rationale for doing more studies. . . . And it suggests that resveratrol may be more useful in prevention than in treatment."

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.

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.

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.
Los Angeles Times October 7th 2007