Chemical's effect on mice, man

Antioxidant great for rodents, but jury still out for humans

October 18, 2007|By Karen Ravn | Karen Ravn,Los Angeles Times

This antioxidant can protect against cancer, heart disease and diabetes. It can lower cholesterol, reduce inflammation and ease pain. Best of all, perhaps, it can help users live 30 percent longer than they would without it.

Resveratrol -- a substance found most notably in red wine -- is sometimes called a "miracle molecule." In labs around the world, scientists are devoting their lives to studying it, and they're writing so many papers about it that mere mortals are hard-pressed to keep up with them all.

In short, the evidence is nearly overwhelming that resveratrol can work wonders for your health.

That is, if you're a mouse.

For humans, the picture is not so clear. To date, little research has been done on how resveratrol acts in people.

"Mice are good models for a lot of things," says Dr. Randall Holcombe, a professor of medicine at the University of California, Irvine. But at the same time he cautions, "They're bad models for a lot of other things."

Some resveratrol researchers are already true believers in its effects, but Holcombe and others are remaining skeptical about the potential benefits of the plant-based chemical (which is also found in peanuts, plums, raspberries and blueberries among other foods).

"Should we change behavior in humans on the basis of evidence in a rodent model?" asks Dr. Dean Brenner of the University of Michigan. "I say no."

Most studies of resveratrol have been done in vitro -- outside of any living organism -- or in animals. But two early clinical trials in people give reason for optimism, and uncertainty, about its possible medical benefits.

One, published in June in Cancer Epidemiology, Biomarkers & Prevention, looked at resveratrol's bioavailability, i.e., how much of it is absorbed, unchanged, into the blood.

"That's a very important question," says Brenner, lead author of the study. "You can take grams and grams, and if none of it gets absorbed, it's moot."

The researchers gave single doses of resveratrol in uncoated immediate-release caplets to 10 volunteers at each of four dose levels -- 0.5, 1, 2.5 and 5 grams -- and then analyzed their blood to see how much resveratrol was absorbed.

Even at the highest dose, peak levels were only about half as high as the level determined in earlier studies to have cancer-preventive effects in vitro. But various resveratrol metabolites -- forms the antioxidant changes into when digested -- were present in very high levels. It's possible, Brenner says, that these have cancer-preventive effects themselves.

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. 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 percent 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 Association for Cancer Research in Los Angeles this April -- showed that the changes were indeed inhibited by about 50 percent, 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."

Karen Ravn wrote this story for the Los Angeles Times.

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