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Resveratrol: nice for mice

October 08, 2007|Karen Ravn | Special to The 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% 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.

Some researchers have proposed that it explains the French paradox, the fact that French people traditionally eat a high-fat diet, yet remain at relatively low risk for heart attacks. (After all, these researchers reason, the French don't just eat a lot of rich food -- they also drink a lot of red wine.)

And a widely publicized study last year seemed to suggest that high doses of resveratrol could help overeaters live as long as their more abstemious brethren.

But the limitations of the research haven't slowed the marketing of the chemical. Labels on resveratrol supplements and wine alternatives tout the chemical's potential to improve cardiovascular health. At least one wine maker boasts of resveratrol content on bottles of its Pinot Noir. And promotional materials for resveratrol supplements sometimes refer to the longevity study -- without always mentioning that it was done with mice.

Which may be a problem.

"Mice are good models for a lot of things," says Dr. Randall Holcombe, a professor of medicine at UC 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."


Scant research on people

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 speculates, that these have cancer-preventive effects themselves, perhaps being re-converted to resveratrol after they're absorbed into tissues.

"There are all kinds of questions," he says. "All we know right now is that resveratrol is absorbed, but it's not absorbed very much."

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."

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