Wine Extract Keeps Mice Fat and Healthy

By SETH BORENSTEIN

WASHINGTON (AP) - Huge amounts of a red wine extract seemed to help obese mice eat a high-fat diet and still live a long and healthy life, suggests a new study that some experts are calling "landmark" research.

The big question is, can it work the same magic in humans?

Scientists say it's far too early to start swilling barrels of red wine. But some are calling the latest research promising and even "spectacular."

The study by the Harvard Medical School and the National Institute of Aging shows that heavy doses of red wine extract lowers the rate of diabetes, liver problems and other fat-related ill effects in obese mice.

Fat-related deaths dropped 31 percent for obese mice on the supplement, compared to untreated obese mice, and the treated mice also lived long after they should have, the study said.

Astoundingly, the organs of the fat mice that got the wine extract looked normal when they shouldn't have, said study lead author Dr. David Sinclair of Harvard Medical School. And Sinclair said other preliminary work still being done in the lab shows the wine ingredient has promise in lengthening the life span of normal-sized mice, too.

Sinclair has a financial stake in the research. He is co-founder of a pharmaceutical firm, Sirtris Pharmaceuticals Inc. of Cambridge, Mass., which is testing the safety of using the extract on humans for treatment of diabetes.

For years, red wine has been linked to numerous health benefits. But the new study, published online in the journal Nature on Thursday, shows that mammals given ultrahigh doses of the red wine extract resveratrol can get the good effects of cutting calories without having the pain of actually doing it.

"If we're right about this, it would mean you could have the benefit of restricting calories without having to feel hungry," Sinclair said. "It's the Holy Grail of aging research."

Resveratrol, produced when plants are under stress, are found in the skin of grapes and in other plants, including peanuts and some berries.

The resveratrol-treated 55 obese mice on a high-calorie diet (one scientist called it a "McDonald's diet") are not only about as healthy as normal mice, they are as agile and active on exercise equipment as their lean cousins, showing what can be considered a normal quality of life, higher than usual for obese mice, said study co-author Rafael de Cabo of the National Institute on Aging.

"These fat old mice can perform as well on this skill test as young lean mice," Sinclair said.

The only major body measurement that didn't improve - aside from weight - was cholesterol and that didn't seem to matter in the overall health of the mice, Sinclair said.

The study is so promising that the aging institute this week is strongly considering a repeat of the same experiment with rhesus monkeys, coming the closest to humans, after successful resveratrol experiments on yeast, worms, fruit flies and now mice, said institute director Dr. Richard Hodes.

Hodes cautions that it's too early for people to start taking non-regulated resveratrol supplements because safety issues haven't been addressed adequately. He pointed to past hyped medical treatments, such as estrogen, that turned out to cause more harm than good.

Sirtris Pharmaceuticals is working on a high-dose resveratrol pill that unlike unregulated supplements on the market now, would be used as a drug and require Food and Drug Administration approval, said company chief executive officer Dr. Christoph Westphal. And that development and federal approval is about five years away, he said.

Sinclair's results are so promising that he rushed the study into the science journal while the obese mice are still alive, not waiting several more weeks or months until they die. That raises some issues, including specific figures about mortality, but is understandable, said outside experts. The obese mice still lived past the median age for mice of their weight.

Even would-be competitors are praising the study.

"It's a fairly spectacular result," said University of Wisconsin medical professor Dr. Richard Weindruch, who co-founded another biotech company that looks at the genetics of aging and drugs that could expand life spans. "People will go to McDonald's and afterwards they'll do super-sized resveratrol."

"This is fantastic," said Brown University molecular biology professor Stephen Helfand, who was the first reviewer for the journal Nature and not part of the team. "This is a historic landmark contribution."

Helfand said he won't be taking red wine extract supplements - but he has put his elderly mother on them. He said he's waiting to see if there are long-term ill effects for humans. Mice, he said, are good initial test subjects for human drugs because their bodies function more similarly to humans than differently. However, he added that those differences can prove crucial.

Sinclair said he takes resveratrol supplements, but doesn't recommend it for others. Sinclair's mice took such high doses of resveratrol that it would be the equivalent of an adult drinking 100 bottles of wine daily.

Resveratrol works by spurring activity and regrowth in cells' mitochondria, which Sinclair called "the energy powerhouses of the cell."
Some scientists, such as Weindruch and Hodes, worry that the research may encourage people to forget about their diets and wait for a red wine cure-all that may never come.

"It's not an excuse to overeat," Sinclair said. But he added that for mice at least, this shows you can be "fat, happy, healthy and vigorous."