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Red Wine Compound Could Boost Endurance

Resveratrol also fights obesity and may even extend life, early mouse study suggests

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By Steven Reinberg
HealthDay Reporter

THURSDAY, Nov. 16, 2006 (HealthDay News) -- Athletes and non-athletes alike may want to raise a glass to resveratrol, an ingredient in red wine that researchers say doubled the physical endurance of mice in a new study, while protecting them against diabetes and obesity.

Mice given high doses of the compound were able to run twice as far on treadmills than they normally could, French researchers reported.

Resveratrol might even help the rodents live longer, they say.

"The compound resveratrol, found in the skin of red grapes and cranberries, was known to activate SIRT1, an enzyme known to be involved in lifespan extension," explained lead researcher Dr. Johan Auwerx, from the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France.

These results, published in the Nov. 16 issue of Cell, add to findings from a recent study that showed that resveratrol improved health and lengthened survival of mice placed on a high-calorie diet.

While studies have so far been limited to mice, the French team said they had also found a genetic link to energy expenditure in humans that looks like it might be similarly affected by resveratrol.

"Our study shows that activation of SIRT1 by resveratrol is a very promising and well-tolerated approach to treat common metabolic diseases, such as obesity and type 2 diabetes," Auwerx said.

The study involved obese mice with a condition that mimicked type 2 diabetes.

Auwerx's team found that resveratrol activated the SIRT1 gene, inducing the activity of mitochondria, the tiny energy factories within cells. By activating mitochondria, resveratrol causes the cells to burn more energy than they normally could.

Burning more energy protects against fat accumulation and type 2 diabetes, the research team explained. Increasing mitochondria activity also improves the performance of certain tissues, most especially skeletal muscles.

"That is why we saw a spectacular increase in endurance in the mice, which doubled the distance they run," Auwerx explained.

"We showed this not only in cultured cells and mice, but also, more importantly, the first time in humans, where we linked the SIRT1 gene with energy expenditure," Auwerx said.

Resveratrol or its analogs could prove useful in treating several diseases that are characterized by abnormal mitochondrial activity, Auwerx said. "In the first case, you can think about applications in the treatment of obesity and type 2 diabetes," he said. "Many more diseases could benefit from increased mitochondrial activity, most notably neurodegenerative disorders, such as Parkinson's disease and Huntington's," he added.

This study was paid for by Sirtris Pharmaceuticals, which developed the compound used in the experiments.

But if you think that drinking more wine or taking resveratrol supplements might turn you into a super-athlete, think again, said Sirtris CEO Dr. Christoph Westphal.

"Native resveratrol from red wine or nutraceuticals cannot reach therapeutic levels in man," he said. "You would need to drink hundreds of glasses of red wine or take hundreds of nutraceutical pills in a day to get a therapeutic dose."

According to Westphal, the company has completed two phase 1 studies with 85 human volunteers of an improved formulation of resveratrol which reaches therapeutic levels in man and is safe.

In addition, Sirtris has started giving diabetic patients its resveratrol compound in a 28-day phase 1 trial to test the safety of the drug and to see how it affects glucose levels.

"We are also initiating a phase 1 study in a rare, very severe mitochondrial disorder called MELAS," Westphal said. The condition -- "mitochondrial myopathy, encephalopathy, lactacidosis, stroke" (MELAS) -- is a progressive neurodegenerative disorder.

One expert was cautious about the findings.

"This is an important addition to the body of work that is showing that you can activate anti-aging genetic pathways," said David Sinclair, an associate professor of pathology at Harvard Medical School, and a cofounder of Sirtris.

He called the study an important sep in the development of new drugs to fight heart disease, Alzheimer's and age-relate other woes. "In five years, we should know if the results obtained in mice can be achieved in people," he said.

The compound's usefulness against diabetes remains unproven, Sinclair said. "A mouse is not a human," he said. "It would be amazing if it worked in humans. But we will have to wait and see."

Another expert expressed similar skepticism.

"It's clear that the authors of the Cell paper want to strongly argue that their data show a causal link between activation of SIRT1 and the effects of resveratrol," said Matt Kaeberlein, an assistant professor of pathology at the University of Washington. "While all of their data is consistent with this model, and the data is compelling, there really is no causal evidence that the effects of resveratrol in mice require SIRT1 activation," he said.

Kaeberlein suggested that to really test their theory, the researchers should have experimented with mice that did not have the SIRT1 gene, to see whether these mice would respond to resveratrol when fed a high-fat diet.

"Also, there is abundant evidence that resveratrol acts on proteins other than SIRT1, so it's premature to conclude that everything seen in this paper is due to effects on SIRT1," he said.

More information

There's more on resveratrol at Oregon State University.

SOURCES: Johan Auwerx, M.D., Ph.D., Institue of Genetics and Molecular and Cellular Biology, CNRS / INSERM, Institut Clinique de la Souris, Illkirch, France; Christoph Westphal, M.D. Ph.D., CEO Sirtris Pharmaceuticals, Cambridge, Mass.; David Sinclair, Ph.D., associate professor of pathology, Harvard Medical School, Boston; Matt Kaeberlein, Ph.D., assistant professor, pathology, University of Washington, Seattle; Nov. 16, 2006, online edition, Cell

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