Red wine ingredient increases endurance, study shows

By NICHOLAS WADE / The New York Times

Published: November 17, 2006

  E-Mail Article

  Listen to Article

  Printer-Friendly

  3-Column Format

  Translate

  Share Article

  Add to Clippings

Text Size

The buzz over sirtuin activators has infected scientists who do research on the aging process, several of whom are already taking resveratrol. Dr. Sinclair has been swallowing resveratrol capsules for three years and has said his parents and half the members of his laboratory do the same. So does Dr. Tomas Prolla at the University of Wisconsin, who said, "The fact that investigators in the field are taking it is a good sign there is something there."

But many others, including Dr. Leonard Guarente of M.I.T., whose 15-year study of sirtuins has laid the basis for the field, say it is premature to take the drug.

It was after working in his laboratory as a postdoctoral student that Dr. Sinclair found in 2003 that resveratrol was a sirtuin activator. Though resveratrol has long been known to be an ingredient of red wine and other foods, its presence there is minuscule compared with the doses used in experiments.

Dr. Sinclair dosed his mice daily with 22 milligrams of resveratrol per kilogram of weight, and Dr. Auwerx used up to 400 milligrams. No one can drink enough red wine to obtain such doses.

Today in Health & Science

Neanderthal DNA tells the story of an early human species

Red wine ingredient increases endurance, study shows

Study on stents is another challenge to conventional medical wisdom

Resveratrol is sold as capsules that contain extracts of red wine and giant knotweed, a plant found in China. The company Longevinex makes capsules containing 40 milligrams of resveratrol that are used by several researchers. Longevinex's president, Bill Sardi, said demand had increased by a factor of 2,400 since Nov. 1. But even Longevinex's capsules would have to be taken in almost impossible quantities to attain doses equivalent to those used in the mice.

Whether much lower doses than those used in the experiments would benefit athletic performance is not clear, Dr. Evans of the Salk Institute said. And higher doses may not be as safe as the small amounts found in foods and nutraceuticals, he added.

Scientists' rule of thumb is to believe nothing until it has been confirmed in at least one other laboratory. The Sinclair and Auwerx experiments, though not the same, both point to powerful beneficial effects of resveratrol. But many of the details remain up in the air, and almost all hopes about resveratrol, especially for people, remain subject to revision.

The science of the field is still in flux, as many central details are unclear. The main theory developed by Dr. Guarente and others is that sirtuins sense the level of energy expenditure in living cells and switch the body's resources from reproduction to tissue maintenance when food is low.

This is an ancient strategy, Dr. Guarente believes, intended to let an organism live through famines and postpone breeding until good times return. The switch to tissue maintenance involves specific action that would stave off the major degenerative diseases of aging like cancer, diabetes, heart disease and degeneration of brain cells.

One major uncertainty is whether resveratrol in the mice experiments even acts through sirtuins, supporting the theory, or in some other way.

Dr. Auwerx cited new evidence that resveratrol did activate sirtuins, but Dr. Evans said the case was not yet convincing.

Dr. Auwerx theorizes that resveratrol activates sirtuin, which in turn activates a substance known as PGC1-alpha in a manner described last year by Dr. Bruce Spiegelman, an expert on fat metabolism at the Harvard Medical School. Subsequent actions by PGC1-alpha then stimulate cells to produce more mitochondria. In an e-mail message, Dr. Spiegelman described Dr. Auwerx's paper as "pretty good."

Increased energy production by mitochondria generates dangerous reactive chemicals that are known to damage cells. So it has long been puzzling that exercise, in which extra energy is expended, is good for health, not bad. The answer, Dr. Auwerx suggested, may have been provided by Dr. Spiegelman, who reported in the journal Cell last month that PGC1-alpha not only increases mitochondria but at the same time also generates extra chemicals that detoxify the energy byproducts.