November 30, 2006

Quest for Youth Drives Craze
For 'Wine' Pills

Recent studies suggesting a substance in red wine could be a possible anti-aging elixir have sparked a surge in sales of dietary supplements containing the ingredient, known as resveratrol.

But some scientists caution that there is no medical consensus on whether the products are effective or even safe for human use. Nor is there much guidance for consumers seeking to distinguish among the supplements' bewildering array of ingredients, dosages and claims.

Longevinex

In two widely publicized studies this month, resveratrol, which is developed naturally in some plants, was found to boost endurance and prolong life span in laboratory mice. But those mice were given very large doses of resveratrol -- equivalent to hundreds of glasses of wine or dozens of dietary-supplement pills a day. The findings were hailed as encouraging but preliminary, and no human studies have shown such benefits.

More than a dozen supplements featuring resveratrol are sold in health-food stores and online. But dietary supplements are only lightly regulated by the Food and Drug Administration, and manufacturers don't have to demonstrate efficacy in order to market a product.

Despite those caveats, several retailers report a large jump in sales of resveratrol supplements. Whole Foods Market Inc., the national health-foods chain, sold out of its resveratrol product at many stores earlier this month, though a spokeswoman declined to give sales figures.

Bill Sardi, founder and president of Resveratrol Partners LLC, which since 2003 has marketed online a supplement derived from giant knotweed, a Chinese plant, says, "I'm having to place rush orders from China because this thing is wild." Mr. Sardi says his company sold as many boxes of its product, Longevinex, in the week after the first study appeared in the journal Nature as it did in the previous six months. Vitacost.com1 Inc., a large online retailer in Boynton Beach, Fla., says sales of its resveratrol supplements increased tenfold in that week. Source Naturals Inc., another supplement maker, says it has seen a "large jump" in sales of its resveratrol product.

Harry Highkin, a retired biologist in Kailua Kona, Hawaii, takes resveratrol by the fistful, popping 36 capsules -- or 1.44 grams -- every day. Though there's no scientific evidence to back him up, Dr. Highkin credits the supplements with keeping him alive after he was diagnosed with a rare precursor of leukemia in 2000. He turned 89 this month.

Dosages vary widely among resveratrol supplements, but none come close to what mice in the most recent studies received. In the Nature study, mice were given 24 milligrams of resveratrol per kilogram of body weight, the equivalent of nearly two grams of resveratrol in a 180-pound human.

The small but growing subculture of resveratrol users across the country also includes David Sinclair, a biologist at Harvard Medical School and lead author of the Nature study. Persuaded by his own research, he says, he began taking a resveratrol supplement three years ago. He won't say what brand or dosage he takes, but says several members of his staff take resveratrol as well.

Still, Dr. Sinclair and other scientists who have studied resveratrol say it's still too early to actually recommend use of the substance, until supplements have undergone more scientific scrutiny in humans. While resveratrol hasn't been found to be toxic, they say, little is known about potential side effects and long-term implications in humans. "It's the worry about the unknown," says Dr. Sinclair.

To some critics, resveratrol is just another example of trends in the dietary-supplement industry outpacing science. "The right place now with resveratrol is to say that this is really intriguing data, but mice aren't humans," says Brent Bauer, director of the complementary and integrative medicine program at the Mayo Clinic in Rochester, Minn. He warns that beta carotene gained widespread popularity as a cancer preventive on the back of encouraging studies before a 1996 study showed that it didn't prevent lung cancer or heart disease and could actually be harmful to smokers.

The National Institute of Environmental Health Services, a federal agency, launched an extensive toxicology review of resveratrol in 2002, but results may not be available for several years. The agency's preliminary study of existing research found little evidence that resveratrol is toxic, even at very high dosages. Scott Masten, a toxicologist for the NIEHS, says the study was prompted by an increasing number of supplements with resveratrol in their formulas.

In the interim, the FDA has taken a skeptical but largely hands-off approach to resveratrol. In 2000, in response to a request for a ruling by a supplement maker, the agency said that the safety of resveratrol supplements hasn't been established. But regulators haven't taken any action against the supplements. Under a 1994 law, the FDA can't prevent dietary supplements from going on the market but can take regulatory action if a product is found to be unsafe.

Several marketers of resveratrol supplements say they expect the agency to scrutinize their products more closely in the wake of this month's attention and sales increase. FDA spokesman Michael Herndon declined to comment on the agency's plans.

Resveratrol comes in two forms: cis-resveratrol and trans-resveratrol. Scientists say trans-resveratrol is the key ingredient to look for in dietary supplements because it activates the SERT1 enzyme that may be responsible for anti-aging effects in mice. The enzyme is thought to mimic calorie restriction, the most-documented method of prolonging life span.

Some supplements, such as Jarrow Formulas Inc.'s Resveratrol Synergy, don't mention trans-resveratrol on their labels at all. Kevin Connolly, the director of product development for Jarrow, says the company's tests have found its product contains about 90% trans-resveratrol. "We might start putting on the label how much trans is in there," he says.

Vitacost, which sells several resveratrol supplements under the Nutraceutical Sciences Institute brand, also doesn't specify trans-resveratrol on its labels. Wayne Gorsek, chief executive, says, "We've never had significant funding where we can afford to do studies."

Another complication arises because resveratrol is prone to oxidation, or breaking down when exposed to air. A resveratrol supplement in the form of a tablet is likely to lose its efficacy over time, according to Dr. Sinclair of Harvard. He says a capsule form may be preferable.

To address the dosage issue, scientists are seeking to develop concentrated drugs that might make it easier to achieve the resveratrol levels of the studies. Many of the Harvard scientists behind the two studies this month founded Sirtris Pharmaceuticals, which is developing a drug based on resveratrol to treat diabetes. CEO Christoph Westphal (who is married to a reporter for The Wall Street Journal) says the company's drugs in development are "over 1,000-fold improved in potency," but the company has yet to publish those findings.

A handful of human studies of wine drinkers have indicated some benefits -- from cardiovascular health to the prevention of Alzheimer's disease -- in the smaller doses of resveratrol that red-wine drinkers ingest. Willamette Valley Vineyards in Colorado now lists resveratrol content on the labels of its pinot noirs. Jim Bernau, president and chairman of Willamette Valley Vineyards, says, "The motivation wasn't to sell pinot noir by touting its resveratrol content. It was just one of those things that help kind of distinguish pinot noir as a grape variety."

Some supplement makers have sought to capitalize on the publicity surrounding resveratrol in their marketing campaigns. Renaissance Health Publishing LLC, based in Boca Raton, Fla., has published a 20-page booklet for potential buyers of its dietary supplement, Revatrol. It begins, "Let me show you the breakthrough discovery for a strong heart, great health and a longer life ... inside this one little capsule."

William S. Gruss, a cardiologist whose image, signature and testimonial -- "there's absolutely no risk" -- are featured prominently in Revatrol's marketing, says Renaissance paid him but declines to say how much.

"Am I going to live longer because of Revatrol? I'll let you know," says Dr. Gruss. "But if it turned out not to live up to all of its promises, well then, no harm done."

Write to Zachary M. Seward at zachary.seward@wsj.com