Whatever science may say about resveratrol—a compound found in red wine and thought to contribute to wellness and longevity—toastmasters will forever exclaim “To your health!” and “Long life!” with undiminished enthusiasm. And well they might. For while resveratrol has indeed been tested and found wanting in a study of Italians who consume a diet rich in the compound, researchers are quick to add that red wine is complex and may well contain other health-protecting agents. The same may be true of dark chocolate, peanuts, berries, and certain Asiatic plant roots, which are also rich in resveratrol and thought to convey health benefits.

Resveratrol, the wine-lover’s favorite polyphenol, has attracted a lot of attention owing to its effects on inflammation, carcinogenesis, and longevity in various studies. These studies, however, did not assess the effects of reasonable dietary levels of resveratrol in humans. Instead, results were extrapolated from in vitro tests, studies in lower organisms, and trials involving supraphysiologic doses of resveratrol in humans.

It was only a matter of time before researchers decided to test whether physiologic levels of dietary resveratrol really were associated with health benefits, particularly since annual sales of resveratrol supplements have reached $30 million in the United States alone.

A proper test was delayed only because the study of resveratrol in humans is difficult. The compound, it turns out, is quickly taken up, metabolized, and excreted. Nonetheless, resveratrol's metabolites in human urine can be tracked with current mass spectrometric methods, so researchers decided that the time was ripe for a population-based cohort study.

A team of scientists led by Richard D. Semba, M.D., M.P.H., a professor of ophthalmology at the Johns Hopkins University School of Medicine, analyzed 24 hours of urine samples from 783 people over the age of 65 for metabolites of resveratrol. After accounting for such factors as age and gender, the researchers found that the people who had the highest concentration of resveratrol metabolites were no less likely to have died of any cause than the people who had no resveratrol found in their urine.

The details of the study appeared May 12 in JAMA, in an article entitled “Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults.” The authors noted that their intent was to move beyond the limitations of past studies, which yielded conflicting human clinical data on metabolic benefits and lacked data concerning the safety of high-dose, long-term resveratrol supplementation, particularly in “older people, who often have multiple comorbidities for which they are taking multiple medications.”

The researchers concluded that “resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.” The population, incidentally, was made up of a random group of people living in Tuscany where supplement use is uncommon and consumption of red wine—a specialty of the region—is the norm.

“The story of resveratrol turns out to be another case where you get a lot of hype about health benefits that doesn’t stand the test of time,” said Dr. Semba. “The thinking was that certain foods are good for you because they contain resveratrol. We didn’t find that at all.”

Despite the negative results, more than mere dregs remain of the notion that red wine benefits its drinkers. For example, studies have shown that consumption of red wine, dark chocolate, and berries reduces inflammation in some people and still appears to protect the heart. “It’s just that the benefits, if they are there, must come from other polyphenols or substances found in those foodstuffs,” Dr. Semba explained. “These are complex foods, and all we really know from our study is that the benefits are probably not due to resveratrol.”

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