Resveratrol Supplements Are Finally Put to the Test

“If one searches the Internet for anti-aging interventions, a vast array of techniques are offered, from starvation regimes to dietary supplements and growth hormones. All are for sale, but none so far have been proven as the magic bullet, despite exorbitant claims on many of the websites.” Resveratrol is one supplement you’ll likely come across, a component of red wine that gained notoriety as a possible explanation for the so-called French Paradox, which turned out to be not so paradoxical after all (see What Explains the French Paradox?).

As I discuss in my video Resveratrol Impairs Exercise Benefits, it turns out that “[c]ountries with high wine consumption are those in which saturated fat consumption used to be low but increased in recent years.” So, the low mortality from ischemic heart disease may just reflect the earlier, lower levels of saturated fat consumption, and the wine may just be a confounding factor. It did, however, help spark interest in resveratrol, the purported active ingredient of red wine about which scientific papers are now published every day.

More than a hundred of those papers on resveratrol have been called into question, though, as one of the leading researchers in the field was found guilty of taking millions in taxpayer money only to fabricate and falsify his data.

Hundreds of studies still remain, though. Does this mean pills can now replace a healthy diet? Even a group of resveratrol scientists don’t think resveratrol is worth supplementing: “In contrast to the lacking data on resveratrol in humans, the animal data are promising and indicate the need for further human clinical trials.” In rodents, resveratrol supplementation decreased cardiovascular risk factors, improved cardiovascular function and physical capacity, and decreased inflammation, leading to improved vascular function. But, when it was put to the test in people, almost the exact opposite was found.

Specifically, combining resveratrol with athletic training abolished the reduction in blood pressure, cholesterol, and triglycerides normally associated with training; had a more arterial-constricting effect than a dilating effect; “and led to a significantly lower increase in the training-induced increase in maximal oxygen uptake.”

Rodents on resveratrol get enhanced exercise performance, but, in people, the resveratrol induced a 45 percent lower increase in maximum aerobic capacity compared with those taking a sugar pill. The human subjects were working out like crazy, and the resveratrol undercut their efforts.

This raises a larger issue. Mouse models are a cornerstone of modern biomedical research, and yet systematic studies as to their usefulness are rarely done. Consider this: nearly 150 human clinical trials testing anti-inflammatory drugs have failed—without exception—after those same drugs had shown promise in trials on mice. In analyzing the carry-over from the mouse trials to the human trials, researchers determined that “[t]he result was surprising, almost shocking: the correlation was not only poor, it was virtually absent for the main study areas: burns, trauma, endotoxemia.” It turns out, for example, that mice may be up to a million times less sensitive to inflammatory endotoxins than humans.

The takeaway is that the negative effects they found add to the growing body of evidence questioning the positive effects of resveratrol supplementation in humans. Maybe the problem, though, was resveratrol supplementation—that is, giving people capsules containing 50 times the resveratrol they would normally get from eating grapes, berries, peanuts, or chocolate. Was it just too much of a good thing? To see if the amount one gets from drinking red wine would be beneficial, we can look to the Chianti region of Tuscany to determine whether resveratrol levels achieved with diet help protect against inflammation, cancer, cardiovascular disease, and death. The answer? None of the above. Despite the fact that U.S. annual sales of resveratrol supplements have reached $30 million, there are limited and conflicting human clinical data demonstrating any human benefits, and there are no data concerning its long-term safety.

The exercise study was supported in part by a manufacturer of resveratrol supplements. To their credit, however, the researchers responded to an angry letter by a supplement company consultant that “it is our opinion that we, as scientists, have a responsibility to report what we find, and not to twist our findings to fit the commercial interests.”

The benefits of red wine over white do not appear to be due to the resveratrol, but to the estrogen synthase blockers. See Breast Cancer Risk: Red Wine vs. White Wine.

What about the role of red wine in the Mediterranean diet? I have a whole series of videos, including:

I just published a whole new series on alcohol. Check it out:

Sadly, the epic failure of resveratrol supplements is par for the course when it comes to trying to get your nutrition in pill form. See, for example:

In health,
Michael Greger, M.D.

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