May 13 2014

Resveratrol – Reason for Skepticism

Dr. Oz recommends resveratrol as a supplement to reduce inflammation and protect the heart. On his website you will find:

While resveratrol has been recommended for fighting the physical effects of aging, a brand new study shows it reduced inflammation of the heart in the study’s participants by 26%. Taking one 500 mg capsule of resveratrol daily with food will help you maintain a strong, healthy heart.

How evidence-based is this recommendation? At present we have preliminary in vitro and in vivo studies showing that resveratrol has interesting biological effects that are potentially beneficial, particularly in heart disease. There are some short term human studies as well.

The question is – how predictive are such early promising research results to later long-term clinical studies? I have written many times arguing that the answer is – not very much. There is researcher bias, exploiting degrees of freedom, and publication bias to contend with, all favoring false positive results in the literature.

Further, pre-clinical studies may not predict net clinical effects. There are other factors to consider that could render an interesting effect in the test tube useless in a living person, such as bioavailability. It doesn’t matter what the effect of the supplement is if it does not get absorbed into the body and transported to the relevant site of action.

Also, biology is complex and there may be mechanisms in place that counteract the desired effect or have unforeseen downstream consequences.

So, no matter how promising a new substance seems, we need clinical studies in people with sufficient follow up before we can say what the net clinical effect of supplementation in various populations will be.

Resveratrol is a polyphenol compound found in grape skins, wine, and peanuts. It seems to have anti-inflammatory activity, which can be potentially useful. It also has been shown to reduce platelet aggregation, and therefore can reduce the risk of blood clots, such as those that can cause stroke or heart attacks. It is also an antioxidant, which gives it a certain marketing appeal, but I am not optimistic about the future of exogenous antioxidants in human health. Resveratrol apparently does not lower lipid levels.

All of this may be sufficient for Dr. Oz and other gurus to recommend resveratrol as the next fountain of youth, and for the health food store shelves (actual and virtual) to be full of resveratrol products with astounding health claims. It is not enough, however, to conclude that resveratrol actually works, and there is a metaphorical graveyard full of failed products with similar preliminary results.

A new clinical study sheds further light on the actual effects of resveratrol. From the abstract:

How the Study Was Conducted: The participants (a sample of 783 men and women 65 years or older) were part of the Aging in the Chianti Region study from 1998 to 2009 in two Italian villages. The authors sought to determine if resveratrol levels achieved through diet were associated with inflammation, cancer, cardiovascular disease, and death. Levels were measured using 24 hour urine collections to look for breakdown products of resveratrol.

Results: During nine years of follow-up, 268 participants (34.3 percent) died; of the 639 participants free of cardiovascular disease at enrollment, 174 (27.2 percent) developed cardiovascular disease during the follow-up; and of the 734 participants who were free of cancer at enrollment, 34 (4.6 percent) developed cancer during the follow-up. Urine resveratrol metabolite levels were not associated with death, inflammation, cardiovascular disease or cancer.

This study was not randomized, so that is a weakness. However, it was a fairly large study that followed many relevant clinical outcomes with a 9 year follow up. It also directly measured resveratrol metabolites in the urine, rather than relying on subject reporting.

This one study is not definitive, nor will it be the final word, but it is a solid study with completely negative results. It is, at the very least, reason for serious skepticism about the clinical benefits of resveratrol.


Resveratrol remains an interesting compound, with a great deal of active research that has the potential of yielding useful results.

However, at the present time, clinical claims for health benefits from resveratrol are premature, and now we have clinical evidence that casts serious doubts on such claims.

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