Editors' ChoiceObesity

Resveratrol: Too Early to Bring Out the Wine?

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Science Translational Medicine  12 Dec 2012:
Vol. 4, Issue 164, pp. 164ec228
DOI: 10.1126/scitranslmed.3005446

The ideal dietary supplement would improve one’s health while providing enjoyment in its partaking. In some ways, resveratrol—a naturally occurring polyphenol that is a constituent of wine and grape skin—fits such criteria. In animal models, the beneficial effects of resveratrol have been widely observed and include improved glucose metabolism, prevention of obesity, reversal of nonalcoholic fatty liver disease, and amelioration of other age-related pathologies. It is hypothesized that resveratrol mimics the health benefits of calorie restriction by targeting silent mating type information regulation 2 homolog 1 (SIRT1). Recently, it was also reported that resveratrol improves glucose metabolism and insulin sensitivity in patients with obesity and type 2 diabetes. Thus, resveratrol had seemed to cement its position as the dream supplement. However, it may be too soon to grant it such a designation. Poulsen et al. now report that high-dose resveratrol supplementation does not improve metabolic function in obese men.

In a randomized, double-blinded, parallel-group trial, 24 obese but otherwise healthy men were treated for 4 weeks with trans-resveratrol (500 mg three times a day) or placebo. A hyperinsulinemic euglycemic clamp study revealed that resveratrol supplementation did not improve insulin sensitivity. In addition, the treatment had no effect on blood pressure, body fat content, or other metabolic parameters.

Another research group has also recently shown that the enthusiasm over resveratrol’s health effects may be premature. Yoshino et al. evaluated the metabolic effects of 12 weeks of resveratrol supplementation (75 mg/day) in nonobese, postmenopausal women with normal glucose tolerance and found no effect on plasma lipids, body composition, or metabolic function. However, since resveratrol is only effective in obese mice but not in normal rodents, it could be expected that resveratrol would have no beneficial metabolic effects in nonobese women.

Although many beneficial effects of resveratrol have been observed in metabolically abnormal mouse models, the impact of this supplement on human metabolism remains controversial. Additional factors such as age and gender, or preexisting obesity and diabetes, may generate considerable variation in the biological responses to this compound. Therefore, because it is more difficult to set up and control experiments with human subjects, further investigation is required to clarify the impact of resveratrol on human health and determine which patients may benefit from a grape prescription after all.

M. M. Poulsen et al., High-dose resveratrol supplementation in obese men: An investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes, published online 28 Nov 2012 (10.2337/db12-0975). [PubMed]

J. Yoshino et al., Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab. 16, 658–664 (2012). [Abstract]

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