Resveratrol Study Results Don’t Tell the Whole Story on Benefits

A recent study investigating the benefits for women of the dietary supplement resveratrol, located in the skins of red grapes and wine, found no significant improvements in insulin sensitivity or cholesterol compared to a control group.

Bad news for resveratrol? Right? Well not exactly! The fact is, this study from US and Italian researchers was evaluating healthy postmenopausal women who had no insulin sensitivity or cholesterol problems to start with. These post-menopausal women were actually, as a group, some of the healthiest people in this age group you could ever meet. The 15 women given a resveratrol supplement for 3 months were all in their late 50’s, were lean or overweight (not obese), and had undergone a complete medical evaluation showing no history or evidence of type 2 diabetes or cardiovascular disease. Additionally none had ever been treated or had a history of abnormal lipids (cholesterol, triglycerides, etc.) or high blood pressure. Statistically speaking, the women investigated in this study were an extremely rare group to find and perhaps that’s why only 15 subjects were actually tested with resveratrol. The fact is the researchers would have had it much easier finding women who had diabetes, heart disease and other conditions that actually could affect metabolic performance. (See Table of common conditions in post-menopausal women) As noted by this group of researchers, many other investigators have looked at the benefits of resveratrol in people with abnormal conditions such as metabolic syndrome (pre-diabetes), actual diabetes, heart disease and abnormal lipids, and have found significant beneficial improvements when taking this dietary supplement. In addition, the researchers conceded that prior animal studies investigating healthy animals using resveratrol (like their human study) had not shown any improvements in insulin sensitivity and blood lipid levels. Knowing these facts, it would appear that this group of investigators had set out to find “super” results from taking resveratrol--to make normal women into “super women” who could possess even better than normal insulin sensitivity, lipid levels, and other metabolic markers. A laudable goal, but several flaws in the study design most likely prevented this from occurring. First and foremost, the study used only 75 mg per day of essentially pure trans-resveratrol. Although others have investigated resveratrol in humans using a daily dose less than 100 mgs, most recent studies showing benefits of resveratrol have used higher dosing. In a study done in 2010 in the United Kingdom, researchers showed a dose-dependent increase in brain blood flow using resveratrol at the 250 mg and 500 mg daily dose levels. Dose-dependent means the greater the dose the greater improvement seen. A better direct comparison to this current study was a study done in 2011 using 150 mg/day of resveratrol in healthy obese men. The researchers from the Netherlands and Switzerland found profound metabolic improvements using resveratrol in blood glucose and lipid reductions. They especially noted reductions of fat in and around the liver, which is common with obesity, and related to the development of type 2 diabetes in obesity. By using a daily dose of only 75 mg/day of resveratrol, these non-beneficial results were most likely destined from the beginning and would not show any significant benefits compared to the placebo group. This study also had a third arm that evaluated the benefits of a calorie reduction diet (5% of body weight average loss) and any metabolic improvements. As was found in the resveratrol arm when using non-obese, healthy, post-menopausal women, no improvements were found from the already normal metabolic levels despite their significant weight loss. It’s hard to make someone significantly better who is already in good shape. In summary, this study, despite the media hype surrounding it, tells us very little about the benefits or non-benefits of resveratrol. Flaws in dosing (too low) and not evaluating subjects that could show improvement (healthy women) make conclusions based on this study difficult at best. Human studies using resveratrol will continue to fascinate both the public and media because of its great potential to improve the human condition. Get the whole story about resveratrol, then decide. Table I: Metabolic and Heart Risk Associated with Postmenopausal Women --Diabetes is the most common disease in the postmenopausal period --Estimated 20% of women > 65 years will also have diabetes --Metabolic changes with menopause may contribute to development of diabetes: increased central body fat, increased LDL, and decreased    HDL, and increased insulin resistance --60 percent increased risk of metabolic syndrome in postmenopausal women --Once a woman reaches the age of 50, the age of natural menopause, her risk for heart disease increases dramatically References http://www.hopkinsguides.com/hopkins/ub/view/Johns_Hopkins_Diabetes_Guide/547089/all/Menopausal+Effects+on+Glycemia Jun Yoshino, Caterina Conte, Luigi Fontana, Bettina Mittendorfer, Shin-ichiro Ima, Kenneth B. Schechtman, Charles Gu, et al, Resveratrol Supplementation Does Not Improve Metabolic Function in Nonobese Women with Normal Glucose Tolerance,  Cell Metabolism 16, 1–7, November 7, 2012 Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF.Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010 Jun;91(6):1590-7. Epub 2010 Mar 31. Silvie Timmers, Ellen Konings, Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans Cell Metabolism 14, 612–622, November 2, 2011