Resveratrol Improves Metabolism in Obese Men

Laird Harrison

November 01, 2011

November 1, 2011 — Resveratrol, an ingredient found in red wine, may improve the health of obese men, according to the results of a small trial published in the November issue of Cell Metabolism.

"Although most of the effects that we observed were modest, they were very consistently pointing toward beneficial metabolic adaptations," write Silvie Timmers, MSc from Top Institute Food and Nutrition, Wageningen, and the Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, the Netherlands, and colleagues.

In previous studies, resveratrol appeared to prolong the life of mice and to reverse some of the damage caused by obesity. This study, the first clinical trial of resveratrol published in a peer-reviewed journal, was too short to show an effect on human lifespan, but it duplicated many of the same metabolic effects seen in mice.

The effects were similar to those seen in severe calorie restriction, which has also been shown to improve metabolism and prolong life in mammals.

To see whether the animal effects could be duplicated in people, the researchers recruited 11 obese but otherwise healthy men to a randomized, double-blind, cross-over trial. The men took placebo or 150 mg of resveratrol in the form of resVida (DSM Nutritional Products) once per day for 30 days. After a 4-week washout period, they then took the other treatment option (ie, resveratrol 150 mg for those who had taken placebo, or placebo for those who had taken resveratrol) for the next 30 days.

Researchers measured a series of metabolic biomarkers each week during each of these trials. They found the following differences in the men after 30 days of resveratrol supplementation compared with after placebo supplementation:

  • Both reseveratrol and dihydroresveratrol total (the sum of conjugated and unconjugated resveratrol) were in the participants' plasma. This confirmed that the men were metabolizing resveratrol.

  • Mean systolic blood pressure was 124.7 (±3.1) with resveratrol vs 130.5 (±2.7) with the placebo, which is a statistically significant difference (P = .006). Diastolic blood pressure remained statistically the same. Mean arterial pressure was significantly lower (94.9 vs 97.9; P = .02).

  • There were no effects on body mass (99.9 ± 3.9 kg vs 99.6 ± 2.5 kg; P = .43).

  • After consuming a liquid test meal, the subjects reached peak glucose and insulin responses in 30 minutes when they were taking the placebo, and 60 minutes when they were taking resveratrol.

  • Leptin level and leukoytes were significantly lower in participants taking resveratrol compared with those taking placebo (P = .04 and P = .03, respectively).

  • Markers of systemic inflammation, including interleukin 6 and tumor necrosis factor alpha, were lower for the resveratrol group, but only tumor necrosis factor alpha was statistically significant (P = .09 and P = .04, respectively).

  • Plasma glucose and insulin concentrations were lower in the resveratrol group (P = .05 and P = .04, respectively), suggesting an improved insulin sensitivity.

  • Plasma triglyceride concentrations were significantly lower in the resveratrol group compared with placebo (P = .03).

  • There were no significant differences in plasma nonsterified fatty acids (P = .59).

  • Respiratory quotient values over the course of 24 hours tended to be higher after resveratrol, (P = .09) mostly because of higher values during the day (P = .001, as opposed to the nighttime difference between resveratrol and placebo, which was P = .18).

  • There were no effects on thermogenesis or the physical activity index.

  • Hepatic lipid accumulation was lower.

  • Sleeping metabolic rate was slower in the resveratrol group (P = .007), even though the participants' 24-hour energy expenditure was similar in both groups (P = .64).

  • A microarray analysis on vastus lateralis muscle biopsies showed 469 genes to be differentially expressed, of which 219 were increased and 250 were decreased. Several gene sets related to mitochondrial oxidative phosphorylation were upregulated, whereas pathways linked to inflammation were downregulated.

  • Basal and postprandial energy expenditure were reduced in the resveratrol group, which is a finding opposite to what studies have found in mice, but is consistent with endurance training and calorie restriction in people.

The researchers noted that the dosage they used was about 200-fold lower than the dosage used in mouse studies. The duration of the trial was also much shorter than the 4 to 6 months seen in the animal studies. However, they said the plasma concentration in this trial was about the same as in the mouse trials.

The supplement did not appear to cause any adverse reactions. The researchers looked at clinical chemistry, hematology and coagulation, and electrocardiograms, but found nothing out of the ordinary.

"The study is surprising because of the relatively low dose and time window that were required to produce benefits," said David Sinclair, PhD, a professor of pathology at Harvard University in Cambridge, Massachusetts, in an email to Medscape Medical News.

Dr. Sinclair conducted some of the earlier mouse studies but was not involved in this trial. He added that other compounds, known as sirtuins, with a similar mechanism of action are being tested. "It's a good first step to confirming some of the mouse results in humans, but more studies are needed to know the effects of consuming resveratrol for longer periods and at higher doses," he said.

The study was funded by the Top Institute Food and Nutrition, as well as grants from the Netherlands Organization for Scientific Research to 2 of the authors and laboratory support from the European Research Council, the Swiss National Science Foundation, the Velux Foundation and École Polytechnique Fédérale de Lausanne. One of the researchers in this study is employed by DSM Nutritional Products, which makes resveratrol supplements and supplied the supplements, along with placebo capsules, for the study. Dr. Sinclair disclosed that he is a consultant to GlaxoSmithKline and OvaScience.

Cell Metabol. 2011;14:612-622. Full text


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