The recent study by Timmers et al. (1) is a valuable randomized, double-blind, crossover clinical trial involving patients with well-controlled type 2 diabetes who were assigned to receive placebo and 150 mg/day resveratrol for 30 days to evaluate insulin sensitivity via hyperinsulinemic-euglycemic clamp. After the intervention, the authors found that hepatic and peripheral insulin sensitivity were not affected by the resveratrol treatment, and additionally, no significant changes in intrahepatic lipid content were found. However, the authors found an increase in intramyocellular lipid content in type 2 muscle fibers, a tendency for blood pressure to decrease, and an improvement of ex vivo mitochondrial function. The authors concluded that resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity, which led them to question the value of adding resveratrol to the therapy of patients with diabetes.
In 2014, Liu et al. (2) performed a meta-analysis of 11 randomized controlled trials to evaluate the effect of resveratrol on glucose control and insulin sensitivity through a strategic literature search in different databases. A total of 388 subjects were included. The authors found that resveratrol consumption significantly reduced fasting glucose, insulin, hemoglobin A1c, and insulin resistance (evaluated by HOMA) in patients with diabetes, but no significant effect of resveratrol was found in participants without diabetes. The trials included in the meta-analysis reported doses of resveratrol ranging from 8 to 1,500 mg/day with treatment periods varying from 2 weeks to 6 months.
In the trial performed by Timmers et al. (1), a dose of 150 mg/day was used with a treatment period of 30 days, which could explain the absence of significant improvements in insulin sensitivity, as it is well known that resveratrol has a low bioavailability and needs to be accumulated in the target organs to exert its therapeutic effects (3). Another explanation could be the use of one of the lowest doses reported in other clinical trials, as the most pronounced effects on glycemic control have been reported with the dose of 1,500 mg/day.
Our study group performed a randomized, double-blind, placebo-controlled clinical trial in 24 patients with metabolic syndrome treated with 1,500 mg/day of resveratrol for 90 days. After resveratrol administration, we found significant differences in total weight, BMI, fat mass, waist circumference, area under the curve of insulin, and total insulin secretion (4).
Our findings suggest that using a higher dose of resveratrol for a longer period of time could lead to significant improvements in some metabolic parameters; however, results from studies to date are not sufficient to fully recommend the use of resveratrol as a treatment for type 2 diabetes.
For this reason, we propose to continue conducting clinical trials with different doses of resveratrol for longer periods of time to demonstrate its effectiveness on glycemic control and other metabolic parameters.
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Acknowledgments. The authors thank L. Michele Brennan-Bourdon (Scientific Communications and Brennan Language Editing Services) for English editorial assistance.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
