Resveratrol yields no effect on insulin sensitivity in overweight adults

Supplementation with resveratrol for 6 months does not provide a beneficial effect on insulin sensitivity, as well as on outcome parameters related to liver fat accumulation, body composition, dyslipidaemia, energy metabolism, physical performance, and quality of life and sleep, compared with placebo, results of a randomized trial have shown.

However, resveratrol supplementation does result in “lower glycated haemoglobin (HbA1c) concentrations compared with the placebo arm,” the researchers noted. “Supplying resveratrol with a higher dose may be needed to achieve more profound health effects.”

Forty-one overweight men and women (body mass index, 27–35 kg/m²) aged 40–70 years were randomly assigned to receive either 150 mg/day of resveratrol (n=20) or placebo (n=21) for 6 months. Insulin sensitivity, measured using the Matsuda Index, was the primary outcome.

Secondary outcomes included intrahepatic lipid (IHL) content, body composition, resting energy metabolism, plasma markers, blood pressure, physical performance, quality of life, and quality of sleep. The researchers assessed postintervention differences between the two arms using ANCOVA, adjusting for corresponding preintervention variables.

No between-group differences were noted prior to intervention. Resveratrol treatment did not affect insulin sensitivity after 6 months (adjusted Matsuda Index, 5.18±0.35 in the resveratrol arm compared with 5.50±0.34 in the placebo arm), but a significant difference was seen in postintervention HbA1c concentrations between the two arms (p=0.007). [Am J Clin Nutr 2020;112:1029-1038]

The adjusted means indicated lower HbA1c postintervention on resveratrol compared with placebo (35.8±0.43 vs 37.6±0.44 mmol/mol). Furthermore, there were no postintervention differences seen in the secondary outcomes between the two groups.

“We did not find statistically significant effects of resveratrol supplementation on IHL content, despite the fact that our group previously established that the same dose of resveratrol did decrease liver fat content in a 30-d clinical trial in healthy obese men,” the researchers said. [Cell Metab 2011;14:612-622]

Other clinical trials which involved patients with disturbed glucose homeostasis also failed to show improvement in IHL upon resveratrol treatment. [Diabetes Care 2016;39:2211-2217; Mol Metab 2018;12:39-47; J Clin Endocrinol Metab 2017;102:1642-1651; Diabetes Obes Metab 2018;20:1793-1797]

“This may suggest that resveratrol only lowers IHL in healthy overweight individuals and that other factors may prevent improvements … in metabolically compromised individuals,” the researchers said.

Of note, resveratrol has been shown to protect against high fat diet-induced weight gain and to stimulate energy expenditure in animals. However, no effects of resveratrol on body weight or composition have been established so far in humans. [Cell Metab 2011;14:612-622; Nutr Res 2012;32:537-541; J Gerontol Ser A Biol Sci Med Sci 2012;67:1307-1312; Cell Metab 2012;16:658-664]

The current study also had certain limitations. First, the oral-glucose-tolerance test (OGTT) was used to measure the effect of resveratrol on insulin sensitivity, but OGTTs have a higher within-subject variability than that of the gold standard hyperinsulinaemic-euglycaemic clamp technique. In addition, the trial was not powered to measure sex differences, and only postmenopausal women were included, so gender effects could be minimal. Finally, no multiple testing correction was applied, which could increase the risk of false positives.

“The main strengths of this study are the randomized, double-blind, placebo-controlled study design; the relatively long treatment period of 6 mo; use of validated methods; high compliance to treatment; and low dropout rate,” the researchers said.