No effect of resveratrol supplementation after 6 months on insulin sensitivity in overweight adults: a randomized trial

Marlies de Ligt, Maaike Bergman, Rodrigo Mancilla Fuentes, Hans Essers, Esther Moonen-Kornips, Bas Havekes, Vera B Schrauwen-Hinderling, Patrick Schrauwen, Marlies de Ligt, Maaike Bergman, Rodrigo Mancilla Fuentes, Hans Essers, Esther Moonen-Kornips, Bas Havekes, Vera B Schrauwen-Hinderling, Patrick Schrauwen

Abstract

Background: Effects of resveratrol on metabolic health have been studied in several short-term human clinical trials, with conflicting results. Next to dose, the duration of the clinical trials may explain the lack of effect in some studies, but long-term studies are still limited.

Objectives: The objective of this study was to investigate the effects of 6-mo resveratrol supplementation on metabolic health outcome parameters.

Methods: Forty-one overweight men and women (BMI: 27-35 kg/m2; aged 40-70 y) completed the study. In this parallel-group, double-blind clinical trial, participants were randomized to receive either 150 mg/d of resveratrol (n = 20) or placebo (n = 21) for 6 mo. The primary outcome of the study was insulin sensitivity, using the Matsuda index. Secondary outcome measures were intrahepatic lipid (IHL) content, body composition, resting energy metabolism, blood pressure, plasma markers, physical performance, quality of life, and quality of sleep. Postintervention differences between the resveratrol and placebo arms were evaluated by ANCOVA adjusting for corresponding preintervention variables.

Results: Preintervention, no differences were observed between the 2 treatment arms. Insulin sensitivity was not affected after 6 mo of resveratrol treatment (adjusted mean Matsuda index: 5.18 ± 0.35 in the resveratrol arm compared with 5.50 ± 0.34 in the placebo arm), although there was a significant difference in postintervention glycated hemoglobin (HbA1c) between the arms (P = 0.007). The adjusted means showed that postintervention HbA1c was lower on resveratrol (35.8 ± 0.43 mmol/mol) compared with placebo (37.6 ± 0.44 mmol/mol). No postintervention differences were found in IHL, body composition, blood pressure, energy metabolism, physical performance, or quality of life and sleep between treatment arms.

Conclusions: After 6 mo of resveratrol supplementation, insulin sensitivity was unaffected in the resveratrol arm compared with the placebo arm. Nonetheless, HbA1c was lower in overweight men and women in the resveratrol arm. This trial was registered at Clinicaltrials.gov as NCT02565979.

Keywords: glycemic control; insulin resistance; intrahepatic lipid content; obesity; resveratrol.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1
FIGURE 1
Plasma concentrations of free + conjugated and dihydro-resveratrol of participants in the RSV treatment arm (n = 20). Plasma samples were obtained in the overnight fasted state on a monthly basis. Data are presented as means ± SEs. RSV, resveratrol.
FIGURE 2
FIGURE 2
Effects of RSV supplementation on insulin sensitivity. Matsuda index, glucose and insulin AUC, and glucose and insulin iAUC were assessed by data from double 2-h 75-g OGTTs pre- and postintervention. Postintervention differences between treatment arms were compared using 1-way ANCOVA, implementing the corresponding preintervention variables as covariates. Postintervention data are presented as adjusted means ± SEs. Data from 1 participant were omitted because of medication usage interfering with glucose homeostasis shortly before postintervention measurements (n = 19 in the RSV arm; n = 21 in the placebo arm). (A) Postintervention Matsuda index as estimate for insulin sensitivity. (B–E) Postintervention plasma glucose and insulin iAUC obtained during 2-h OGTTs. Plasma glucose and insulin iAUC were based on 5 and 3 blood sampling points, respectively. iAUC, incremental AUC; OGTT, oral-glucose-tolerance test; RSV, resveratrol.
FIGURE 3
FIGURE 3
Effect of RSV supplementation on IHL content. IHL content was determined pre- and postintervention by proton magnetic spectroscopy (1H-MRS) on a 3-T MRI scanner. Data are given as T2 corrected ratios of the CH2 peak relative to unsuppressed water resonance, expressed as percentage. Postintervention differences between treatment arms were compared with 1-way ANCOVA, implementing the corresponding preintervention variables as covariates. Postintervention data are presented as adjusted means ± SEs. Data from 2 participants were missing due to claustrophobia, and data from 2 measurements were omitted because of motion artifacts (n = 19 in the RSV arm; n = 18 in the placebo arm). IHL, intrahepatic lipid; RSV, resveratrol.
FIGURE 4
FIGURE 4
Effects of RSV supplementation on body composition. Body composition was determined pre- and postintervention using DXA. Postintervention differences between treatment arms were compared using 1-way ANCOVA, implementing the corresponding preintervention variables as covariates. Postintervention data are presented as adjusted means ± SEs, n = 20 in the RSV arm and n = 21 in the placebo arm. RSV, resveratrol.
FIGURE 5
FIGURE 5
Effects of RSV on functional parameters of physical performance. Physical performance tests were performed pre- and postintervention. Postintervention differences between treatment arms were compared using 1-way ANCOVA, implementing the corresponding preintervention variables as covariates. Postintervention data are presented as adjusted means ± SEs. (A) Post-treatment distance covered during the 6-min walk test per treatment arm. Data from 5 participants were omitted because of pain in the ankle, hip, or knee (n = 17 in the RSV arm; n = 19 in the placebo arm). (B) Postintervention time to complete the timed chair-stand test. Data from 2 participants were omitted because of pain in the ankle or hip (n = 19 in the RSV arm; n = 20 in the placebo arm). (C, D) Postintervention maximal isometric muscle extension and flexion strength measured by the Biodex system by isometric test. Data from 4 participants were not obtained because of technical problems (n = 18 in the RSV arm; n = 19 in the placebo arm). (E, F) Postintervention muscle isokinetic extension and flexion endurance, expressed as the slope of the trend lines measured by the Biodex system by isokinetic test. Data from 4 participants were not included because of technical problems, and those from 10 participants were not included because of no decline in muscle endurance over the 30 repetitions (n = 12 in the RSV arm; n = 14 in the placebo arm). RSV, resveratrol.

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