Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial

Background: The obese insulin-resistant state is characterized by impairments in lipid metabolism. We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal (HFMM) test in men. Objective: The present study aimed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity. Design: In this randomized double-blind study, 38 overweight and obese subjects [18 men; aged 38 +/- 2 y; body mass index (kg/m(2)): 29.7 +/- 0.5] received either EGCG+RES (282 and 80 mg/d, respectively) or placebo for 12 wk. Before and after the intervention, oxidative capacity and gene expression were assessed in skeletal muscle. Fasting and postprandial (HFMM) lipid metabolism was assessed by using indirect calorimetry, blood sampling, and microdialysis. Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-H-2(2)]-glucose infusion. Results: EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass tended to decrease after the intervention compared with placebo (P-time X treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers (P-time X treatment <0.05, P-EGCG+RES <0.05). Moreover, EGCG+RES reduced fasting (P-time X treatment = 0.03) and postprandial respiratory quotient (P-time X treatment = 0.01) compared with placebo. Fasting and postprandial fat oxidation was not significantly affected by EGCG +RES (P-EGCG+RES = 0.46 and 0.38, respectively) but declined after placebo (P-placebo = 0.05 and 0.03, respectively). Energy expenditure was not altered (P-time X treatment = 0.96). Furthermore, EGCG+RES supplementation attenuated the increase in plasma triacylglycerol concentrations during the HFMM test that was observed after placebo (P-time X treatment = 0.04, P-placebo = 0.01). Finally, EGCG+RES had no effect on insulin-stimulated glucose disposal, suppression of endogenous glucose production, or lipolysis. Conclusion: Twelve weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects.