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 byimpairments in lipid metabolism.We previously showed that 3-d supplementationof combined epigallocatechin-3-gallate and resveratrol(EGCG+RES) increased energy expenditure and improved thecapacity to switch from fat toward carbohydrate oxidation witha high-fat mixed meal (HFMM) test in men.Objective: The present study aimed to investigate the longer-termeffect of EGCG+RES supplementation on metabolic profile, mitochondrialcapacity, fat oxidation, lipolysis, and tissue-specific insulinsensitivity.Design: In this randomized double-blind study, 38 overweightand obese subjects [18 men; aged 38 6 2 y; body mass index(kg/m2): 29.7 6 0.5] received either EGCG+RES (282 and80 mg/d, respectively) or placebo for 12 wk. Before and after theintervention, oxidative capacity and gene expression were assessedin skeletal muscle. Fasting and postprandial (HFMM) lipid metabolismwas assessed by using indirect calorimetry, blood sampling,and microdialysis. Tissue-specific insulin sensitivity was assessedby a hyperinsulinemic-euglycemic clamp with [6,6-2H2]-glucoseinfusion.Results: EGCG+RES supplementation did not affect the fastingplasma metabolic profile. Although whole-body fat mass was notaffected, visceral adipose tissue mass tended to decrease after theintervention compared with placebo (P-time 3 treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacityin permeabilized muscle fibers (P-time 3 treatment ,0.05, P-EGCG+RES , 0.05). Moreover, EGCG+RES reduced fasting(P-time 3 treatment = 0.03) and postprandial respiratory quotient(P-time 3 treatment = 0.01) compared with placebo. Fasting andpostprandial fat oxidation was not significantly affected by EGCG+RES (P-EGCG+RES = 0.46 and 0.38, respectively) but declinedafter placebo (P-placebo = 0.05 and 0.03, respectively). Energy expenditurewas not altered (P-time 3 treatment = 0.96). Furthermore,EGCG+RES supplementation attenuated the increase in plasmatriacylglycerol concentrations during the HFMM test that was observedafter placebo (P-time 3 treatment = 0.04, P-placebo =0.01). Finally, EGCG+RES had no effect on insulin-stimulated glucosedisposal, suppression of endogenous glucose production, orlipolysis.Conclusion: Twelve weeks of EGCG+RES supplementation increasedmitochondrial capacity and stimulated fat oxidation comparedwith placebo, but this did not translate into increased tissue-specificinsulin sensitivity in overweight and obese subjects. This trial wasregistered at clinicaltrials.gov as NCT02381145.