title: 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.
abstract: 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.
  
  
  METHODS
  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-(2)H2]-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 × treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers (P-time × treatment < 0.05, P-EGCG+RES < 0.05). Moreover, EGCG+RES reduced fasting (P-time × treatment = 0.03) and postprandial respiratory quotient (P-time × 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 × 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 × 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.
  
  
  CONCLUSIONS
  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. This trial was registered at clinicaltrials.gov as NCT02381145.
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands;
authors.forename: Jasper
authors.initials: J
authors.lastname: Most
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands;
authors.forename: Silvie
authors.initials: S
authors.lastname: Timmers
authors.affiliation: Research and Development, Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland; and.
authors.forename: Ines
authors.initials: I
authors.lastname: Warnke
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands;
authors.forename: Johan We
authors.initials: JW
authors.lastname: Jocken
authors.affiliation: Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: van Boekschoten
authors.affiliation: Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: de Groot
authors.affiliation: Research and Development, Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland; and.
authors.forename: Igor
authors.initials: I
authors.lastname: Bendik
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands;
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands;
authors.forename: Gijs H
authors.initials: GH
authors.lastname: Goossens
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands; e.blaak@maastrichtuniversity.nl.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019587:Dietary Supplements; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D019518:Postprandial Period; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010936:Plant Extracts; D013267:Stilbenes; D002392:Catechin; C045651:epigallocatechin gallate; D000077185:Resveratrol
keywords: insulin sensitivity; mitochondrial capacity; obesity; polyphenols; resveratrol