Background and Objectives:Impaired regulation of lipid oxidation inflexibility) is associated with obesity and type 2 diabetes mellitus. evidence has indicated that dietary polyphenols may modulate function, substrate metabolism and energy expenditure in humans. The study investigated the effects of short-term supplementation of two of polyphenols on energy expenditure (EE) and substrate metabolism in subjects.Subjects and Methods:18 healthy overweight volunteers (9 women, age 35+/-2.5 yrs; BMI 28.9+/-0.4 kg/m2) participated in a randomized, double-blind cross-over trial. Combinations of Epigallocatechin-gallate mg/d)+Resveratrol (R, 200 mg/d), and E+R+80 mg/d soy isoflavones (S), or capsules (PLA) were supplemented twice daily for a period of 3 days. On circulating metabolite concentrations, energy expenditure and substrate (using indirect calorimetry) were measured during fasting and conditions for 6 h (high-fat-mixed meal (2.6 MJ, 61.2 E% supplementation of E+R increased resting EE (E+R vs. PLA: 5.45+/-0.24 vs 5.23+/-0.25 kJ/min, P=0.039), whereas both E+R (699+/-18 kJ/120 min vs kJ/120 min, P=0.028) and E+R+S (704+/-18 kJ/120 min vs 676+/-20 kJ/120 P=0.014) increased 2-4 h-postprandial EE compared with PLA. Metabolic flexibility, calculated as the postprandial increase to highest quotient (RQ) achieved, tended to be improved by E+R compared with PLA only in men (E+R vs PLA: 0.11+/-0.02 vs 0.06+/-0.02, P=0.059; E+R+S: P=0.009). E+R+S significantly increased fasting plasma free fatty acid and glycerol (P=0.021) concentrations compared with PLA.Conclusions:We demonstrated for the first time that combined E+R supplementation for 3 significantly increased fasting and postprandial EE, which was improved metabolic flexibility in men but not women. Addition of soy partially reversed these effects possibly due to their higher lipolytic potential. The present findings may imply that long-term supplementation dosages of epigallocatechin-gallate combined with resveratrol may metabolic health and body weight regulation.International Journal of accepted article preview online, 9 December 2013.