Background and Objectives:
Impaired regulation of lipid oxidation (metabolic inflexibility) is associated with obesity and type 2 diabetes mellitus. Recent evidence has indicated that dietary polyphenols may modulate mitochondrial function, substrate metabolism and energy expenditure in humans. The present study investigated the effects of short-term supplementation of two combinations of polyphenols on energy expenditure (EE) and substrate metabolism in overweight subjects.
Subjects and Methods:
Eighteen healthy overweight volunteers (9 women, 9 men; age 35±2.5 years; body mass index 28.9±0.4 kg m−2) participated in a randomized, double-blind cross-over trial. Combinations of epigallocatechin-gallate (E, 282 mg day−1)+resveratrol (R, 200 mg day−1) and E+R+80 mg day−1 soy isoflavones (S) or placebo capsules (PLA) were supplemented twice daily for a period of 3 days. On day 3, circulating metabolite concentrations, EE and substrate oxidation (using indirect calorimetry) were measured during fasting and postprandial conditions for 6 h (high-fat-mixed meal (2.6 MJ, 61.2 E% fat)).
Short-term supplementation of E+R increased resting EE (E+R vs PLA: 5.45±0.24 vs 5.23±0.25 kJ min−1, P=0.039), whereas both E+R (699±18 kJ 120 min−1 vs 676±20 kJ 120 min−1, P=0.028) and E+R+S (704±18 kJ 120 min−1 vs 676±20 kJ 120 min−1, P=0.014) increased 2–4 h-postprandial EE compared with PLA. Metabolic flexibility, calculated as the postprandial increase to the highest respiratory quotient achieved, tended to be improved by E+R compared with PLA and E+R+S only in men (E+R vs PLA: 0.11±0.02 vs 0.06±0.02, P=0.059; E+R+S: 0.03±0.02, P=0.009). E+R+S significantly increased fasting plasma free fatty acid (P=0.064) and glycerol (P=0.021) concentrations compared with PLA.
We demonstrated for the first time that combined E+R supplementation for 3 days significantly increased fasting and postprandial EE, which was accompanied by improved metabolic flexibility in men but not in women. Addition of soy isoflavones partially reversed these effects possibly due to their higher lipolytic potential. The present findings may imply that long-term supplementation of these dosages of epigallocatechin-gallate combined with resveratrol may improve metabolic health and body weight regulation.
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Corpeleijn E, Saris WH, Blaak EE . Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle. Obes Rev 2009; 10: 178–193.
Goossens GH . The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol Behav 2008; 94: 206–218.
Lara-Castro C, Garvey WT . Intracellular lipid accumulation in liver and muscle and the insulin resistance syndrome. Endocrinol Metab Clin North Am 2008; 37: 841–856.
Mensink M, Blaak EE, van Baak MA, Wagenmakers AJ, Saris WH . Plasma free fatty acid uptake and oxidation are already diminished in subjects at high risk for developing type 2 diabetes. Diabetes 2001; 50: 2548–2554.
Blaak EE, Hul G, Verdich C, Stich V, Martinez A, Petersen M et al. Fat oxidation before and after a high fat load in the obese insulin-resistant state. J Clin Endocrinol Metab 2006; 91: 1462–1469.
Chomentowski P, Coen PM, Radikova Z, Goodpaster BH, Toledo FG . Skeletal muscle mitochondria in insulin resistance: differences in intermyofibrillar versus subsarcolemmal subpopulations and relationship to metabolic flexibility. J Clin Endocrinol Metab 2011; 96: 494–503.
van de Weijer T, Sparks LM, Phielix E, Meex RC, van Herpen NA, Hesselink MK et al. Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus. PLoS One 2013; 8: e51648.
Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–1350.
Roumen C, Corpeleijn E, Feskens EJ, Mensink M, Saris WH, Blaak EE . Impact of 3-year lifestyle intervention on postprandial glucose metabolism: the SLIM study. Diabet Med 2008; 25: 597–605.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337–342.
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127: 1109–1122.
Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 2011; 14: 612–622.
Boschmann M, Thielecke F . The effects of epigallocatechin-3-gallate on thermogenesis and fat oxidation in obese men: a pilot study. J Am Coll Nutr 2007; 26: 389S–395SS.
Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999; 70: 1040–1045.
Thielecke F, Rahn G, Bohnke J, Adams F, Birkenfeld AL, Jordan J et al. Epigallocatechin-3-gallate and postprandial fat oxidation in overweight/obese male volunteers: a pilot study. Eur J Clin Nutr 2010; 64: 704–713.
Berube-Parent S, Pelletier C, Dore J, Tremblay A . Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men. Br J Nutr 2005; 94: 432–436.
Gregersen NT, Bitz C, Krog-Mikkelsen I, Hels O, Kovacs EM, Rycroft JA et al. Effect of moderate intakes of different tea catechins and caffeine on acute measures of energy metabolism under sedentary conditions. Br J Nutr 2009; 102: 1187–1194.
Lonac MC, Richards JC, Schweder MM, Johnson TK, Bell C . Influence of short-term consumption of the caffeine-free, epigallocatechin-3-gallate supplement, Teavigo, on resting metabolism and the thermic effect of feeding. Obesity (Silver Spring) 2010; 19: 298–304.
Venables MC, Hulston CJ, Cox HR, Jeukendrup AE . Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. Am J Clin Nutr 2008; 87: 778–784.
Van Can J, Van Dijk J-W, Goossens G, Jocken J, Hospers J, Blaak E . A 3 day EGCG supplementation reduced lactate in skeletal muscle in overweight subjects. Obes Rev 2010; 11: 206.
Mohamed Salih S, Nallasamy P, Muniyandi P, Periyasami V, Carani Venkatraman A . Genistein improves liver function and attenuates non-alcoholic fatty liver disease in a rat model of insulin resistance. J Diabetes 2009; 1: 278–287.
Cederroth CR, Vinciguerra M, Kuhne F, Madani R, Doerge DR, Visser TJ et al. A phytoestrogen-rich diet increases energy expenditure and decreases adiposity in mice. Environ Health Perspect 2007; 115: 1467–1473.
Llaneza P, Gonzalez C, Fernandez-Inarrea J, Alonso A, Diaz F, Perez-Lopez FR . Soy isoflavones improve insulin sensitivity without changing serum leptin among postmenopausal women. Climacteric 2012; 15: 611–620.
Arunkumar E, Anuradha CV . Genistein promotes insulin action through adenosine monophosphate-activated protein kinase activation and p70 ribosomal protein S6 kinase 1 inhibition in the skeletal muscle of mice fed a high energy diet. Nutr Res 2012; 32: 617–625.
Poulsen MM, Vestergaard PF, Clasen BF, Radko Y, Christensen LP, Stodkilde-Jorgensen H et al. High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes 2012; 62: 1186–1195.
Rayalam S, Della-Fera MA, Yang JY, Park HJ, Ambati S, Baile CA . Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes. J Nutr 2007; 137: 2668–2673.
Schoffelen PF, Westerterp KR, Saris WH, Ten Hoor F . A dual-respiration chamber system with automated calibration. J Appl Physiol 1997; 83: 2064–2072.
Chen CY, Bakhiet RM, Hart V, Holtzman G . Isoflavones improve plasma homocysteine status and antioxidant defense system in healthy young men at rest but do not ameliorate oxidative stress induced by 80% VO2pk exercise. Ann Nutr Metab 2005; 49: 33–41.
Ullmann U, Haller J, Bakker GC, Brink EJ, Weber P . Epigallocatechin gallate (EGCG) (TEAVIGO) does not impair nonhaem-iron absorption in man. Phytomedicine 2005; 12: 410–415.
Weir JB . New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 1949; 109: 1–9.
Frayn KN . Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 1983; 55: 628–634.
Cardoso GA, Salgado JM, Cesar Mde C, Donado-Pestana CM . The effects of green tea consumption and resistance training on body composition and resting metabolic rate in overweight or obese women. J Med Food 2012; 16: 120–127.
Diepvens K, Kovacs EM, Nijs IM, Vogels N, Westerterp-Plantenga MS . Effect of green tea on resting energy expenditure and substrate oxidation during weight loss in overweight females. Br J Nutr 2005; 94: 1026–1034.
Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai S, Schechtman KB et al. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 2012; 16: 658–664.
Arias N, Macarulla MT, Aguirre L, Martinez-Castano MG, Gomez-Zorita S, Miranda J et al. The combination of resveratrol and conjugated linoleic acid is not useful in preventing obesity. J Physiol Biochem 2012; 67: 471–477.
Kim S, Jin Y, Choi Y, Park T . Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem Pharmacol 2011; 81: 1343–1351.
Klaus S, Pultz S, Thone-Reineke C, Wolfram S . Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. Int J Obes (Lond) 2005; 29: 615–623.
Murase T, Haramizu S, Shimotoyodome A, Nagasawa A, Tokimitsu I . Green tea extract improves endurance capacity and increases muscle lipid oxidation in mice. Am J Physiol Regul Integr Comp Physiol 2005; 288: R708–R715.
Thandapilly SJ, Wojciechowski P, Behbahani J, Louis XL, Yu L, Juric D et al. Resveratrol prevents the development of pathological cardiac hypertrophy and contractile dysfunction in the SHR without lowering blood pressure. Am J Hypertens 2011; 23: 192–196.
Woo SC, Na GM, Lim DY . Resveratrol inhibits nicotinic stimulation-evoked catecholamine release from the adrenal medulla. Korean J Physiol Pharmacol 2008; 12: 155–164.
Rosenbaum M, Murphy EM, Heymsfield SB, Matthews DE, Leibel RL . Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002; 87: 2391–2394.
Szkudelski T, Nogowski L, Pruszynska-Oszmalek E, Kaczmarek P, Szkudelska K . Genistein restricts leptin secretion from rat adipocytes. J Steroid Biochem Mol Biol 2005; 96: 301–307.
Klaus S, Keipert S, Rossmeisl M, Kopecky J . Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase. Genes Nutr 2012; 7: 369–386.
Lee MS, Kim Y . (-)-Epigallocatechin-3-gallate enhances uncoupling protein 2 gene expression in 3T3-L1 adipocytes. Biosci Biotechnol Biochem 2009; 73: 434–436.
Timmers S, Auwerx J, Schrauwen P . The journey of resveratrol from yeast to human. Aging (Albany NY) 2012; 4: 146–158.
Yeung EH, Zhang C, Mumford SL, Ye A, Trevisan M, Chen L et al. Longitudinal study of insulin resistance and sex hormones over the menstrual cycle: the BioCycle Study. J Clin Endocrinol Metab 2010; 95: 5435–5442.
Kang W, Hong HJ, Guan J, Kim DG, Yang EJ, Koh G et al. Resveratrol improves insulin signaling in a tissue-specific manner under insulin-resistant conditions only: in vitro and in vivo experiments in rodents. Metabolism 2011; 61: 424–433.
Zhang J, Chen L, Zheng J, Zeng T, Li H, Xiao H et al. The protective effect of resveratrol on islet insulin secretion and morphology in mice on a high-fat diet. Diabetes Res Clin Pract 2012; 97: 474–482.
Szkudelska K, Nogowski L, Szkudelski T . Genistein affects lipogenesis and lipolysis in isolated rat adipocytes. J Steroid Biochem Mol Biol 2000; 75: 265–271.
Hoeks J, van Herpen NA, Mensink M, Moonen-Kornips E, van Beurden D, Hesselink MKC et al. Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance. Diabetes 2010; 59: 2117–2125.
Timmers S, Hesselink MK, Schrauwen P . Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues for health benefits? Ann NY Acad Sci 2013; 1290: 83–89.
Poulsen MM, Jorgensen JO, Jessen N, Richelsen B, Pedersen SB . Resveratrol in metabolic health: an overview of the current evidence and perspectives. Ann NY Acad Sci 2013; 1290: 74–82.
Hamman RF, Wing RR, Edelstein SL, Lachin JM, Bray GA, Delahanty L et al. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care 2006; 29: 2102–2107.
We thank the study participants, as well as Jos Stegen and Wendy Sluijsmans for their excellent technical support. Furthermore, we would like to thank the ALPRO foundation for funding this study. The authors’ contributions are as follows: JM executed the study; all the authors critically read the manuscript, provided suggestions for improvement and approved the final version. Supplements were kindly provided by Pure Encapsulations Inc. Trial registration: ClinicalTrials.gov, NCT01302639
The authors declare no conflict of interest.
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Most, J., Goossens, G., Jocken, J. et al. Short-term supplementation with a specific combination of dietary polyphenols increases energy expenditure and alters substrate metabolism in overweight subjects. Int J Obes 38, 698–706 (2014). https://doi.org/10.1038/ijo.2013.231
- human substrate metabolism
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