Two weeks of early time-restricted feeding (eTRF) improves skeletal muscle insulin and anabolic sensitivity in healthy men

Robert Jones, Pardeep Pabla, Joanne Mallinson, Aline Nixon, Tariq Taylor, Andrew Bennett, Kostas Tsintzas, Robert Jones, Pardeep Pabla, Joanne Mallinson, Aline Nixon, Tariq Taylor, Andrew Bennett, Kostas Tsintzas

Abstract

Background: Altering the temporal distribution of energy intake (EI) and introducing periods of intermittent fasting (IF) exert important metabolic effects. Restricting EI to earlier in the day [early time-restricted feeding (eTRF)] is a novel type of IF.

Objectives: We assessed the chronic effects of eTRF compared with an energy-matched control on whole-body and skeletal muscle insulin and anabolic sensitivity.

Methods: Sixteen healthy males (aged 23 ± 1 y; BMI 24.0 ± 0.6 kg·m-2) were assigned to 2 groups that underwent either 2 wk of eTRF (n = 8) or control/caloric restriction (CON:CR; n = 8) diet. The eTRF diet was consumed ad libitum and the intervention was conducted before the CON:CR, in which the diet was provided to match the reduction in EI and body weight observed in eTRF. During eTRF, daily EI was restricted to between 08:00 and 16:00, which prolonged the overnight fast by ∼5 h. The metabolic responses to a carbohydrate/protein drink were assessed pre- and post-interventions following a 12-h overnight fast.

Results: When compared with CON:CR, eTRF improved whole-body insulin sensitivity [between-group difference (95% CI): 1.89 (0.18, 3.60); P = 0.03; η2p = 0.29] and skeletal muscle uptake of glucose [between-group difference (95% CI): 4266 (261, 8270) μmol·min-1·kg-1·180 min; P = 0.04; η2p = 0.31] and branched-chain amino acids (BCAAs) [between-group difference (95% CI): 266 (77, 455) nmol·min-1·kg-1·180 min; P = 0.01; η2p = 0.44]. eTRF caused a reduction in EI (∼400 kcal·d-1) and weight loss (-1.04 ± 0.25 kg; P = 0.01) that was matched in CON:CR (-1.24 ± 0.35 kg; P = 0.01).

Conclusions: Under free-living conditions, eTRF improves whole-body insulin sensitivity and increases skeletal muscle glucose and BCAA uptake. The metabolic benefits of eTRF are independent of its effects on weight loss and represent chronic adaptations rather than the effect of the last bout of overnight fast. This trial was registered at clinicaltrials.gov as NCT03969745.

Keywords: body composition; energy balance and metabolism; free-living intervention; insulin sensitivity; skeletal muscle; time-restricted feeding.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram of study protocol. CGM, continuous glucose monitoring; CON:CR, control/caloric restriction; DXA, dual-energy X-ray absorptiometry; eTRF, early time-restricted feeding; PA, physical activity.
FIGURE 2
FIGURE 2
Schematic of experimental design and metabolic testing protocol. B, vastus lateralis biopsy; BF, brachial artery blood flow; BS, blood sampling; CGM, continuous glucose monitoring; CON:CR, control/caloric restriction; CR, caloric restriction; DXA, dual-energy X-ray absorptiometry; EI, energy intake; eTRF, early time-restricted feeding; IC, indirect calorimetry; PA, physical activity.
FIGURE 3
FIGURE 3
Diurnal interstitial glucose concentrations during eTRF and CON:CR. Data are means; n = 8 per group. The vertical dotted lines in (A) and (B) represent the start and end of the eating window during eTRF. CON:CR, control/caloric restriction; eTRF, early time-restricted feeding. Mixed-design 2-factor ANOVA (intervention group compared with pre-post trial) revealed no differences in any of the main effects or interaction between groups in mean 24-h interstitial glucose concentrations (C).
FIGURE 4
FIGURE 4
(A, B) Arterialized plasma FFA and (C, D) serum TAG in response to consumption of a liquid test meal before (pre) and after (post) 2 wk of dietary intervention. All data are means ± SEMs; n = 8 per group. P values displayed in text boxes refer to mixed-design 3-factor ANOVA (intervention group × pre-post trial × sampling time) performed for the entire postprandial period. CON:CR, control/caloric restriction; eTRF, early time-restricted feeding; FFA, free fatty acid; TAG, triglyceride.
FIGURE 5
FIGURE 5
Indices of whole-body insulin sensitivity: (A, B) arterialized blood glucose, (C) iAUC for glucose, (D, E) arterialized serum insulin, (F) iAUC for insulin, and (G) Matsuda index of insulin sensitivity in response to consumption of a liquid test meal before (pre) and after (post) 2 wk of dietary intervention. All data are means ± SEMs; n = 8 per group. P values displayed in text boxes refer to mixed-design 3-factor ANOVA (intervention group × pre-post trial × sampling time) performed for the entire postprandial period (A, B, D, and E) and mixed-design 2-factor ANOVA (intervention group × pre-post trial) performed for iAUC data (C, F). CON:CR, control/caloric restriction; eTRF, early time-restricted feeding; iAUC, incremental area under the curve; M-ISI, Matsuda index of insulin sensitivity.
FIGURE 6
FIGURE 6
(A, B) Arteriovenous glucose differences, (C, D) brachial artery blood flow, and (E–G) forearm (skeletal muscle) glucose uptake in response to consumption of a liquid test meal before (pre) and after (post) 2 wk of dietary intervention. Data are means ± SEMs. n = 8 for eTRF and n = 6 for CON:CR. Blood flow and glucose uptake are standardized relative to lean forearm mass (in kg) determined by DXA. P values displayed in text boxes refer to mixed-design 3-factor ANOVA (intervention group × pre-post trial × sampling time) performed for the entire postprandial period (A–F) and mixed-design 2-factor ANOVA (intervention group × pre-post trial) performed for iAUC data (G). CON:CR, control/caloric restriction; eTRF, early time-restricted feeding.
FIGURE 7
FIGURE 7
(A, B) Arteriovenous plasma BCAA differences and (C–E) forearm (skeletal muscle) BCAA uptake in response to consumption of a liquid test meal before (pre) and after (post) 2 wk of dietary intervention. Data are means ± SEMs. n = 8 for eTRF and n = 6 for CON:CR. Forearm BCAA uptake is expressed relative to lean forearm mass (in kg) determined by DXA. P values displayed in text boxes refer to mixed-design 3-factor ANOVA (intervention group × pre-post trial × sampling time) performed for the entire postprandial period (A–D) and mixed-design 2-factor ANOVA (intervention group × pre-post trial) performed for incremental area under the curve data (E). BCAA, branched-chain amino acids; CON:CR, control/caloric restriction; eTRF, early time-restricted feeding.

References

    1. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA et al. . Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012;15(6):848–60.
    1. Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014;20(6):991–1005.
    1. Woodie LN, Luo Y, Wayne MJ, Graff EC, Ahmed B, O'Neill AM, Greene MW. Restricted feeding for 9h in the active period partially abrogates the detrimental metabolic effects of a Western diet with liquid sugar consumption in mice. Metabolism. 2018;82:1–13.
    1. Chen C, Williams PF, Cooney GJ, Caterson ID, Turtle JR. The effects of fasting and refeeding on liver glycogen synthase and phosphorylase in obese and lean mice. Horm Metab Res. 1992;24(4):161–6.
    1. Rothman DL, Magnusson I, Katz LD, Shulman RG, Shulman GI. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science. 1991;254(5031):573–6.
    1. Moro T, Tinsley G, Bianco A, Marcolin G, Pacelli QF, Battaglia G, Palma A, Gentil P, Neri M, Paoli A. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med. 2016;14(1):290.
    1. Tinsley GM, Moore ML, Graybeal AJ, Paoli A, Kim Y, Gonzales JU, Harry JR, VanDusseldorp TA, Kennedy DN, Cruz MR. Time-restricted feeding plus resistance training in active females: a randomized trial. Am J Clin Nutr. 2019;110(3):628–40.
    1. Tinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB, Grandjean PW. Time-restricted feeding in young men performing resistance training: a randomized controlled trial. Eur J Sport Sci. 2017;17(2):200–7.
    1. Antoni R, Robertson TM, Robertson MD, Johnston JD. A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects. J Nutr Sci. 2018;7:e22.
    1. Anton SD, Lee SA, Donahoo WT, McLaren C, Manini T, Leeuwenburgh C, Pahor M. The effects of time restricted feeding on overweight, older adults: a pilot study. Nutrients. 2019;11(7):1500.
    1. Gabel K, Hoddy KK, Varady KA. Safety of 8-h time restricted feeding in adults with obesity. Appl Physiol Nutr Metab. 2019;44(1):107–9.
    1. Gill S, Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits. Cell Metab. 2015;22(5):789–98.
    1. Hutchison AT, Regmi P, Manoogian ENC, Fleischer JG, Wittert GA, Panda S, Heilbronn LK. Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial. Obesity (Silver Spring). 2019;27(5):724–32.
    1. Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM. Early time-restricted feeding improves 24-hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients. 2019;11(6):1234.
    1. Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. 2018;27(6):1212–21..e3.
    1. Ravussin E, Beyl RA, Poggiogalle E, Hsia DS, Peterson CM. Early time-restricted feeding reduces appetite and increases fat oxidation but does not affect energy expenditure in humans. Obesity. 2019;27(8):1244–54.
    1. Wilkinson MJ, Manoogian ENC, Zadourian A, Lo H, Fakhouri S, Shoghi A, Wang X, Fleischer JG, Navlakha S, Panda S et al. . Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome. Cell Metab. 2020;31(1):92.
    1. Kelley D, Mitrakou A, Marsh H, Schwenk F, Benn J, Sonnenberg G, Arcangeli M, Aoki T, Sorensen J, Berger M. Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load. J Clin Invest. 1988;81(5):1563–71.
    1. Bowen AJ, Reeves RL. Diurnal variation in glucose tolerance. Arch Intern Med. 1967;119(3):261–4.
    1. Aparicio NJ, Puchulu FE, Gagliardino JJ, Ruiz M, Llorens JM, Ruiz J, Lamas A, De Miguel R. Circadian variation of the blood glucose, plasma insulin and human growth hormone levels in response to an oral glucose load in normal subjects. Diabetes. 1974;23(2):132–7.
    1. Bandín C, Scheer FA, Luque AJ, Ávila-Gandía V, Zamora S, Madrid JA, Gómez-Abellán P, Garaulet M. Meal timing affects glucose tolerance, substrate oxidation and circadian-related variables: a randomized, crossover trial. Int J Obes. 2015;39(5):828–33.
    1. Bo S, Fadda M, Castiglione A, Ciccone G, De Francesco A, Fedele D, Guggino A, Parasiliti Caprino M, Ferrara S, Vezio Boggio M et al. . Is the timing of caloric intake associated with variation in diet-induced thermogenesis and in the metabolic pattern? A randomized cross-over study. Int J Obes. 2015;39(12):1689–95.
    1. Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes. 2013;37(4):604–11.
    1. Jakubowicz D, Barnea M, Wainstein J, Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity. 2013;21(12):2504–12.
    1. LeCheminant JD, Christenson E, Bailey BW, Tucker LA. Restricting night-time eating reduces daily energy intake in healthy young men: a short-term cross-over study. Br J Nutr. 2013;110(11):2108–13.
    1. Brage S, Ekelund U, Brage N, Hennings MA, Froberg K, Franks PW, Wareham NJ. Hierarchy of individual calibration levels for heart rate and accelerometry to measure physical activity. J Appl Physiol. 2007;103(2):682–92.
    1. Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975;35(7):609–16.
    1. Hennessey JV, Chromiak JA, Della Ventura S, Guertin J, MacLean DB. Increase in percutaneous muscle biopsy yield with a suction-enhancement technique. J Appl Physiol. 1997;82(6):1739–42.
    1. Frayn KN. Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(2):628–34.
    1. Weir JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949;109(1–2):1–9.
    1. Morgan CR, Lazarow A. Immunoassay of insulin using a two-antibody system. Exp Biol Med. 1962;110:29–32.
    1. Beckett PR, Hardin DS, Davis TA, Nguyen HV, Wray-Cahen D, Copeland KC. Spectrophometric assay for measuring branched-chain amino acid concentrations: application for measuring the sensitivity of protein metabolism to insulin. Anal Biochem. 1996;240(1):48–53.
    1. Wilhelmsen AJ, Mallinson J, Jones R, Cooper S, Taylor T, Tsintzas K. Chronic effects of high intensity interval training on postprandial lipaemia in healthy males. J Appl Physiol. 2019;127(6):1763–71.
    1. Harris RC, Hultman E, Nordesjö LO. Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest: methods and variance of values. Scand J Clin Lab Invest. 1974;33(2):109–20.
    1. Constantin-Teodosiu D, Cederblad G, Hultman E. A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue. Anal Biochem. 1991;198(2):347–51.
    1. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–70.
    1. Halberg N, Henriksen M, Soderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol. 2005;99(6):2128–36.
    1. Gabel K, Hoddy KK, Haggerty N, Song J, Kroeger CM, Trepanowski JF, Panda S, Varady KA. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: a pilot study. Nutr Healthy Aging. 2018;4(4):345–53.
    1. BaHammam A, Alrajeh M, Albabtain M, Bahammam S, Sharif M. Circadian pattern of sleep, energy expenditure, and body temperature of young healthy men during the intermittent fasting of Ramadan. Appetite. 2010;54(2):426–9.
    1. Lessan N, Saadane I, Alkaf B, Hambly C, Buckley AJ, Finer N, Speakman JR, Barakat MT. The effects of Ramadan fasting on activity and energy expenditure. Am J Clin Nutr. 2018;107(1):54–61.
    1. Heilbronn LK, Smith SR, Martin CK, Anton SD, Ravussin E. Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr. 2005;81(1):69–73.
    1. Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab. 1998;83(8):2773–6.
    1. Facchini FS, Hua N, Abbasi F, Reaven GM. Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab. 2001;86(8):3574–8.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel