Background: Protein intake provides the essential amino acids (EAA) necessary for promoting muscle protein synthesis. Branched-chain amino acids (BCAA) belonging to the EAA in particular are known to have more potent effects. We developed BCAA-enriched essential amino acids (BEAA？) to improve muscle health and performance. Therefore, we aimed at comparing the effects of BEAA？ and whey protein intake in combination with exercise on muscle mass and strength in humans. Methods: A randomized, single-blind, placebo-controlled, parallel-group study was conducted to evaluate the impact of BEAA？ and exercise on the muscles in healthy participants. Seventy-five healthy male participants were enrolled and randomly divided into three groups; the BCAA-enriched essential amino acids (BEAA), whey protein (WHEY), and placebo (PLA) groups. The participants consumed either the food containing BEAA？ 3 g, whey protein 20 g, or dextrin 3 g for 12 weeks. The participants exercised five times weekly, and the exercise load was gradually increased. The primary (muscle mass) and secondary (muscle strength) outcomes were evaluated. Results: Whole-body muscle mass and lower-limb muscle mass showed statistical significance in the BEAA group compared to the PLA group (P < 0.05), whereas there was no difference between the WHEY group and the PLA group. Regarding the knee joint extensor muscle strength, no significant differences were observed between the BEAA group and the WHEY group when compared to the PLA group. No adverse events attributable to the test foods were observed during the study period. Conclusions: Overall, BEAA？ was shown to increase muscle mass in healthy adult males when combined with exercise.
References
[1]
Yasuda, J., Asako, M., Arimitsu, T. and Fujita, S. (2019) Association of Protein Intake in Three Meals with Muscle Mass in Healthy Young Subjects: A Cross-Sectional Study. Nutrients, 11, Article 612. https://doi.org/10.3390/nu11030612
[2]
Tipton, K.D., Ferrando, A.A., Phillips, S.M., Doyle, D. and Wolfe, R.R. (1999) Postexercise Net Protein Synthesis in Human Muscle from Orally Administered Amino Acids. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 276, E628-E634. https://doi.org/10.1152/ajpendo.1999.276.4.e628
[3]
Biolo, G., Maggi, S.P., Williams, B.D., Tipton, K.D. and Wolfe, R.R. (1995) Increased Rates of Muscle Protein Turnover and Amino Acid Transport after Resistance Exercise in Humans. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 268, E514-E520. https://doi.org/10.1152/ajpendo.1995.268.3.e514
[4]
Witard, O.C., Jackman, S.R., Breen, L., Smith, K., Selby, A. and Tipton, K.D. (2014) Myofibrillar Muscle Protein Synthesis Rates Subsequent to a Meal in Response to Increasing Doses of Whey Protein at Rest and after Resistance Exercise. TheAmericanJournalofClinicalNutrition, 99, 86-95. https://doi.org/10.3945/ajcn.112.055517
[5]
Park, S., Church, D.D., Azhar, G., Schutzler, S.E., Ferrando, A.A. and Wolfe, R.R. (2020) Anabolic Response to Essential Amino Acid Plus Whey Protein Composition Is Greater than Whey Protein Alone in Young Healthy Adults. JournaloftheInternationalSocietyofSportsNutrition, 17, Article ID: 9. https://doi.org/10.1186/s12970-020-0340-5
[6]
Koopman, R., Saris, W.H.M., Wagenmakers, A.J.M. and van Loon, L.J.C. (2007) Nutritional Interventions to Promote Post-Exercise Muscle Protein Synthesis. SportsMedicine, 37, 895-906. https://doi.org/10.2165/00007256-200737100-00005
[7]
Ham, D.J., Caldow, M.K., Lynch, G.S. and Koopman, R. (2014) Leucine as a Treatment for Muscle Wasting: A Critical Review. ClinicalNutrition, 33, 937-945. https://doi.org/10.1016/j.clnu.2014.09.016
[8]
Borgenvik, M., Apró, W. and Blomstrand, E. (2012) Intake of Branched-Chain Amino Acids Influences the Levels of Mafbx Mrna and Murf-1 Total Protein in Resting and Exercising Human Muscle. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 302, E510-E521. https://doi.org/10.1152/ajpendo.00353.2011
[9]
Apró, W. and Blomstrand, E. (2010) Influence of Supplementation with Branched-Chain Amino Acids in Combination with Resistance Exercise on P70s6 Kinase Phosphorylation in Resting and Exercising Human Skeletal Muscle. ActaPhysiologica, 200, 237-248. https://doi.org/10.1111/j.1748-1708.2010.02151.x
[10]
Jackman, S.R., Witard, O.C., Philp, A., Wallis, G.A., Baar, K. and Tipton, K.D. (2017) Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein Synthesis Following Resistance Exercise in Humans. FrontiersinPhysiology, 8, Article 390. https://doi.org/10.3389/fphys.2017.00390
[11]
Tipton, K. (1999) Nonessential Amino Acids Are Not Necessary to Stimulate Net Muscle Protein Synthesis in Healthy Volunteers. TheJournalofNutritionalBiochemistry, 10, 89-95. https://doi.org/10.1016/s0955-2863(98)00087-4
[12]
Gonzalez, A.M., Church, D.D., Townsend, J.R. and Bagheri, R. (2020) Emerging Nutritional Supplements for Strength and Hypertrophy: An Update of the Current Literature. Strength&ConditioningJournal, 42, 57-70. https://doi.org/10.1519/ssc.0000000000000552
[13]
Bird, S.P., Tarpenning, K.M. and Marino, F.E. (2006) Independent and Combined Effects of Liquid Carbohydrate/essential Amino Acid Ingestion on Hormonal and Muscular Adaptations Following Resistance Training in Untrained Men. EuropeanJournalofAppliedPhysiology, 97, 239-239. https://doi.org/10.1007/s00421-006-0173-1
[14]
Takegaki, J., Sase, K., Yasuda, J., Shindo, D., Kato, H., Toyoda, S., et al. (2020) The Effect of Leucine-Enriched Essential Amino Acid Supplementation on Anabolic and Catabolic Signaling in Human Skeletal Muscle after Acute Resistance Exercise: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial. Nutrients, 12, Article 2421. https://doi.org/10.3390/nu12082421
[15]
Atherton, P.J., Smith, K., Etheridge, T., Rankin, D. and Rennie, M.J. (2009) Distinct Anabolic Signalling Responses to Amino Acids in C2C12 Skeletal Muscle Cells. AminoAcids, 38, 1533-1539. https://doi.org/10.1007/s00726-009-0377-x
[16]
Doi, M., Yamaoka, I., Fukunaga, T. and Nakayama, M. (2003) Isoleucine, a Potent Plasma Glucose-Lowering Amino Acid, Stimulates Glucose Uptake in C2C12 Myotubes. BiochemicalandBiophysicalResearchCommunications, 312, 1111-1117. https://doi.org/10.1016/j.bbrc.2003.11.039
[17]
Doi, M., Yamaoka, I., Nakayama, M., Mochizuki, S., Sugahara, K. and Yoshizawa, F. (2005) Isoleucine, a Blood Glucose-Lowering Amino Acid, Increases Glucose Uptake in Rat Skeletal Muscle in the Absence of Increases in Amp-Activated Protein Kinase Activity. TheJournalofNutrition, 135, 2103-2108. https://doi.org/10.1093/jn/135.9.2103
[18]
Doi, M., Yamaoka, I., Nakayama, M., Sugahara, K. and Yoshizawa, F. (2007) Hypoglycemic Effect of Isoleucine Involves Increased Muscle Glucose Uptake and Whole Body Glucose Oxidation and Decreased Hepatic Gluconeogenesis. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 292, E1683-E1693. https://doi.org/10.1152/ajpendo.00609.2006
[19]
Church, D.D., Hirsch, K.R., Park, S., Kim, I., Gwin, J.A., Pasiakos, S.M., et al. (2020) Essential Amino Acids and Protein Synthesis: Insights into Maximizing the Muscle and Whole-Body Response to Feeding. Nutrients, 12, Article 3717. https://doi.org/10.3390/nu12123717
[20]
Atherton, P.J. and Smith, K. (2012) Muscle Protein Synthesis in Response to Nutrition and Exercise. TheJournalofPhysiology, 590, 1049-1057. https://doi.org/10.1113/jphysiol.2011.225003
[21]
Bohé, J., Low, J.F.A., Wolfe, R.R. and Rennie, M.J. (2001) Latency and Duration of Stimulation of Human Muscle Protein Synthesis during Continuous Infusion of Amino Acids. TheJournalofPhysiology, 532, 575-579. https://doi.org/10.1111/j.1469-7793.2001.0575f.x
[22]
Phillips, S.M., Tipton, K.D., Aarsland, A., Wolf, S.E. and Wolfe, R.R. (1997) Mixed Muscle Protein Synthesis and Breakdown after Resistance Exercise in Humans. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 273, E99-E107. https://doi.org/10.1152/ajpendo.1997.273.1.e99
[23]
MacDougall, J.D., Gibala, M.J., Tarnopolsky, M.A., MacDonald, J.R., Interisano, S.A. and Yarasheski, K.E. (1995) The Time Course for Elevated Muscle Protein Synthesis Following Heavy Resistance Exercise. CanadianJournalofAppliedPhysiology, 20, 480-486. https://doi.org/10.1139/h95-038
[24]
Edman, S., Söderlund, K., Moberg, M., Apró, W. and Blomstrand, E. (2019) mTORC1 Signaling in Individual Human Muscle Fibers Following Resistance Exercise in Combination with Intake of Essential Amino Acids. FrontiersinNutrition, 6, Article 96. https://doi.org/10.3389/fnut.2019.00096
[25]
Wolfe, R.R. (2002) Regulation of Muscle Protein by Amino Acids. TheJournalofNutrition, 132, 3219S-3224S. https://doi.org/10.1093/jn/131.10.3219s
[26]
Bohé, J., Low, A., Wolfe, R.R. and Rennie, M.J. (2003) Human Muscle Protein Synthesis Is Modulated by Extracellular, Not Intramuscular Amino Acid Availability: A Dose‐response Study. TheJournalofPhysiology, 552, 315-324. https://doi.org/10.1113/jphysiol.2003.050674
[27]
Cuthbertson, D., Smith, K., Babraj, J., Leese, G., Waddell, T., Atherton, P., et al. (2004) Anabolic Signaling Deficits Underlie Amino Acid Resistance of Wasting, Aging Muscle. TheFASEBJournal, 19, 1-22. https://doi.org/10.1096/fj.04-2640fje
[28]
Pennings, B., Boirie, Y., Senden, J.M., Gijsen, A.P., Kuipers, H. and van Loon, L.J. (2011) Whey Protein Stimulates Postprandial Muscle Protein Accretion More Effectively than Do Casein and Casein Hydrolysate in Older Men. TheAmericanJournalofClinicalNutrition, 93, 997-1005. https://doi.org/10.3945/ajcn.110.008102
[29]
West, D.W., Burd, N.A., Coffey, V.G., Baker, S.K., Burke, L.M., Hawley, J.A., et al. (2011) Rapid Aminoacidemia Enhances Myofibrillar Protein Synthesis and Anabolic Intramuscular Signaling Responses after Resistance Exercise. TheAmericanJournalofClinicalNutrition, 94, 795-803. https://doi.org/10.3945/ajcn.111.013722
[30]
Adibi, S.A., Gray, S.J. and Menden, E. (1967) The Kinetics of Amino Acid Absorption and Alteration of Plasma Composition of Free Amino Acids after Intestinal Perfusion of Amino Acid Mixtures. TheAmericanJournalofClinicalNutrition, 20, 24-33. https://doi.org/10.1093/ajcn/20.1.24
[31]
Hoffman, J.R., Ratamess, N.A., Tranchina, C.P., Rashti, S.L., Kang, J. and Faigenbaum, A.D. (2009) Effect of Protein-Supplement Timing on Strength, Power, and Body-Composition Changes in Resistance-Trained Men. InternationalJournalofSportNutritionandExerciseMetabolism, 19, 172-185. https://doi.org/10.1123/ijsnem.19.2.172
[32]
Biolo, G., Declan Fleming, R.Y. and Wolfe, R.R. (1995) Physiologic Hyperinsulinemia Stimulates Protein Synthesis and Enhances Transport of Selected Amino Acids in Human Skeletal Muscle. JournalofClinicalInvestigation, 95, 811-819. https://doi.org/10.1172/jci117731
[33]
Gore, D.C., Wolf, S.E., Sanford, A.P., Herndon, D.N. and Wolfe, R.R. (2004) Extremity Hyperinsulinemia Stimulates Muscle Protein Synthesis in Severely Injured Patients. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 286, E529-E534. https://doi.org/10.1152/ajpendo.00258.2003
[34]
Fryburg, D.A., Jahn, L.A., Hill, S.A., Oliveras, D.M. and Barrett, E.J. (1995) Insulin and Insulin-Like Growth Factor-I Enhance Human Skeletal Muscle Protein Anabolism during Hyperaminoacidemia by Different Mechanisms. JournalofClinicalInvestigation, 96, 1722-1729. https://doi.org/10.1172/jci118217
[35]
Gelfand, R.A. and Barrett, E.J. (1987) Effect of Physiologic Hyperinsulinemia on Skeletal Muscle Protein Synthesis and Breakdown in Man. JournalofClinicalInvestigation, 80, 1-6. https://doi.org/10.1172/jci113033
[36]
Milner, R.D.G. (1969) Stimulation of Insulin Secretion in Vitro by Essential Aminoacids. TheLancet, 293, 1075-1076. https://doi.org/10.1016/s0140-6736(69)91709-7
[37]
Knudsen, P., Kofod, H., Lernmark, A. and Hedeskov, C.J. (1983) L-Leucine Methyl ester Stimulates Insulin Secretion and Islet Glutamate Dehydrogenase. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 245, E338-E346. https://doi.org/10.1152/ajpendo.1983.245.4.e338
[38]
Pallotta, J.A. and Kennedy, P.J. (1968) Response of Plasma Insulin and Growth Hormone to Carbohydrate and Protein Feeding. Metabolism, 17, 901-908. https://doi.org/10.1016/0026-0495(68)90156-x
[39]
van Loon, L.J., Saris, W.H., Verhagen, H. and Wagenmakers, A.J. (2000) Plasma Insulin Responses after Ingestion of Different Amino Acid or Protein Mixtures with Carbohydrate. TheAmericanJournalofClinicalNutrition, 72, 96-105. https://doi.org/10.1093/ajcn/72.1.96
[40]
Rabinowitz, D., Merimee, T.J., Maffezzoli, R. and Burgess, J.A. (1966) Patterns of Hormonal Release after Glucose, Protein, and Glucose Plus Protein. TheLancet, 288, 454-457. https://doi.org/10.1016/s0140-6736(66)92767-x
[41]
Zawadzki, K.M., Yaspelkis, B.B. and Ivy, J.L. (1992) Carbohydrate-protein Complex Increases the Rate of Muscle Glycogen Storage after Exercise. JournalofAppliedPhysiology, 72, 1854-1859. https://doi.org/10.1152/jappl.1992.72.5.1854
[42]
Miller, S.L., Tipton, K.D., Chinkes, D.L., Wolf, S.E. and Wolfe, R.R. (2003) Independent and Combined Effects of Amino Acids and Glucose after Resistance Exercise. Medicine&ScienceinSports&Exercise, 35, 449-455. https://doi.org/10.1249/01.mss.0000053910.63105.45
[43]
Jones, D.A. and Rutherford, O.M. (1987) Human Muscle Strength Training: The Effects of Three Different Regimens and the Nature of the Resultant Changes. TheJournalofPhysiology, 391, 1-11. https://doi.org/10.1113/jphysiol.1987.sp016721
[44]
Baker, D., Wilson, G. and Carlyon, B. (1994) Generality versus Specificity: A Comparison of Dynamic and Isometric Measures of Strength and Speed-Strength. EuropeanJournalofAppliedPhysiologyandOccupationalPhysiology, 68, 350-355. https://doi.org/10.1007/bf00571456
[45]
Moritani, T. (1993) Neuromuscular Adaptations during the Acquisition of Muscle Strength, Power and Motor Tasks. JournalofBiomechanics, 26, 95-107. https://doi.org/10.1016/0021-9290(93)90082-p
