Essential amino acid-enriched whey enhances post-exercise whole-body protein balance during energy deficit more than iso-nitrogenous whey or a mixed-macronutrient meal: a randomized, crossover study

Jess A Gwin, David D Church, Adrienne Hatch-McChesney, Jillian T Allen, Marques A Wilson, Alyssa N Varanoske, Christopher T Carrigan, Nancy E Murphy, Lee M Margolis, John W Carbone, Robert R Wolfe, Arny A Ferrando, Stefan M Pasiakos, Jess A Gwin, David D Church, Adrienne Hatch-McChesney, Jillian T Allen, Marques A Wilson, Alyssa N Varanoske, Christopher T Carrigan, Nancy E Murphy, Lee M Margolis, John W Carbone, Robert R Wolfe, Arny A Ferrando, Stefan M Pasiakos

Abstract

Background: The effects of ingesting varying essential amino acid (EAA)/protein-containing food formats on protein kinetics during energy deficit are undetermined. Therefore, recommendations for EAA/protein food formats necessary to optimize both whole-body protein balance and muscle protein synthesis (MPS) during energy deficit are unknown. We measured protein kinetics after consuming iso-nitrogenous amounts of free-form essential amino acid-enriched whey (EAA + W; 34.7 g protein, 24 g EAA sourced from whey and free-form EAA), whey (WHEY; 34.7 g protein, 18.7 g EAA), or a mixed-macronutrient meal (MEAL; 34.7 g protein, 11.4 g EAA) after exercise during short-term energy deficit.

Methods: Ten adults (mean ± SD; 21 ± 4 y; 25.7 ± 1.7 kg/m2) completed a randomized, double-blind crossover study consisting of three, 5 d energy-deficit periods (- 30 ± 3% of total energy requirements), separated by 14 d. Whole-body protein synthesis (PS), breakdown (PB), and net balance (NET) were determined at rest and in response to combination exercise consisting of load carriage treadmill walking, deadlifts, and box step-ups at the end of each energy deficit using L-[2H5]-phenylalanine and L-[2H2]-tyrosine infusions. Treatments were ingested immediately post-exercise. Mixed-muscle protein synthesis (mixed-MPS) was measured during exercise through recovery.

Results: Change (Δ postabsorptive + exercise to postprandial + recovery [mean treatment difference (95%CI)]) in whole-body (g/180 min) PS was 15.8 (9.8, 21.9; P = 0.001) and 19.4 (14.8, 24.0; P = 0.001) greater for EAA + W than WHEY and MEAL, respectively, with no difference between WHEY and MEAL. ΔPB was - 6.3 (- 11.5, - 1.18; P = 0.02) greater for EAA + W than WHEY and - 7.7 (- 11.9, - 3.6; P = 0.002) greater for MEAL than WHEY, with no difference between EAA + W and MEAL. ΔNET was 22.1 (20.5, 23.8; P = 0.001) and 18.0 (16.5, 19.5; P = 0.00) greater for EAA + W than WHEY and MEAL, respectively, while ΔNET was 4.2 (2.7, 5.6; P = 0.001) greater for MEAL than WHEY. Mixed-MPS did not differ between treatments.

Conclusions: While mixed-MPS was similar across treatments, combining free-form EAA with whey promotes greater whole-body net protein balance during energy deficit compared to iso-nitrogenous amounts of whey or a mixed-macronutrient meal.

Trial registration: ClinicalTrials.gov, Identifier no. NCT04004715 . Retrospectively registered 28 June 2019, first enrollment 6 June 2019.

Keywords: And energy restriction; Free-form amino acids; Muscle protein synthesis; Whole-body protein turnover.

Conflict of interest statement

JAG, DDC, AHM, JTA, MAW, ANV, CTC, NEM, LMM, JWC, AAF, and SMP have no conflicts of interest associated with this research. RRW is an inventor of patent entitled “Composition for Stimulating Muscle Growth, Repair, and Maintenance,” US Patent (16; 382,984). RRW is a shareholder in Essential Blends, LLC, and The Amino Company, LLC. RRW was not involved in data collection or analyses and was blinded to all data until final consolidation into manuscript form by JAG and SMP.

Figures

Fig. 1
Fig. 1
Volunteer enrollment and retention
Fig. 2
Fig. 2
Schematic of the infusion studies. Muscle biopsy and blood samples were used in combination with primed, constant infusions of L-[2H5]-phenylalanine and L-[2H2]-tyrosine to determine the effects of EAA + W, WHEY, or MEAL ingestion on whole-body protein turnover following whole-body exercise as well as mixed muscle protein synthesis throughout an exercise and recovery period during energy deficit
Fig. 3
Fig. 3
Mean ± SD (n = 10). Stable-isotope enrichments during the infusion studies
Fig. 4
Fig. 4
a: Mean ± SD (n = 10). Postabsorptive plus exercise and postprandial post-exercise recovery whole-body protein synthesis after WHEY, EAA + W, and MEAL intake during energy deficit. *indicates post hoc difference between postabsorptive and postprandial within the same treatment (P = 0.001) and different lowercase letters indicate post hoc difference between treatments within the same condition (both, P < 0.01). b: Mean ± SD (n = 10). Postabsorptive plus exercise and postprandial post-exercise recovery whole-body protein breakdown after WHEY, EAA + W, and MEAL intake during energy deficit. *indicates post hoc difference between postabsorptive and postprandial within the same treatment (P = 0.011) and different lowercase letters indicate post hoc difference between treatments within the same condition (both, P = 0.001). c: Mean ± SD (n = 10). Postabsorptive plus exercise and postprandial post-exercise recovery whole-body net balance after WHEY, EAA + W, and MEAL intake during energy deficit. *indicates post hoc difference between postabsorptive and postprandial within the same treatment (P = 0.001) and different lowercase letters indicate post hoc difference between treatments within the same condition (both, P = 0.001). d: Mean ± SD (n = 10). Change in postabsorptive plus exercise and postprandial post-exercise recovery whole-body protein turnover after WHEY, EAA + W, and MEAL intake during energy deficit. Different lowercase letters indicate difference between treatments within the protein synthesis, protein breakdown, and net balance measures (all, P < 0.05). e: Change in postabsorptive plus exercise and postprandial post-exercise recovery whole-body protein synthesis relative to EAA intake after WHEY, EAA + W, and MEAL intake during energy deficit. Different lowercase letters indicate difference between treatments (all, P < 0.05). f: Mean ± SD (n = 10). Postabsorptive plus exercise and postprandial post-exercise recovery phenylalanine hydroxylation after WHEY, EAA + W, and MEAL intake during energy deficit. *indicates post hoc difference between postabsorptive and postprandial within the same treatment (P = 0.001) and different lowercase letters indicate post hoc difference between treatments within the same condition (both, P = 0.001)
Fig. 5
Fig. 5
a Mean ± SD (n = 10). Mixed-muscle protein synthesis responses to whole-body exercise plus post exercise recovery feeding with WHEY, EAA + W, and MEAL intake during energy deficit. No difference between treatments (P = 0.68). b Mean ± SD (n = 10). Relative mixed-muscle protein synthesis responses, expressed relative to study treatment energy, to whole-body exercise plus post exercise recovery feeding with WHEY, EAA + W, and MEAL intake during energy deficit. Different lowercase letters indicate difference between treatment (both, P < 0.05)
Fig. 6
Fig. 6
a Mean ± SD (n = 10). Plasma essential amino acid concentrations after WHEY, EAA + W, and MEAL intake during energy deficit. Different symbols indicate post hoc difference (all, P < 0.05) between treatments within a time point. Different lowercase letters indicate post hoc difference between time points within a treatment (all, P < 0.05). b Plasma leucine concentrations after WHEY, EAA + W, and MEAL intake during energy deficit. Different symbols indicate post hoc difference (all, P < 0.02) between treatments within a time point. Different lowercase letters indicate post hoc difference between time points within a treatment (P < 0.03). c Plasma phenylalanine concentrations after WHEY, EAA + W, and MEAL intake during energy deficit. Different symbols indicate post hoc difference (all, P < 0.02) between treatments within a time point. Different lowercase letters indicate post hoc difference between time points within a treatment (P < 0.05). d Plasma tyrosine concentrations after WHEY, EAA + W, and MEAL intake during energy deficit. Different symbols indicate post hoc difference (all, P < 0.04) between treatments within a time point. Different lowercase letters indicate post hoc difference between time points within a treatment (P < 0.03). e Mean ± SD (n = 10). Plasma insulin concentrations after WHEY, EAA + W, and MEAL intake during energy deficit. Different symbols indicate difference between treatment independent of time point (P = 0.04). Different lowercase letters indicate difference between time points independent of treatment (P < 0.01)

References

    1. Carbone JW, McClung JP, Pasiakos SM. Recent advances in the characterization of skeletal muscle and whole-body protein responses to dietary protein and exercise during negative energy balance. Adv Nutr. 2019;10(1):70–79. doi: 10.1093/advances/nmy087.
    1. Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84(3):475–482. doi: 10.1093/ajcn/84.3.475.
    1. Friedl KE, Moore RJ, Martinez-Lopez LE, Vogel JA, Askew EW, Marchitelli LJ, et al. Lower limit of body fat in healthy active men. J Appl Physiol. 1994;77(2):933–940. doi: 10.1152/jappl.1994.77.2.933.
    1. Biolo G, Fleming RY, Maggi SP, Nguyen TT, Herndon DN, Wolfe RR. Inverse regulation of protein turnover and amino acid transport in skeletal muscle of hypercatabolic patients. J Clin Endocrinol Metab. 2002;87(7):3378–3384. doi: 10.1210/jcem.87.7.8699.
    1. Hector AJ, Marcotte GR, Churchward-Venne TA, Murphy CH, Breen L, von Allmen M, et al. Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults. J Nutr. 2014;145(2):246–252. doi: 10.3945/jn.114.200832.
    1. Volpi E, Ferrando AA, Yeckel CW, Tipton KD, Wolfe RR. Exogenous amino acids stimulate net muscle protein synthesis in the elderly. J Clin Invest. 1998;101(9):2000–2007. doi: 10.1172/JCI939.
    1. Ferrando AA, Williams BD, Stuart CA, Lane HW, Wolfe RR. Oral branched-chain amino acids decrease whole-body proteolysis. JPEN J Parenter Enteral Nutr. 1995;19(1):47–54. doi: 10.1177/014860719501900147.
    1. Kim IY, Deutz NEP, Wolfe RR. Update on maximal anabolic response to dietary protein. Clin Nutr. 2018;37(2):411–418. doi: 10.1016/j.clnu.2017.05.029.
    1. Gwin JA, Church DD, Hatch-McChesney A, Howard EE, Carrigan CT, Murphy NE, et al. Effects of high versus standard essential amino acid intakes on whole-body protein turnover and mixed muscle protein synthesis during energy deficit: a randomized, crossover study. Clin Nutr. 2020;S0261-5614(20)30384–8. 10.1016/j.clnu.2020.07.019.
    1. Tang JE, Phillips SM. Maximizing muscle protein anabolism: the role of protein quality. Curr Opin Clin Nutr Metab Care. 2009;12(1):66–71. doi: 10.1097/MCO.0b013e32831cef75.
    1. Bukhari SS, Phillips BE, Wilkinson DJ, Limb MC, Rankin D, Mitchell WK, et al. Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise. Am J Physiol Endocrinol Metab. 2015;308(12):E1056–E1E65. doi: 10.1152/ajpendo.00481.2014.
    1. Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ, Mitchell CJ, Moore DR, et al. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial. Am J Clin Nutr. 2013;99(2):276–286. doi: 10.3945/ajcn.113.068775.
    1. Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, et al. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012;590(11):2751–2765. doi: 10.1113/jphysiol.2012.228833.
    1. Booth CK, Coad RA, Forbes-Ewan CH, Thomson GF, Niro PJ. The physiological and psychological effects of combat ration feeding during a 12-day training exercise in the tropics. Mil Med. 2003;168(1):63–70. doi: 10.1093/miled.168.1.63.
    1. Jaeger SR, Cardello AV. A construct analysis of meal convenience applied to military foods. Appetite. 2007;49(1):231–239. doi: 10.1016/j.appet.2007.02.001.
    1. Devries MC, Phillips SM. Supplemental protein in support of muscle mass and health: advantage whey. J Food Sci. 2015;80(Suppl 1):A8–a15. doi: 10.1111/1750-3841.12802.
    1. Pasiakos SM, McClung HL, Margolis LM, Murphy NE, Lin GG, Hydren JR, et al. Human muscle protein synthetic responses during weight-bearing and non-weight-bearing exercise: a comparative study of exercise modes and recovery nutrition. PLoS One. 2015;10(10):e0140863. doi: 10.1371/journal.pone.0140863.
    1. Pasiakos SM, McClung HL, McClung JP, Margolis LM, Andersen NE, Cloutier GJ, et al. Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. Am J Clin Nutr. 2011;94(3):809–818. doi: 10.3945/ajcn.111.017061.
    1. Kim IY, Schutzler S, Schrader A, Spencer HJ, Azhar G, Ferrando AA, et al. The anabolic response to a meal containing different amounts of protein is not limited by the maximal stimulation of protein synthesis in healthy young adults. Am J Physiol Endocrinol Metab. 2016;310(1):E73–E80. doi: 10.1152/ajpendo.00365.2015.
    1. Phillips SM, Tipton KD, Aarsland A, Wolf SE, Wolfe RR. Mixed muscle protein synthesis and breakdown following resistance exercise in humans. Am J Physiol Endocrinol Metab. 1997;273(36):E99–E107. doi: 10.1152/ajpendo.1997.273.1.E99.
    1. Harris JA, Benedict FG. A biometric study of basal metabolism in man: Carnegie institution of Washington. 1919.
    1. Mifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA, Koh YO. A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr. 1990;51(2):241–247. doi: 10.1093/ajcn/51.2.241.
    1. Abumrad NN, Rabin D, Diamond MP, Lacy WW. Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man. Metab Clin Exp. 1981;30(9):936–940. doi: 10.1016/0026-0495(81)90074-3.
    1. Armstrong L, Balady GJ, Berry MJ, Davis SE, Davy BM, Medicine ACoS . ACSM’s guidelines for exercise testing and prescription. Baltimore: Lippincott Williams & Wilkins; 2006.
    1. Landers J. Maximum based on repetitions. Natl Strength Cond Assoc. 1985;6:60–61.
    1. Volpi E, Chinkes DL, Rasmussen BB. Sequential muscle biopsies during a 6-h tracer infusion do not affect human mixed muscle protein synthesis and muscle phenylalanine kinetics. Am J Physiol Endocrinol Metab. 2008;295(4):E959–E963. doi: 10.1152/ajpendo.00671.2007.
    1. Carbone JW, Margolis LM, McClung JP, Cao JJ, Murphy NE, Sauter ER, et al. Effects of energy deficit, dietary protein, and feeding on intracellular regulators of skeletal muscle proteolysis. FASEB J. 2013;27(12):5104–5111. doi: 10.1096/fj.13-239228.
    1. Drummond MJ, Fry CS, Glynn EL, Timmerman KL, Dickinson JM, Walker DK, et al. Skeletal muscle amino acid transporter expression is increased in young and older adults following resistance exercise. J Appl Physiol. 2011;111(1):135–142. doi: 10.1152/japplphysiol.01408.2010.
    1. de Betue CT, Joosten KF, Deutz NE, Vreugdenhil AC, van Waardenburg DA. Arginine appearance and nitric oxide synthesis in critically ill infants can be increased with a protein-energy-enriched enteral formula. Am J Clin Nutr. 2013;98(4):907–916. doi: 10.3945/ajcn.112.042523.
    1. Paddon-Jones D, Sheffield-Moore M, Zhang XJ, Volpi E, Wolf SE, Aarsland A, et al. Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab. 2004;286(3):E321–E328. doi: 10.1152/ajpendo.00368.2003.
    1. Volpi E, Mittendorfer B, Wolf SE, Wolfe RR. Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction. Am J Phys. 1999;277(3):E513–E520.
    1. Wolfe RR, Chinkes DL. Isotope tracers in metabolic research. 2. Hoboken: Wiley; 2005.
    1. Reeds PJ, Hachey DL, Patterson BW, Motil KJ, Klein PD. VLDL apolipoprotein B-100, a potential indicator of the isotopic labeling of the hepatic protein synthetic precursor pool in humans: studies with multiple stable isotopically labeled amino acids. J Nutr. 1992;122(3):457–466. doi: 10.1093/jn/122.3.457.
    1. Biolo G, Fleming RY, Maggi SP, Wolfe RR. Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle. Am J Phys. 1995;268(1 Pt 1):E75–E84.
    1. Rutherfurd SM, Fanning AC, Miller BJ, Moughan PJ. Protein digestibility-corrected amino acid scores and digestible indispensable amino acid scores differentially describe protein quality in growing male rats. J Nutr. 2015;145(2):372–379. doi: 10.3945/jn.114.195438.
    1. Oberli M, Marsset-Baglieri A, Airinei G, Santé-Lhoutellier V, Khodorova N, Rémond D, et al. High true Ileal digestibility but not postprandial utilization of nitrogen from bovine meat protein in humans is moderately decreased by high-temperature, long-duration cooking. J Nutr. 2015;145(10):2221–2228. doi: 10.3945/jn.115.216838.
    1. Baumann PQ, Stirewalt WS, O'Rourke BD, Howard D, Nair KS. Precursor pools of protein synthesis: a stable isotope study in a swine model. Am J Phys. 1994;267(2 Pt 1):E203–E209.
    1. Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD. Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Am J Clin Nutr. 2014;99(1):86–95. doi: 10.3945/ajcn.112.055517.
    1. Macnaughton LS, Wardle SL, Witard OC, McGlory C, Hamilton DL, Jeromson S, Lawrence CE, Wallis GA, Tipton KD. The response of muscle protein synthesis following whole-body resistance exercise is greater following 40 g than 20 g of ingested whey protein. Physiol Rep. 2016;4(15):e12893. 10.14814/phy2.12893.
    1. Symons TB, Sheffield-Moore M, Mamerow MM, Wolfe RR, Paddon-Jones D. The anabolic response to resistance exercise and a protein-rich meal is not diminished by age. J Nutr Health Aging. 2011;15(5):376–381. doi: 10.1007/s12603-010-0319-z.
    1. Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology. 2003;28(7):916–931. doi: 10.1016/S0306-4530(02)00108-7.
    1. Park S, Church DD, Azhar G, Schutzler SE, Ferrando AA, Wolfe RR. Anabolic response to essential amino acid plus whey protein composition is greater than whey protein alone in young healthy adults. J Int Soc Sports Nutr. 2020;17(1):9. doi: 10.1186/s12970-020-0340-5.
    1. Bohe J, Low A, Wolfe RR, Rennie MJ. Human muscle protein synthesis is modulated by extracellular, not intramuscular amino acid availability: a dose-response study. J Physiol. 2003;552(Pt 1):315–324. doi: 10.1113/jphysiol.2003.050674.
    1. Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? J Int Soc Sports Nutr. 2017;14:30. doi: 10.1186/s12970-017-0184-9.
    1. Volpi E, Kobayashi H, Sheffield-Moore M, Mittendorfer B, Wolfe RR. Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. Am J Clin Nutr. 2003;78(2):250–258. doi: 10.1093/ajcn/78.2.250.
    1. Nygren J, Nair KS. Differential regulation of protein dynamics in splanchnic and skeletal muscle beds by insulin and amino acids in healthy human subjects. Diabetes. 2003;52(6):1377–1385. doi: 10.2337/diabetes.52.6.1377.
    1. Schutz Y. Protein turnover, ureagenesis and gluconeogenesis. Int J Vitam Nutr Res. 2011;81(2–3):101–107. doi: 10.1024/0300-9831/a000064.
    1. Karl JP, Smith TJ, Wilson MA, Bukhari AS, Pasiakos SM, McClung HL, et al. Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults. Metab Clin Exp. 2016;65(4):416–427. doi: 10.1016/j.metabol.2015.11.001.

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