Abstract
Endurance exercise alters amino acid (AA) metabolism that necessitates greater AA intake in the post exercise recovery period to support recovery. Thus, daily AA ingestion during a period of endurance training may affect the metabolically active plasma free AA pool, which is otherwise maintained during periods of inadequate protein intake by the breakdown of skeletal muscle proteins. Nine endurance-trained males completed a 4-day running protocol (20 km, 5 km, 10 km and 20 km on days 1–4, respectively) on three occasions with a controlled diet providing different protein intakes [0.94(LOW), 1.20(MOD) or 1.83gprotein kgbody mass−1 day−1 (HIGH)]. Urine collected over 24 h on day-4 and plasma collected after an overnight fast on day-5 were analyzed for free AA (plasma) and 3-methylhistidine (3MH; plasma and urine), a marker of myofibrillar protein breakdown. There was an effect of protein intake (HIGH > MOD/LOW; P < 0.05) on fasted plasma essential AA, branched chain AA and 3MH but no effect on 24-h urinary 3-MH excretion. Consuming a previously determined optimal daily protein intake of 1.83 g kg−1 day−1 during endurance training maintains fasted plasma free AA and may attenuate myofibrillar protein catabolism, although this latter effect was not detected in 24-h urinary excretion. The maintenance of the metabolically active free plasma AA pool may support greater recovery from exercise and contribute to the previously determined greater whole-body net protein balance in this athletic population. TRN: NCT02801344 (June 15, 2016).
Similar content being viewed by others
data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
References
Ashley DV, Barclay DV, Chauffard FA et al (1982) Plasma amino acid responses in humans to evening meals of differing nutritional composition. Am J Clin Nutr 36:143–153. https://doi.org/10.1093/ajcn/36.1.143
Ballard FJ, Tomas FM (1983) 3-Methylhistidine as a measure of skeletal muscle protein breakdown in human subjects: the case for its continued use. Clin Sci 65:209–215. https://doi.org/10.1042/cs0650209
Borgenvik M, Nordin M, Mattsson CM et al (2012) Alterations in amino acid concentrations in the plasma and muscle in human subjects during 24 h of simulated adventure racing. Eur J Appl Physiol 112:3679–3688. https://doi.org/10.1007/s00421-012-2350-8
Bowtell JL, Leese GP, Smith K et al (2000) Effect of oral glucose on leucine turnover in human subjects at rest and during exercise at two levels of dietary protein. J Physiol 525:271–281. https://doi.org/10.1111/j.1469-7793.2000.00271.x
Churchward-Venne TA, Pinckaers PJM, Smeets JSJ et al (2020) Dose-response effects of dietary protein on muscle protein synthesis during recovery from endurance exercise in young men: a double-blind randomized trial. Am J Clin Nutr 112:303–317. https://doi.org/10.1093/ajcn/nqaa073
Costa RJS, Snipe RMJ, Kitic CM, Gibson PR (2017) Systematic review: exercise-induced gastrointestinal syndrome-implications for health and intestinal disease. Aliment Pharmacol Ther 46:246–265. https://doi.org/10.1111/apt.14157
Décombaz J, Reinhardt P, Anantharaman K et al (1979) Biochemical changes in a 100 km run: free amino acids, urea, and creatinine. Eur J Appl Physiol 41:61–72. https://doi.org/10.1007/BF00424469
Di Donato DM, West DWD, Churchward-Venne TA et al (2014) Influence of aerobic exercise intensity on myofibrillar and mitochondrial protein synthesis in young men during early and late postexercise recovery. Am J Physiol Endo-Crinol Metab 306:E1025–E1032. https://doi.org/10.1152/ajpendo.00487.2013
Fernstrom JD, Wurtman RJ, Hammarstrom-Wiklund B et al (1979) Diurnal variations in plasma concentrations of tryptophan, tryosine, and other neutral amino acids: effect of dietary protein intake. Am J Clin Nutr 32:1912–1922. https://doi.org/10.1093/ajcn/32.9.1912
Fouillet H, Gaudichon C, Mariotti F et al (2001) Energy nutrients modulate the splanchnic sequestration of dietary nitrogen in humans: a compartmental analysis. Am J Physiol Endocrinol Metab 281:E248-260. https://doi.org/10.1152/ajpendo.2001.281.2.E248
Fukutake N, Ueno M, Hiraoka N et al (2015) a novel multivariate index for pancreatic cancer detection based on the plasma free amino acid profile. PLoS ONE. https://doi.org/10.1371/journal.pone.0132223
Genton L, Pichard C (2011) Protein catabolism and requirements in severe illness. Int J Vitam Nutr Res 81:143–152. https://doi.org/10.1024/0300-9831/a000058
Henriksson J (1991) Effect of exercise on amino acid concentrations in skeletal muscle and plasma. J Exp Biol. https://doi.org/10.1242/jeb.160.1.149
Hisamatsu T, Okamoto S, Hashimoto M et al (2012) Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. PLoS ONE 7:e31131. https://doi.org/10.1371/journal.pone.0031131
Holm E, Sedlaczek O, Grips E (1999) Amino acid metabolism in liver disease. Curr Opin Clin Nutr Metab Care 2:47–53. https://doi.org/10.1097/00075197-199901000-00009
Howarth KR, Phillips SM, MacDonald MJ et al (2010) Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery. J Appl Physiol 109:431–438. https://doi.org/10.1152/japplphysiol.00108.2009
Hulston CJ, Wolsk E, Grøndahl TS et al (2011) Protein intake does not increase vastus lateralis muscle protein synthesis during cycling. Med Sci Sports Exerc 43:1635–1642. https://doi.org/10.1249/MSS.0b013e31821661ab
Huq F, Thompson M, Ruell P (1993) Changes in serum amino acid concentrations during prolonged endurance running. Jpn J Physiol. https://doi.org/10.2170/jjphysiol.43.797
Kato H, Suzuki K, Bannai M, Moore DR (2016) Protein requirements are elevated in endurance athletes after exercise as determined by the indicator amino acid oxidation method. PLoS ONE 11:e0157406. https://doi.org/10.1371/journal.pone.0157406
Kato H, Suzuki K, Bannai M, Moore DR (2018) Branched-chain amino acids are the primary limiting amino acids in the diets of endurance-trained men after a bout of prolonged exercise. J Nutr. https://doi.org/10.1093/jn/nxy048
Kochlik B, Gerbracht C, Grune T, Weber D (2018) The influence of dietary habits and meat consumption on plasma 3-methylhistidine—a potential marker for muscle protein turnover. Mol Nutr Food Res 62:1–9. https://doi.org/10.1002/mnfr.201701062
Koopman R, Pannemans DLE, Jeukendrup AE et al (2004) Combined ingestion of protein and carbohydrate improves protein balance during ultra-endurance exercise. Am J Physiol Endocrinol Metab 287:E712–E720. https://doi.org/10.1152/ajpendo.00543.2003
Long CL, Dillard DR, Bodzin JH et al (1988) Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans. Metabolism 37:844–849. https://doi.org/10.1016/0026-0495(88)90118-7
Lukaski HC, Mendez J, Buskirk ER, Cohn SH (1981) Relationship between endogenous 3-methylhistidine excretion and body composition. Am J Physiol-Endocrinol Metab. https://doi.org/10.1152/ajpendo.1981.240.3.E302
Manary MJ, Broadhead RL, Yarasheski KE (1998) Whole-body protein kinetics in marasmus and kwashiorkor during acute infection. Am J Clin Nutr 67:1205–1209. https://doi.org/10.1093/ajcn/67.6.1205
Margolis LM, Karl JP, Wilson MA et al (2021) Serum branched-chain amino acid metabolites increase in males when aerobic exercise is initiated with low muscle glycogen. Metabolites. https://doi.org/10.3390/metabo11120828
Mazzulla M, Parel JT, Beals JW et al (2017) Endurance exercise attenuates postprandial whole-body leucine balance in trained men. Med Sci Sports Exerc 49:2585–2592. https://doi.org/10.1249/mss.0000000000001394
Meredith CN, Zackin MJ, Frontera WR (1989) Dietary protein requirements and body protein metabolism in endurance-trained men. J Appl Physiol (1985) 66:2850–2856. https://doi.org/10.1152/jappl.1989.66.6.2850
Morrison WL, Gibson JN, Rennie MJ (1988) Skeletal muscle and whole body protein turnover in cardiac cachexia: influence of branched-chain amino acid administration. Eur J Clin Invest 18:648–654. https://doi.org/10.1111/j.1365-2362.1988.tb01282.x
Munro HN, Young VR (1978) Urinary excretion of N gamma-methylihistidine (3-methylihistidine): a tool to study metabolic responses in relation to nutrient and hormonal status in health and disease of man. Am J Clin Nutr. https://doi.org/10.1093/ajcn/31.9.1608
Nishioka M, Imaizumi A, Ando T, Tochikubo O (2013) The Overnight Effect of Dietary Energy Balance on Postprandial Plasma Free Amino Acid (PFAA) Profiles in Japanese Adult Men. PLoS ONE 8:e62929–e62929. https://doi.org/10.1371/journal.pone.0062929
Paul GL, DeLany JP, Snook JT et al (1989) Serum and urinary markers of skeletal muscle tissue damage after weight lifting exercise. Eur J Appl Physiol 58:786–790. https://doi.org/10.1007/BF00637392
Pozefsky T, Felig P, Tobin JD et al (1969) Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels. J Clin Invest. https://doi.org/10.1172/JCI106193
Pozefsky T, Tancredi RG, Moxley RT et al (1976) Effects of brief starvation on muscle amino acid metabolism in nonobese man. J Clin Invest 57:444–449. https://doi.org/10.1172/JCI108295
Rennie MJ, Edwards RH, Krywawych S et al (1981) Effect of exercise on protein turnover in man. Clin Sci 61:627–639. https://doi.org/10.1042/cs0610627
Res PT, Groen B, Pennings B et al (2012) Protein ingestion before sleep improves postexercise overnight recovery. Med Sci Sports Exerc 44:1560–1569. https://doi.org/10.1249/MSS.0b013e31824cc363
Riazi R, Rafii M, Wykes LJ et al (2003) Valine may be the first limiting branched-chain amino acid in egg protein in men. J Nutr 133:3533–3539. https://doi.org/10.1093/jn/133.11.3533
Rowlands DS, Rössler K, Thorp RM et al (2008) Effect of dietary protein content during recovery from high-intensity cycling on subsequent performance and markers of stress, inflammation, and muscle damage in well-trained men. Appl Physiol Nutr Metab 33:39–51. https://doi.org/10.1139/H07-136
Shimbo K, Oonuki T, Yahashi A et al (2009) Precolumn derivatization reagents for high-speed analysis of amines and amino acids in biological fluid using liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom RCM. https://doi.org/10.1002/rcm.4026
Shingyoji M, Iizasa T, Higashiyama M et al (2013) The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer. BMC Cancer. https://doi.org/10.1186/1471-2407-13-77
Sjölin J, Hjort G, Friman G, Hambraeus L (1987) Urinary excretion of 1-methylhistidine: a qualitative indicator of exogenous 3-methylhistidine and intake of meats from various sources. Metabolism 36:1175–1184. https://doi.org/10.1016/0026-0495(87)90245-9
Suryawan A, Hawes JW, Harris RA et al (1998) A molecular model of human branched-chain amino acid metabolism. Am J Clin Nutr 68:72–81. https://doi.org/10.1093/ajcn/68.1.72
Tarnopolsky M (2004) Protein requirements for endurance athletes. Nutrition 20:662–668. https://doi.org/10.1016/j.nut.2004.04.008
Thomas DT, Erdman KA, Burke LM (2016) American College of Sports Medicine Joint Position Statement. Nutrition and athletic performance. Med Sci Sports Exerc 48:543–568. https://doi.org/10.1249/MSS.0000000000000852
Tipton KD, Hamilton DL, Gallagher IJ (2018) Assessing the role of muscle protein breakdown in response to nutrition and exercise in humans. Sports Med. https://doi.org/10.1007/s40279-017-0845-5
van Loon LJC, Saris WHM, Verhagen H, Wagenmakers AJM (2000) Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. Am J Clin Nutr 72:96–105. https://doi.org/10.1093/ajcn/72.1.96
Vendelbo MH, Møller AB, Christensen B et al (2014) Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling. PLoS ONE 9:e102031. https://doi.org/10.1371/journal.pone.0102031
Viru A (1987) Mobilisation of structural proteins during exercise. Sports Med Auckl NZ 4:95–128. https://doi.org/10.2165/00007256-198704020-00003
Wagenmakers AJ, Brookes JH, Coakley JH et al (1989) Exercise-induced activation of the branched-chain 2-oxo acid dehydrogenase in human muscle. Eur J Appl Physiol Occup Physiol 59:159–167. https://doi.org/10.1007/bf02386181
Wahren J, Felig P, Hagenfeldt L (1976) Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus. J Clin Invest 57:987–999. https://doi.org/10.1172/JCI108375
Waskiw-Ford M, Hannaian S, Duncan J et al (2020) Leucine-enriched essential amino acids improve recovery from post-exercise muscle damage independent of increases in integrated myofibrillar protein synthesis in young men. Nutrients 12:E1061. https://doi.org/10.3390/nu12041061
Wassner SJ, Schlitzer JL, Li JB (1980) A rapid, sensitive method for the determination of 3-methylhistidine levels in urine and plasma using high-pressure liquid chromatography. Anal Biochem. https://doi.org/10.1016/0003-2697(80)90076-7
Williamson E, Kato H, Volterman KA et al (2019) The effect of dietary protein on protein metabolism and performance in endurance-trained males. Med Sci Sports Exerc 51:352–360. https://doi.org/10.1249/MSS.0000000000001791
Wolfe RR, Wolfe MH, Nadel ER, Shaw JH (1984) Isotopic determination of amino acid-urea interactions in exercise in humans. J Appl Physiol 56:221–229. https://doi.org/10.1152/jappl.1984.56.1.221
Yamakado M, Nagao K, Imaizumi A et al (2015) Plasma free amino acid profiles predict four-year risk of developing diabetes, metabolic syndrome, dyslipidemia, and hypertension in Japanese population. Sci Rep. https://doi.org/10.1038/srep11918
Acknowledgements
Funding was provided by Ajinomoto Co. Inc.
Author information
Authors and Affiliations
Contributions
EW, HK, KS, and DRM conceived and designed the experiments; EW, HK, and KAV performed the experiments; EWn and HK analyzed the data; EW wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
Study funding provided to Daniel R. Moore by Ajinomoto Co. Inc. Hiroyuki Kato and Katsuya Suzuki are employees of Ajinomoto Co. Inc. Daniel R. Moore has received research funding from Dairy Management Inc. and Iovate Health Sciences Inc and speakers fees from Gatorade Sports Sciences Institute. Eric Williamson and Kimberly A. Volterman have no financial interests to declare.
Additional information
Handling editor: L. v. Loon.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Williamson, E., Kato, H., Volterman, K.A. et al. Greater plasma essential amino acids and lower 3-methylhistidine with higher protein intake during endurance training: a randomised control trial. Amino Acids 55, 1285–1291 (2023). https://doi.org/10.1007/s00726-022-03210-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-022-03210-z