Top

Journal of the International Society of Sports Nutrition

Published in:

Open Access 01-12-2020 | Research article

Acute supplementation with an amino acid mixture suppressed the exercise-induced cortisol response in recreationally active healthy volunteers: a randomized, double-blinded, placebo-controlled crossover study

Authors: Yuichi Tsuda, Rika Murakami, Makoto Yamaguchi, Taiichiro Seki

Published in: Journal of the International Society of Sports Nutrition | Issue 1/2020

Abstract

Background

Few studies have demonstrated the suppressive effects of amino acids (AAs) on the level of cortisol during exercise in humans. We hypothesized that an AA mixture containing arginine, which promotes lipid metabolism, valine, which effectively decreases the level of glucocorticoid, and serine, a substrate in the production of phosphatidylserine that is reported to blunt increases in cortisol, would suppress the exercise-induced cortisol response by combining the positive effects of the AAs synergistically.

Methods

A randomized, double-blinded, placebo-controlled crossover trial was conducted. Twenty healthy recreationally active males ingested either an AA mixture containing 1.8 g of arginine, 1.1 g of valine, and 0.1 g of serine or a placebo. Thirty minutes after ingestion, subjects performed an exercise trial on a cycle ergometer for 80 min at 50% maximal oxygen consumption. Plasma cortisol and other blood parameters immediately before and after the exercise were evaluated.

Results

Plasma cortisol concentrations after exercise were significantly higher than those before exercise in the placebo condition (9.51 ± 0.85 vs 14.39 ± 2.15, p < 0.05), while there was no significant difference in the AA condition (9.71 ± 0.93 vs 9.99 ± 1.23, p = 0.846). In addition, the increase in plasma cortisol before and after exercise was significantly lower in the AA condition than in the placebo condition (0.28 [− 2.75, 3.31] vs 4.87 [0.89, 8.86], p < 0.05). For the level of adrenocorticotropin, there was a significant difference between before and after exercise only in the placebo condition (24.21 ± 2.91 vs 53.17 ± 6.97, p < 0.01) but not in the AA condition (27.33 ± 3.60 vs 46.92 ± 10.41, p = 0.057). Blood glucose, plasma lactate, plasma ammonia, serum creatine phosphokinase, serum total ketone body, and serum free fatty acid were also significantly changed by the exercise load in both conditions, but no significant differences were observed between the two conditions.

Conclusions

The present study demonstrated that the AA mixture suppressed the cortisol response during exercise without affecting exercise-related biological parameters such as glucose or lipid metabolism.

Trial registration

UMIN Clinical Trials Registry, UMIN000023587. Registered 19 August 2016.

Adinoff B, Junghanns K, Kiefer F, Krishnan-Sarin S. Suppression of the hpa axis stress-response: implications for relapse. Alcohol Clin Exp Res. 2005;29:1351–5.PubMedPubMedCentral

Hackney AC. Stress and the neuroendocrine system: the role of exercise as a stressor and modifier of stress. Expert Rev Endocrinol Metab. 2006;1:783–92.PubMedPubMedCentral

Kanaley JA, Weltman JY, Pieper KS, Weltman A, Hartman ML. Cortisol and growth hormone responses to exercise at different times of day. J Clin Endocrinol Metab. 2001;86:2881–9.PubMed

Jacks DE, Sowash J, Anning J, Mcgloughlin T, Andres F. Effect of exercise at three exercise intensities on salivary cortisol. J Strength Cond Res. 2002;16:286–9.PubMed

Tsigos C, Chrousos GP. Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53:865–71.PubMed

Hill E, Zack E, Battaglini C, Viru M, Viru A, Hackney A. Exercise and circulating cortisol levels: the intensity threshold effect. J Endocrinol Investig. 2008;31:587–91.

Tabata I, Atomi Y, Miyashita M. Blood glucose concentration dependent acth and cortisol responses to prolonged exercise. Clin Physiol. 1984;4:299–307.PubMed

Tabata I, Ogita F, Miyachi M, Shibayama H. Effect of low blood glucose on plasma crf, acth, and cortisol during prolonged physical exercise. J Appl Physiol. 1991;71:1807–12.PubMed

McGuigan MR, Egan AD, Foster C. Salivary cortisol responses and perceived exertion during high intensity and low intensity bouts of resistance exercise. J Sports Sci Med. 2004;3:8.PubMedPubMedCentral

10.

Caetano Júnior P, Castilho M, Raniero L. Salivary cortisol responses and session ratings of perceived exertion to a rugby match and fatigue test. Percept Mot Skills. 2017;124:649–61.PubMed

11.

Luger A, Deuster PA, Kyle SB, Gallucci WT, Montgomery LC, Gold PW, et al. Acute hypothalamic–pituitary–adrenal responses to the stress of treadmill exercise. N Engl J Med. 1987;316:1309–15.PubMed

12.

Simmons PS, Miles JM, Gerich J, Haymond MW. Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range. J Clin Invest. 1984;73:412–20.PubMedPubMedCentral

13.

Darmaun D, Matthews DE, Bier DM. Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production. Am J Physiol Endocrinol Metab. 1988;255:E366–73.

14.

Brillon D, Zheng B, Campbell R, Matthews D. Effect of cortisol on energy expenditure and amino acid metabolism in humans. Am J Physiol Endocrinol Metab. 1995;268:E501–13.

15.

Tomas FM, Munro HN, Young VR. Effect of glucocorticoid administration on the rate of muscle protein breakdown in vivo in rats, as measured by urinary excretion of n τ-methylhistidine. Biochem J. 1979;178:139–46.PubMedPubMedCentral

16.

Schakman O, Kalista S, Barbé C, Loumaye A, Thissen J-P. Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol. 2013;45:2163–72.PubMed

17.

Schakman O, Gilson H, Kalista S, Thissen J-P. Mechanisms of muscle atrophy induced by glucocorticoids. Horm Res Paediatr. 2009;72:36–41.

18.

Mitchell J, Costill D, Houmard J, Flynn M, Fink W, Beltz J. Influence of carbohydrate ingestion on counterregulatory hormones during prolonged exercise. Int J Sports Med. 1990;11:33–6.PubMed

19.

Anderson RA, Bryden NA, Polansky MM, Thorp JW. Effects of carbohydrate loading and underwater exercise on circulating cortisol, insulin and urinary losses of chromium and zinc. Eur J Appl Physiol Occup Physiol. 1991;63:146–50.PubMed

20.

Deuster PA, Singh A, Hofmann A, Moses FM, Chrousos GC. Hormonal responses to ingesting water or a carbohydrate beverage during a 2 h run. Med Sci Sports Exerc. 1992;24:72–9.PubMed

21.

Carli G, Bonifazi M, Lodi L, Lupo C, Martelli G, Viti A. Changes in the exercise-induced hormone response to branched chain amino acid administration. Eur J Appl Physiol Occup Physiol. 1992;64:272–7.PubMed

22.

Hoffman JR, Ratamess NA, Ross R, Shanklin M, Kang J, Faigenbaum AD. Effect of a pre-exercise energy supplement on the acute hormonal response to resistance exercise. J Strength Cond Res. 2008;22:874–82.PubMed

23.

Fu WJ, Haynes TE, Kohli R, Hu J, Shi W, Spencer TE, et al. Dietary l-arginine supplementation reduces fat mass in zucker diabetic fatty rats. J Nutr. 2005;135:714–21.PubMed

24.

Jobgen W, Meininger CJ, Jobgen SC, Li P, Lee M-J, Smith SB, et al. Dietary l-arginine supplementation reduces white fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. J Nutr. 2008;139:230–7.PubMed

25.

McKnight JR, Satterfield MC, Jobgen WS, Smith SB, Spencer TE, Meininger CJ, et al. Beneficial effects of l-arginine on reducing obesity: potential mechanisms and important implications for human health. Amino Acids. 2010;39:349–57.PubMed

26.

Tsuda Y, Iwasawa K, Yamaguchi M. Acute supplementation of valine reduces fatigue during swimming exercise in rats. Biosci Biotechnol Biochem. 2018;82:856–61.PubMed

27.

Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr. 2008;5:11.PubMedPubMedCentral

28.

Tsuda Y, Yamaguchi M, Noma T, Okaya E, Itoh H. Combined effect of arginine, valine, and serine on exercise-induced fatigue in healthy volunteers: a randomized, double-blinded, placebo-controlled crossover study. Nutrients. 2019;11:862.PubMedCentral

29.

Sato H, Suzuki K, Nakaji S, Sugawara K, Totsuka M, Sato K. Effects of acute endurance exercise and 8 week training on the production of reactive oxygen species from neutrophils in untrained men. Jpn J Hyg. 1998;53:431–40.

30.

Rubinow DR, Roca CA, Schmidt PJ, Danaceau MA, Putnam K, Cizza G, et al. Testosterone suppression of crh-stimulated cortisol in men. Neuropsychopharmacology. 2005;30:1906.PubMedPubMedCentral

31.

De Leo V, La Marca A, Talluri B, D'Antona D, Morgante G. Hypothalamo-pituitary-adrenal axis and adrenal function before and after ovariectomy in premenopausal women. Eur J Endocrinol. 1998;138:430–5.PubMed

32.

de Jong MF, Molenaar N, Beishuizen A, Groeneveld AJ. Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study. Crit Care. 2015;19:1.PubMedPubMedCentral

33.

Gore DC, Jahoor F, Wolfe RR, Herndon DN. Acute response of human muscle protein to catabolic hormones. Ann Surg. 1993;218:679.PubMedPubMedCentral

34.

Vijayan M, Leatherland J. Cortisol-induced changes in plasma glucose, protein, and thyroid hormone levels, and liver glycogen content of coho salmon (oncorhynchus kisutch walbaum). Can J Zool. 1989;67:2746–50.

35.

Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, et al. Beneficial effects of a long-term oral l-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2006;291:E906–12.PubMed

36.

Hurt RT, Ebbert JO, Schroeder DR, Croghan IT, Bauer BA, McClave SA, et al. L-arginine for the treatment of centrally obese subjects: a pilot study. J Diet Suppl. 2014;11:40–52.PubMed

37.

Baird MF, Graham SM, Baker JS, Bickerstaff GF. Creatine-kinase-and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab. 2012;2012.

38.

Peake JM, Suzuki K, Wilson G, Hordern M, Nosaka K, Mackinnon L, et al. Exercise-induced muscle damage, plasma cytokines, and markers of neutrophil activation. Med Sci Sports Exerc. 2005;37:737–45.PubMed

39.

Greer BK, Woodard JL, White JP, Arguello EM, Haymes EM. Branched-chain amino acid supplementation and indicators of muscle damage after endurance exercise. Int J Sport Nutr Exerc Metab. 2007;17:595–607.PubMed

40.

Fernholz KM. The effects of phosphatidylserine on markers of muscular stress in endurance runners. St Cloud State University; 2000.

41.

Mutch B, Banister E. Ammonia metabolism in exercise and fatigue: a review. Med Sci Sports Exerc. 1983;15:41–50.PubMed

42.

Banister E, Cameron B. Exercise-induced hyperammonemia: peripheral and central effects. Int J Sports Med. 1990;11:S129–42.PubMed

43.

Schaefer A, Piquard F, Geny B, Doutreleau S, Lampert E, Mettauer B, et al. L-arginine reduces exercise-induced increase in plasma lactate and ammonia. Int J Sports Med. 2002;23:403–7.PubMed

44.

Sapienza MA, Kharitonov SA, Horvath I, Chung KF, Barnes PJ. Effect of inhaled l-arginine on exhaled nitric oxide in normal and asthmatic subjects. Thorax. 1998;53:172–5.PubMedPubMedCentral

45.

Jankord R, McAllister RM, Ganjam VK, Laughlin MH. Chronic inhibition of nitric oxide synthase augments the acth response to exercise. Am J Physiol Regul Integr Comp Physiol. 2009;296:R728–34.PubMedPubMedCentral

46.

Rivier C, Shen GH. In the rat, endogenous nitric oxide modulates the response of the hypothalamic-pituitary-adrenal axis to interleukin-1 beta, vasopressin, and oxytocin. J Neurosci. 1994;14:1985–93.PubMedPubMedCentral

47.

Heisler LK, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L, et al. Serotonin activates the hypothalamic–pituitary–adrenal axis via serotonin 2c receptor stimulation. J Neurosci. 2007;27:6956–64.PubMedPubMedCentral

48.

Tomonaga S, Yamasaki I, Nagasawa M, Ogino Y, Uotsu N, Teramoto S, et al. Oral administration of l-serine increases l-and d-serine levels in the plasma and brain of fasted rats. Lett Drug Des Discov. 2012;9:663–7.

49.

Mozzi R, Buratta S, Goracci G. Metabolism and functions of phosphatidylserine in mammalian brain. Neurochem Res. 2003;28:195–214.PubMed

Title: Acute supplementation with an amino acid mixture suppressed the exercise-induced cortisol response in recreationally active healthy volunteers: a randomized, double-blinded, placebo-controlled crossover study
Authors: Yuichi Tsuda
Rika Murakami
Makoto Yamaguchi
Taiichiro Seki
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: Journal of the International Society of Sports Nutrition / Issue 1/2020
Electronic ISSN: 1550-2783
DOI: https://doi.org/10.1186/s12970-020-00369-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Acute supplementation with an amino acid mixture suppressed the exercise-induced cortisol response in recreationally active healthy volunteers: a randomized, double-blinded, placebo-controlled crossover study

Abstract

Background

Methods

Results

Conclusions

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2020

Coenzyme Q10 status, glucose parameters, and antioxidative capacity in college athletes

Effects of skim milk and isotonic drink consumption before exercise on fluid homeostasis and time-trial performance in cyclists: a randomized cross-over study

Time-restricted eating effects on performance, immune function, and body composition in elite cyclists: a randomized controlled trial

Correction to: Beta alanine supplementation effects on metabolic contribution and swimming performance

Effect of D-ribose supplementation on delayed onset muscle soreness induced by plyometric exercise in college students

The effect of vitamin D supplementation on serum total 25(OH) levels and biochemical markers of skeletal muscles in runners