European Journal of Applied Physiology

, Volume 110, Issue 2, pp 341–351 | Cite as

l-Citrulline-malate influence over branched chain amino acid utilization during exercise

  • Antoni Sureda
  • Alfredo Córdova
  • Miguel D. Ferrer
  • Gerardo Pérez
  • Josep A. Tur
  • Antoni Pons
Original Article

Abstract

Exhaustive exercise induces disturbances in metabolic homeostasis which can result in amino acid catabolism and limited l-arginine availability. Oral l-citrulline supplementation raises plasma l-arginine concentration and augments NO-dependent signalling. Our aim was to evaluate the effects of diet supplementation with l-citrulline-malate prior to intense exercise on the metabolic handle of plasma amino acids and on the products of metabolism of arginine as creatinine, urea and nitrite and the possible effects on the hormonal levels. Seventeen voluntary male pre-professional cyclists were randomly assigned to one of two groups: control or supplemented (6 g l-citrulline-malate 2 h prior exercise) and participated in a 137-km cycling stage. Blood samples were taken in basal conditions, 15 min after the race and 3 h post race (recovery). Most essential amino acids significantly decreased their plasma concentration as a result of exercise; however, most non-essential amino acids tended to significantly increase their concentration. Citrulline-malate ingestion significantly increased the plasma concentration of citrulline, arginine, ornithine, urea, creatinine and nitrite (p < 0.05) and significantly decreased the isoleucine concentration from basal measures to after exercise (p < 0.05). Insulin levels significantly increased after exercise in both groups (p < 0.05) returning to basal values at recovery. Growth hormone increased after exercise in both groups, although the increase was higher in the citrulline-malate supplemented group (p < 0.05). l-citrulline-malate supplementation can enhance the use of amino acids, especially the branched chain amino acids during exercise and also enhance the production of arginine-derived metabolites such as nitrite, creatinine, ornithine and urea.

Keywords

Oxidative stress Insulin Growth hormone Nitric oxide Arginine 

References

  1. Aguiló A, Castano E, Tauler P, Guix MP, Serra N, Pons A (2000) Participation of blood cells in the changes of blood amino acid concentrations during maximal exercise. J Nutr Biochem 11:81–86CrossRefPubMedGoogle Scholar
  2. Bode-Boger SM, Boger RH, Loffler M, Tsikas D, Brabant G, Frolich JC (1999) l-arginine stimulates NO-dependent vasodilation in healthy humans—effect of somatostatin pretreatment. J Investig Med 47:43–50PubMedGoogle Scholar
  3. Brosnan JT, Brosnan ME (2007) Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu Rev Nutr 27:241–261CrossRefPubMedGoogle Scholar
  4. Calles-Escandon J, Cunningham JJ, Snyder P, Jacob R, Huszar G, Loke J, Felig P (1984) Influence of exercise on urea, creatinine, and 3-methylhistidine excretion in normal human subjects. Am J Physiol 246:E334–E338PubMedGoogle Scholar
  5. Cases N, Aguiló A, Tauler P, Sureda A, Llompart I, Pons A, Tur JA (2005) Differential response of plasma and immune cell’s vitamin E levels to physical activity and antioxidant vitamin supplementation. Eur J Clin Nutr 59:781–788CrossRefPubMedGoogle Scholar
  6. Cases N, Sureda A, Maestre I, Tauler P, Aguiló A, Cordova A, Roche E, Tur JA, Pons A (2006) Response of antioxidant defences to oxidative stress induced by prolonged exercise: antioxidant enzyme gene expression in lymphocytes. Eur J Appl Physiol 98:263–269CrossRefPubMedGoogle Scholar
  7. Colantoni A, de Maria N, Caraceni P, Bernardi M, Floyd RA, Van Thiel DH (1998) Prevention of reoxygenation injury by sodium salicylate in isolated-perfused rat liver. Free Radic Biol Med 25:87–94CrossRefPubMedGoogle Scholar
  8. Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau VJ, Cooke JP (1992) l-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest 90:1248–1253CrossRefPubMedGoogle Scholar
  9. Dejam A, Hunter CJ, Schechter AN, Gladwin MT (2004) Emerging role of nitrite in human biology. Blood Cells Mol Dis 32:423–429CrossRefPubMedGoogle Scholar
  10. Evans RW, Fernstrom JD, Thompson J, Morris SM Jr, Kuller LH (2004) Biochemical responses of healthy subjects during dietary supplementation with l-arginine. J Nutr Biochem 15:534–539CrossRefPubMedGoogle Scholar
  11. Flynn NE, Meininger CJ, Haynes TE, Wu G (2002) The metabolic basis of arginine nutrition and pharmacotherapy. Biomed Pharmacother 56:427–438CrossRefPubMedGoogle Scholar
  12. Fogelholm G, Naveri H, Kiilavuori K, Harkonen M (1993) Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weight lifters. Int J Sport Nutr 3:290–297PubMedGoogle Scholar
  13. Gilad VH, Rabey JM, Kimiagar Y, Gilad GM (2001) The polyamine stress response: tissue-, endocrine-, and developmental-dependent regulation. Biochem Pharmacol 61:207–213CrossRefPubMedGoogle Scholar
  14. Goodman MN, Ruderman NB (1982) Influence of muscle use on amino acid metabolism. Exerc Sport Sci Rev 10:1–26CrossRefPubMedGoogle Scholar
  15. Goodwin BL, Solomonson LP (2004) Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. J Biol Chem 279:18353–18360CrossRefPubMedGoogle Scholar
  16. Hickner RC, Tanner CJ, Evans CA, Kagan VE (2006) l-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc 38:660–666CrossRefPubMedGoogle Scholar
  17. Husson A, Brasse-Lagnel C, Fairand A, Renouf S, Lavoinne A (2003) Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem 270:1887–1899CrossRefPubMedGoogle Scholar
  18. Isidori A, Lo Monaco A, Cappa M (1981) A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin 7:475–481PubMedGoogle Scholar
  19. Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G (2006) Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem 17:571–588CrossRefPubMedGoogle Scholar
  20. Kargotich S, Goodman C, Keast D, Fry RW, Garcia-Webb P, Crawford PM, Morton AR (1997) Influence of exercise-induced plasma volume changes on the interpretation of biochemical data following high-intensity exercise. Clin J Sport Med 7:185–191CrossRefPubMedGoogle Scholar
  21. Kelijman M, Frohman L (1991) The role of the cholinergic pathway in growth hormone feedback. J Clin Endocrinol Metab 72:1081–1087CrossRefPubMedGoogle Scholar
  22. Kohli R, Meininger CJ, Haynes TE, Yan W, Self JT, Wu G (2004) Dietary l-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats. J Nutr 134:600–608PubMedGoogle Scholar
  23. Konturek PC, Brzozowski T, Konturek SJ, Szlachcic A, Hahn EG (1998) Polyamines and epidermal growth factor in the recovery of gastric mucosa from stress-induced gastric lesions. J Clin Gastroenterol 27(Suppl 1):S97–104CrossRefPubMedGoogle Scholar
  24. Liaudet L, Soriano FG, Szabo C (2000) Biology of nitric oxide signaling. Crit Care Med 28:N37–52CrossRefPubMedGoogle Scholar
  25. Marcell TJ, Taaffe DR, Hawkins SA, Tarpenning KM, Pyka G, Kohlmeier L, Wiswell RA, Marcus R (1999) Oral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adults. J Gerontol A Biol Sci Med Sci 54:395–399Google Scholar
  26. McConell GK (2007) Effects of l-arginine supplementation on exercise metabolism. Curr Opin Clin Nutr Metab Care 10:46–51CrossRefPubMedGoogle Scholar
  27. McConell GK, Huynh NN, Lee-Young RS, Canny BJ, Wadley GD (2006) l-Arginine infusion increases glucose clearance during prolonged exercise in humans. Am J Physiol Endocrinol Metab 290:E60–E66CrossRefPubMedGoogle Scholar
  28. Mori M (2007) Regulation of nitric oxide synthesis and apoptosis by arginase and arginine recycling. J Nutr 137:1616–1620Google Scholar
  29. Nussler AK, Billiar TR, Liu ZZ, Morris SM Jr (1994) Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production. J Biol Chem 269:1257–1261PubMedGoogle Scholar
  30. Refsum HE, Gjessing LR, Stromme SB (1979) Changes in plasma amino acid distribution and urine amino acids excretion during prolonged heavy exercise. Scand J Clin Lab Invest 39:407–413CrossRefPubMedGoogle Scholar
  31. Solomonson LP, Flam BR, Pendleton LC, Goodwin BL, Eichler DC (2003) The caveolar nitric oxide synthase/arginine regeneration system for NO production in endothelial cells. J Exp Biol 206:2083–2087CrossRefPubMedGoogle Scholar
  32. Stechmiller JK, Childress B, Cowan L (2005) Arginine supplementation and wound healing. Nutr Clin Pract 20:52–61CrossRefPubMedGoogle Scholar
  33. Thompson DL, Weltman JY, Rogol AD, Metzger DL, Veldhuis JD, Weltman A (1993) Cholinergic and opioid involvement in release of growth hormone during exercise and recovery. J Appl Physiol 75:870–878PubMedGoogle Scholar
  34. Wagenmakers AJ (1998) Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. Exerc Sport Sci Rev 26:287–314CrossRefPubMedGoogle Scholar
  35. Wood W (1984) Luminescence immunoassays: problems and possibilities. J Clin Chem Clin Biochem 22:905–918PubMedGoogle Scholar
  36. Wu G, Bazer FW, Cudd TA, Jobgen WS, Kim SW, Lassala A, Li P, Matis JH, Meininger CJ, Spencer TE (2007) Pharmacokinetics and safety of arginine supplementation in animals. J Nutr 137:1673S–1680SPubMedGoogle Scholar
  37. Wu G, Bazer FW, Davis TA, Kim SW, Li P, Marc Rhoads J, Carey Satterfield M, Smith SB, Spencer TE, Yin Y (2009) Arginine metabolism and nutrition in growth, health and disease. Amino Acids 37:153–168CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Antoni Sureda
    • 1
  • Alfredo Córdova
    • 2
  • Miguel D. Ferrer
    • 1
  • Gerardo Pérez
    • 3
  • Josep A. Tur
    • 1
  • Antoni Pons
    • 1
  1. 1.Research Group on Community Nutrition and Oxidative Stress, Laboratory of Physical Activity Sciences, Departament de Biologia Fonamental i Ciències de la SalutUniversity of Balearic IslandsPalma de MallorcaSpain
  2. 2.Department of Physiology and Biochemistry, School of PhysiotherapyUniversity of ValladolidSoriaSpain
  3. 3.Laboratory of Clinical Analysis, Hospital Son DuretaINSALUDPalma de MallorcaSpain

Personalised recommendations