Amino Acids

, Volume 39, Issue 2, pp 321–333 | Cite as

Effect of beta-alanine supplementation on muscle carnosine concentrations and exercise performance

Review Article

Abstract

High-intensity exercise results in reduced substrate levels and accumulation of metabolites in the skeletal muscle. The accumulation of these metabolites (e.g. ADP, Pi and H+) can have deleterious effects on skeletal muscle function and force generation, thus contributing to fatigue. Clearly this is a challenge to sport and exercise performance and, as such, any intervention capable of reducing the negative impact of these metabolites would be of use. Carnosine (β-alanyl-l-histidine) is a cytoplasmic dipeptide found in high concentrations in the skeletal muscle of both vertebrates and non-vertebrates and is formed by bonding histidine and β-alanine in a reaction catalysed by carnosine synthase. Due to the pKa of its imidazole ring (6.83) and its location within skeletal muscle, carnosine has a key role to play in intracellular pH buffering over the physiological pH range, although other physiological roles for carnosine have also been suggested. The concentration of histidine in muscle and plasma is high relative to its Km with muscle carnosine synthase, whereas β-alanine exists in low concentration in muscle and has a higher Km with muscle carnosine synthase, which indicates that it is the availability of β-alanine that is limiting to the synthesis of carnosine in skeletal muscle. Thus, the elevation of muscle carnosine concentrations through the dietary intake of carnosine, or chemically related dipeptides that release β-alanine on absorption, or supplementation with β-alanine directly could provide a method of increasing intracellular buffering capacity during exercise, which could provide a means of increasing high-intensity exercise capacity and performance. This paper reviews the available evidence relating to the effects of β-alanine supplementation on muscle carnosine synthesis and the subsequent effects on exercise performance. In addition, the effects of training, with or without β-alanine supplementation, on muscle carnosine concentrations are also reviewed.

Keywords

Beta-alanine Carnosine Exercise performance and capacity Muscle buffering 

References

  1. Abe H (2000) Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry 65:757–765PubMedGoogle Scholar
  2. Asatoor AM, Baudoh JK, Lant AF, Milne MD, Navab F (1970) Intestinal absorption of carnosine and its constituent amino acids in man. Gut 11:250–254CrossRefPubMedGoogle Scholar
  3. Baguet A, Reyngoudt H, Pottier A, Everaert I, Callens S, Achten E, Derave W (2009) Carnosine loading and washout in human skeletal muscles. J Appl Physiol 106:837–842CrossRefPubMedGoogle Scholar
  4. Baguet A, Koppo K, Pottier A, Derave W (in press) β-alanine supplementation reduces acidosis but not oxygen uptake response during high-intensity cycling exercise. Eur J Appl PhysiolGoogle Scholar
  5. Bakardjiev A (1997) Biosynthesis of carnosine in primary cultures of rat olfactory bulb. Neurosci Lett 227:115–118CrossRefPubMedGoogle Scholar
  6. Bakardjiev A, Bauer WJ (1994) Transport of β-alanine and biosynthesis of carnosine by skeletal muscle cells in primary culture. Eur J Biochem 225:617–623CrossRefPubMedGoogle Scholar
  7. Bate-Smith EC (1938) The buffering of muscle in rigour: protein, phosphate and carnosine. J Physiol 92:336–343Google Scholar
  8. Batrukova MA, Rubtsov AM (1997) Histidine-containing dipeptides as endogenous regulators of the activity of sarcoplasmic reticulum Ca-release channels. Biochim Biophys Acta 1324:142–150CrossRefPubMedGoogle Scholar
  9. Bishop D, Edge J, Goodman C (2004) Muscle buffer capacity and aerobic fitness are associated with repeated-sprint ability in women. Eur J Appl Physiol 92:540–547CrossRefPubMedGoogle Scholar
  10. Bogdanis GC, Nevill ME, Boobis LH, Lakomy HKA, Nevill AM (1995) Recovery of power output and muscle metabolites following 30s of maximal sprint cycling in man. J Physiol 482:467–480PubMedGoogle Scholar
  11. Bogdanis GC, Nevill ME, Lakomy HKA, Boobis LH (1998) Power output and muscle metabolism during and following recovery from 10 and 20s of maximal sprint exercise in humans. Acta Physiol Scand 163:261–272CrossRefPubMedGoogle Scholar
  12. Boldyrev AA (1993) Does carnosine possess direct antioxidant activity? Int J Biochem 25:1101–1107CrossRefPubMedGoogle Scholar
  13. Boldyrev AA, Dupin AM, Bunin AY, Babizhaev MA, Severin SE (1987) The antioxidative properties of carnosine, a natural histidine containing dipeptide. Biochem Int 15:1105–1113PubMedGoogle Scholar
  14. Bonfanti L, Peretto P, de Marchis S, Fasolo A (1999) Carnosine related dipeptides in the mammalian brain. Prog Neurobiol 59:333–353CrossRefPubMedGoogle Scholar
  15. Bueding E, Goldfarb W (1941) The effect of sodium fluoride and sodium iodoacetate on glycolysis in human blood. J Biol Chem 141:539–544Google Scholar
  16. Chan WKM, Decker EA, Chow CK, Bossonneault GA (1994) Effect of dietary carnosine on plasma and tissue antioxidant concentrations and on lipid oxidation in rat skeletal muscle. Lipids 29:461–466CrossRefPubMedGoogle Scholar
  17. Crozier RA, Ajit SK, Kaftan EJ, Pausch MH (2007) MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability. J Neurosci 27:4492–4496CrossRefPubMedGoogle Scholar
  18. Davey CL (1960) The effects of carnosine and anserine on glycolytic reactions in skeletal muscle. Arch Biochem Biophys 98:296–302CrossRefGoogle Scholar
  19. de Vries HA (1968) Method for evaluation of muscle fatigue and endurance from electromyographic fatigue curves. Am J Phys Med 47:125–135Google Scholar
  20. de Vries HA, Tichy MW, Housh TJ, Smyth KD, Tichy AM, Housh DJ (1987) A method for estimating physical working capacity at the fatigue threshold (PWCFT). Ergonomics 30:1195–1204CrossRefGoogle Scholar
  21. Derave W, Ozdemir MS, Harris RC, Pottier A, Reyngoudt H, Koppo K, Wise JA, Achten E (2007) β-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. J Appl Physiol 103:1736–1743CrossRefPubMedGoogle Scholar
  22. Dunnett M, Harris RC (1992) Determination of carnosine and other biogenic imidazoles in equine plasma by isocratic reversed-phase ion-pair high-performance liquid chromatography. J Chromatogr 579:45–53CrossRefPubMedGoogle Scholar
  23. Dunnett M, Harris RC (1997) High-performance liquid chromatographic determination of imidazole dipeptides, histidine, 1-methylhistidine and 3-methylhistidine in equine and camel muscle and individual muscle fibres. J Chromatogr B Biomed Appl 688:47–55CrossRefGoogle Scholar
  24. Dunnett M, Harris RC (1999) Influence of oral β-alanine and l-histidine supplementation on the carnosine content of the gluteus medius. Equine Vet J 30:499–504Google Scholar
  25. Dutka TL, Lamb GD (2004) Effect of carnosine on excitation-contraction coupling in mechanically-skinned rat skeletal muscle. J Muscle Res Cell Motil 25:203–213CrossRefPubMedGoogle Scholar
  26. Gulewitsch WS, Amiradzhibi S (1900) Uber der carnosin, eine neue organische base des fleischextrakten. Ber Dtsch Chem Ges 33:1902–1903CrossRefGoogle Scholar
  27. Hama T, Tamaki N, Miyamoto F, Kita M, Tsunemori F (1976) Intestinal absorption of β-alanine, anserine and carnosine in rats. J Nutr Sci Vitaminol 22:147–157PubMedGoogle Scholar
  28. Harris RC, Marlin DJ, Dunnett M, Snow DH, Hultman E (1990) Muscle buffering capacity and dipeptide content in the thoroughbred horse, greyhound dog and man. Comp Biochem Physiol 97A:249–251CrossRefGoogle Scholar
  29. Harris RC, Soderlund K, Hultman E (1992) Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 83:367–374PubMedGoogle Scholar
  30. Harris RC, Dunnett M, Greenhaff PL (1998) Carnosine and taurine contents in individual fibres of human vastus lateralis muscle. J Sports Sci 16:639–643CrossRefGoogle Scholar
  31. Harris RC, Tallon MJ, Dunnett M, Boobis LH, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, Wise JA (2006a) The absorption of orally supplied β-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 30:279–289CrossRefPubMedGoogle Scholar
  32. Harris RC, Ponte J, Hill CA, Sale C, Jones GA, Kim HJ, Wise JA, Kraemer WJ (2006b) Effect of 14 days β-alanine supplementation on isometric strength of the knee extensors. Med Sci Sports Exerc 38:S125–S126Google Scholar
  33. Hill CA (2007) β-Alanine supplementation and high-intensity exercise. Unpublished doctoral thesis, University of SouthamptonGoogle Scholar
  34. Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, Wise JA (2007) Influence of β-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 32:225–233CrossRefPubMedGoogle Scholar
  35. Hipkiss AR, Carmichael PL, Zimmermann B (1993) Metabolism of crystallin fragments in cell-free extracts of bovine lens: effects of ageing and oxygen free-radicals. Acta Biol Hung 42:243–263Google Scholar
  36. Hipkiss AR, Michaelis J, Syrris P (1995) Non-enzymatic glycosylation of the dipeptide l-carnosine, a potential anti-protein-cross-linking agent. FEBS Lett 28:81–85CrossRefGoogle Scholar
  37. Hipkiss AR, Brownson C, Carrier MJ (2001) Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev 15:1431–1445CrossRefGoogle Scholar
  38. Hoffman JR, Ratamess NA, Faigenbaum AD, Ross R, Kang J, Stout JR, Wise JA (2008) Short duration β-alanine supplementation increases training volume and reduces subjective feelings of fatigue in college football players. Nutr Res 28:31–35CrossRefPubMedGoogle Scholar
  39. Horinishi H, Grillo M, Margolis FL (1978) Purification and characterization of carnosine synthetase from mouse olfactory bulbs. J Neurochem 31:909–919CrossRefPubMedGoogle Scholar
  40. Kendrick IP, Harris RC, Kim HJ, Kim CK, Dang VH, Lam TQ, Bui TT, Smith M, Wise JA (2008) The effects of 10 weeks of resistance training combined with beta-alanine supplementation on whole body strength, force production, muscular endurance and body composition. Amino Acids 34:547–554CrossRefPubMedGoogle Scholar
  41. Kendrick IP, Kim HJ, Harris RC, Kim CK, Dang VH, Lam TQ, Bui TT, Wise JA (2009) The effect of 4 weeks β-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres. Eur J Appl Physiol 106:131–138CrossRefPubMedGoogle Scholar
  42. Krimberg R (1906) Zur Kenntnis der Extraktivstoffe der muskelin. IV. Mutterlung. Uberdas vorkommen des carnosins, carnitins und methylguanidins im fleisch. Hoppe Seylers Z Physiol Chem 48:412Google Scholar
  43. Krimberg R (1908) Zur Kenntnis der Extraktivstoffe der muskelin. X. Mitteilung. Uber die identitat des novsains mit dem carnitin. Hoppe Seylers Z Physiol Chem 55:466Google Scholar
  44. Lamont C, Miller DJ (1992) Calcium sensitizing action of carnosine and other endogenous imidazoles in chemically skinned striated muscle. J Physiol 454:421–434PubMedGoogle Scholar
  45. Lenney JF, Peppers SC, Kucera-Orallo CM, George RP (1985) Characterization of human tissue carnosinase. Biochem J 228:653–660PubMedGoogle Scholar
  46. Mannion AF, Jakeman PM, Dunnett M, Harris RC, Willian PL (1992) Carnosine and anserine concentrations in the quadricepts femoris muscle of healthy humans. Eur J Appl Physiol 64:47–50CrossRefGoogle Scholar
  47. Mannion AF, Jakeman PM, Willan PLT (1994) Effects of isokinetic training of the knee extensors on high-intensity exercise performance and skeletal muscle buffering. Eur J Appl Physiol 68:356–361CrossRefGoogle Scholar
  48. Mannion AF, Jakeman PM, Willan PL (1995) Skeletal muscle buffer value, fibre type distribution and high intensity exercise performance in man. Exp Physiol 80:89–101PubMedGoogle Scholar
  49. Maynard ML, Bossonneault GA, Chow CK, Bruckner GA (2001) High levels of dietary carnosine are associated with increased concentrations of carnosine and histidine in rat soleus muscle. J Nutr 131:287–290PubMedGoogle Scholar
  50. Miyamoto Y, Nakamura H, Hoshi T, Ganapathy V, Leibach FH (1990) Uphill transport of β-alanine in intestinal brush-border membrane vesicles. Am J Physiol 259:G372–G379PubMedGoogle Scholar
  51. Mori M, Gahwiler BH, Gerber U (2002) Beta-alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro. J Physiol 15:191–200CrossRefGoogle Scholar
  52. Moritani T, Takaishi T, Matsumoto T (1993) Determination of maximal power output at neuromuscular fatigue threshold. J Appl Physiol 74:1729–1734PubMedGoogle Scholar
  53. Ng RH, Marshall FD (1978) Regional and subcellular distribution of homocarnosine-carnosine synthetase in the central nervous system of rats. J Neurochem 30:187–190CrossRefGoogle Scholar
  54. Otani H, Okumura A, Nagai K, Okumura N (2008) Colocalization of a carnosine-splitting enzyme, tissue carnosinase (CN2)/cytosolic non-specific dipeptidase 2 (CNDP2), with histidine decarboxylase in the tuberomammillary nucleus of the hypothalamus. Neurosci Lett 445:166–169CrossRefPubMedGoogle Scholar
  55. Parkhouse WS, McKenzie DC, Hochachka PW, Ovalle WK (1985) Buffering capacity of deproteinized human vastus lateralis muscle. J Appl Physiol 58:14–17PubMedGoogle Scholar
  56. Penafiel R, Ruzafa C, Monserrat F, Cremades A (2004) Gender-related differences in carnosine, anserine and lysine content of murine skeletal muscle. Amino Acids 26:53–58CrossRefPubMedGoogle Scholar
  57. Perry TL, Hansen S, Tischler B, Bunting R, Berry K (1967) Carnosinemia: a new metabolic disorder associated with neurologic disease and mental defect. N Engl J Med 277:1219–1226PubMedGoogle Scholar
  58. Ramamoorthy S, Leibach FH, Mahesh VB, Han H, Yang-Feng T, Blakely RD, Ganapathy V (1994) Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J 300:893–900PubMedGoogle Scholar
  59. Rawson ES, Persky AM, Price TB, Clarkson PM (2004) Effects of repeated creatine supplementation on muscle, plasma and urine creatine levels. J Strength Cond Res 18:162–167CrossRefPubMedGoogle Scholar
  60. Rubtsov AM (2001) Molecular mechanisms of regulation of the activity of sarcoplasmic reticulum Ca-release channels (ryanodine receptors), muscle fatigue, and Severin’s phenomenon. Biochemistry 66:1132–1143PubMedGoogle Scholar
  61. Sassoe-Pognetto MM, Cantino D, Panzanelli P, Verdun di Cantogno L, Giustetto M, Margolis FL, De Biasi S, Fasolo A (1993) Presynaptic colocalization of carnosine and glutamate in olfactory neurones. Neuroreport 5:7–10CrossRefPubMedGoogle Scholar
  62. Severin SE, Kirzon MV, Kaftanova TM (1953) Effect of carnosine and anserine on action of isolated frog muscles. Dokl Akad Nauk SSSR 91:691–701PubMedGoogle Scholar
  63. Sewell DA, Harris RC, Dunnett M (1991) Carnosine accounts for most of the variation in physico-chemical buffering in equine muscle. Equine Exerc Physiol 3:276–280Google Scholar
  64. Sewell DA, Harris RC, Marlin DJ, Dunnett M (1992) Estimation of the carnosine content of different fibre types in the middle gluteal muscle of the thoroughbred horse. J Physiol 455:447–453PubMedGoogle Scholar
  65. Skaper SD, Das S, Marshall FD (1973) Some properties of a homocarnosine-carnosine synthetase isolated from rat brain. J Neurochem 21:1429–1445CrossRefPubMedGoogle Scholar
  66. Smith AE, Moon JR, Kendall KL, Graef JL, Lockwood CM, Walter AA, Beck TW, Cramer JT, Stout JR (2009a) The effects of beta-alanine supplementation and high-intensity interval training on neuromuscular fatigue and muscle function. Eur J Appl Physiol 105:357–363CrossRefPubMedGoogle Scholar
  67. Smith AE, Walter AA, Graef JL, Kendall KL, Moon JR, Lockwood CM, Fakuda DH, Beck TW, Cramer JT, Stout JR (2009b) Effects of β-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial. J Int Soc Sports Nutr 6:5CrossRefPubMedGoogle Scholar
  68. Stout JR, Cramer JT, Mielke M, O’Kroy J, Torok DJ, Zoeller RF (2006) Effects of twenty-eight days of beta-alanine and creatine monohydrate supplementation on the physical working capacity at neuromuscular fatigue threshold. J Strength Cond Res 20:928–931CrossRefPubMedGoogle Scholar
  69. Stout JR, Cramer JT, Zoeller RF, Torok D, Costa P, Hoffman JR, Harris RC, O’Kroy J (2007) Effects of β-alanine supplementation on the onset of neuromuscular fatigue and ventilatory threshold in women. Amino Acids 32:381–386CrossRefPubMedGoogle Scholar
  70. Stout JR, Graves BS, Smith AE, Hartman MJ, Cramer JT, Beck TW, Harris RC (2008) The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55–92 years): a double-blind randomized study. J Int Soc Sports Nutr 5:21–26CrossRefPubMedGoogle Scholar
  71. Suzuki Y, Ito O, Mukai N, Takahashi H, Takamatsu K (2002) High levels of skeletal muscle carnosine contributes to the latter half of exercise performance during maximal cycle ergometer sprinting. Jpn J Physiol 52:199–205CrossRefPubMedGoogle Scholar
  72. Suzuki Y, Ito O, Takahashi H, Takamatsu K (2004) The effect of sprint training on skeletal muscle carnosine in humans. Int J Sport Health Sci 2:105–110Google Scholar
  73. Syrotuik DG, Bell GJ (2004) Acute creatine monohydrate supplementation: a descriptive physiological profile of responder vs nonresponders. J Strength Cond Res 18:610–617CrossRefPubMedGoogle Scholar
  74. Tallon MJ, Harris RC, Boobis LH, Fallowfield JL, Wise JA (2005) The carnosine content of vastus lateralis is elevated in resistance-trained bodybuilders. J Strength Cond Res 19:725–729CrossRefPubMedGoogle Scholar
  75. Tamaki N, Tsunemori F, Wakabayashi M, Hama T (1977) Effect of histidine-free and -excess diets on anserine and carnosine contents in rat gastrocnemius muscle. J Nutr Sci Vitaminol 23:331–340PubMedGoogle Scholar
  76. Tamaki N, Ikeda T, Fujimoto S, Mizutani N (1985) Carnosine as a histidine source: transport and hydrolysis of exogenous carnosine by rat intestine. J Nutr Sci Vitaminol 31:607–618PubMedGoogle Scholar
  77. Tanokura M, Tasumi M, Miyazawa T (1976) 1H nuclear magnetic resonance studies of histidine containing di and tripeptides. Estimation of the effects of charged groups on the pK a value of the imidiazole ring. Biopolymers 15:393–401CrossRefPubMedGoogle Scholar
  78. Tokutomi N, Kaneda M, Akaike N (1989) What confers specificity on glycine for its receptor site? Br J Pharmacol 97:353–360PubMedGoogle Scholar
  79. van Thienen R, van Proeyen K, vanden Eynde B, Puype J, Lefere T, Hespel P (2009) β-alanine improves sprint performance in endurance cycling. Med Sci Sports Exerc 41:898–903CrossRefPubMedGoogle Scholar
  80. Wang DS, Zhu HL, Li JS (2003) Beta-alanine acts on glycine receptors in the rat sacral dorsal commissural neurons. Int J Neurosci 113:293–305CrossRefPubMedGoogle Scholar
  81. Zoeller RF, Stout JR, O’Kroy J, Torok D, Mielke M (2007) Effects of 28 days of beta-alanine and creatine monohydrate supplementation on aerobic power, ventilatory and lactate thresholds and time to exhaustion. Amino Acids 33:505–510CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.School of Science and TechnologyNottingham Trent UniversityNottinghamUK
  2. 2.School of Sport, Exercise and Health SciencesUniversity of ChichesterChichesterUK

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