A kinetic model of carnosine synthesis in human skeletal muscle

Abstract

Drawing on previously published data, a mathematical model is proposed to describe the synthesis of carnosine in muscle using a slow release β-alanine supplement (SR-CarnoSyn®). The model pre-supposes that the rate of synthesis for any given dose of β-alanine (within the range 1.6–6.4 g day−1) is constant with time, but is first order with respect to daily β-alanine dose. Simultaneously with synthesis, decay in carnosine is also assumed to be occurring, the rate in this case being a function of the concentration of carnosine. Decay in carnosine appears describable by first-order kinetics. By integration of the two rate reactions, a single mathematical equation was derived to describe the synthesis of carnosine and which closely fitted the experimental data over 56 days. The model, if validated by additional studies, could be used to compliment empirical observations of the changes in carnosine in muscle with supplementation, and allow objective examination of a number of possible influences affecting the rate constants of synthesis and decay.

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References

  1. 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 106:837–842

    Article  PubMed  CAS  Google Scholar 

  2. Baguet A, Bourgois J, Vanhee L, Achten E, Derave W (2010) Important role of muscle carnosine in rowing performance. J Appl Physiol 109:1096–1101

    Article  PubMed  Google Scholar 

  3. Baguet A, Everaert I, De Naeyer H, Reyngoudt H, Stegen S, Beeckman S, Achten E, Vanhee L, Volkaert A, Petrovic M, Taes Y, Derave W (2011) Effects of sprint training combined with vegetarian or mixed diet on muscle carnosine content and buffering capacity. Eur J Appl Physiol 111:2571–2580

    Article  PubMed  CAS  Google Scholar 

  4. Bergström J (1962) Muscle electrolytes in man. Determined by neutron activation analysis on needle biopsy specimens. A study on normal subjects, kidney patients, and patients with chronic diarrhoea. Scandinavian Journal Clinical Laboratory Investigation. Supplement: 68

  5. Blancquaert L, Everaert I, Missinne M, Baguet A, Stegen S, Volkaert A, Petrovic M, Vervaet C, Achten E, Maeyer DE, Henauw M, Derave W (2017) Effects of histidine and β-alanine supplementation on human muscle carnosine storage. Med Sci Sports Exerc 49:602–609

    Article  PubMed  CAS  Google Scholar 

  6. Blancquaert L, Baguet A, Bex T, Volkaert A, Everaert I, Delanghe J, Petrovic M, Vervaet C, De Henauw S, Constantin-Teodosiu D, Greenhaff P, Derave W (2018) Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial. Br J Nutr 119:759–770

    Article  PubMed  CAS  Google Scholar 

  7. Boldyrev AA, Aldini G, Derave W (2013) Physiology and pathophysiology of carnosine. Physiol Rev 93:1803–1845

    Article  PubMed  CAS  Google Scholar 

  8. Chung W, Baguet A, Bex T, Bishop DJ, Derave W (2014) Doubling of muscle carnosine concentration does not improve laboratory 1-hr cycling time-trial performance. Int J Sport Nutr Exerc Metab 24:315–324

    Article  PubMed  CAS  Google Scholar 

  9. Church DD, Hoffman JR, Varanoske AN, Wang R, Baker KM, La Monica MB, Beyer KS, Dodd SJ, Oliveira LP, Harris RC, Fukuda DH, Stout JR (2017) Comparison of two β-alanine dosing protocols on muscle carnosine elevations. J Am Coll Nutr 36:608–616

    Article  PubMed  CAS  Google Scholar 

  10. Ducker KJ, Dawson B, Wallman KE (2013) Effect of beta-alanine supplementation on 2000 m Rowing ergometer performance. Int J Sport Nutr Exerc Metab 23:336–343

    Article  PubMed  CAS  Google Scholar 

  11. Dunnett M, Harris RC, Dunnett CE, Harris PA (2002) Plasma carnosine concentration: diurnal variation and effects of age, exercise and muscle damage. Equine Vet J Suppl 34:283–287

    Article  Google Scholar 

  12. Harris RC, Dunnett M, Snow DH (1991) Muscle carnosine content is unchanged during maximal intermittant exercise. Equine Exerc Physiol 3:257–261

    Google Scholar 

  13. Harris RC, Tallon MJ, Dunnett M, Boobis L, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, Wise JA (2006) The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 30:279–289

    Article  PubMed  CAS  Google Scholar 

  14. Harris RC, Jones G, Hill CH, Kendrick IP, Boobis L, Kim CK, Kim HJ, Dang VH, Edge J, Wise JA (2007) The carnosine content of V Lateralis in vegetarians and omnivores. FASEB J 21(769):20

    Google Scholar 

  15. Harris RC, Jones GA, Kim HJ, Kim CK, Price KA, Wise JA (2009) Changes in muscle carnosine of subjects with 4 weeks supplementation with a controlled release formulation of beta-alanine (CarnosynTM), and for 6 weeks post. FASEB J 23(599):4

    Google Scholar 

  16. Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, Wise JA (2007) Influence of ß-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 32:225–233

    Article  PubMed  CAS  Google Scholar 

  17. Hobson RM, Harris RC, Martin D, Smith P, Macklin B, Gualano B, Sale C (2013) Effect of β-alanine, with & without sodium bicarbonate, on 2000 m rowing performance. Int J Sport Nutr Exerc Metab 23:480–487

    Article  PubMed  CAS  Google Scholar 

  18. Kendrick IP, Kim HJ, Harris RC, Kim CK, Dang VH, Bui TT, Wise JA (2009) The effect of 4 weeks ß-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres. Eur J Appl Physiol 106:131–138

    Article  PubMed  CAS  Google Scholar 

  19. Saunders B, De Salles Painelli V, De Oliveira LF, Da Eira Silva V, Da Silva RP, Riani L, Franchi M, Gonçalves LS, Harris RC, Roschel H, Artioli GG, Sale C, Gualano B (2017) Med Sci Sports Exerc 49:896–906

    Article  PubMed  CAS  Google Scholar 

  20. Stellingwerff T, Anwander H, Egger A, Buehler T, Kreis R, Decombaz J, Boesch C (2012a) Effect of two β-alanine dosing protocols on muscle carnosine synthesis and washout. Amino Acids 42:2461–2472

    Article  PubMed  CAS  Google Scholar 

  21. Stellingwerff T, Decombaz J, Harris RC, Boesch C (2012b) Optimizing human in vivo dosing and delivery of β-alanine supplements for muscle carnosine synthesis. Amino Acids 43:57–65

    Article  PubMed  CAS  Google Scholar 

  22. Varanoske AN, Hoffman JR, Church DD, Coker NA, Baker KM, Dodd SJ, Roger C, Harris RC, Oliveira LP, Dawson VL, Wang R, Fukuda DH, Jeffrey R, Stout JR (2018) Comparison of sustained-release and rapid-release β-alanine formulations on changes in skeletal muscle carnosine content and isokinetic performance. Amino Acids (this issue)

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Correspondence to Roger Charles Harris.

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Conflict of interest

Since retiring from academic life in 2009, R Harris has been engaged as a consultant by a company with commercial interests in β-alanine.

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This article does not contain any studies (not previously published) with human participants performed by any of the authors.

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Handling Editor: S. P. Baba.

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Spelnikov, D., Harris, R.C. A kinetic model of carnosine synthesis in human skeletal muscle. Amino Acids 51, 115–121 (2019). https://doi.org/10.1007/s00726-018-2646-z

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Keywords

  • Supplementation
  • β-Alanine
  • Carnosine
  • Muscle
  • Mathematical model