Advertisement

Amino Acids

, Volume 43, Issue 1, pp 57–65 | Cite as

Optimizing human in vivo dosing and delivery of β-alanine supplements for muscle carnosine synthesis

  • Trent StellingwerffEmail author
  • Jacques Decombaz
  • Roger C. Harris
  • Chris Boesch
Review Article

Abstract

Interest into the effects of carnosine on cellular metabolism is rapidly expanding. The first study to demonstrate in humans that chronic β-alanine (BA) supplementation (~3–6 g BA/day for ~4 weeks) can result in significantly augmented muscle carnosine concentrations (>50%) was only recently published. BA supplementation is potentially poised for application beyond the niche exercise and performance-enhancement field and into other more clinical populations. When examining all BA supplementation studies that directly measure muscle carnosine (n = 8), there is a significant linear correlation between total grams of BA consumed (of daily intake ranges of 1.6–6.4 g BA/day) versus both the relative and absolute increases in muscle carnosine. Supporting this, a recent dose–response study demonstrated a large linear dependency (R 2 = 0.921) based on the total grams of BA consumed over 8 weeks. The pre-supplementation baseline carnosine or individual subjects’ body weight (from 65 to 90 kg) does not appear to impact on subsequent carnosine synthesis from BA consumption. Once muscle carnosine is augmented, the washout is very slow (~2%/week). Recently, a slow-release BA tablet supplement has been developed showing a smaller peak plasma BA concentration and delayed time to peak, with no difference in the area under the curve compared to pure BA in solution. Further, this slow-release profile resulted in a reduced urinary BA loss and improved retention, while at the same time, eliciting minimal paraesthesia symptoms. However, our complete understanding of optimizing in vivo delivery and dosing of BA is still in its infancy. Thus, this review will clarify our current knowledge of BA supplementation to augment muscle carnosine as well as highlight future research questions on the regulatory points of control for muscle carnosine synthesis.

Keywords

β-Alanine Carnosine Muscle Synthesis Washout Dose–response 

Notes

Conflict of interest

All authors declare that they have no conflict of interest.

References

  1. Abe H (2000) Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Mosc) 65(7):757–765Google Scholar
  2. Artioli GG, Gualano B, Smith A, Stout J, Lancha AH Jr (2010) Role of beta-alanine supplementation on muscle carnosine and exercise performance. Med Sci Sports Exerc 42(6):1162–1173. doi: 10.1249/MSS.0b013e3181c74e38 PubMedGoogle 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(3):837–842. doi: 10.1152/japplphysiol.91357.2008 PubMedCrossRefGoogle Scholar
  4. Baguet A, Bourgois J, Vanhee L, Achten E, Derave W (2010) Important role of muscle carnosine in rowing performance. J Appl Physiol 109(4):1096–1101. doi: 10.1152/japplphysiol.00141.2010 PubMedCrossRefGoogle Scholar
  5. Baguet A, Everaert I, Achten E, Thomis M, Derave W (2011a) The influence of sex, age and heritability on human skeletal muscle carnosine content. Amino Acids. doi: 10.1007/s00726-011-1197-3
  6. 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 (2011b) Effects of sprint training combined with vegetarian or mixed diet on muscle carnosine content and buffering capacity. Eur J Appl Physiol 111(10):2571–2580. doi: 10.1007/s00421-011-1877-4 PubMedCrossRefGoogle Scholar
  7. Baguet A, Everaert I, Hespel P, Petrovic M, Achten E, Derave W (2011c) A new method for non-invasive estimation of human muscle fiber type composition. PLoS ONE 6(7):e21956. doi: 10.1371/journal.pone.0021956 PubMedCrossRefGoogle Scholar
  8. Bakardjiev A, Bauer K (1994) Transport of beta-alanine and biosynthesis of carnosine by skeletal muscle cells in primary culture. Eur J Biochem/FEBS 225(2):617–623CrossRefGoogle Scholar
  9. Begum G, Cunliffe A, Leveritt M (2005) Physiological role of carnosine in contracting muscle. Int J Sport Nutr Exerc Metab 15(5):493–514PubMedGoogle Scholar
  10. Bergstrom J, Furst P, Noree LO, Vinnars E (1974) Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol 36(6):693–697PubMedGoogle Scholar
  11. Boldyrev AA, Severin SE (1990) The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance. Adv Enzyme Regul 30:175–194PubMedCrossRefGoogle Scholar
  12. Crozier RA, Ajit SK, Kaftan EJ, Pausch MH (2007) MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability. J Neurosci 27(16):4492–4496. doi: 10.1523/JNEUROSCI.4932-06.2007 PubMedCrossRefGoogle Scholar
  13. Decombaz J, Beaumont B, Vuichoud J, Bouisset F, Stellingwerff T (2011) Effect of slow-release b-alanine tablets on absorption kinetics and paresthesia. Amino Acids. doi: 10.1007/s00726-011-1169-7
  14. del Favero S, Roschel H, Solis MY, Hayashi AP, Artioli GG, Otaduy MC, Benatti FB, Harris RC, Wise JA, Leite CC, Pereira RM, de Sá-Pinto AL, Lancha-Junior AH, Gualano B (2011) Beta-alanine (Carnosyn™) supplementation in elderly subjects (60-80 years): effects on muscle carnosine content and physical capacity. Amino Acids. doi: 10.1007/s00726-011-1190-x
  15. Deldicque L, Decombaz J, Foncea HZ, Vuichoud J, Poortmans JR, Francaux M (2008) Kinetics of creatine ingested as a food ingredient. Eur J Appl Physiol 102(2):133–143. doi: 10.1007/s00421-007-0558-9 PubMedCrossRefGoogle Scholar
  16. Derave W, Sale C (2011) Carnosine in Exercise and Disease: an introduction to the International Congress held at the University of Ghent, Belgium, July 2011. Amino Acids: Ghent Carnosine Conference Special Edition update post acceptanceGoogle Scholar
  17. Derave W, Ozdemir MS, Harris RC, Pottier A, Reyngoudt H, Koppo K, Wise JA, Achten E (2007) Beta-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. J Appl Physiol 103(5):1736–1743PubMedCrossRefGoogle Scholar
  18. Derave W, Everaert I, Beeckman S, Baguet A (2010) Muscle carnosine metabolism and beta-alanine supplementation in relation to exercise and training. Sports Med 40(3):247–263. doi: 10.2165/11530310-000000000-00000 PubMedCrossRefGoogle Scholar
  19. Dieck ST, Heuer H, Ehrchen J, Otto C, Bauer K (1999) The peptide transporter PepT2 is expressed in rat brain and mediates the accumulation of the fluorescent dipeptide derivative beta-Ala-Lys-Nepsilon-AMCA in astrocytes. Glia 25(1):10–20PubMedCrossRefGoogle Scholar
  20. Drozak J, Veiga-da-Cunha M, Vertommen D, Stroobant V, Van Schaftingen E (2010) Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J Biol Chem 285(13):9346–9356. doi: 10.1074/jbc.M109.095505 PubMedCrossRefGoogle Scholar
  21. Dunnett M, Harris RC (1999) Influence of oral beta-alanine and l-histidine supplementation on the carnosine content of the gluteus medius. Equine Vet J Suppl 30:499–504PubMedGoogle Scholar
  22. Everaert I, Mooyaart A, Baguet A, Zutinic A, Baelde H, Achten E, Taes Y, De Heer E, Derave W (2011) Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans. Amino Acids 40(4):1221–1229. doi: 10.1007/s00726-010-0749-2 PubMedCrossRefGoogle Scholar
  23. Flancbaum L, Fitzpatrick JC, Brotman DN, Marcoux AM, Kasziba E, Fisher H (1990) The presence and significance of carnosine in histamine-containing tissues of several mammalian species. Agents Actions 31(3–4):190–196PubMedCrossRefGoogle Scholar
  24. Fritzson P (1957) The catabolism of C14-labeled uracil, dihydrouracil, and beta-ureidopropionic acid in rat liver slices. J Biol Chem 226(1):223–228PubMedGoogle Scholar
  25. Gardner ML, Illingworth KM, Kelleher J, Wood D (1991) Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose. J Physiol 439:411–422PubMedGoogle Scholar
  26. Gualano B, Everaert I, Stegen S, Artioli GG, Taes Y, Roschel H, Achten E, Otaduy MC, Lancha-Junior AH, Roger Harris RC, Derave W (2011) Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients. Amino Acids. doi: 10.1007/s00726-011-1165-y
  27. Gulewitsch W, Amiradzibi S (1900) Uber das carnosine, eine neue organische Base des Fleischextraktes. Ber Dtsch Chem Ges 33:1902–1904CrossRefGoogle Scholar
  28. Harris RC (2010) Simultaneous changes in muscle carnosine and taurine during and following supplementation with β-Alanine. In: American College of Sports Medicine, Baltimore, Maryland, USA, vol 5, p 107. doi: 10.1249/01.MSS.0000385977.18201.74
  29. 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 A 97(2):249–251PubMedCrossRefGoogle Scholar
  30. Harris RC, Soderlund K, Hultman E (1992) Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 83(3):367–374Google Scholar
  31. 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
  32. 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(3):279–289PubMedCrossRefGoogle Scholar
  33. Harris RC, Wise JA, Price KA, Kim HJ, Kim CK, Sale C (2012) Determinants of muscle carnosine content. Amino Acids. doi: 10.1007/s00726-012-1233-y
  34. Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, Wise JA (2007) Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 32(2):225–233PubMedCrossRefGoogle Scholar
  35. Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL (1996) Muscle creatine loading in men. J Appl Physiol 81(1):232–237PubMedGoogle Scholar
  36. 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(4):547–554PubMedCrossRefGoogle Scholar
  37. Kendrick IP, Kim HJ, Harris RC, Kim CK, Dang VH, Lam TQ, Bui TT, Wise JA (2009) The effect of 4 weeks beta-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres. Eur J Appl Physiol 106(1):131–138. doi: 10.1007/s00421-009-0998-5 PubMedCrossRefGoogle Scholar
  38. Kohen R, Yamamoto Y, Cundy KC, Ames BN (1988) Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc Natl Acad Sci USA 85(9):3175–3179PubMedCrossRefGoogle Scholar
  39. Lu H, Klaassen C (2006) Tissue distribution and thyroid hormone regulation of Pept1 and Pept2 mRNA in rodents. Peptides 27(4):850–857. doi: 10.1016/j.peptides.2005.08.012 PubMedCrossRefGoogle Scholar
  40. Parkhouse WS, McKenzie DC, Hochachka PW, Ovalle WK (1985) Buffering capacity of deproteinized human vastus lateralis muscle. J Appl Physiol 58(1):14–17PubMedGoogle Scholar
  41. Phillips SM, Van Loon LJ (2011) Dietary protein for athletes: from requirements to optimum adaptation. J Sports Sci 29(Suppl 1):S29–S38. doi: 10.1080/02640414.2011.619204 PubMedCrossRefGoogle Scholar
  42. Quinn PJ, Boldyrev AA, Formazuyk VE (1992) Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Med 13(5):379–444PubMedCrossRefGoogle Scholar
  43. Sale C, Saunders B, Harris RC (2010) Effect of beta-alanine supplementation on muscle carnosine concentrations and exercise performance. Amino Acids 39(2):321–333. doi: 10.1007/s00726-009-0443-4 PubMedCrossRefGoogle Scholar
  44. Sauerhofer S, Yuan G, Braun GS, Deinzer M, Neumaier M, Gretz N, Floege J, Kriz W, van der Woude F, Moeller MJ (2007) l-carnosine, a substrate of carnosinase-1, influences glucose metabolism. Diabetes 56(10):2425–2432. doi: 10.2337/db07-0177 PubMedCrossRefGoogle Scholar
  45. Stellingwerff T, Anwander H, Egger A, Buehler T, Kreis R, Decombaz J, Boesch C (2011) Effect of two beta-alanine dosing protocols on muscle carnosine synthesis and washout. Amino Acids. doi: 10.1007/s00726-011-1054-4
  46. Tarnopolsky MA (2011) Creatine as a therapeutic strategy for myopathies. Amino Acids 40(5):1397–1407. doi: 10.1007/s00726-011-0876-4 PubMedCrossRefGoogle Scholar
  47. Teufel M, Saudek V, Ledig JP, Bernhardt A, Boularand S, Carreau A, Cairns NJ, Carter C, Cowley DJ, Duverger D, Ganzhorn AJ, Guenet C, Heintzelmann B, Laucher V, Sauvage C, Smirnova T (2003) Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem 278(8):6521–6531. doi: 10.1074/jbc.M209764200 PubMedCrossRefGoogle Scholar
  48. Thwaites DT, Anderson CM (2007) H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp Physiol 92(4):603–619. doi: 10.1113/expphysiol.2005.029959 PubMedCrossRefGoogle Scholar
  49. Tiedje KE, Stevens K, Barnes S, Weaver DF (2010) Beta-alanine as a small molecule neurotransmitter. Neurochem Int 57(3):177–188. doi: 10.1016/j.neuint.2010.06.001 PubMedCrossRefGoogle Scholar
  50. Tomi M, Tajima A, Tachikawa M, Hosoya K (2008) Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells. Biochim Biophys Acta 1778(10):2138–2142. doi: 10.1016/j.bbamem.2008.04.012 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Trent Stellingwerff
    • 1
    • 2
    Email author
  • Jacques Decombaz
    • 1
  • Roger C. Harris
    • 3
  • Chris Boesch
    • 4
  1. 1.Nestlé Research CenterLausanneSwitzerland
  2. 2.Canadian Sports Center: PacificPacific Institute for Sport ExcellenceVictoriaCanada
  3. 3.Junipa LtdNewmarketUK
  4. 4.University of BernBernSwitzerland

Personalised recommendations