Skip to main content

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

Amino Acids volume 43, pages 57–65 (2012)Cite this 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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  • Abe H (2000) Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Mosc) 65(7):757–765

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  Google Scholar 

  • 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

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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):617–623

    Article  CAS  Google Scholar 

  • Begum G, Cunliffe A, Leveritt M (2005) Physiological role of carnosine in contracting muscle. Int J Sport Nutr Exerc Metab 15(5):493–514

    PubMed  CAS  Google Scholar 

  • Bergstrom J, Furst P, Noree LO, Vinnars E (1974) Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol 36(6):693–697

    PubMed  CAS  Google Scholar 

  • Boldyrev AA, Severin SE (1990) The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance. Adv Enzyme Regul 30:175–194

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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

  • 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

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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 acceptance

  • 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):1736–1743

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  Google Scholar 

  • 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):10–20

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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 30:499–504

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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):190–196

    PubMed  Article  CAS  Google Scholar 

  • Fritzson P (1957) The catabolism of C14-labeled uracil, dihydrouracil, and beta-ureidopropionic acid in rat liver slices. J Biol Chem 226(1):223–228

    PubMed  CAS  Google Scholar 

  • 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 439:411–422

    PubMed  CAS  Google Scholar 

  • 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

  • Gulewitsch W, Amiradzibi S (1900) Uber das carnosine, eine neue organische Base des Fleischextraktes. Ber Dtsch Chem Ges 33:1902–1904

    Article  CAS  Google Scholar 

  • 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

  • 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):249–251

    PubMed  Article  CAS  Google Scholar 

  • 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):367–374

    CAS  Google Scholar 

  • Harris RC, Dunnett M, Greenhaff PL (1998) Carnosine and taurine contents in individual fibres of human vastus lateralis muscle. J Sports Sci 16:639–643

    Article  Google Scholar 

  • 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):279–289

    PubMed  Article  CAS  Google Scholar 

  • 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

  • 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):225–233

    PubMed  Article  CAS  Google Scholar 

  • Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL (1996) Muscle creatine loading in men. J Appl Physiol 81(1):232–237

    PubMed  CAS  Google Scholar 

  • 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):547–554

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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):3175–3179

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • Parkhouse WS, McKenzie DC, Hochachka PW, Ovalle WK (1985) Buffering capacity of deproteinized human vastus lateralis muscle. J Appl Physiol 58(1):14–17

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Article  Google Scholar 

  • Quinn PJ, Boldyrev AA, Formazuyk VE (1992) Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Med 13(5):379–444

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  Google Scholar 

  • 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

  • Tarnopolsky MA (2011) Creatine as a therapeutic strategy for myopathies. Amino Acids 40(5):1397–1407. doi:10.1007/s00726-011-0876-4

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

  • 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

    PubMed  Article  CAS  Google Scholar 

Download references

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Nestlé Research Center, Lausanne, Switzerland

    Trent Stellingwerff & Jacques Decombaz

  2. Canadian Sports Center: Pacific, Pacific Institute for Sport Excellence, 4371 Interurban Road, Victoria, BC, V9E 2C5, Canada

    Trent Stellingwerff

  3. Junipa Ltd, Newmarket, UK

    Roger C. Harris

  4. University of Bern, Bern, Switzerland

    Chris Boesch

Authors
  1. Trent Stellingwerff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacques Decombaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roger C. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chris Boesch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Trent Stellingwerff.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Stellingwerff, T., Decombaz, J., Harris, R.C. et al. Optimizing human in vivo dosing and delivery of β-alanine supplements for muscle carnosine synthesis. Amino Acids 43, 57–65 (2012). https://doi.org/10.1007/s00726-012-1245-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-012-1245-7

Keywords

  • β-Alanine
  • Carnosine
  • Muscle
  • Synthesis
  • Washout
  • Dose–response