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Overview of Creatine Metabolism

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Essentials of Creatine in Sports and Health

Abstract

Creatine (Cr) was first discovered as an organic constituent of meat some time in the early 1800s. Later in the 1800s, Cr was consistently detected in muscle tissue extracted from various mammals. It was noted that foxes killed in a hunt immediately after running, contained significantly more Cr than normal, providing the first indication that muscular contraction results in an accumulation of Cr. Around the same time, a substance called creatinine (Crn) was detected in the urine and later determined to be a breakdown product of Cr. Phosphocreatine (PCr) was first isolated from muscle tissue in 1927 and found to play an important role in the transfer of energy. Around the same time, two researchers who consumed large quantities of Cr noted that a percentage of the Cr ingested could not be accounted for by excretion in the urine (1). This study was one of the first to indicate that “Cr loading” in muscle is possible when large amounts of Cr are consumed. A great deal of research has been done since this early work to further define the importance of Cr in humans, and the impact of Cr supplementation. In this chapter, the basic metabolism and function of Cr in humans will be overviewed. To what extent and what factors influence blood- and muscle-Cr levels in response to Cr supplementation will be discussed. Also some of the proposed mechanisms that account for the ergogenic effects from Cr usage observed in many studies will be explored.

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References

  1. Chanutin A, Guy LP. The fate of creatine when administered to man. J Biol Chem 1926; 67:29–41.

    CAS  Google Scholar 

  2. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000; 80:1107–1213.

    PubMed  CAS  Google Scholar 

  3. Walker JB. Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 1979; 50:177–242.

    Article  PubMed  CAS  Google Scholar 

  4. Hoberman HD, Sims EAH, Engstrom WW. The effect of methyltestosterone on the rate of synthesis of creatine. J Biol Chem 1948; 173:111–116.

    PubMed  CAS  Google Scholar 

  5. Verhoeven NM, Salomons GS, Jakobs C. Laboratory diagnosis of defects of creatine biosynthesis and transport. Clin Chim Acta 2005; 361:1–9.

    Article  PubMed  CAS  Google Scholar 

  6. Fatterpaker P, Marfatia U, Sreenivasan A. Influence of folic acid and vitamin B12 on formation of creatine in vitro and in vivo. Nature 1951; 167:1067–1068.

    Article  PubMed  CAS  Google Scholar 

  7. Stekol JA, Weiss S, Smith P, Weiss K. The synthesis of choline and creatine in rats under various dietary conditions. J Biol Chem 1953; 201:299–316.

    PubMed  CAS  Google Scholar 

  8. Hoogwerf BJ, Laine DC, Greene E. Urine C-peptide and creatinine (Jaffe method) excretion in healthy young adults on varied diets: sustained effects of varied carbohydrate, protein, and meat content. Am J Clin Nutr 1986; 43:350–360.

    PubMed  CAS  Google Scholar 

  9. Harris RC, Nevill M, Harris DB, Fallowfield JL, Bogdanis GC, Wise JA. Absorption of creatine supplied as a drink, in meat or in solid form. J Sports Sci 2002; 20:147–151.

    Article  PubMed  Google Scholar 

  10. Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L, Hespel P. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997; 83:2055–2063.

    PubMed  CAS  Google Scholar 

  11. Rossiter HB, Cannell ER, Jakeman PM. The effect of oral creatine supplementation on the 1000-m performance of competitive rowers. J Sports Sci 1996; 14:175–179.

    Article  PubMed  CAS  Google Scholar 

  12. Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 1992; 83:367–374.

    CAS  Google Scholar 

  13. Guerrero-Ontiveros ML, Wallimann T. Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle. Mol Cell Biochem 1998; 184:427–437.

    Article  PubMed  CAS  Google Scholar 

  14. Loike JD, Zalutsky DL, Kaback E, Miranda AF, Silverstein SC. Extracellular creatine regulates creatine transport in rat and human muscle cells. Proc Natl Acad Sci USA 1988; 85:807–811.

    Article  PubMed  CAS  Google Scholar 

  15. Snow RJ, Murphy RM. Creatine and the creatine transporter: a review. Mol Cell Biochem 2001; 224:169–181.

    Article  PubMed  CAS  Google Scholar 

  16. Balsom PD, Soderlund K, Sjodin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand 1995; 154:303–310.

    Article  PubMed  CAS  Google Scholar 

  17. Casey A, Constantin-Teodosiu D, Howell S, Hultman E, Greenhaff PL. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 1996; 271:E31–E37.

    PubMed  CAS  Google Scholar 

  18. Meyer RA, Brown TR, Kushmerick MJ. Phosphorus nuclear magnetic resonance of fast-and slow-twitch muscle. Am J Physiol 1985; 248:C279–C287.

    PubMed  CAS  Google Scholar 

  19. Kushmerick MJ, Moerland TS, Wiseman RW. Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. Proc Natl Acad Sci USA 1992; 89: 7521–7525.

    Article  PubMed  CAS  Google Scholar 

  20. Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff PL. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am J Physiol 1996; 271:E821–E826.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Maughan RJ. Creatine supplementation and exercise performance. Int J Sport Nutr 1995; 5:94–101.

    PubMed  CAS  Google Scholar 

  23. Lukaszuk JM, Robertson RJ, Arch JE, et al. Effect of creatine supplementation and a lacto-ovo-vegetarian diet on muscle creatine concentration. Int J Sport Nutr Exerc Metab 2002; 12:336–348.

    PubMed  CAS  Google Scholar 

  24. Snow RJ, Murphy RM. Factors influencing creatine loading into human skeletal muscle. Exerc Sport Sci Rev 2003; 31:154–158.

    Article  PubMed  Google Scholar 

  25. Virgili F, Maiani G, Zahoor ZH, Ciarapica D, Raguzzini A, Ferro-Luzzi A. Relationship between fat-free mass and urinary excretion of creatinine and 3-methylhistidine in adult humans. J Appl Physiol 1994; 76:1946–1950.

    Article  PubMed  CAS  Google Scholar 

  26. Bogdanis GC, Nevill ME, Boobis LH, Lakomy HK. Contribution of phosphocreatine and aerobic metabolism to energy supply during repeated sprint exercise. J Appl Physiol 1996; 80:876–884.

    PubMed  CAS  Google Scholar 

  27. Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994; 266:E725–E730.

    PubMed  CAS  Google Scholar 

  28. van Leemputte M, Vandenberghe K, Hespel P. Shortening of muscle relaxation time after creatine loading. J Appl Physiol 1999; 86:840–844.

    PubMed  Google Scholar 

  29. McArdle WD, Frank I. Katch, Victor L. Katch. Sports and Exercise Nutrition. 2nd ed. Lippincott, Williams, and Wilkins, Baltimore, 2005.

    Google Scholar 

  30. Bessman SP, Geiger PJ. Transport of energy in muscle: the phosphorylcreatine shuttle. Science 1981; 211:448–452.

    Article  PubMed  CAS  Google Scholar 

  31. Ogut O, Brozovich FV. Creatine phosphate consumption and the actomyosin crossbridge cycle in cardiac muscles. Circ Res 2003; 93:54–60.

    Article  PubMed  CAS  Google Scholar 

  32. Meyer RA, Sweeney HL, Kushmerick MJ. A simple analysis of the “phosphocreatine shuttle”. Am J Physiol 1984; 246:C365–C377.

    PubMed  CAS  Google Scholar 

  33. Thompson CH, Kemp GJ, Sanderson AL, et al. Effect of creatine on aerobic and anaerobic metabolism in skeletal muscle in swimmers. Br J Sports Med 1996; 30:222–225.

    Article  PubMed  CAS  Google Scholar 

  34. Volek JS, Duncan ND, Mazzetti SA, et al. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 1999; 31:1147–1156.

    Article  PubMed  CAS  Google Scholar 

  35. Green AL, Simpson EJ, Littlewood JJ, Macdonald IA, Greenhaff PL. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand 1996; 158:195–202.

    Article  PubMed  CAS  Google Scholar 

  36. Steenge GR, Simpson EJ, Greenhaff PL. Protein-and carbohydrate-induced augmentation of whole body creatine retention in humans. J Appl Physiol 2000; 89:1165–1171.

    PubMed  CAS  Google Scholar 

  37. Preen D, Dawson B, Goodman C, Beilby J, Ching S. Creatine supplementation: a comparison of loading and maintenance protocols on creatine uptake by human skeletal muscle. Int J Sport Nutr Exerc Metab 2003; 13:97–111.

    PubMed  CAS  Google Scholar 

  38. Robinson TM, Sewell DA, Hultman E, Greenhaff PL. Role of submaximal exercise in promoting creatine and glycogen accumulation in human skeletal muscle. J Appl Physiol 1999; 87:598–604.

    PubMed  CAS  Google Scholar 

  39. Zange J, Kornblum C, Muller K, et al. Creatine supplementation results in elevated phosphocreatine/adenosine triphosphate (ATP) ratios in the calf muscle of athletes but not in patients with myopathies. Ann Neurol 2002; 52:126, author reply 126, 127.

    Article  PubMed  CAS  Google Scholar 

  40. Murphy RM, Tunstall RJ, Mehan KA, et al. Human skeletal muscle creatine transporter mRNA and protein expression in healthy, young males and females. Mol Cell Biochem 2003; 244:151–157.

    Article  PubMed  CAS  Google Scholar 

  41. Parise G, Mihic S, MacLennan D, Yarasheski KE, Tarnopolsky MA. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol 2001; 91:1041–1047.

    PubMed  CAS  Google Scholar 

  42. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev 2001; 53:161–176.

    PubMed  CAS  Google Scholar 

  43. Rawson ES, Gunn B, Clarkson PM. The effects of creatine supplementation on exercise-induced muscle damage. J Strength Cond Res 2001; 15:178–184.

    Article  PubMed  CAS  Google Scholar 

  44. Francaux M, Poortmans JR. Effects of training and creatine supplement on muscle strength and body mass. Eur J Appl Physiol Occup Physiol 1999; 80:165–168.

    Article  PubMed  CAS  Google Scholar 

  45. Low SY, Rennie MJ, Taylor PM. Modulation of glycogen synthesis in rat skeletal muscle by changes in cell volume. J Physiol 1996; 495(Pt 2):299–303.

    PubMed  CAS  Google Scholar 

  46. Derave W, Eijnde BO, Verbessern P, et al. Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans. J Appl Physiol 2003; 94:1910–1916.

    PubMed  CAS  Google Scholar 

  47. Nelson AG, Arnall DA, Kokkonen J, Day R, Evans J. Muscle glycogen supercompensation is enhanced by prior creatine supplementation. Med Sci Sports Exerc 2001; 33:1096–1100.

    PubMed  CAS  Google Scholar 

  48. Op’t Eijnde B, Urso B, Richter EA, Greenhaff PL, Hespel P. Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization. Diabetes 2001; 50:18–23.

    Article  CAS  Google Scholar 

  49. van Loon LJ, Murphy R, Oosterlaar AM, et al. Creatine supplementation increases glycogen storage but not GLUT-4 expression in human skeletal muscle. Clin Sci (Lond) 2004; 106:99–106.

    Article  Google Scholar 

  50. Maughan RJ, Poole DC. The effects of a glycogen-loading regimen on the capacity to perform anaerobic exercise. Eur J Appl Physiol Occup Physiol 1981; 46:211–219.

    Article  PubMed  CAS  Google Scholar 

  51. Pizza FX, Flynn MG, Duscha BD, Holden J, Kubitz ER. A carbohydrate loading regimen improves high intensity, short duration exercise performance. Int J Sport Nutr 1995; 5:110–116.

    PubMed  CAS  Google Scholar 

  52. Haff G, Stone MH, Warren BJ, et al The effect of carbohydrate supplementation on multiple sessions and bouts of resistance exercise. J Strength Cond Res 1999; 13:111.

    Article  Google Scholar 

  53. Haff GG, Koch AJ, Potteiger JA, et al. Carbohydrate supplementation attenuates muscle glycogen loss during acute bouts of resistance exercise. Int J Sport Nutr Exerc Metab 2000; 10:326–339.

    PubMed  CAS  Google Scholar 

  54. Kreider RB, Ferreira M, Wilson M, et al. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 1998; 30:73–82.

    PubMed  CAS  Google Scholar 

  55. Hespel P, Op’t Eijnde B, Van Leemputte M, et al. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol 2001; 536:625–633.

    Article  PubMed  CAS  Google Scholar 

  56. Willoughby DS, Rosene J. Effects of oral creatine and resistance training on myosin heavy chain expression. Med Sci Sports Exerc 2001; 33:1674–1681.

    Article  PubMed  CAS  Google Scholar 

  57. Willoughby DS, Rosene JM. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc 2003; 35:923–929.

    Article  PubMed  CAS  Google Scholar 

  58. Buckingham M, Bajard L, Chang T, et al. The formation of skeletal muscle: from somite to limb. J Anat 2003; 202:59–68.

    Article  PubMed  Google Scholar 

  59. Rosenblatt JD, Parry DJ. Adaptation of rat extensor digitorum longus muscle to gamma irradiation and overload. Pflugers Arch 1993; 423:255–264.

    Article  PubMed  CAS  Google Scholar 

  60. Barton-Davis ER, Shoturma DI, Sweeney HL. Contribution of satellite cells to IGFI induced hypertrophy of skeletal muscle. Acta Physiol Scand 1999; 167:301–305.

    Article  PubMed  CAS  Google Scholar 

  61. Dangott B, Schultz E, Mozdziak PE. Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med 2000; 21:13–16.

    Article  PubMed  CAS  Google Scholar 

  62. Vierck JL, Icenoggle DL, Bucci L, Dodson MV. The effects of ergogenic compounds on myogenic satellite cells. Med Sci Sports Exerc 2003; 35:769–776.

    Article  PubMed  CAS  Google Scholar 

  63. Olsen S, Aagaard P, Kadi F, et al. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol 2006; 573:525–534.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Kinesiology, University of Connecticut, Storrs, Connecticut

    Jeff S. Volek PhD, RD, Kevin D. Ballard MS & Cassandra E. Forsythe MS

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  1. Jeff S. Volek PhD, RD
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  2. Kevin D. Ballard MS
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  3. Cassandra E. Forsythe MS
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Editors and Affiliations

  1. Department of Health and Sports Science, University of Oklahoma, Norman, Oklahoma

    Jeffrey R. Stout PhD

  2. International Society of Sports Nutrition, Deerfield Beach, Florida

    Jose Antonio PhD

  3. Division of Nutrition and Endocrinology, Miami Research Associates, Miami, Florida

    Douglas Kalman PhD, RD

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© 2008 Humana Press Inc., Totowa, NJ

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Volek, J.S., Ballard, K.D., Forsythe, C.E. (2008). Overview of Creatine Metabolism. In: Stout, J.R., Antonio, J., Kalman, D. (eds) Essentials of Creatine in Sports and Health. Humana Press. https://doi.org/10.1007/978-1-59745-573-2_1

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  • DOI: https://doi.org/10.1007/978-1-59745-573-2_1

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