Ergogenic Effects of Creatine in Sports and Rehabilitation

  • Peter Hespel
  • Wim Derave
Part of the Subcellular Biochemistry book series (SCBI, volume 46)


The daily oral ingestion of supplementary creatine monohydrate can substantially elevate the creatine content of human skeletal muscle. This chapter aims to summarize the current knowledge regarding the impact muscle creatine loading can have on exercise performance and rehabilitation. The major part of the elevation of muscle creatine content is already obtained after one week of supplementation, and the response can be further enhanced by a concomitant exercise or insulin stimulus. The elevated muscle creatine content moderately improves contractile performance in sports with repeated high-intensity exercise bouts. More chronic ergogenic effects of creatine are to be expected when combined with several weeks of training. A more pronounced muscle hypertrophy and a faster recovery from atrophy have been demonstrated in humans involved in resistance training. The mechanism behind this anabolic effect of creatine may relate to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling. An additional effect of creatine supplementation, mostly when combined with training, is enhanced muscle glycogen accumulation and glucose transporter (GLUT4) expression. Thus, creatine may also be beneficial in sport competition and training characterized by daily glycogen depletion, as well as provide therapeutic value in the insulin-resistant state


Resistance Training Extensor Digitorum Longus Creatine Supplementation Extensor Digitorum Longus Muscle Ergogenic Effect 
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  1. Baron, A.D., 1994, Hemodynamic actions of insulin. Am. J. Physiol. 267: E187–E202.PubMedGoogle Scholar
  2. Brannon, T.A., Adams, G.R., Conniff, C.L., and Baldwin, K.M., 1997, Effects of creatine loading and training on running performance and biochemical properties of rat skeletal muscle. Med. Sci. Sports Exerc. 29: 489–495.PubMedGoogle Scholar
  3. Brault, J.J., and Terjung, R.L., 2003, Creatine uptake and creatine transporter expression among rat skeletal muscle fiber types. Am. J. Physiol. Cell Physiol. 284: C1481–C1489.PubMedGoogle Scholar
  4. Casey, A., Constantin-Teodosiu, D., Howell, S., Hultman, E., and Greenhaff, P.L., 1996, Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am. J. Physiol. Endocrinol. Metab. 271: E31–E37.Google Scholar
  5. Ceddia, R.B., and Sweeney, G., 2004, Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells. J. Physiol. 555: 409–421.PubMedCrossRefGoogle Scholar
  6. Christie, D.L., 2007, Functional insights into the creatine transporter. Subcell. Biochem. 46: 99–118.PubMedGoogle Scholar
  7. Dangott, B., Schultz, E., and Mozdziak, P.E., 2000, Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int. J. Sports Med. 21: 13–16.PubMedCrossRefGoogle Scholar
  8. Deldicque, L., Louis, M., Theisen, D., Nielens, H., Dehoux, M., Thissen, J.P., Rennie, M.J., and Francaux, M., 2005, Increased IGF mRNA in human skeletal muscle after creatine supplementation. Med. Sci. Sports Exerc. 37: 731–736.PubMedCrossRefGoogle Scholar
  9. Derave, W., Eijnde, B.O., and Hespel, P., 2003a, Creatine supplementation in health and disease: what is the evidence for long-term efficacy? Mol. Cell. Biochem. 244: 49–55.CrossRefGoogle Scholar
  10. Derave, W., Eijnde, B.O., Verbessem, P., Ramaekers, M., Van Leemputte, M., Richter, E.A., and Hespel, P., 2003b, Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans. J. Appl. Physiol. 94: 1910–1916.Google Scholar
  11. Derave, W., Straumann, N., Olek, R.A., and Hespel, P., 2006, Electrolysis stimulates creatine transport and transporter cell surface expression in incubated mouse skeletal muscle: potential role of ROS. Am. J. Physiol. Endocrinol. Metab. 291: E1250–E1257.PubMedCrossRefGoogle Scholar
  12. Eijnde, B.O., Derave, W., Wojtaszewski, J.F., Richter, E.A., and Hespel, P., 2005, AMP kinase expression and activity in human skeletal muscle: effects of immobilization, retraining, and creatine supplementation. J. Appl. Physiol. 98: 1228–1233.PubMedCrossRefGoogle Scholar
  13. Eijnde, B.O., Lebacq, J., Ramaekers, M., and Hespel, P., 2004, Effect of muscle creatine content manipulation on contractile properties in mouse muscles. Muscle Nerve 29: 428–435.PubMedCrossRefGoogle Scholar
  14. Eijnde, B.O., Van Leemputte, M., Goris, M., Labarque, V., Taes, Y., Verbessem, P., Vanhees, L., Ramaekers, M., Vanden Eynde, B., Van Schuylenbergh, R., Dom, R., Richter, E.A., and Hespel, P., 2003, Effects of creatine supplementation and exercise training on fitness in males 55 to 75 years old. J. Appl. Physiol. 95: 818–828.PubMedGoogle Scholar
  15. Ferrante, R.J., Andreassen, O.A., Jenkins, B.G., Dedeoglu, A., Kuemmerle, S., Kubilus, J.K., Kaddurah-Daouk, R., Hersch, S.M., and Beal, M.F., 2000, Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J. Neurosci. 20: 4389–4397.PubMedGoogle Scholar
  16. Gaitanos, G.C., Williams, C., Boobis, L.H., and Brooks, S., 1993, Human muscle metabolism during intermittent maximal exercise. J. Appl. Physiol. 75: 712–719.PubMedGoogle Scholar
  17. Green, A.L., Hultman, E., MacDonald, I.A., Sewell, D.A., and Greenhaff, P.L., 1996a, Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am. J. Physiol. Endocrinol. Metab. 271: E821–E826.Google Scholar
  18. Green, A.L., Simpson, E.J., Littlewood, J.J., MacDonald, I.A., and Greenhaff, P.L., 1996b, Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol. Scand. 158: 195–202.CrossRefGoogle Scholar
  19. Greenhaff, P.L., Bodin, K., Soderlund, K., and Hultman, E., 1994, Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am. J. Physiol. 266: E725–E730.PubMedGoogle Scholar
  20. Greenhaff, P.L., Casey, A., Short, A.H., Harris, R., and Söderlund, K., 1993, Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise in man. Clin. Sci. 84: 565–571.PubMedGoogle Scholar
  21. Harris, R.C., Söderlund, K., and Hultman, E., 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin. Sci. 83: 367–374.PubMedGoogle Scholar
  22. Haugland, R.B., and Chang, D.T., 1975, Insulin effect on creatine transport in skeletal muscle. Proc. Soc. Exp. Biol. Med. 148: 1–4.PubMedGoogle Scholar
  23. Hespel, P., Op ’t Eijnde, B., Derave, W., and Richter, E.A., 2001a, Creatine supplementation: exploring the role of the creatine kinase/phosphocreatine system in human muscle. Can. J. Appl. Physiol. 26 (Suppl.): S79–S102.Google Scholar
  24. Hespel, P., Op ’t Eijnde, B., and Van Leemputte, M., 2002, Opposite actions of caffeine and creatine on muscle relaxation time in humans. J. Appl. Physiol. 92: 513–518.PubMedGoogle Scholar
  25. Hespel, P., Op ’t Eijnde, B., Van Leemputte, M., Urso, B., Greenhaff, P.L., Labarque, V., Dymarkowski, S., Van Hecke, P., and Richter, E.A., 2001b, Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters expression of muscle myogenic factors in humans. J. Physiol. (London) 536: 625–633.CrossRefGoogle Scholar
  26. Holloszy, J., and Narahara, H., 1967, Enhanced permeability to sugar associated with muscle contraction. J. Gen. Physiol. 50: 551–562.PubMedCrossRefGoogle Scholar
  27. Hultman, E., Soderlund, K., Timmons, J.A., Cederblad, G., and Greenhaff, P.L., 1996, Breakdown and resynthesis of phosphorylcreatine and adenosine triphosphate in connection with muscular work in man. Scand. J. Clin. Lab. Invest. 19: 56–66.Google Scholar
  28. Juhn, M.S., and Tarnopolsky, M., 1998, Oral creatine supplementation and athletic performance: a critical review. Clin. J. Sport Med. 8: 286–297.PubMedCrossRefGoogle Scholar
  29. Koszalka, T.R., and Andrew, C.L., 1972, Effect of insulin on the uptake of creatine-1-14C by skeletal muscle in normal and X-irradiated rats. Proc. Soc. Exp. Biol. Med. 139: 1265–1271.PubMedGoogle Scholar
  30. Kreider, R.B., Ferreira, M., Wilson, M., Grindstaff, P., Plisk, S., Reinardy, J., Cantler, E., and Almada, A.L., 1998, Effects of creatine supplementation on body composition, strength, and sprint performance. Med. Sci. Sports Exerc. 30: 73–82.PubMedGoogle Scholar
  31. Louis, M., Poortmans, J.R., Francaux, M., Berre, J., Boisseau, N., Brassine, E., Cuthbertson, D.J., Smith, K., Babraj, J.A., Waddell, T., and Rennie, M.J., 2003a, No effect of creatine supplementation on human myofibrillar and sarcoplasmic protein synthesis after resistance exercise. Am. J. Physiol. Endocrinol. Metab. 285: E1089–E1094.Google Scholar
  32. Louis, M., Poortmans, J.R., Francaux, M., Hultman, E., Berre, J., Boisseau, N., Young, V.R., Smith, K., Meier-Augenstein, W., Babraj, J.A., Waddell, T., and Rennie, M.J., 2003b, Creatine supplementation has no effect on human muscle protein turnover at rest in the postabsorptive or fed states. Am. J. Physiol. Endocrinol. Metab. 284: E764–E770.Google Scholar
  33. Louis, M., Van Beneden, R., Dehoux, M., Thissen, J.P., and Francaux, M., 2004, Creatine increases IGF-I and myogenic regulatory factor mRNA in C2C12 cells. FEBS Lett. 557: 243–247.PubMedCrossRefGoogle Scholar
  34. McMillen, J., Donovan, C.M., Messer, J.I., and Willis, W.T., 2001, Energetic driving forces are maintained in resting rat skeletal muscle after dietary creatine supplementation. J. Appl. Physiol. 90: 62–66.PubMedGoogle Scholar
  35. Murphy, R., McConell, G., Cameron-Smith, D., Watt, K., Ackland, L., Walzel, B., Wallimann, T., and Snow, R., 2001, Creatine transporter protein content, localization, and gene expression in rat skeletal muscle. Am. J. Physiol. Cell Physiol. 280: C415–C422.PubMedGoogle Scholar
  36. Narahara, H.T., and Holloszy, J.O., 1974, The actions of insulin, trypsin, and electrical stimulation on amino acid transport in muscle. J. Biol. Chem. 249: 5435–5443.PubMedGoogle Scholar
  37. Nelson, A.G., Arnall, D.A., Kokkonen, J., Day, A.R., and Evans, J., 2001, Muscle glycogen supercompensation is enhanced by prior creatine supplementation. Med. Sci. Sports Exerc. 33: 1096–1100.PubMedGoogle Scholar
  38. Newman, J.E., Hargreaves, M., Garnham, A., and Snow, R.J., 2003, Effect of creatine ingestion on glucose tolerance and insulin sensitivity in men. Med. Sci. Sports Exerc. 35: 69–74.PubMedCrossRefGoogle Scholar
  39. Nissen, S.L., and Sharp, R.L., 2003, Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis. J. Appl. Physiol. 94: 651–659.PubMedGoogle Scholar
  40. Olsen, S., Aagaard, P., Kadi, F., Tufekovic, G., Verney, J., Olesen, J.L., Suetta, C., and Kjaer, M., 2006, Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J. Physiol. 573: 525–534.PubMedCrossRefGoogle Scholar
  41. Op ’t Eijnde, B., Jijakli, H., Hespel, P., and Malaisse, W.J., 2006, Creatine supplementation increases soleus muscle creatine content and lowers the insulinogenic index in an animal model of inherited type 2 diabetes. Int. J. Mol. Med. 17: 1077–1084.Google Scholar
  42. Op ’t Eijnde, B., Richter, E.A., Henquin, J.C., Kiens, B., and Hespel, P., 2001a, Effect of creatine supplementation on creatine and glycogen content in rat skeletal muscle. Acta Physiol. Scand. 171: 169–176.CrossRefGoogle Scholar
  43. Op ’t Eijnde, B., Urso, B., Richter, E.A., Greenhaff, P.L., and Hespel, P., 2001b, Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization. Diabetes 50: 18–23.CrossRefGoogle Scholar
  44. Parise, G., Mihic, S., MacLennan, D., Yarasheski, K.E., and Tarnopolsky, M.A., 2001, Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J. Appl. Physiol. 91: 1041–1047.PubMedGoogle Scholar
  45. Pischel, I., and Gastner, T., 2007, Creatine – its chemical synthesis, chemistry, and legal status. Subcell. Biochem. 46: 291–307.CrossRefPubMedGoogle Scholar
  46. Poortmans, J.R., and Francaux, M., 2000, Adverse effects of creatine supplementation: fact or fiction? Sports Med. 30: 155–170.PubMedCrossRefGoogle Scholar
  47. Preen, D., Dawson, B., Goodman, C., Beilby, J., and Ching, S., 2003, Creatine supplementation: a comparison of loading and maintenance protocols on creatine uptake by human skeletal muscle. Int. J. Sport Nutr. Exerc. Metab. 13: 97–111.PubMedGoogle Scholar
  48. Preen, D., Dawson, B., Goodman, C., Lawrence, S., Beilby, J., and Ching, S., 2002, Pre-exercise oral creatine ingestion does not improve prolonged intermittent sprint exercise in humans. J. Sports Med. Phys. Fitness 42: 320–329.PubMedGoogle Scholar
  49. Robinson, T.M., Sewell, D.A., Hultman, E., and Greenhaff, P.L., 1999, Role of submaximal exercise in promoting creatine and glycogen accumulation in human skeletal muscle. J. Appl. Physiol. 87: 598–604.PubMedGoogle Scholar
  50. Schroeder, C., Potteiger, J., Randall, J., Jacobsen, D., Magee, L., Benedict, S., and Hulver, M., 2001, The effects of creatine dietary supplementation on anterior compartment pressure in the lower leg during rest and following exercise. Clin. J. Sport Med. 11: 87–95.PubMedCrossRefGoogle Scholar
  51. Snow, R.J., and Murphy, R.M., 2003, Factors influencing creatine loading into human skeletal muscle. Exerc. Sport Sci. Rev. 31: 154–158.PubMedCrossRefGoogle Scholar
  52. Speer, O., Neukomm, L.J., Murphy, R.M., Zanolla, E., Schlattner, U., Henry, H., Snow, R.J., and Wallimann, T., 2004, Creatine transporters: a reappraisal, Mol. Cell. Biochem. 256–257: 407–424.PubMedCrossRefGoogle Scholar
  53. Spriet, L.L., 1995, Anaerobic metabolism during high-intensity exercise. In: Hargreaves, M., ed., Exercise Metabolism, Human Kinetics, Champaign, IL, USA, pp. 1–40.Google Scholar
  54. Steenge, G.R., Simpson, E.J., and Greenhaff, P.L., 2000, Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. J. Appl. Physiol. 89: 1165–1171.PubMedGoogle Scholar
  55. Terjung, R.L., Clarkson, P., Eichner, E.R., Greenhaff, P.L., Hespel, P.J., Israel, R.G., Kraemer, W.J., Meyer, R.A., Spriet, L.L., Tarnopolsky, M.A., Wagenmakers, A.J., and Williams, M.H., 2000, American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med. Sci. Sports Exerc. 32: 706–717.PubMedCrossRefGoogle Scholar
  56. Van Leemputte, M., Vandenberghe, K., and Hespel, P., 1999, Shortening of muscle relaxation time after creatine loading. J. Appl. Physiol. 86: 840–844.PubMedGoogle Scholar
  57. Vandebuerie, F., Vanden Eynde, B., Vandenberghe, K., and Hespel, P., 1998, Effect of creatine loading on endurance capacity and sprint power in cyclists. Int. J. Sports Med. 19: 490–495.PubMedCrossRefGoogle Scholar
  58. Vandenberghe, K., Gillis, N., Van Leemputte, M., Van Hecke, P., Vanstapel, F., and Hespel, P., 1996, Caffeine counteracts the ergogenic action of muscle creatine loading. J. Appl. Physiol. 80: 452–457.PubMedGoogle Scholar
  59. Vandenberghe, K., Goris, M., Van Hecke, P., Van Leemputte, M., Vangerven, L., and Hespel, P., 1997, Long-term creatine intake is beneficial to muscle performance during resistance training. J. Appl. Physiol. 83: 2055–2063.PubMedGoogle Scholar
  60. Walker, J.B., 1979, Creatine: Biosynthesis, regulation and function. Adv. Enzymol. Relat. Areas Mol. Biol. 50: 177–242.PubMedCrossRefGoogle Scholar
  61. Willott, C.A., Young, M.E., Leighton, B., Kemp, G.J., Boehm, E.A., Radda, G.K., and Clarke, K., 1999, Creatine uptake in isolated soleus muscle: kinetics and dependence on sodium, but not on insulin. Acta Physiol. Scand. 166: 99–104.PubMedCrossRefGoogle Scholar
  62. Willoughby, D.S., and Rosene, J., 2001, Effects of oral creatine and resistance training on myosin heavy chain expression. Med. Sci. Sports Exerc. 33: 1674–1681.PubMedCrossRefGoogle Scholar
  63. Willoughby, D.S., and Rosene, J.M., 2003, Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med. Sci. Sports Exerc. 35: 923–929.PubMedCrossRefGoogle Scholar
  64. Young, J.C., and Young, R.E., 2002, The effect of creatine supplementation on glucose uptake in rat skeletal muscle. Life Sci. 71: 1731–1737.PubMedCrossRefGoogle Scholar
  65. Zheng, D., Maclean, P.S., Pohnert, S.C., Knight, J.B., Olson, A.L., Winder, W.W., and Dohm, G.L., 2001, Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase. J. Appl. Physiol. 91: 1073–1083.PubMedGoogle Scholar
  66. Ziegenfuss, T.M., Lowery, L.M., and Lemon, P.W., 1998, Acute fluid volume changes in men during three days of creatine supplementation. J. Exerc. Physiol. 1: 1–9.Google Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Peter Hespel
    • 1
  • Wim Derave
    • 2
  1. 1.Faculty of Kinesiology and Rehabilitation SciencesResearch Center for Exercise and HealthK.U. LeuvenBelgium
  2. 2.Faculty of Medicine and Health SciencesDepartment of Movement and Sport SciencesGhent UniversityBelgium

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