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Oral Creatine Supplementation and Skeletal Muscle Metabolism in Physical Exercise

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Abstract

Creatine is the object of growing interest in the scientific literature. This is because of the widespread use of creatine by athletes, on the one hand, and to some promising results regarding its therapeutic potential in neuromuscular disease on the other. In fact, since the late 1900s, many studies have examined the effects of creatine supplementation on exercise performance. This article reviews the literature on creatine supplementation as an ergogenic aid, including some basic aspects relating to its metabolism, pharmacokinetics and side effects. The use of creatine supplements to increase muscle creatine content above ~20 mmol/kg dry muscle mass leads to improvements in high-intensity, intermittent high-intensity and even endurance exercise (mainly in nonweightbearing endurance activities). An effective supplementation scheme is a dosage of 20 g/day for 4–6 days, and 5 g/day thereafter. Based on recent pharmacokinetic data, new regimens of creatine supplementation could be used. Although there are opinion statements suggesting that creatine supplementation may be implicated in carcinogenesis, data to prove this effect are lacking, and indeed, several studies showing anticarcinogenic effects of creatine and its analogues have been published. There is a shortage of scientific evidence concerning the adverse effects following creatine supplementation in healthy individuals even with long-term dosage. Therefore, creatine may be considered as a widespread, effective and safe ergogenic aid.

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References

  1. Cathcart EP. The influence of carbohydrates and fats on protein metabolism. J Physiol 1909; 39: 311–30

    PubMed  CAS  Google Scholar 

  2. Mendel LB, Rose WC. Experimental studies on creatine and creatinine: the role of the carbohydrates in creatine-creatinine metabolism. J Biol Chem 1911; 10: 213–53

    Google Scholar 

  3. Benedict SR, Osterberg E. Studies in creatine and creatinine metabolism, III: on the origin of creatine. J Biol Chem 1914; 18: 195–214

    CAS  Google Scholar 

  4. Chanutin A. The fate of creatine when administered to man. J Biol Chem 1926; 67: 29–37

    CAS  Google Scholar 

  5. Chanutin A. A study of the effect of creatine on growth and its distribution in the tissues of normal rats. J Biol Chem 1927; 75: 549–57

    CAS  Google Scholar 

  6. Chanutin A. A study of the effect of feeding creatine on growth and its distribution in the liver and muscle of normal mice. J Biol Chem 1928; 78: 167–80

    CAS  Google Scholar 

  7. Hunter A. Monographs on biochemistry: creatine and creatinine. London: Longmans, Green and Company, 1928

    Google Scholar 

  8. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000; 80: 1107–213

    PubMed  CAS  Google Scholar 

  9. Williams MH, Kreider RB, Branch JD. Creatine - the power supplement: what it is, how it works, when it helps. Champaign (IL): Human Kinetics, 1999

    Google Scholar 

  10. Vorgerd M, Grehl T, Jager M, et al. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo controlled crossover trial. Arch Neurol 2000; 57: 923–4

    Article  Google Scholar 

  11. Felber S, Skladal D, Wyss M, et al. Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Neurol Res 2000; 22: 145–50

    PubMed  CAS  Google Scholar 

  12. Xu CJ, Klunk WE, Kanfer JN, et al. Phosphocreatine-dependent glutamate uptake by synaptic vesicles: a comparison with ATP dependent glutamate uptake. J Biol Chem 1996; 271: 13435–40

    Article  PubMed  CAS  Google Scholar 

  13. Matthews RT, Yang L, Jenkins BG, et al.Neuroprotective effect of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci 1998; 18: 156–63

    PubMed  CAS  Google Scholar 

  14. Klivenyi P, Ferrante RJ, Matthews RT, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat Med 1999; 5: 347–50

    Article  PubMed  CAS  Google Scholar 

  15. Ferrante RJ, Andreassen OA, Jenkins BG, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J Neurosci 2000; 20: 4389–97

    PubMed  CAS  Google Scholar 

  16. Saks VA, Strumia E. Phosphocreatine: molecular and cellular aspects of the mechanism of cardioprotective action. Curr Ther Res 1993; 53: 565–98

    Article  CAS  Google Scholar 

  17. McCarty MF. Supplemental creatine may decrease serum homocysteine and abolish the homocysteine ’gender gap’ by suppressing endogenous creatine synthesis. Med Hypotheses 2001; 56: 5–7

    Article  PubMed  CAS  Google Scholar 

  18. Martin KJ, WinslowER, Kaddurah-Daouk R. Cell cycle studies of cyclocreatine, a new anticancer agent. Cancer Res 1994; 54: 5160–5

    PubMed  CAS  Google Scholar 

  19. Martin KJ, Chen SF, Clark GM, et al. Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells. J Natl Cancer Inst 1994; 86: 608–13

    Article  PubMed  CAS  Google Scholar 

  20. Bloch K, Schoenheimer R. The biological precursors of creatine. J Biol Chem 1941; 138: 167–94

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Loike JD, Somes M, Silverstein SC. Creatine uptake, metabolism, and efflux in human monocytes and macrophages. Am J Physiol 1986; 251: C128–35

    Google Scholar 

  23. Wallimann T, Wyss M, Brdiczka D, et al. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the phosphocreatine circuit for cellular energy homeostasis. Biochem J 1992; 281: 21–40

    PubMed  CAS  Google Scholar 

  24. Sandberg AA, Hecht HH, Tyler FH. Studies in disorders of muscle X: the site of creatine synthesis in the human. Metabolism 1953; 2: 22–9

    PubMed  CAS  Google Scholar 

  25. Balsom PD, Söderlund K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med 1994; 18: 268–80

    Article  PubMed  CAS  Google Scholar 

  26. Hoberman HD, Sims EAH, Peters JH. Creatine and creatinine metabolism in the normal male adult studied with the aid of isotopic nitrogen. J Biol Chem 1948; 172: 45–58

    PubMed  CAS  Google Scholar 

  27. Walker JB. Metabolic control of creatine biosynthesis, I: effect of dietary creatine. J Biol Chem 1960; 235: 2357–61

    PubMed  CAS  Google Scholar 

  28. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev 2001; 53: 161–76

    PubMed  CAS  Google Scholar 

  29. Marescau B, De Deyn P, Wiechert P, et al. Comparative study of guanidino compounds in serum and brain of mouse, rat, rabbit, and man. J Neurochem 1986; 46: 717–20

    Article  PubMed  CAS  Google Scholar 

  30. Harris RC, Söderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992; 83: 367–74

    PubMed  CAS  Google Scholar 

  31. Delanghe J, De Slypere JP, De Buyzere M, et al. Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians [letter]. Clin Chem 1989; 35: 1802–3

    PubMed  CAS  Google Scholar 

  32. Odoom JE, Kemp GJ, Radda GK. The regulation of total creatine content in a myoblast cell line. Mol Cell Biochem 1996; 158: 179–88

    Article  PubMed  CAS  Google Scholar 

  33. Guimbal C, Kilimann MW. A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney: cDNA cloning and functional expression. J Biol Chem 1993; 268: 8418–21

    PubMed  CAS  Google Scholar 

  34. Dai W, Vinnakota SS, Qian X, et al.Molecular characterization of the human CRT-1 creatine transporter expressed in Xenopus oocytes. Arch Biochem Biophys 1999; 361: 75–84

    Article  PubMed  CAS  Google Scholar 

  35. Sora I, Richman J, Santoro G, et al. The cloning and expression of a human creatine transporter. Biochem Biophys Res Commun 1994; 204: 419–27

    Article  PubMed  CAS  Google Scholar 

  36. Zorzano A, Fandos C, Palacín M.Role of plasma membrane transporters in muscle metabolism. Biochem J 2000; 349: 667–88

    PubMed  CAS  Google Scholar 

  37. Palacin M, Estevez R, Bertran J, et al. Molecular biology of mammalian plasma membrane amino acid transporters. Physiol Rev 1998; 78: 969–1054

    PubMed  CAS  Google Scholar 

  38. Mayser W, Schloss P, Betz H. Primary structure and functional expression of a choline transporter expressed in the rat nervous. FEBS Lett 1992; 305: 31–6

    Article  PubMed  CAS  Google Scholar 

  39. Guimbal C, Kilimann MW. A creatine transporter cDNA from Torpedo illustrates structure/function relationships in the GABA/noradrenaline transporter family. J Mol Biol 1994; 241: 317–24

    Article  PubMed  CAS  Google Scholar 

  40. Nash SR, Giros B, Kingsmore SF, et al. Cloning, pharmacological characterization, and genomic localization of the human creatine transporter. Receptors Channels 1994; 2: 165–74

    PubMed  CAS  Google Scholar 

  41. Sandoval N, Bauer D, Brenner V, et al. The genomic organization of a human creatine transporter (CRTR) gene located in Xq28. Genomics 1996; 35: 383–5

    Article  PubMed  CAS  Google Scholar 

  42. Murphy R, McConell G, Cameron-Smith D, et al. Creatine transporter protein content, localization, and gene expression in rat skeletal muscle. Am J Physiol 2001; 280: C415–22

    Google Scholar 

  43. Tarnopolsky MA, Parshad A, Walzel B, et al. Creatine transporter and mitochondrial creatine kinase protein content in myopathies. Muscle Nerve 2001; 24: 682–8

    Article  PubMed  CAS  Google Scholar 

  44. Schloss P, Mayser W, Betz H. The putative rat choline transporter CHOt1 transports creatine and is highly expressed in neural and muscle-rich tissues. Biochem Biophys Res Commun 1994; 198: 637–45

    Article  PubMed  CAS  Google Scholar 

  45. Greenhaff P. The nutritional biochemistry of creatine. J Nutr Biochem 1997; 8: 610–8

    Article  CAS  Google Scholar 

  46. Picou D, Reeds PJ, Jackson A, et al. The measurement of muscle mass in children using [15N]creatine. Pediatr Res 1976; 10: 184–8

    Article  PubMed  CAS  Google Scholar 

  47. Crim MC, Calloway DH, Margen S. Creatine metabolism in men: creatine pool size and turnover in relation to creatine intake. J Nutr 1976; 106: 371–81

    CAS  Google Scholar 

  48. Kargotich S, Goodman C, Keast D, et al. Influence of exercise induced plasma volume changes on the interpretation of biochemical data following high-intensity exercise. Clin J Sport Med 1997; 7: 185–91

    Article  PubMed  CAS  Google Scholar 

  49. Bjornsson TD. Use of serum creatinine concentration to determine renal function. Clin Pharmacokinet 1979; 4: 200–22

    Article  PubMed  CAS  Google Scholar 

  50. Berlet HH, Bonsmann I, Birringer H. Occurrence of free creatine, phosphocreatine and creatine phosphokinase in adipose tissue. Biochim Biophys Acta 1976; 437: 166–74

    Article  PubMed  CAS  Google Scholar 

  51. Christensen M, Hartmund T, Gesser H. Creatine kinase, energyrich phosphates and energy metabolism in heart muscle of different vertebrates. J Comp Physiol B 1994; 164: 118–23

    Article  PubMed  CAS  Google Scholar 

  52. Kushmerick MJ, Moerland TS, Wiseman RW. Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. Proc Natl Acad Sci U S A 1992; 89: 7521–5

    Article  PubMed  CAS  Google Scholar 

  53. Lee HJ, Fillers WS, Iyengar MR. Phosphocreatine, an intracellular high-energy compound, is found I the extracellular fluid of the seminal vesicles in mice and rats. Proc Natl Acad Sci U S A 1988; 85: 7265–9

    Article  PubMed  CAS  Google Scholar 

  54. Loike JD, Cao L, Brett J, et al. Hypoxia induces glucose transporter expression in endothelial cells. Am J Physiol 1992; 263: C326–33

    Google Scholar 

  55. Wallimann T, Moser H, Zurbriggen B, et al. Creatine kinase isoenzymes in spermatozoa. J Muscle Res Cell Motil 1986; 7: 25–34

    Article  PubMed  CAS  Google Scholar 

  56. Wallimann T, Wegmann G, Moser H, et al. High content of creatine kinase in chicken retina: compartmentalized localization of creatine kinase isoenzymes in photoreceptor cells. Proc Natl Acad Sci U S A 1986; 83: 3816–9

    Article  PubMed  CAS  Google Scholar 

  57. Harris RC, Hultman E, Nordesjo LO. Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest: methods and variance of values. Scand J Clin Lab Invest 1974; 33: 109–20

    Article  PubMed  CAS  Google Scholar 

  58. Harris RC. Muscle energy metabolism in man in response to isometric contraction [PhD thesis]. Aberystwyth: University College of Wales, 1981

    Google Scholar 

  59. Harris RC, Viru M, Greenhaff PL, et al. The effect of oral creatine supplementation on running performance duringmaximal short term exercise [abstract]. J Physiol 1993; 467: 74P

    Google Scholar 

  60. Connet RJ. Analysis of metabolic control: new insights using scaled creatine kinase model. Am J Physiol 1988; 254: R949–59

    Google Scholar 

  61. Casey A, Constantin-Teodosiu D, Howell S, et al. Metabolic response of type I and II muscle fibers during repeated bouts of maximal exercise in humans. Am J Physiol 1996; 271: E38–43

    Google Scholar 

  62. Wyss M, Wallimann T. I-4 creatine metabolism and the consequences of creatine depletion in muscle. Mol Cell Biochem 1994; 133/134: 51–66

    Article  PubMed  Google Scholar 

  63. Söderlund K, Hultman E. ATP and phosphocreatine changes in single muscle fibers after intense electrical stimulation. Am J Physiol 1991; 261: E737–41

    Google Scholar 

  64. Clark JF, Odoom J, Tracey I, et al. Experimental observations of creatine and creatine phosphate metabolism. In: Conway MA, Clark JF, editors. Creatine and creatine phosphate: scientific and clinical perspectives. San Diego (CA): Academic Press, 1996: 33–50

    Google Scholar 

  65. Essén B. Studies on the regulation of metabolism in human skeletal muscle using intermittent exercise as an experimental model. Aust J Sci Med Sport 1978; 454: 1–64

    Google Scholar 

  66. Tesch PA, Thorsson A, Fujitsuka N. Creatine phosphate in fiber types of skeletal muscle before and after exhaustive exercise. J Appl Physiol 1989; 66: 1756–9

    PubMed  CAS  Google Scholar 

  67. Vandenborne K, Walter G, Ploutz-Snyder L, et al. Energy-rich phosphates in slow and fast human skeletal muscle. Am J Physiol 1995; 268: C869–76

    Google Scholar 

  68. Saltin B, Wharen J, Pernow B. Phosphagen and carbohydrate metabolism during exercise in trainedmiddle-agemen. Scand J Clin Lab Invest 1974; 33: 71–7

    Article  PubMed  CAS  Google Scholar 

  69. Neumann G. Anpassungen des Stoffwechsels unter dem Einflub des sportlichen trainings. In: Strauzenberg SE, Gürtler H, Hannemann D, et al., editors. Sportmedizin. Leipzig: Johann Ambrosius Barth, 1990: 89–142

    Google Scholar 

  70. Karatzaferi C, de Haan A, Ferguson RA, et al. Phosphocreatine and ATP content in human single muscle fibres before and after maximum dynamic exercise. Pflugers Arch 2001; 442: 467–74

    Article  PubMed  CAS  Google Scholar 

  71. Moller P, Bergstrom J, Furst P, et al. Effect of aging on energyrich phosphagens in human skeletal muscles. Clin Sci 1980; 58: 553–5

    PubMed  CAS  Google Scholar 

  72. McCully KK, Forciea MA, Hack LM, et al.Muscle metabolism in older subjects using (31)P magnetic resonance spectroscopy. Can J Physiol Pharmacol 1991; 69: 576–80

    Article  PubMed  CAS  Google Scholar 

  73. Schunk K, Pitton M, Duber C, et al. Dynamic phosphorus-31 magnetic resonance spectroscopy of the quadriceps muscle: effects of age and sex on spectroscopic results. Invest Radiol 1999; 34: 116–25

    Article  PubMed  CAS  Google Scholar 

  74. Smith SA, Montain SJ, Matott RP, et al. Creatine supplementation and age influence muscle metabolism during exercise. J Appl Physiol 1998; 85: 1349–56

    PubMed  CAS  Google Scholar 

  75. Coggan AR, Spina RJ, King DS, et al. Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. J Gerontol 1992; 47: B71–6

    Article  Google Scholar 

  76. Pastoris O, Boschi F, Verri M, et al. The effects of aging on enzyme activities and metabolite concentrations in skeletal muscle from sedentary male and female subjects. Exp Gerontol 2000; 35: 95–104

    Article  PubMed  CAS  Google Scholar 

  77. Fosberg AM, Nillson E, Werneman JM. Muscle composition in relation to age and sex. Clin Sci 1991; 81: 249–56

    Google Scholar 

  78. Balsom PD, Söderlund K, Sjödin B, et al. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand 1995; 154: 303–10

    Article  PubMed  CAS  Google Scholar 

  79. Forsum E, Forsberg AM, Nilsson E, et al. Electrolytes, water, RNA, total creatine and calculated resting membrane potential in muscle tissue from pregnant women. Ann Nutr Metab 2000; 44: 144–9

    Article  PubMed  CAS  Google Scholar 

  80. Gariod L, Binzoni T, Feretti G. Standardization of 31-phosphorus nuclear magnetic resonance spectroscopy determinations of high-energy phosphates in humans. Eur J Appl Physiol 1994; 68: 107–10

    Article  CAS  Google Scholar 

  81. Bernus G, González de Suso JM, Alonso J, et al. 31P-MRS of quadriceps reveals quantitative differences between sprinters and long-distance runners. Med Sci Sports Exerc 1993; 25: 479–84

    PubMed  CAS  Google Scholar 

  82. McCully KK. 31P-MRS of quadriceps reveals quantitative differences between sprinters and long-distance runners. Med Sci Sports Exerc 1993; 25: 1299–300

    Article  PubMed  CAS  Google Scholar 

  83. Maurer J, Konstanczak P, Sollner O, et al. Muscle metabolism of professional athletes using 31P-spectroscopy. Acta Radiol 1999; 40: 73–7

    PubMed  CAS  Google Scholar 

  84. Greenhaff PL, Bodin K, Söderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994; 266: 725–30

    Google Scholar 

  85. Karatzaferi C, de Haan A, van Mechelen W, et al. Metabolism changes in single human fibres during brief maximal exercise. Exp Physiol 2001; 86: 411–5

    Article  PubMed  CAS  Google Scholar 

  86. Terjung RL, Clarkson P, Eichner ER, et al. American College of Sports Medicine Roundtable: the physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 2000; 32: 706–17

    Article  PubMed  CAS  Google Scholar 

  87. Gaitanos GC, Williams C, Boobis LH, et al. Human muscle metabolism during intermittent maximal exercise. J Appl Physiol 1993; 75: 712–9

    PubMed  CAS  Google Scholar 

  88. Spriet LL. Anaerobic metabolism during high-intensity exercise. In: Hargreaves M, editor. Exercise metabolism. Champaign (IL): Human Kinetics, 1995: 1–40

    Google Scholar 

  89. Di Pramispero PE, Margaria R. Mechanical efficiency of phosphagen (ATP+CP) splitting and its speed of resynthesis. Pfluegers Arch 1969; 308: 197–202

    Article  Google Scholar 

  90. Meyer RA. A linear model of muscle respiration explains monoexponential phosphocreatine changes. Am J Physiol 1988; 254: C548–53

    Google Scholar 

  91. Bogdanis GC, Nevill ME, Boobis LH, et al. Recovery of power output and muscle metabolites following 30s of maximal sprint cycling in man. J Physiol 1995; 482: 467–80

    PubMed  CAS  Google Scholar 

  92. Harris RC, Edwards RHT, Hultman E, et al. The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man. Pfluegers Arch 1976; 367: 137–42

    Article  CAS  Google Scholar 

  93. McCann DJ, Mole PA, Caton JR. Phosphocreatine kinetics in humans during exercise and recovery. Med Sci Sports Exerc 1995; 27: 378–87

    PubMed  CAS  Google Scholar 

  94. Kushmerick MJ, Meyer RA, Brown TR. Regulation of oxygen consumption in fast- and slow-twitch muscle. Am J Physiol 1992; 263: C598–606

    Google Scholar 

  95. Nevill AM, Jones DA, McIntyre D, et al. A model for phosphocreatine resynthesis. J Appl Physiol 1997; 82: 329–35

    PubMed  CAS  Google Scholar 

  96. Sahlin K, Harris RC, Hultman E. Resynthesis of creatine phosphate in human muscle after after exercise in relation to intramuscular pH and availability of oxygen. Scand J Clin Lab Invest 1979; 39: 551–8

    Article  PubMed  CAS  Google Scholar 

  97. Sahlin K, Harris R, Hultman E. Creatine kinase equilibrium and lactate content compared with muscle pH in tissue samples obtained after isometric exercise. Biochem J 1975; 152: 173–80

    PubMed  CAS  Google Scholar 

  98. Mahler M. First-order kinetics of muscle oxygen consumption, and an equivalent proportionality between QO2 and phosphorylcreatine level: implications for the control of respiration. J Gen Physiol 1985; 86: 135–65

    Article  PubMed  CAS  Google Scholar 

  99. Taylor DJ, Styles P, Matthews PM, et al. Energetics of human muscle: exercise-induced ATP depletion. Magn Reson Med 1986; 3: 44–54

    Article  PubMed  CAS  Google Scholar 

  100. Kemp GJ, Taylor DJ, Radda GK. Control of phosphocreatine resynthesis during recovery from exercise in human skeletal muscle. NMR Biomed 1993; 6: 66–72

    Article  PubMed  CAS  Google Scholar 

  101. McCully KK, Fielding RA, Evans WJ, et al. Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles. J Appl Physiol 1993; 75: 813–9

    PubMed  CAS  Google Scholar 

  102. Takahashi H, Inaki M, Fujimoto K, et al. Control of the rate of phosphocreatine resynthesis after exercise in trained and untrained human quadriceps muscles. Eur J Appl Physiol 1995; 71: 396–404

    Article  CAS  Google Scholar 

  103. Thompson CH, Kemp GJ, Sanderson AL, et al. Skeletal muscle mitochondrial function studied by kinetic analysis of postexercise phosphocreatine resynthesis. J Appl Physiol 1995; 78: 2131–9

    PubMed  CAS  Google Scholar 

  104. Conley KE, Cress ME, Jubrias SA, et al. From muscle properties to human performance, using magnetic resonance. J Gerontol A Biol Sci Med Sci 1995; 50: 35–40

    PubMed  Google Scholar 

  105. McCully KK, Kakihira H, Vandenborne K, et al. Noninvasive measurements of activity-induced changes inmusclemetabolism. J Biomech 1991; 24: 153–61

    Article  PubMed  Google Scholar 

  106. McCully K, Posner J. Measuring exercise-induced adaptations and injury with magnetic resonance spectroscopy. Int J Sports Med 1992; 13: S147–9

    Article  Google Scholar 

  107. Belister VA, Tsybakova ET. The mechanism of phosphorylation associated with respiration. Biokhimiya 1939; 4: 516–34

    Google Scholar 

  108. Bessman SP, Fonyo A. The possible role of mitochondrial bound creatine kinase in regulation of mitochondrial respiration. Biochem Biophys Res Commun 1966; 22: 597–602

    Article  PubMed  CAS  Google Scholar 

  109. Bessman SP, Geiger PJ. Transport of energy in muscle: the phosphorylcreatine shuttle. Science 1981; 211: 448–52

    Article  PubMed  CAS  Google Scholar 

  110. Bessman SP, Savabi F. The role of the phosphocreatine energy shuttle in exercise and muscle hypertrophy. In: Taylor AW, Gollnick PD, Green HJ, editors. Biochemistry of exercise VII. Champaign (IL): Human Kinetics, 1990: 167–78

    Google Scholar 

  111. Saks VA, Rosenshtraukh LV, Smirnov VN, et al. Role of creatine phosphokinase in cellular function and metabolism. Can J Physiol Pharmacol 1978; 56: 691–705

    Article  PubMed  CAS  Google Scholar 

  112. Saks VA, Belikova YO, Kuznetsov AV, et al. Phosphocreatine pathway for energy transport: ADP diffusion and cardiomyopathy. Am J Physiol 1991; 261: S30–8

    PubMed  CAS  Google Scholar 

  113. Savabi F, Geiger PJ, Bessman SP.Myofibrillar end of the creatine phosphate energy shuttle. Am J Physiol 1984; 247: C424–32

    Google Scholar 

  114. Seraydarian MW, Artaza L, Abbott BC. Creatine and the control of energy metabolism in cardiac and skeletal muscle cells in culture. J Moll Cell Cardiol 1974; 6: 405–13

    Article  CAS  Google Scholar 

  115. Seraydarian MW, Artaza L. Regulation of energy metabolism by creatine in cardiac and skeletal muscle cells in culture. J Moll Cell Cardiol 1976; 8: 669–78

    Article  CAS  Google Scholar 

  116. O’Gorman E, Beutner G, Wallimann T, et al. Differential effects of creatine depletion on the regulation of enzyme activities and on creatine stimulated mitochondrial respiration in skeletal muscle, heart, and brain. Biochim Biophys Acta 1996; 1276: 161–70

    Article  PubMed  Google Scholar 

  117. Ren JM, Semenkovich CF, Holloszy JO. Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transporter expression. Am J Physiol 1993; 264: C146–50

    Google Scholar 

  118. Harris RC, Nevill M, Harris DB, et al. Absorption of creatine supplied as a drink, in meat or in solid form. J Sports Sci 2002; 20: 147–51

    Article  PubMed  Google Scholar 

  119. Green AL, Simpson EJ, Littlewood JJ, et al. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand 1996; 158: 195–202

    Article  PubMed  CAS  Google Scholar 

  120. Schedel JM, Tanaka H, Kiyonaga A, et al. Acute creatine ingestion in human: consequences on serumcreatine and creatinine concentrations. Life Sci 1999; 65: 2463–70

    Article  PubMed  CAS  Google Scholar 

  121. Fitch C, Sinton D. A study of creatine metabolism in diseases causing muscle wasting. J Clin Invest 1964; 43: 444–52

    Article  PubMed  CAS  Google Scholar 

  122. Hultman E, Söderlund K, Timmons JA, et al. Muscle creatine loading in men. J Appl Physiol 1996; 81: 232–7

    PubMed  CAS  Google Scholar 

  123. Kamber M, Koster M, Kreis R, et al. Creatine supplementation, Part I: performance, clinical chemistry, and muscle volume. Med Sci Sports Exerc 1999; 31: 1763–9

    Article  PubMed  CAS  Google Scholar 

  124. Robinson TM, Sewell DA, Casey A, et al. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med 2000; 34: 284–8

    Article  PubMed  CAS  Google Scholar 

  125. Tarnopolsky MA, Parise G, Yardley NJ, et al. Creatine-dextrose and protein-dextrose induce similar strength gains during training. Med Sci Sports Exerc 2001; 33: 2044–52

    Article  PubMed  CAS  Google Scholar 

  126. Jowko E, Ostaszewski P, Jank M, et al. Creatine and ß-hydroxyß- methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition 2001; 17: 558–66

    Article  PubMed  CAS  Google Scholar 

  127. Millard-Stafford ML, Snow TK, Rosskopf LB. Limited side effects associated with creatine supplementation [abstract]. Med Sci Sports Exerc 2000; 32: S133

    Google Scholar 

  128. Kreider R, Rasmussen C, Melton C, et al. Long-term creatine supplementation does not adversely affect clinical markers of health [abstract]. Med Sci Sports Exerc 2000; 32: S134

    Google Scholar 

  129. Kuehl K, Koehler S, Dulacki K, et al. Effects of oral creatine monohydrate supplementation on renal function in adults [abstract]. Med Sci Sports Exerc 2000; 32: S168

    Google Scholar 

  130. 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 

  131. Izquierdo M, Ibanez J, Gonzalez-Badillo JJ, et al. Effects of creatine supplementation on muscle power, endurance, and sprint performance. Med Sci Sports Exerc 2002; 34: 332–43

    Article  PubMed  CAS  Google Scholar 

  132. Burke DG, Smith-Palmer T, Holt LE, et al. The effect of 7 days of creatine supplementation on 24-hour urinary creatine excretion. J Strength Cond Res 2001; 15: 59–62

    PubMed  CAS  Google Scholar 

  133. Steenge GR, Simpson EJ, Greenhaff PL. Protein- and carbohydrate- induced augmentation of whole body creatine retention in humans. J Appl Physiol 2000; 89: 1165–71

    PubMed  CAS  Google Scholar 

  134. Green AL, Hultman E, MacDonald IA, et al. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am J Physiol 1996; 271: E821–6

    Google Scholar 

  135. Casey A, Constantin-Teodosiu D, Howell S, et al. Creatine ingestion favourably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 1996; 271: E31–7

    Google Scholar 

  136. Febbraio MA, Flanagan TR, Snow RJ, et al. Effect of creatine supplementation on intramuscular TCr, metabolism and performance during intermittent, supramaximal exercise in humans. Acta Physiol Scand 1995; 155: 387–95

    Article  PubMed  CAS  Google Scholar 

  137. 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: 1147–56

    Article  PubMed  CAS  Google Scholar 

  138. Greenhaff PL, Casey A, Short AH, et al. Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci 1993; 84: 565–71

    PubMed  CAS  Google Scholar 

  139. Koszalka TR, Andrew CL. Effect of insulin on creatinuria and hypercreatinemia induced by creatine loading. Proc Soc Exp Biol Med 1970; 135: 905–10

    CAS  Google Scholar 

  140. Koszalka TR, Andrew CL. Effect of insulin on the uptake of creatine-1–14C by skeletal muscle in normal and X-irradiated rats. Proc Soc Exp Biol Med 1972; 139: 1265–71

    PubMed  CAS  Google Scholar 

  141. Haughland RB, Chang DT. Insulin effects on creatine transport in skeletal muscle. Proc Soc Exp Biol Med 1975; 148: 1–4

    Google Scholar 

  142. Steenge GR, Lambourne J, Casey A, et al. Stimulatory effect of insulin on creatine accumulation in human skeletalmuscle. Am J Physiol 1998; 275: E974–9

    Google Scholar 

  143. Baron A. Hemodynamic actions of insulin. Am J Physiol 1994; 267: E187–202

    Google Scholar 

  144. Hundal HS, Marette A, Mitsumoto Y, et al. Insulin induces translocation of the α2 and β1 subunits of the Na+/K+-ATPase from intracellular compartments to the plasma membrane inmammalian skeletal muscle. J Biol Chem 1992; 267: 5040–3

    PubMed  CAS  Google Scholar 

  145. Ipsiroglu OS, Stromberger C, Ilas J, et al.Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animals species. Life Sci 2001; 69: 1805–15

    Article  PubMed  CAS  Google Scholar 

  146. Greenhaff PL. Creatine and its application as an ergogenic aid. Int J Sport Nutr 1995; 5: S100–10

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  148. Loike JD, Zalutsky DL, Kaback E, et al. Extracellular creatine regulates creatine transport in rat and human muscle cells. Proc Natl Acad Sci U S A 1988; 85: 807–11

    Article  PubMed  CAS  Google Scholar 

  149. Guerrero-Ontiveros ML, Wallimann T. Creatine supplementation in health and disease: effects of chronic creatine supplementation in vivo: down regulation of the expression of creatine transporter isoforms in skeletal muscle. Mol Cell Biochem 1998; 184: 427–37

    Article  PubMed  CAS  Google Scholar 

  150. Alsever RN, Georg RH, Sussman KE. Stimulation of insulin secretion by guanidinoacetic acid and other guanidine derivates. Endocrinology 1970; 86: 332–6

    Article  PubMed  CAS  Google Scholar 

  151. Gerbitz KD, Gempel K, Brdiczka D. Mitochondria and diabetes: genetic, biochemical, and clinical implications of the cellular energy circuit. Diabetes 1996; 45: 113–26

    Article  PubMed  CAS  Google Scholar 

  152. Willott CA, Young ME, Leighton B, et al. Creatine uptake in isolated soleus muscle: kinetics and dependence on sodium, but not on insulin. Acta Physiol Scand 1999; 166: 99–104

    Article  PubMed  CAS  Google Scholar 

  153. Kreis R, Kamber M, Koster M, et al. Creatine supplementation, Part II: in vivo magnetic resonance spectroscopy. Med Sci Sports Exerc 1999; 31: 1770–7

    Article  PubMed  CAS  Google Scholar 

  154. Rawson ES, Clarkson PM, Price TB, et al. Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects. Acta Physiol Scand 2002; 174: 57–65

    Article  PubMed  CAS  Google Scholar 

  155. Robinson TM, Sewell DA, Hultman E, et al. 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 

  156. Redondo DR, Dowling EA, Graham BL, et al. The effect of oral creatine monohydrate supplementation on running velocity. Int J Sport Nutr 1996; 6: 213–21

    PubMed  CAS  Google Scholar 

  157. Fitch CD, Shields RP. Creatine metabolism in skeletal muscle, I: creatine movement across muscle membranes. J Biol Chem 1996; 15: 3611–4

    Google Scholar 

  158. Tran TT, Dai W, Sarkar HK. Cyclosporin A inhibits creatine uptake by altering surface expression of the creatine transporter. J Biol Chem 2000; 275: 35708–14

    Article  PubMed  CAS  Google Scholar 

  159. Gerber GB, Gerber G, Koszalka TR, et al. Creatine metabolism in vitamin E deficiency in the rat. Am J Physiol 1962; 202: 453–60

    PubMed  CAS  Google Scholar 

  160. Vandenberghe K, Gillis N, Van Leemputte M, et al. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996; 80: 452–7

    PubMed  CAS  Google Scholar 

  161. Hespel P, Op’t Eijnde BO, Van Leemputte M. Opposite actions of caffeine and creatine on muscle relaxation time in humans. J Appl Physiol 2002; 92: 513–8

    PubMed  CAS  Google Scholar 

  162. Preen D, Dawson B, Goodman C, et al. Effect of creatine loading on long-term sprint exercise performance and metabolism. Med Sci Sports Exerc 2001; 33: 814–21

    PubMed  CAS  Google Scholar 

  163. McMillen J, Donovan CM, Messer JI, et al. Energetic driving forces are maintained in resting rat skeletal muscle after dietary creatine supplementation. J Appl Physiol 2001; 90: 62–6

    PubMed  CAS  Google Scholar 

  164. Sipila I, Rapola J, Simell O, et al. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. N Engl J Med 1981; 304: 867–70

    Article  PubMed  CAS  Google Scholar 

  165. Romer LM, Barrington JP, Jeukendrup AE. Effects of oral creatine supplementation on high intensity, intermittent exercise performance in competitive squash players. Int J Sports Med 2001; 22: 546–52

    Article  PubMed  CAS  Google Scholar 

  166. Tarnopolsky MA, MacLennan DP. Creatine monohydrate supplementation enhances high-intensity exercise performance in males and females. Int J Sport Nutr 2000; 10: 452–63

    CAS  Google Scholar 

  167. Miura A, Kino F, Kajitani S, et al. The effect of oral creatine supplementation on the curvature constant parameter of the power-duration curve for cycle ergometry in humans. Jpn J Physiol 1999; 49: 169–74

    Article  PubMed  CAS  Google Scholar 

  168. Bosco C, Tihanyi J, Pucspk J, et al. Effect of oral creatine supplementation on jumping and running performance. Int J Sports Med 1997; 18: 369–72

    Article  PubMed  CAS  Google Scholar 

  169. Skare OC, Skadberg \/O, Wisnes AR. Creatine supplementation improves sprint performance in male sprinters. Scand J Med Sci Sports 2001; 11: 96–102

    Article  PubMed  CAS  Google Scholar 

  170. Shomrat A, Weinstein Y, Katz A. Effect of creatine feeding on maximal exercise performance in vegetarians. Eur J Appl Physiol 2000; 82: 321–5

    Article  PubMed  CAS  Google Scholar 

  171. Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc 2000; 32: 654–8

    Article  PubMed  CAS  Google Scholar 

  172. Stone MH, Sanborn K, Smith LL, et al. Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr 1999; 9: 146–65

    PubMed  CAS  Google Scholar 

  173. Hamilton KL, Meyers MC, Skelly WA, et al. Oral creatine supplementation and upper extremity anaerobic response in females. Int J Sport Nutr 2000; 10: 277–89

    CAS  Google Scholar 

  174. Schedel JM, Terrier P, Schutz Y. The biomechanic origin of sprint performance enhancement after one-week creatine supplementation. Jpn J Physiol 2000; 50: 273–6

    Article  PubMed  CAS  Google Scholar 

  175. Stout J, Eckerson J, Ebersole K, et al. Effect of creatine loading on neuromuscular fatigue threshold. J Appl Physiol 2000; 88: 109–12

    PubMed  CAS  Google Scholar 

  176. Kurosawa Y, Iwane H, Hamaoka T, et al. Effects of oral creatine supplementation on high and low intensity grip exercise performance [abstract]. Med Sci Sports Exerc 1997; 28: S251

    Google Scholar 

  177. Maganaris CN, Maughan RJ. Creatine supplementation enhances maximum voluntary isometric force and endurance capacity in resistance trained men. Acta Physiol Scand 1998; 163: 279–87

    Article  PubMed  CAS  Google Scholar 

  178. Urbanski RL, Vincent WJ, Yaspelkis BB. Creatine supplementation differentially affects maximal isometric strength and time to fatigue in large and small muscle groups. Int J Sport Nutr 1999; 9: 136–45

    PubMed  CAS  Google Scholar 

  179. Earnest CP, Snell PG, Rodriguez R, et al. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 1995; 153: 207–9

    Article  PubMed  Google Scholar 

  180. Becque M, Lochmann J, Melrose D. Effect of creatine supplementation during strength training on 1-RM and body composition. Med Sci Sports Exerc 1997; 29: S146–52

    Google Scholar 

  181. Brenner M, Rankin JW, Sebolt D. The effect of creatine supplementation during resistance training in women. J Strength Cond Res 2000; 14: 207–13

    Google Scholar 

  182. Vandenberghe K, Van Hecke P, Van Leemputte M, et al. Phosphocreatine resynthesis is not affected by creatine loading. Med Sci Sports Exerc 1999; 31: 236–42

    Article  PubMed  CAS  Google Scholar 

  183. Arciero PJ, Hannibal NS, Nindl BC, et al. Comparison of creatine ingestion and resistance training on energy expenditure and limb blood flow. Metabolism 2001; 50: 1429–34

    Article  PubMed  CAS  Google Scholar 

  184. Burke DG, Silver S, Holt LE, et al. The effect of continuous low dose creatine supplementation on force, power, and total work. Int J Sport Nutr 2000; 10: 235–44

    CAS  Google Scholar 

  185. Rawson ES, Clarkson PM. Acute creatine supplementation in older men. Int J Sports Med 2000; 21: 71–5

    Article  PubMed  CAS  Google Scholar 

  186. Bermon S, Venembre P, Sachet C, et al. Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiol Scand 1998; 164: 147–55

    Article  PubMed  CAS  Google Scholar 

  187. Javierre C, Lizarraga MA, Ventura JL, et al. Creatine supplementation does not improve physical performance in a 150 m race. Rev Esp Fisiol 1997; 53: 343–8

    PubMed  CAS  Google Scholar 

  188. Burke LM, Pyne DB, Telford RD. Effect of oral creatine supplementation on single-effort sprint performance in elite swimmers. Int J Sport Nutr 1996; 6: 222–33

    PubMed  CAS  Google Scholar 

  189. Cooke WH, Grandjean PW, Barnes WS. Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry. J Appl Physiol 1995; 78: 670–3

    PubMed  CAS  Google Scholar 

  190. Dawson B, Cutler M, Moody A, et al. Effects of oral creatine loading on single and repeated maximal short sprints. Aust J Sci Med Sport 1995; 27: 56–61

    PubMed  CAS  Google Scholar 

  191. Mujika I, Chatard JC, Lacoste L, et al. Creatine supplementation does not improve sprint performance in competitive swimmers. Med Sci Sports Exerc 1996; 28: 1435–41

    Article  PubMed  CAS  Google Scholar 

  192. Odland LM, MacDougall JD, Tarnopolsky MA, et al. Effect of oral creatine supplementation on muscle [PCr] and short-term maximum power output. Med Sci Sports Exerc 1997; 29: 216–9

    PubMed  CAS  Google Scholar 

  193. Deutekom M, Beltman JG, de Ruiter CJ, et al. No acute effects of short-term creatine supplementation on muscle properties and sprint performance. Eur J Appl Physiol 2000; 82: 223–9

    Article  PubMed  CAS  Google Scholar 

  194. Jakobi JM, Rice CL, Curtin SV, et al. Contractile properties, fatigue and recovery are not influenced by short-term creatine supplementation in human muscle. Exp Physiol 2000; 85: 451–60

    Article  PubMed  CAS  Google Scholar 

  195. Op’t Eijnde B, Vergauwen L, Hespel P. Creatine loading does not impact on stroke performance in tennis. Int J Sports Med 2001; 22: 76–80

    Article  Google Scholar 

  196. Snow RJ, McKenna MJ, Selig SE, et al. Effect of creatine supplementation on sprint exercise performance and muscle metabolism. J Appl Physiol 1998; 84: 1667–73

    PubMed  CAS  Google Scholar 

  197. Greenhaff PL. Creatine supplementation: recent developments. Br J Sports Med 1996; 30: 276–7

    Article  PubMed  CAS  Google Scholar 

  198. Smith SA, Montain SJ, Matott RP, et al. Effects of creatine supplementation on the energy cost of muscle contraction: a 31P-MRS study. J Appl Physiol 1999; 87: 116–23

    PubMed  CAS  Google Scholar 

  199. Williams MH, Branch JD. Creatine supplementation and exercise performance: an update. J Am Coll Nutr 1998; 17: 216–34

    PubMed  CAS  Google Scholar 

  200. 200. Opt Eijnde B, Richter EA, Van Leemputte M, et al. Prevention and treatment of muscle disuse atrophy by oral creatine intake [abstract]. Proceedings of the 4th Annual Congress of the European College of Sports Science; 1999 Jul 14–17, Rome: 31

  201. Schedel JM, Tanaka H, Kiyonaga A, et al. Acute creatine loading enhances human growth hormone secretion. J Sports Med Phys Fitness 2000; 40: 336–42

    PubMed  CAS  Google Scholar 

  202. B. Opt Eijnde, Hespel P. Short-term creatine supplementation does not alter the hormonal response to resistance training. Med Sci Sports Exerc 2001; 33: 449–53

    Article  CAS  Google Scholar 

  203. Ingwall JS, Morales MF, Stockdale FE. Creatine and the control of myosin synthesis in differentiating skeletal muscle. Proc Natl Acad Sci U S A 1972; 69: 2250–3

    Article  PubMed  CAS  Google Scholar 

  204. Silber ML, Litvinova VN, Morozov VI, et al. The creatine effect on RNA and protein synthesis in growing culture of chick embryo myoblasts. Biochimia 1975; 40: 854–60

    Google Scholar 

  205. Ingwall JS, Weiner CD, Morales MF, et al. Specificity of creatine in the control of muscle protein synthesis. J Cell Biol 1974; 62: 145–51

    Article  PubMed  CAS  Google Scholar 

  206. Ingwall JS, Morales MF, Stockdale FE, et al. Creatine: a possible stimulus skeletal cardiac muscle hypertrophy. Recent Adv Stud Card Struct Metab 1975; 8: 467–81

    CAS  Google Scholar 

  207. Ingwall JS. Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res 1976; 38 (5 Suppl. 1): 1115–23

    Google Scholar 

  208. Ingwall JS, Wildenthal K. Role of creatine in the regulation of cardiac protein synthesis. J Cell Biol 1976; 68: 159–63

    Article  PubMed  CAS  Google Scholar 

  209. Flisinska-Bojanowska A. Effects of oral creatine administration on skeletal muscle protein and creatine levels. Biol Sport 1996; 13: 39–46

    Google Scholar 

  210. Söderlund K, Balsom PD, Ekblom B. Creatine supplementation and high intensity exercise: influence on performance and muscle metabolism. Clin Sci 1994; 87: S120–1

    Google Scholar 

  211. Van Deursen J, Jap P, Heerschap A, et al. Effects of the creatine analogue β-guanidinopropionic acid on skeletal muscles of mice deficient in muscle creatine kinase. Biochim Biophys Acta 1994; 1185: 327–35

    Article  PubMed  Google Scholar 

  212. Laskowski MB, Chevli R, Fitch CD. Biochemical and ultrastructural changes in skeletal muscle induced by a creatine antagonist. Metabolism 1981; 30: 1080–5

    Article  PubMed  CAS  Google Scholar 

  213. Willoughby DS, Rosene J. Effects of oral creatine and resistance training on myosin heavy chain expression. Med Sci Sports Exerc 2001; 33: 1674–81

    Article  PubMed  CAS  Google Scholar 

  214. Dangott B, Schultz E, Mozdziak PE. Dietary creatinemonohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med 2000; 21: 13–6

    Article  PubMed  CAS  Google Scholar 

  215. Ziegenfuss TN, Lemon PWR, Rogers MR, et al. Acute creatine ingestion: effects on muscle volume, anaerobic power, fluid volumes, and protein turnover [abstract]. Med Sci Sports Exerc 1997; 29: S127

    Google Scholar 

  216. Fry DM, Morales MF. A re-examination of the effects of creatine on muscle protein synthesis in tissue culture. J Cell Biol 1980; 84: 294–7

    Article  PubMed  CAS  Google Scholar 

  217. Young RB, Denome RM. Effect of creatine on contents ofmyosin heavy chain and myosin-heavy-chain mRNA in steady-state chicken muscle-cell cultures. Biochem J 1984; 218: 871–6

    PubMed  CAS  Google Scholar 

  218. Brannon TA, Adams GR, Conniff CL, et al. Effects of creatine loading and training on running performance and biochemical properties of rat skeletal muscle. Med Sci Sports Exerc 1997; 29: 489–95

    Article  PubMed  CAS  Google Scholar 

  219. Parise G, Mihic S, MacLennan D, et al. Creatine monohydrate supplementation does not increase whole body ormixedmuscle fractional protein synthetic rates in males and females [abstract]. Med Sci Sports Exerc 2000; 32: S289

    Google Scholar 

  220. Parise G, Mihic S, MacLennan D, et al. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed muscle protein synthesis. J Appl Physiol 2001; 91: 1041–7

    PubMed  CAS  Google Scholar 

  221. Jacobs I, Bleue S, Goodman J. Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit. Can J Appl Physiol 1997; 22: 231–43

    Article  PubMed  CAS  Google Scholar 

  222. McNaughton LR, Dalton B, Tarr J. The effects of creatine supplementation on high-intensity exercise performance in elite performers. Eur J Appl Physiol 1998; 78: 236–40

    Article  CAS  Google Scholar 

  223. Viru M, Oopik V, Nurmekivi A, et al. Effect of creatine intake on the performance capacity in middle-distance runners. Coach Sport Sci J 1994; 1: 31–6

    Google Scholar 

  224. Roussel M, Bendahan D, Mattei JP, et al. 31P magnetic resonance spectroscopy study of phosphocreatine recovery kinetics in skeletal muscle: the issue of intersubject variability. Biochim Biophys Acta 2000; 1457: 18–26

    Article  PubMed  CAS  Google Scholar 

  225. Birch R, Noble D, Greenhaff PL. The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. Eur J Appl Physiol 1994; 69: 268–76

    Article  CAS  Google Scholar 

  226. Prevost MC, Nelson AG, Morris GS. Creatine supplementation enhances intermittent work performance. Res Q Exerc Sport 1997; 68: 233–40

    PubMed  CAS  Google Scholar 

  227. Aaserud R, Gramvik P, Olsen SR, et al. Creatine supplementation delays onset of fatigue during repeated bouts of sprint running. Scand J Med Sci Sports 1998; 8: 247–51

    Article  PubMed  CAS  Google Scholar 

  228. Peyrebrune MC, Nevill ME, Donaldson FJ, et al. The effects of oral creatine supplementation on performance in single and repeated sprint swimming. J Sports Sci 1998; 16: 271–9

    Article  PubMed  CAS  Google Scholar 

  229. Leenders NM, Lamb DR,Nelson TE. Creatine supplementation and swimming performance. Int J Sport Nutr 1999; 9: 251–62

    PubMed  CAS  Google Scholar 

  230. Lemon P, Boska M, Bredle D, et al. Effect of oral creatine supplementation on energetics during repeated maximal muscle contractions [abstract]. Med Sci Sports Exerc 1995; 27: S204

    Google Scholar 

  231. Jones AM, Atter T, Georg KP. Oral creatine supplementation improves multiple sprint performance in elite ice-hockey players. J Sports Med Phys Fitness 1999; 39: 189–96

    PubMed  CAS  Google Scholar 

  232. Mújika I, Padilla S, Ibáñez J, et al. Creatine supplementation and sprint performance in soccer players. Med Sci Sports Exerc 2000; 32: 518–25

    Article  PubMed  Google Scholar 

  233. Schneider DA, McDonough PJ, Fadel PJ, et al. Creatine supplementation and the total work performed during 15-s and 1-min bouts of maximal cycling. Aust J Sci Med Sport 1997; 29: 65–8

    PubMed  CAS  Google Scholar 

  234. Grindstaff PD, Kreider R, Bishop R, et al. Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Int J Sport Nutr 1997; 7: 330–46

    PubMed  CAS  Google Scholar 

  235. Balsom PD, Ekblom B, Söderlund K, et al. Creatine supplementation and dynamic high-intensity intermittent exercise. Scand J Med Sci Sports 1993; 3: 143–9

    Article  Google Scholar 

  236. Rossouw F, Krüger PE, Rossouw J. The effect of creatine monohydrate loading on maximal intermittent high intensity exercise and sport-specific strength in well trained power-lifters. Nutr Res 2000; 20: 505–14

    Article  CAS  Google Scholar 

  237. Cottrell GT, Coast JR, Herb RA. Effect of recovery interval on multiple-bout sprint cycling performance after acute creatine supplementation. J Strength Cond Res 2002; 16: 109–16

    PubMed  Google Scholar 

  238. Theodorou AS, Cooke CB, King RF, et al. The effect of longer term creatine supplementation on elite swimming performance after an acute creatine loading. J Sports Sci 1999; 17: 853–9

    Article  PubMed  CAS  Google Scholar 

  239. Vandebuerie F, Vanden Eynde B, et al. Effect of creatine loading on endurance capacity and sprint power in cyclists. Int J Sports Med 1998; 19: 490–5

    Article  PubMed  CAS  Google Scholar 

  240. Engelhardt M, Neumann G, Berbalk A, et al. Creatine supplementation in endurance sports. Med Sci Sports Exerc 1998; 30: 1123–9

    Article  PubMed  CAS  Google Scholar 

  241. Barnett C, Hinds M, Jenkins DG. Effects of creatine supplementation on multiple sprint cycle performance. Aust J Sci Med Sport 1996; 28: 35–9

    PubMed  CAS  Google Scholar 

  242. Gilliam JD, Hohzorn C, Martin D, et al. Effect of oral creatine supplementation on isokinetic torque production. Med Sci Sports Exerc 2000; 32: 993–6

    PubMed  CAS  Google Scholar 

  243. Cooke WH, Barnes WS. The influence of recovery duration on high-intensity exercise performance after oral creatine supplementation. Can J Appl Physiol 1997; 22: 454–67

    Article  PubMed  CAS  Google Scholar 

  244. McKenna MJ, Morton J, Selig SE, et al. Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance. J Appl Physiol 1999; 87: 2244–52

    PubMed  CAS  Google Scholar 

  245. Francaux M, Demeure R, Goudemant JF, et al. Effect of exogenous creatine supplementation on muscle PCr metabolism. Int J Sports Med 2000; 21: 139–45

    Article  PubMed  CAS  Google Scholar 

  246. Finn JP, Ebert TR, Withers RT, et al. Effect of creatine supplementation on metabolism and performance in humans during intermittent sprint cycling. Eur J Appl Physiol 2001; 84: 238–43

    Article  PubMed  CAS  Google Scholar 

  247. Tullson PC, Terjung RL. Adenine nucleotide metabolism in contracting skeletal muscle. Exerc Sports Sci Rev 1991; 19: 507–37

    Article  CAS  Google Scholar 

  248. Stathis CG, Febbraio MA, Carey MF, et al. Influence of sprint training on human muscle purine nucleotide metabolism. J Appl Physiol 1994; 76: 1802–9

    PubMed  CAS  Google Scholar 

  249. Tullson PC, Bangsbo J, Hellsten Y, et al. IMP metabolism in human skeletal muscle after exhaustive exercise. J Appl Physiol 1995; 78: 146–52

    PubMed  CAS  Google Scholar 

  250. Zhao S, Snow RJ, Stathis CG, et al. Muscle adenine nucleotide metabolism during and in recovery from maximal exercise in humans. J Appl Physiol 2000; 88: 1513–9

    PubMed  CAS  Google Scholar 

  251. Harris RC, Marlin DJ, Snow DH, et al. Muscle ATP loss and lactate accumulation at different work intensities in the exercising thoroughbred horse. Eur J Appl Physiol 1991; 62: 235–44

    Article  CAS  Google Scholar 

  252. Ishizaki S, Aoki J. The effect of oral creatine supplementation on power output during long-term intermittent exercise in men [abstract]. Med Sci Sports Exerc 1999; 31: S264

    Article  Google Scholar 

  253. Faria EW, White MT, Coragan C, et al. Effect of oral creatine supplementation on AOD, AT, and blood lactate in oarswomen [abstract]. Med Sci Sports Exerc 2000; 32: S136

    Google Scholar 

  254. Vukovich MD, Peeters BM. Effects of creatine supplementation on exercise performance: a meta-analytical review [abstract]. Med Sci Sports Exerc 1999; 31: S263

    Google Scholar 

  255. Stroud MA, Holliman D, Bell D, et al. Effect of oral creatine supplementation on respiratory gas exchange and blood lactate accumulation during steady-state incremental treadmill exercise and recovery in man. Clin Sci 1994; 87: 707–10

    PubMed  CAS  Google Scholar 

  256. Balsom PD, Harridge SD, Soderlund K, et al. Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993; 149: 521–3

    Article  PubMed  CAS  Google Scholar 

  257. Vanakoski J, Kosunen V, Meririnne E, et al. Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations. Int J Clin Pharmacol Ther 1998; 36: 258–62

    PubMed  CAS  Google Scholar 

  258. Terrillion KA, Kolkhorst FW, Dolgener FA, et al. The effect of creatine supplementation on two 700-m maximal running bouts. Int J Sport Nutr 1997; 7: 138–43

    PubMed  CAS  Google Scholar 

  259. Rico-Sanz J, Marco MMT. Creatine enhances oxygen uptake and performance during alternating intensity exercise. Med Sci Sports Exerc 2000; 32: 379–85

    Article  PubMed  CAS  Google Scholar 

  260. Nelson AG, Day R, Glickman-Weiss EL, et al. Creatine supplementation alters the response to a graded cycle ergometer test. Eur J Appl Physiol 2000; 83: 89–94

    Article  PubMed  CAS  Google Scholar 

  261. Rossiter HB, Cannell ER, Jakeman PM. The effect of oral creatine supplementation on the 1000m performance of competitive rowers. J Sports Sci 1996; 14: 175–9

    Article  PubMed  CAS  Google Scholar 

  262. Smith JC, Stephens DP, Hall EL, et al. Effect of oral creatine ingestion on parameters on the work rate-time relationship and time to exhaustion in high-intensity cycling. Eur J Appl Physiol 1998; 77: 360–5

    Article  CAS  Google Scholar 

  263. Bellinger BM, Bold A, Wilson GR, et al. Oral creatine supplementation decreases plasma markers of adenine nucleotide degradation during a 1-h cycle test. Acta Physiol Scand 2000; 170: 217–24

    Article  PubMed  CAS  Google Scholar 

  264. 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: 222–5

    Article  PubMed  CAS  Google Scholar 

  265. Rico-Sanz J. Creatine reduces human muscle PCr and pH decrements and P(i) accumulation during low-intensity exercise. J Appl Physiol 2000; 88: 1181–91

    Article  PubMed  CAS  Google Scholar 

  266. Nelson AG, Day R, Glickman-Weiss EL, et al. Creatine supplementation raises anaerobic threshold [abstract]. FASEB J 1998; 11: A589

    Google Scholar 

  267. Jones AM, Carter H, Pringle JSM, et al. Effect of creatine supplementation on oxygen uptake kinetics during submaximal cycle exercise. J Appl Physiol 2002; 92: 2571–7

    PubMed  CAS  Google Scholar 

  268. Kunz WS. Control of oxidative phosphorylation in skeletal muscle. Biochim Biophys Acta 2001; 1504: 12–9

    Article  PubMed  CAS  Google Scholar 

  269. Kay L, Nicolay K, Wieringa B, et al. Direct evidence for the control of mitochondrial respiration by mitochondrial creatine kinase in oxidative muscle cells in situ. J Biol Chem 2000; 275: 6937–44

    Article  PubMed  CAS  Google Scholar 

  270. Apple FS, Rogers MA. Mitochondrial creatine kinase activity alterations in skeletal muscle during long-distance running. J Appl Physiol 1986; 61: 482–5

    PubMed  CAS  Google Scholar 

  271. Schmitt T, Pette D. Increased mitochondrial creatine kinase in chronically stimulated fast-twitch rabbit muscle. FEBS Lett 1985; 188: 341–4

    Article  PubMed  CAS  Google Scholar 

  272. Schneider C, Stull GA, Apple FS. Kinetic characterization of human heart and skeletal muscle CK isoenzymes. Enzyme 1988; 39: 220–6

    PubMed  CAS  Google Scholar 

  273. Sherman WM, Costill DL, Fink WJ, et al. Effect of exercise-diet manipulation on muscle glycogen and its subsequent utilization during performance. Int J Sports Med 1981; 2: 114–8

    Article  PubMed  CAS  Google Scholar 

  274. Nelson AG, Arnall DA, Kokkonen J, et al. Muscle glycogen super compensation is enhanced by prior creatine supplementation. Med Sci Sports Exerc 2001; 33: 1096–100

    PubMed  CAS  Google Scholar 

  275. Op’t Eijnde B, Urs\/o B, Richter EA, et al. Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization. Diabetes 2001; 50: 18–23

    Article  Google Scholar 

  276. Hardie DG, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 1998; 67: 821–55

    Article  PubMed  CAS  Google Scholar 

  277. Holmes BF, Kurth-Kraczek EJ, Winder WW. Chronic activation of 5’-AMP-activated protein kinase increases GLUT4, hexokinase, and glycogen in muscle. J Appl Physiol 1999; 87: 1990–5

    PubMed  CAS  Google Scholar 

  278. Low SY, Rennie MJ, Taylor PM. Modulation of glycogen synthesis in rat skeletalmuscle by changes in cell volume. J Physiol 1996; 495: 299–303

    PubMed  CAS  Google Scholar 

  279. Op’t Eijnde B, Richter EA, Henquin JC, et al. Effect of creatine supplementation on creatine and glycogen content in rat skeletal muscle. Acta Physiol Scand 2001; 171: 169–76

    Article  Google Scholar 

  280. Haussinger D, Roth E, Lang F, et al. Cellular hydration status: an important determinant of protein catabolism in health and disease. Lancet 1993; 341: 1330–2

    Article  PubMed  CAS  Google Scholar 

  281. Kuznetsov AV, Tiivel T, Sikk P, et al. Striking differences between the kinetics of regulation of respiration by ADP in slow-twitch and fast-twitch muscles in vivo. Eur J Biochem 1996; 241: 909–15

    Article  PubMed  CAS  Google Scholar 

  282. Tonkonogi M, Harris B, Sahlin K. Mitochondrial oxidative function in human saponin-skinned fibers: effects of prolonged exercise. J Physiol 1998; 510: 270–86

    Article  Google Scholar 

  283. Bergstrom M, Hultman E. Energy cost and fatigue during intermittent electrical stimulation of human skeletal muscle. J Appl Physiol 1988; 65: 1500–5

    PubMed  CAS  Google Scholar 

  284. Van Leemputte M, Vandenberghe K, Hespel P. Shortening of muscle relaxation time after creatine loading. J Appl Physiol 1999; 86: 840–4

    PubMed  Google Scholar 

  285. Wakatsuki T, Ohira Y, Yasui W, et al. Responses of contractile properties in rat soleus to high-energy phosphates and/or unloading. Jpn J Physiol 1994; 44: 193–204

    Article  PubMed  CAS  Google Scholar 

  286. Gillis JM. Relaxation of vertebrate skeletal muscle: a synthesis of the biochemical and physiological approaches. Biochim Biophys Acta 1985; 811: 97–145

    Article  PubMed  CAS  Google Scholar 

  287. Dux L. Muscle relaxation and sarcoplasmic reticulum function in different muscle types. Rev Physiol Biochem Pharmacol 1993; 122: 69–141

    Article  PubMed  CAS  Google Scholar 

  288. Pulido SM, Passaquin AC, Leijendekker WJ, et al. Creatine supplementation improves intracellular Ca(++) handling and survival mdx skeletal muscle cells. FEBS Lett 1998; 439: 357–62

    Article  PubMed  CAS  Google Scholar 

  289. Kammermeier H. Efficiency of energy conversion from metabolic substrates to ATP and mechanical and chemiosmotic energy. Basic Res Cardiol 1993; 88: 15–20

    Article  PubMed  CAS  Google Scholar 

  290. Gutierrez A, Gonzalez-Gross M, Delgado M, et al. Three days fast in sportsmen decrease physical work capacity but not strength or perception-reaction time. Int J Sport Nutr 2001; 11: 415–24

    Google Scholar 

  291. Rockwell JA, Rankin JW, Toderico B. Creatine supplementation affects muscle creatine during energy restriction. Med Sci Sports Exerc 2001; 33: 61–8

    PubMed  CAS  Google Scholar 

  292. Oopik V, Paasuke M, Timpmann S, et al. Effect of creatine supplementation during rapid body mass reduction on metabolism and isokinetic muscle performance capacity. Eur J Appl Physiol 1998; 78: 83–92

    Article  CAS  Google Scholar 

  293. Kraemer WJ, Volek JS. Creatine supplementation: its role in human performance. Clin Sports Med 1999; 18: 651–66

    Article  PubMed  CAS  Google Scholar 

  294. Pearson DR, Hamby DG, Russel W, et al. Long-term effects of creatine monohydrate on strength and power. J Strength Cond Res 1999; 13: 187–92

    Google Scholar 

  295. Volek JS, Kraemer WJ. Creatine supplementation: its effect on human muscular performance and body composition. J Strength Cond Res 1996; 10: 200–10

    Google Scholar 

  296. Volek JS, Kraemer WJ, Bush JA, et al. Creatine supplementation enhances muscular performance during high-intensity resistance exercise. J Am Diet Assoc 1997; 97: 765–70

    Article  PubMed  CAS  Google Scholar 

  297. Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med 2000; 30: 155–70

    Article  PubMed  CAS  Google Scholar 

  298. Kreider RB. Dietary supplements and the promotion of muscle growth with resistance exercise. Sports Med 1999; 27: 97–110

    Article  PubMed  CAS  Google Scholar 

  299. Clarkson PM, Rawson ES. Nutritional supplements to increase muscle mass. Crit Rev Food Sci Nutr 1999; 39: 317–28

    Article  PubMed  CAS  Google Scholar 

  300. Mihic S, MacDonald JR, McKenzie S, et al. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med Sci Sports Exerc 2000; 32: 291–6

    Article  PubMed  CAS  Google Scholar 

  301. Vandenberghe K, GorisM, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997; 83: 2055–63

    PubMed  CAS  Google Scholar 

  302. Rawson ES, Wehnert ML, Clarkson PM. Effects of 30 days of creatine ingestion in oldermen. Eur J Appl Physiol 1999; 80: 139–44

    Article  CAS  Google Scholar 

  303. Gotshalk LA, Volek JS, Staron RS, et al. Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc 2002; 34: 537–43

    Article  PubMed  CAS  Google Scholar 

  304. Jakobi JM, Rice CL, Curtin SV, et al. Neuromuscular properties and fatigue in older men following acute creatine supplementation. Eur J Appl Physiol 2001; 84: 321–8

    Article  PubMed  CAS  Google Scholar 

  305. Wiroth JB, Bermon S, Andreï S, et al. Effects of oral creatine supplementation on maximal pedalling performance in older adults. Eur J Appl Physiol 2001; 84: 533–9

    Article  PubMed  CAS  Google Scholar 

  306. Ziegenfuss TN, Lowery LM, Lemon PWR. Acute fluid volume changes in men during three days of creatine supplementation. J Exerc Physiol 1998; 1: 1–9

    Google Scholar 

  307. Francaux M, Poortmans J. Effects of training and creatine supplement on muscle strength and body mass. Eur J Appl Physiol 1999; 80: 165–8

    Article  CAS  Google Scholar 

  308. Kern M, Podewils LJ, Vukovich M, et al. Physiological response to exercise in the heat following creatine supplementation. J Exerc Physiol 2001; 4: 18–27

    Google Scholar 

  309. Hulver MW, Campbell A, Haff G, et al. The effects of creatine supplementation on total body fluids, performance, and muscle cramping during exercise [abstract]. Med Sci Sports Exerc 2000; 32: S133

    Google Scholar 

  310. Juhn MS, Tarnopolsky M. Oral creatine supplementation and athletic performance: a critical review. Clin J Sport Med 1998; 8: 286–97

    Article  PubMed  CAS  Google Scholar 

  311. Schnirring L. Creatine supplements face scrutiny: will users pay later? Physician Sportsmed 1998; 6: 15–22

    Google Scholar 

  312. Schroeder C, Potteiger J, Randall J, et al. The effects of creatine dietary supplementation on anterior compartment pressure in the lower leg during rest and following exercise. Clin J Sport Med 2001; 11: 87–95

    Article  PubMed  CAS  Google Scholar 

  313. Volek JS, Mazzetti SA, Farquhar WB, et al. Physiological responses to short-term exercise in the heat after creatine loading. Med Sci Sports Exerc 2001; 33: 1101–8

    PubMed  CAS  Google Scholar 

  314. Papadopoulos C, Imamura R, Bandon LJ. The effect of creatine supplementation on repeated bouts of high-intensity exercise in the heat [abstract]. Med Sci Sports Exerc 2001; 33: S203

    Google Scholar 

  315. McArthur PD, Webster MJ, Body JC, et al. Creatine supplementation and acute dehydration [abstract]. Med Sci Sports Exerc 1999; 31: S263

    Google Scholar 

  316. Webster MJ, Vogel RA, Erdmann LD, et al. Creatine supplementation: effect on exercise performance at two levels of acute dehydration [abstract]. Med Sci Sports Exerc 1999; 31: S263

    Google Scholar 

  317. Greenwood M, Kreider R, Rasmussen C, et al. Creatine supplementation does not increase incidence of cramping or injury during college football training: II. J Strength Cond Res 1999; 13: 425–6

    Google Scholar 

  318. Kreider R, Melton C, Hunt J, et al. Creatine does not increase incidence of cramping or injury during pre-season college football training: I [abstract]. Med Sci Sports Exerc 1999; 31: S355

    Google Scholar 

  319. Greenwood M, Greenwood LD, Kreider R, et al. Effects of creatine supplementation on the incidence of cramping/injury during college football three a day training [abstract]. Med Sci Sports Exerc 2000; 32: S136

    Google Scholar 

  320. Greenwood LD, Greenwood M, Kreider R, et al. Effects of creatine supplementation on the incidence of cramping/injury during collegiate fall baseball [abstract]. Med Sci Sports Exerc 2000; 32: S136

    Google Scholar 

  321. Greenwood M, Farris J, Kreider R, et al. Creatine supplementation patterns and perceived effects in select division I collegiate athletes. Clin J Sport Med 2000; 10: 191–4

    Article  PubMed  CAS  Google Scholar 

  322. Greenwood M, Kreider R, Melton C, et al. Creatine supplementation during college football training does not increase the incidence of cramping or injury. 6th International Conference on Guanidino Compounds in Biology and Medicine; 2001 Sep 1, Cincinnati (OH)

  323. Hunt J, Kreider R, Melton C, et al. Creatine does not increase incidence of cramping or injury during pre-season college football training: II [abstract]. Med Sci Sports Exerc 1999; 31: S355

    Google Scholar 

  324. Kreider R, Rasmussen C, Ransom J, et al. Effects of creatine supplementation during training on the incidence of muscle cramping, injuries and GI distress [abstract]. J Strength Cond Res 1998; 12: 275

    Google Scholar 

  325. Kreider R, Melton C, Ransom J, et al. Creatine supplementation does not increase incidence of cramping or injury during college football training I [abstract]. J Strength Cond Res 1999; 13: 428

    Google Scholar 

  326. Rasmussen C, Kreider R, Ransom J, et al. Creatine supplementation during pre-season football training does not affect fluid or electrolyte status [abstract]. Med Sci Sports Exerc 1999; 31: S299

    Google Scholar 

  327. Sullivan PG, Geiger JD, Mattson MP, et al. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol 2000; 48: 723–9

    Article  PubMed  CAS  Google Scholar 

  328. Ortega Gallo PA, Dimeo F, Batista J, et al. Creatine supplementation in soccer players, effects in body composition and incidence of sport-related injuries [abstract]. Med Sci Sports Exerc 2000; 32: S134

    Google Scholar 

  329. Juhn MS, O’Kane JW, Vinci DM. Oral creatine supplementation in male collegiate athletes: a survey of dosing habits and side effects. J Am Diet Assoc 1999; 99: 593–5

    Article  PubMed  CAS  Google Scholar 

  330. Vanderberie F, Vandeneynde BM, Vandenberghe K, et al. Effect of creatine on endurance capacity and sprint power in cyclists. Int J Sports Med 1998; 8: 2055–63

    Google Scholar 

  331. Kuehl K, Goldber L, Elliot D. Renal insufficiency after creatine supplementation in a college football athlete [abstract]. Med Sci Sports Exerc 1998; 30: S235

    Google Scholar 

  332. Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements. Lancet 1998; 351: 1252–3

    Article  PubMed  CAS  Google Scholar 

  333. Koshy KM, Griswold E, Schneeberger EE. Interstitial nephritis in a patient taking creatine. N Engl J Med 1999; 340: 814–5

    Article  PubMed  CAS  Google Scholar 

  334. Loud K, Rozycki A, Chobanian M. Creatine nephropathy: lacrosse [abstract]. Med Sci Sports Exerc 2001; 33: S10

    Google Scholar 

  335. Poortmans JR, Francaux M. Renal dysfunction accompanying oral creatine supplements [letter]. Lancet 1998; 352: 234

    Article  PubMed  CAS  Google Scholar 

  336. Greenhaff PL. Renal dysfunction accompanying oral creatine supplements [letter]. Lancet 1998; 352: 233–4

    Article  PubMed  CAS  Google Scholar 

  337. Poortmans JR, Auquier H, Renaut V, et al. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol 1997; 76: 566–7

    Article  CAS  Google Scholar 

  338. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 1999; 31: 1108–10

    Article  PubMed  CAS  Google Scholar 

  339. Rasmussen C, Kreider R, Melton C, et al. Long-term creatine supplementation during football training does not affect markers of renal stress [abstract]. J Strength Cond Res 1999; 13: 431

    Google Scholar 

  340. Almada AL, Kreider R, Melton C, et al. Long-term creatine supplementation does not affect markers of renal stress in athletes [abstract]. J Strength Cond Res 2000; 14: 359

    Google Scholar 

  341. Kreider R, Melton C, Rasmussen C, et al. Effects of long-term creatine supplementation on renal function and muscle & liver enzyme efflux [abstract]. Med Sci Sports Exerc 2001; 33: S207

    Google Scholar 

  342. Earnest CP, Almada AL, Mitchell TL. Influence of chronic creatine supplementation on hepatorenal function [abstract]. FASEB J 1996; 10: 4588

    Google Scholar 

  343. Almada AL, Mitchell TL, Earnest CP. Impact of chronic creatine supplementation on serum enzyme concentration [abstract]. FASEB J 1996; 10: A791

    Google Scholar 

  344. Ransom J, Kreider R, Hunt J, et al. Effects of creatine supplementation during training on markers of catabolism and muscle and liver enzymes [abstract]. Med Sci Sports Exerc 1999; 31: S265

    Google Scholar 

  345. Ransom J, Kreider R, Rasmussen C, et al. Effects of long-term creatine supplementation during training on markers of catabolism and enzyme efflux [abstract]. J Strength Cond Res 1999; 13: 431

    Google Scholar 

  346. Schilling BK, Stone MH, Utter A, et al. Creatine supplementation and health variables: a retrospective study. Med Sci Sports Exerc 2001; 33: 183–8

    PubMed  CAS  Google Scholar 

  347. Pérès G. L’évaluation des risques présentés par la créatine pour le consommateur et véracitédes allégations relatives à la performance sportive ou à l’augmentation de la masse musculaire. Rapport du Comité d’experts spécialisé Nutrition humaine (CES Nutrition Humaine) auprès de la Direction de l’évaluation des risques nutritionnels et sanitaires (DERNS) de l’Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Paris, 23 de Enero de 2001. Available from URL: http://www.afssa.fr/ftp/actu/Rapport_ Creatine.pdf [Accessed 2002May 10]

  348. Yu PH, Deng Y. Potential cytotoxic effect of chronic administration of creatine, a nutrition supplement to augment athletic performance. Med Hypotheses 2000; 54: 726–8

    Article  PubMed  CAS  Google Scholar 

  349. Quievryn G, Zhitkovich A. Loss of DNA-protein crosslinks from formaldehyde-exposed cells occurs through spontaneous hydrolysis and an active repair process linked to proteosome function. Carcinogenesis 2000; 21: 1573–80

    Article  PubMed  CAS  Google Scholar 

  350. Headlam HA, Mortimer A, Easton CJ, et al. Beta-Scission of C-3 (beta-carbon) alkoxyl radicals on peptides and proteins: a novel pathway which results in the formation of alpha carbon radicals and the loss of amino acid side chains. Chem Res Toxicol 2000; 13: 1087–95

    Article  PubMed  CAS  Google Scholar 

  351. Blasiak J, Trzeciak A, Malecka-Panas E, et al. In vitro genotoxicity of ethanol and acetaldehyde in human lymphocytes and the gastrointestinal tract mucosa cells. Toxicol In Vitro 2000; 14: 287–95

    Article  PubMed  CAS  Google Scholar 

  352. Miller EE, Evans AE, Cohn M. Inhibition of rate of tumor growth by creatine and cyclocreatine. Proc Natl Acad Sci U S A 1993; 90: 3304–8

    Article  PubMed  CAS  Google Scholar 

  353. Schiffenbauer YS, Meir G, Cohn M, et al. Cyclocreatine transport and cytotoxicity in rat glioma and human ovarian carcinoma cells: 31P-NMR spectroscopy. Am J Physiol 1996; 270: C160–9

    Google Scholar 

  354. Ara G, Gravelin LM, Kaddurah-Daouk R, et al. Antitumor activity of creatine analogs produced by alterations in pancreatic hormones and glucose metabolism. In Vivo 1998; 12: 223–31

    PubMed  CAS  Google Scholar 

  355. Kristensen CA, Askenasy N, Jain RK, et al. Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies. Br J Cancer 1999; 79: 278–85

    Article  PubMed  CAS  Google Scholar 

  356. Jeong KS, Park SJ, Lee CS, et al. Effects of cyclocreatine in rat hepatocarcinogenesis model. Anticancer Res 2000; 20: 1627–33

    PubMed  CAS  Google Scholar 

  357. Sugimura T, Nagao M, Kawachi T, et al. Mutagens-carcinogens in foods, with special reference to highly mutagenic pyrolytic products in broiled foods. In: Hiatt HH, Watson JD, Winsten JA, editors. Origins of human cancer. New York: Cold Spring Harbor Laboratory Press, 1977: 1561–77

    Google Scholar 

  358. Commoner B, Vithayathil AJ, Dolara P, et al. Formation of mutagens in beef and beef extract during cooking. Science 1978; 201: 913–6

    Article  PubMed  CAS  Google Scholar 

  359. Sugimura T. Mutagens, carcinogens and tumor promoters in our daily food. Cancer 1982; 49: 1970–84

    Article  PubMed  CAS  Google Scholar 

  360. Felton JS, Knize MG. Occurrence, identification and bacterial mutagenicity of heterocyclic amines in cooked food. Mutat Res 1991; 259: 205–17

    Article  PubMed  CAS  Google Scholar 

  361. Wakabayashi K, Ushiyama H, Takahashi M, et al. Exposure to heterocyclic amines. Environ Health Perspect 1993; 99: 129–33

    Article  PubMed  CAS  Google Scholar 

  362. Skog K. Cooking procedures and food mutagens: a literature review. Food Chem Toxicol 1993; 31: 655–75

    Article  PubMed  CAS  Google Scholar 

  363. Robbana-Barnat S, Rabache M, Rialland E, et al. Heterocyclic amines: occurrence and prevention in cooked food. Environ Health Perspect 1996; 104: 280–8

    Article  PubMed  CAS  Google Scholar 

  364. Kim IS, Wakabayashi K, Kurosaka R, et al. Isolation and identification of a new mutagen, 2-amino-4-hydroxy-methyl-3,8- dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx), from beef extract. Carcinogenesis 1994; 15: 21–6

    Article  PubMed  CAS  Google Scholar 

  365. Vikse R, Joner PE. Mutagenicity, creatine and nutrient contents of pan fried meat from various animal species. Acta Vet Scand 1993; 34: 363–70

    PubMed  CAS  Google Scholar 

  366. Oguri A, Nagao M, Arakawa N, et al. Mutagen formation after heating of mixtures of guanidino compounds amino acids and glucose. Proc Jpn Acad 1994; 70: 67–70

    CAS  Google Scholar 

  367. Sinha R, Rothman N, Brown ED, et al. High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method. Cancer Res 1995; 55: 4516–9

    PubMed  CAS  Google Scholar 

  368. Gross GA, Grüter A. Quantitation of mutagenic/carcinogenic heterocyclic aromatic amines in food products. J Chromatogr 1992; 592: 271–8

    Article  PubMed  CAS  Google Scholar 

  369. Bemben MG, Bemben DA, Loftiss DD, et al. Creatine supplementation during resistance training in college football athletes. Med Sci Sports Exerc 2001; 33: 1667–73

    Article  PubMed  CAS  Google Scholar 

  370. Greenwood M, Kreider R, Melton C, et al. Short- and long-term creatine supplementation does not affect hematological markers of health. J Strength Cond Res 2000; 14: 362–3

    Google Scholar 

  371. Vannas-Sulonen K, Sipila I, Vannas A, et al. Gyrate atrophy of the choroid and retina: a five-year follow-up of creatine supplementation. Ophthalmology 1985; 92: 1719–27

    PubMed  CAS  Google Scholar 

  372. Stockler S, Hanefeld F. Guanidinoacetate methyltransferase deficiency: a newly recognized inborn error of creatine biosynthesis. Wien Klin Wochenschr 1997; 109: 86–8

    PubMed  CAS  Google Scholar 

  373. Stockler S, Hanefeld F, Frahm J. Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 1996; 348: 789–90

    Article  PubMed  CAS  Google Scholar 

  374. Stockler S, Holzbach U, Hanefeld F, et al. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 1994; 36: 409–13

    Article  PubMed  CAS  Google Scholar 

  375. Stockler S, Isbrandt D, Hanefeld F, et al. Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet 1996; 58: 914–22

    PubMed  CAS  Google Scholar 

  376. Stockler S, Marescau B, De Deyn PP, et al. Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism 1997; 46: 1189–93

    Article  PubMed  CAS  Google Scholar 

  377. Schulze A, Hess T, Wevers R, et al. Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism. J Pediatr 1997; 131: 626–31

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Dr Conrad Earnest for his assistance in reviewing the manuscript and the provision of highly valuable information. This paper has been prepared without any external funding. No present or past conflict of interest exists for any of the authors or their institutions.

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  1. Department of Physiology, School of Medicine, University of Granada, E-18071, Granada, Spain

    José L. M. Mesa, Jonatan R. Ruiz, M. Marcela González-Gross, Ángel Gutiérrez Sáinz & Manuel J. Castillo Garzón

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  1. José L. M. Mesa
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  2. Jonatan R. Ruiz
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  3. M. Marcela González-Gross
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Correspondence to Manuel J. Castillo Garzón.

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Dedicated to the memory of our admired Carlos Osorio Peláez (19.09.1932-27.06.2001), Professor of Physiology and Biochemistry at the School of Medicine of the University of Granada.

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Mesa, J.L.M., Ruiz, J.R., González-Gross, M.M. et al. Oral Creatine Supplementation and Skeletal Muscle Metabolism in Physical Exercise. Sports Med 32, 903–944 (2002). https://doi.org/10.2165/00007256-200232140-00003

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