Skip to main content
SpringerLink
Log in

Pharmacokinetics of the Dietary Supplement Creatine

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Creatine is a nonessential dietary component that, when supplemented in the diet, has shown physiological benefits in athletes, in animal-based models of disease and in patients with various muscle, neurological and neuromuscular disease. The clinical relevance of creatine supplementation is based primarily on its role in ATP generation, and cells may be able to better handle rapidly changing energy demands with supplementation.

Although the pharmacological outcome measures of creatine have been investigated, the behaviour of creatine in the blood and muscle is still not fully understood. Creatine is most probably actively absorbed from the gastrointestinal tract in a similar way to amino acids and peptides. The distribution of creatine throughout the body is largely determined by the presence of creatine transporters. These transporters not only serve to distribute creatine but serve as a clearance mechanism because of creatine ‘trapping’ by skeletal muscle. Besides the pseudo-irreversible uptake by skeletal muscle, creatine clearance also depends on renal elimination and degradation to creatinine.

Evidence suggests that creatine pharmacokinetics are nonlinear with respect to dose size and frequency. Skeletal muscle, the largest depot of creatine, has a finite capacity to store creatine. As such, when these stores are saturated, both volume of distribution and clearance can decrease, thus leading to complex pharmacokinetic situations. Additionally, other dietary components such as caffeine and carbohydrate can potentially affect pharmacokinetics by their influence on the creatine transporter. Disease and age may also affect the pharmacokinetics, but more information is needed.

Overall, there are very limited pharmacokinetic data available for creatine, and further studies are needed to define absorption characteristics, clearance kinetics and the effect of multiple doses. Additionally, the relationship between plasma creatine and muscle creatine needs to be elucidated to optimise administration regimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Fig. 2
Fig. 3
Table II
Fig. 4
Table III
Fig. 5
Table IV

Similar content being viewed by others

Notes

  1. Since the time of writing this review, Persky et al., published results from a clinical study that supports many of the hypotheses from this review.

References

  1. Schnirring L. Creatine supplements face scrutiny: will users pay later?. Phys Sportsmed 1998; 26(6): 15–23

    Google Scholar 

  2. Steenge GR, Lambourne J, Casey A, et al. Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. Am J Physiol 1998; 275(6 Pt 1): E974–9

    PubMed  CAS  Google Scholar 

  3. Steenge GR, Simpson EJ, Greenhaff PL. Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. J Appl Physiol 2000; 89(3): 1165–71

    PubMed  CAS  Google Scholar 

  4. Harris RC, Söderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 1992; 83(3): 367–74

    CAS  Google Scholar 

  5. Schedel JM, Tanaka H, Kiyonaga A, et al. Acute creatine ingestion in human: consequences on serum creatine and creatinine concentrations. Life Sci 1999; 65(23): 2463–70

    Article  PubMed  CAS  Google Scholar 

  6. 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(5): 258–62

    PubMed  CAS  Google Scholar 

  7. Green AL, Simpson EJ, Littlewood JJ, et al. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand 1996; 158(2): 195–202

    Article  PubMed  CAS  Google Scholar 

  8. Fitch CD, Sinton D. A study of creatine metabolism is diseases causing muscle wasting. J Clin Invest 1964; 43(3): 444–52

    Article  PubMed  CAS  Google Scholar 

  9. 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 

  10. 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(3): 347–50

    Article  PubMed  CAS  Google Scholar 

  11. Mazzini L, Balzarmi C, Colombo R, et al. Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results. J Neurol Sci 2001; 191(1–2): 139–44

    Article  PubMed  CAS  Google Scholar 

  12. Willer B, Stucki G, Hoppeler H, et al. Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis. Rheumatology (Oxford) 2000; 39(3): 293–8

    Article  CAS  Google Scholar 

  13. Andrews R, Greenhaff P, Curtis S, et al. The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure. Eur Heart J 1998; 19(4): 617–22

    Article  PubMed  CAS  Google Scholar 

  14. Field ML. Creatine supplementation in congestive heart failure. Cardiovasc Res 1996; 31(1): 174–6

    PubMed  CAS  Google Scholar 

  15. Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995; 30(3): 413–8

    PubMed  CAS  Google Scholar 

  16. Hespel P, Eijnde BO, Van Leemputte M, et al. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol 2001; 536(Pt 2): 625–33

    Article  PubMed  CAS  Google Scholar 

  17. Heinanen K, Nanto-Salonen K, Komu M, et al. Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia. Eur J Clin Invest 1999; 29(12): 1060–5

    Article  PubMed  CAS  Google Scholar 

  18. 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(12): 1719–27

    PubMed  CAS  Google Scholar 

  19. 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(15): 867–70

    Article  PubMed  CAS  Google Scholar 

  20. Andreassen OA, Dedeoglu A, Ferrante RJ, et al. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiol Dis 2001; 8(3): 479–91

    Article  PubMed  CAS  Google Scholar 

  21. 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(12): 4389–97

    PubMed  CAS  Google Scholar 

  22. Matthews RT, Yang L, Jenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci 1998; 18(1): 156–63

    PubMed  CAS  Google Scholar 

  23. Vorgerd M, Grehl T, Jager M, et al. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebocontrolled crossover trial. Arch Neurol 2000; 57(7): 956–63

    Article  PubMed  CAS  Google Scholar 

  24. Vorgerd M, Zange J, Kley R, et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Arch Neurol 2002; 59(1): 97–101

    Article  PubMed  Google Scholar 

  25. Tarnopolsky MA, Martin J. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology 1999; 52: 854–7

    Article  PubMed  CAS  Google Scholar 

  26. Doherty TJ, Lougheed K, Markez J, et al. Creatine monohydrate does not increase strength in patients with hereditary neuropathy. Neurology 2001; 57(3): 559–60

    Article  PubMed  CAS  Google Scholar 

  27. Ikeda K, Kinoshita M, Iwasaki Y, et al. Creatine monohydrate increases strength in patients with neuromuscular disease [letter]. Neurology 2000; 54(2): 537

    Article  PubMed  CAS  Google Scholar 

  28. Klopstock T, Querner V, Schmidt F, et al. A placebo-controlled crossover trial of creatine in mitochondrial diseases. Neurology 2000; 55(11): 1748–51

    Article  PubMed  CAS  Google Scholar 

  29. Hagenfeldt L, von Dobeln U, Solders G, et al. Creatine treatment in MELAS [letter]. Muscle Nerve 1994; 17(10): 1236–7

    PubMed  CAS  Google Scholar 

  30. Tarnopolsky MA, Roy BD, MacDonald JR. A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve 1997; 20(12): 1502–9

    Article  PubMed  CAS  Google Scholar 

  31. Passaquin AC, Renard M, Kay L, et al. Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Neuromuscul Disord 2002; 12(2): 174–82

    Article  PubMed  Google Scholar 

  32. 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(2): 145–50

    PubMed  CAS  Google Scholar 

  33. Pulido SM, Passaquin AC, Leijendekker WJ, et al. Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells. FEBS Lett 1998; 439(3): 357–62

    Article  PubMed  CAS  Google Scholar 

  34. Walter MC, Lochmuller H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: a double-blind, placebo-controlled clinical study. Neurology 2000; 54(9): 1848–50

    Article  PubMed  CAS  Google Scholar 

  35. Sullivan PG, Geiger JD, Mattson MP, et al. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol 2000; 48(5): 723–9

    Article  PubMed  CAS  Google Scholar 

  36. Wilken B, Ramirez JM, Probst I, et al. Anoxic ATP depletion in neonatal mice brainstem is prevented by creatine supplementation. Arch Dis Child Fetal Neonatal Ed 2000; 82(3): F224–7

    Article  PubMed  CAS  Google Scholar 

  37. Balestrino M, Rebaudo R, Lunardi G. Exogenous creatine delays anoxic depolarization and protects from hypoxic damage: dose-effect relationship. Brain Res 1999; 816: 124–30

    Article  PubMed  CAS  Google Scholar 

  38. Brewer G, Wallimann T. Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons. J Neurochem 2000; 74: 1968–78

    Article  PubMed  CAS  Google Scholar 

  39. Kaemmerer WF, Rodrigues CM, Steer CJ, et al. Creatinesupplemented diet extends Purkinje cell survival in spinocerebellar ataxia type 1 transgenic mice but does not prevent the ataxic phenotype. Neuroscience 2001; 103(3): 713–24

    Article  PubMed  CAS  Google Scholar 

  40. Malcon C, Kaddurah-Daouk R, Beal M. Neuroprotective effects of creatine administration against NMDA and malonate toxicity. Brain Res 2000; 860: 195–8

    Article  PubMed  CAS  Google Scholar 

  41. Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol 1999; 157(1): 142–9

    Article  PubMed  CAS  Google Scholar 

  42. Brustovetsky N, Brustovetsky T, Dubinsky JM. On the mechanisms of neuroprotection by creatine and phosphocreatine. J Neurochem 2001; 76(2): 425–34

    Article  PubMed  CAS  Google Scholar 

  43. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev 2001; 53(2): 161–76

    PubMed  CAS  Google Scholar 

  44. Sahlin K, Tonkonogi M, Söderlund K. Energy supply and muscle fatigue in humans. Acta Physiol Scand 1998; 162(3): 261–6

    Article  PubMed  CAS  Google Scholar 

  45. Hultman E, Söderlund K, Timmons JA, et al. Muscle creatine loading in men. J Appl Physiol 1996; 81(1): 232–7

    PubMed  CAS  Google Scholar 

  46. Casey A, Constantin-Teodosiu D, Howell S, et al. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 1996; 271(1 Pt 1): E31–7

    PubMed  CAS  Google Scholar 

  47. Greenhaff PL, Bodin K, Söderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994; 266(5 Pt 1): E725–30

    PubMed  CAS  Google Scholar 

  48. 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(5 Pt 1): E821–6

    PubMed  CAS  Google Scholar 

  49. 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(3): 303–10

    Article  PubMed  CAS  Google Scholar 

  50. Dechent P, Pouwels PJ, Wilken B, et al. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol 1999; 277(3 Pt 2): R698–704

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  52. Michaelis T, Wick M, Fujimori H, et al. Proton MRS of oral creatine supplementation in rats: cerebral metabolite concentrations and ischemic challenge. NMR Biomed 1999; 12(5): 309–14

    Article  PubMed  CAS  Google Scholar 

  53. Greenhaff PL, Casey A, Short AH, et al. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci (Lond) 1993; 84(5): 565–71

    CAS  Google Scholar 

  54. Vandenberghe K, Van Hecke P, Van Leemputte M, et al. Phosphocreatine resynthesis is not affected by creatine loading. Med Sci Sports Exerc 1999; 31(2): 236–42

    Article  PubMed  CAS  Google Scholar 

  55. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000; 80(3): 1107–213

    PubMed  CAS  Google Scholar 

  56. Walker J. Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 1979; 50: 117–242

    Google Scholar 

  57. 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(2): 147–51

    Article  PubMed  Google Scholar 

  58. Stockler S, Holzbach U, Hanefeld F, et al. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 1994; 36(3): 409–13

    Article  PubMed  CAS  Google Scholar 

  59. Kamber M, Koster M, Kreis R, et al. Creatine supplementation: part I. performance, clinical chemistry, and muscle volume. Med Sci Sports Exerc 1999; 31(12): 1763–9

    Article  PubMed  CAS  Google Scholar 

  60. Volek JS, Duncan ND, Mazzetti SA, et al. No effect of heavy resistance training and creatine supplementation on blood lipids. Int J Sport Nutr Exerc Metab 2000; 10(2): 144–56

    PubMed  CAS  Google Scholar 

  61. 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(2): 291–6

    Article  PubMed  CAS  Google Scholar 

  62. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 1999; 31(8): 1108–10

    Article  PubMed  CAS  Google Scholar 

  63. 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(6): 566–7

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  65. Dash AK, Miller DW, Huai-Yan H, et al. Evaluation of creatine transport using Caco-2 monolayers as an in vitro model for intestinal absorption. J Pharm Sci 2001; 90(10): 1593–8

    Article  PubMed  CAS  Google Scholar 

  66. Borsook H, Dubnoff J. The hydrolysis of phosphocreatine and the origin of urinary creatinine. J Biol Chem 1947; 168: 493–511

    PubMed  CAS  Google Scholar 

  67. Cannan R, Shore A. The creatine-creatinine equilibrium: the apparent dissociation constants of creatine and creatinine. Bio-chem J 1928; 22: 921–9

    Google Scholar 

  68. Edgar G, Shiver H. The equilibrium between creatine and creatinine, in aqueous solution: the effect of hydrogen ion. J Am Chem Soc 1925; 47: 1170–88

    Article  Google Scholar 

  69. Wixom RL, Davis GE, Flynn MA, et al. Excretion of creatine and creatinine in feces of man. Proc Soc Exp Biol Med 1979; 161(4): 452–7

    PubMed  CAS  Google Scholar 

  70. Twort F, Mellanby E. On creatine-destroying Bacilli in the intestine and their isolation. J Physiol 1912; 44: 43–9

    PubMed  CAS  Google Scholar 

  71. Persky AM, Hochhaus G, Brazeau GA. Validation of a simple HPLC assay for creatine suitable for pharmacokinetic applications, determination of plasma protein binding and verification of percent labeled claim of various creatine products. J Chromatog B Biomed Appl. In review

  72. Snow RJ, Murphy RM. Creatine and the creatine transporter: a review. Mol Cell Biochem 2001; 224(1–2): 169–81

    Article  PubMed  CAS  Google Scholar 

  73. Guerrero-Ontiveros ML, Wallimann T. Creatine supplementation in health and disease: effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle. Mol Cell Biochem 1998; 184(1–2): 427–37

    Article  PubMed  CAS  Google Scholar 

  74. 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(12): 8418–21

    PubMed  CAS  Google Scholar 

  75. Soral, Richman J, Santoro G, et al. The cloning and expression of a human creatine transporter. Biochem Biophys Res Commun 1994; 204(1): 419–27

    Article  Google Scholar 

  76. Iyer GS, Krahe R, Goodwin LA, et al. Identification of a testisexpressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28. Genomics 1996; 34(1): 143–6

    Article  PubMed  CAS  Google Scholar 

  77. Neubauer S, Remkes H, Spindler M, et al. Downregulation of the Na+-creatine cotransporter in failing human myocardium and in experimental heart failure. Circulation 1999; 100(18): 1847–50

    Article  PubMed  CAS  Google Scholar 

  78. Tarnopolsky MA, Parshad A, Walzel B, et al. Creatine transporter and mitochondrial creatine kinase protein content in myopathies. Muscle Nerve 2001; 24(5): 682–8

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  80. Saltarelli MD, Bauman AL, Moore KR, et al. Expression of the rat brain creatine transporter in situ and in transfected HeLa cells. Dev Neurosci 1996; 18(5-6): 524–34

    Article  PubMed  CAS  Google Scholar 

  81. Dodd JR, Zheng T, Christie DL. Creatine accumulation and exchange by HEK293 cells stably expressing high levels of a creatine transporter. Biochim Biophys Acta 1999; 1472(1–2): 128–36

    Article  PubMed  CAS  Google Scholar 

  82. Ku CP, Passow H. Creatine and creatinine transport in old and young human red blood cells. Biochim Biophys Acta 1980; 600(1): 212–27

    Article  PubMed  CAS  Google Scholar 

  83. Loike JD, Somes M, Silverstein SC. Creatine uptake, metabolism, and efflux in human monocytes and macrophages. Am J Physiol 1986; 251(1 Pt 1): C128–35

    PubMed  CAS  Google Scholar 

  84. Moller A, Hamprecht B. Creatine transport in cultured cells of rat and mouse brain. J Neurochem 1989; 52(2): 544–50

    Article  PubMed  CAS  Google Scholar 

  85. 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(2): 637–45

    Article  PubMed  CAS  Google Scholar 

  86. 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(2): 99–104

    Article  PubMed  CAS  Google Scholar 

  87. 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 

  88. 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(2): 109–20

    Article  PubMed  CAS  Google Scholar 

  89. Meyer RA, Brown TR, Kushmerick MJ. Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle. Am J Physiol 1985; 248(3 Pt 1): C279–87

    PubMed  CAS  Google Scholar 

  90. 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(16): 7521–5

    Article  PubMed  CAS  Google Scholar 

  91. Odoom JE, Kemp GJ, Radda GK. The regulation of total creatine content in a myoblast cell line. Mol Cell Biochem 1996; 158(2): 179–88

    Article  PubMed  CAS  Google Scholar 

  92. 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(2): 598–604

    PubMed  CAS  Google Scholar 

  93. Thorell A, Hirshman MF, Nygren J, et al. Exercise and insulin cause GLUT-4 translocation in human skeletal muscle. Am J Physiol 1999; 277(4 Pt 1): E733–41

    PubMed  CAS  Google Scholar 

  94. Fitch CD, Lucy DD, Bornhofen JH, et al. Creatine metabolism in skeletal muscle: II. creatine kinetics in man. Neurology 1968; 18(1 Pt 1): 32–42

    Article  PubMed  CAS  Google Scholar 

  95. Kuwabara T, Kobayashi S, Sugiyama Y. Pharmacokinetics and pharmacodynamics of a recombinant human granulocyte colony-stimulating factor. Drug Metab Rev 1996; 28(4): 625–58

    Article  PubMed  CAS  Google Scholar 

  96. 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(2): 147–55

    Article  PubMed  CAS  Google Scholar 

  97. Rawson ES, Clarkson PM. Acute creatine supplementation in older men. Int J Sports Med 2000; 21(1): 71–5

    Article  PubMed  CAS  Google Scholar 

  98. Rawson ES, Wehnert ML, Clarkson PM. Effects of 30 days of creatine ingestion in older men. Eur J Appl Physiol 1999; 80(2): 139–44

    Article  CAS  Google Scholar 

  99. 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(8): 1147–56

    Article  PubMed  CAS  Google Scholar 

  100. Gillette JR. Factors affecting drug metabolism. Ann N Y Acad Sci 1971; 179: 43–66

    Article  PubMed  CAS  Google Scholar 

  101. Pitts RF. The clearance of creatine in dog and man. Am J Physiol 1934; 109: 532–41

    CAS  Google Scholar 

  102. Sims E, Seldin D. Reabsorption of creatine and guanidoacetic acid by the renal tubules. Am J Physiol 1949; 157(14): 14–20

    PubMed  CAS  Google Scholar 

  103. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997; 83(6): 2055–63

    PubMed  CAS  Google Scholar 

  104. Pasternack A, Kuhlback B. Diurnal variations of serum and urine creatine and creatinine. Scand J Clin Invest 1971; 27: 1–7

    Article  PubMed  CAS  Google Scholar 

  105. Crim MC, Calloway DH, Margen S. Creatine metabolism in men: urinary creatine and creatinine excretions with creatine feeding. J Nutr 1975; 105(4): 428–38

    PubMed  CAS  Google Scholar 

  106. Crim M, Calloway D, 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 

  107. 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(3): 706–17

    Article  PubMed  CAS  Google Scholar 

  108. Maganaris CN, Maughan RJ. Creatine supplementation enhances maximum voluntary isometric force and endurance capacity in resistance trained men. Acta Physiol Scand 1998; 163(3): 279–87

    Article  PubMed  CAS  Google Scholar 

  109. Boroujerdi M. A nonlinear tissue-binding model for creatine: estimation of creatine turnover time and creatinine production rate. Res Commun Chem Pathol Pharmacol 1986; 53(3): 361–71

    PubMed  CAS  Google Scholar 

  110. Elias E, Gibson GJ, Greenwood LF, et al. The slowing of gastric emptying by monosaccharides and disaccharides in test meals. J Physiol 1968; 194(2): 317–26

    PubMed  CAS  Google Scholar 

  111. Vandenberghe K, Gillis N, Van Leemputte M, et al. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996; 80(2): 452–7

    PubMed  CAS  Google Scholar 

  112. Chrusch MJ, Chilibeck PD, Chad KE, et al. Creatine supplementation combined with resistance training in older men. Med Sci Sports Exerc 2001; 33(12): 2111–7

    Article  PubMed  CAS  Google Scholar 

  113. Wiroth JB, Bermon S, Andrei S, et al. Effects of oral creatine supplementation on maximal pedalling performance in older adults. Eur J Appl Physiol 2001; 84(6): 533–9

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Mrs. Patricia Kahn for her help in preparation of the manuscript. Preparation of this manuscript was supported, in part, by The Experimental and Applied Science (EAS) Research Grant on Nutrition and Human Performance from the American College of Sport Medicine Foundation.There are no conflicts of interest relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA

    Adam M. Persky & Günther Hochhaus

  2. Department of Pharmacy Practice and Pharmaceutics, State University of New York at Buffalo, Amherst, New York, USA

    Gayle A. Brazeau

Authors
  1. Adam M. Persky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gayle A. Brazeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Günther Hochhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adam M. Persky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Persky, A.M., Brazeau, G.A. & Hochhaus, G. Pharmacokinetics of the Dietary Supplement Creatine. Clin Pharmacokinet 42, 557–574 (2003). https://doi.org/10.2165/00003088-200342060-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200342060-00005

Keywords

Search

Navigation