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Amino Acids

, Volume 38, Issue 1, pp 31–44 | Cite as

Exploring the therapeutic role of creatine supplementation

  • Bruno GualanoEmail author
  • Guilherme Giannini Artioli
  • Jacques R. Poortmans
  • Antonio Herbert Lancha Junior
Review Article

Abstract

Creatine (Cr) plays a central role in energy provision through a reaction catalyzed by phosphorylcreatine kinase. Furthermore, this amine enhances both gene expression and satellite cell activation involved in hypertrophic response. Recent findings have indicated that Cr supplementation has a therapeutic role in several diseases characterized by atrophic conditions, weakness, and metabolic disturbances (i.e., in the muscle, bone, lung, and brain). Accordingly, there has been an evidence indicating that Cr supplementation is capable of attenuating the degenerative state in some muscle disorders (i.e., Duchenne and inflammatory myopathies), central nervous diseases (i.e., Parkinson’s, Huntington’s, and Alzheimer’s), and bone and metabolic disturbances (i.e., osteoporosis and type II diabetes). In light of this, Cr supplementation could be used as a therapeutic tool for the elderly. The aim of this review is to summarize the main studies conducted in this field and to highlight the scientific and clinical perspectives of this promising therapeutic supplement.

Keywords

Nutritional supplementation Creatine Therapeutic effects 

Notes

Acknowledgments

Bruno Gualano is grateful to Conselho Nacional de Pesquisa e Desenvolvimento (CNPq). All authors contributed equally to this manuscript.

Conflict of interest statement

The authors declare that there is no conflict of interest.

References

  1. Adcock KH, Nedelcu J, Loenneker T, Martin E, Wallimann T, Wagner BP (2002) Neuroprotection of creatine supplementation in neonatal rats with transient cerebral hypoxia-ischemia. Dev Neurosci 24:382–388. doi: 10.1159/000069043 PubMedGoogle Scholar
  2. Aksenov MY, Aksenova MV, Payne RM, Smith CD, Markesbery WR, Carney JM (1997) The expression of creatine kinase isoenzymes in neocortex of patients with neurodegenerative disorders: Alzheimer’s and Pick’s disease. Exp Neurol 146:458–465. doi: 10.1006/exnr.1997.6550 PubMedGoogle Scholar
  3. Alam M, Schmidt WJ (2002) Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 136:317–324. doi: 10.1016/S0166-4328(02)00180-8 PubMedGoogle Scholar
  4. Almeida LS, Salomons GS, Hogenboom F, Jakobs C, Schoffelmeer AN (2006) Exocytotic release of creatine in rat brain. Synapse 60:118–123. doi: 10.1002/syn.20280 PubMedGoogle Scholar
  5. Amital D, Vishne T, Roitman S, Kotler M, Levine J (2006a) Open study of creatine monohydrate in treatment-resistant posttraumatic stress disorder. J Clin Psychiatry 67:836–837PubMedGoogle Scholar
  6. Amital D, Vishne T, Rubinow A, Levine J (2006b) Observed effects of creatine monohydrate in a patient with depression and fibromyalgia. Am J Psychiatry 163:1840–1841. doi: 10.1176/appi.ajp.163.10.1840-b PubMedGoogle Scholar
  7. Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR (2008) Functions and effects of creatine in the central nervous system. Brain Res Bull 76:329–343. doi: 10.1016/j.brainresbull.2008.02.035 PubMedGoogle Scholar
  8. Andrews R, Greenhaff P, Curtis S, Perry A, Cowley AJ (1998) The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure. Eur Heart J 19:617–622. doi: 10.1053/euhj.1997.0767 PubMedGoogle Scholar
  9. Battini R, Alessandri MG, Leuzzi V, Moro F, Tosetti M, Bianchi MC, Cioni G (2006) Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: early treatment can prevent phenotypic expression of the disease. J Pediatr 148:828–830. doi: 10.1016/j.jpeds.2006.01.043 PubMedGoogle Scholar
  10. Bender A, Auer DP, Merl T, Reilmann R, Saemann P, Yassouridis A, Bender J, Weindl A, Dose M, Gasser T, Klopstock T (2005) Creatine supplementation lowers brain glutamate levels in Huntington’s disease. J Neurol 252:36–41. doi: 10.1007/s00415-005-0595-4 PubMedGoogle Scholar
  11. Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M, Gekeler F, Muller-Myhsok B, Gasser T, Tatsch K, Klopstock T (2006) Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 67:1262–1264. doi: 10.1212/01.wnl.0000238518.34389.12 PubMedGoogle Scholar
  12. Bender A, Beckers J, Schneider I, Holter SM, Haack T, Ruthsatz T, Vogt-Weisenhorn DM, Becker L, Genius J, Rujescu D, Irmler M, Mijalski T, Mader M, Quintanilla-Martinez L, Fuchs H, Gailus-Durner V, de Angelis MH, Wurst W, Schmidt J, Klopstock T (2008) Creatine improves health and survival of mice. Neurobiol Aging 29:1404–1411. doi: 10.1016/j.neurobiolaging.2007.03.001 PubMedGoogle Scholar
  13. Bourgeois JM, Nagel K, Pearce E, Wright M, Barr RD, Tarnopolsky MA (2008) Creatine monohydrate attenuates body fat accumulation in children with acute lymphoblastic leukemia during maintenance chemotherapy. Pediatr Blood Cancer 51:183–187. doi: 10.1002/pbc.21571 PubMedGoogle Scholar
  14. Braissant O, Henry H (2008) AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: a review. J Inherit Metab Dis (Epub ahead of print)Google Scholar
  15. Braissant O, Henry H, Villard AM, Zurich MG, Loup M, Eilers B, Parlascino G, Matter E, Boulat O, Honegger P, Bachmann C (2002) Ammonium-induced impairment of axonal growth is prevented through glial creatine. J Neurosci 22:9810–9820PubMedGoogle Scholar
  16. Brewer GJ, Wallimann TW (2000) Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons. J Neurochem 74:1968–1978. doi: 10.1046/j.1471-4159.2000.0741968.x PubMedGoogle Scholar
  17. Brose A, Parise G, Tarnopolsky MA (2003) Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J Gerontol A Biol Sci Med Sci 58:11–19PubMedGoogle Scholar
  18. Browne SE, Yang L, DiMauro JP, Fuller SW, Licata SC, Beal MF (2006) Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS. Neurobiol Dis 22:599–610. doi: 10.1016/j.nbd.2006.01.001 PubMedGoogle Scholar
  19. Cagnon L, Braissant O (2007) Hyperammonemia-induced toxicity for the developing central nervous system. Brain Res Rev 56:183–197. doi: 10.1016/j.brainresrev.2007.06.026 PubMedGoogle Scholar
  20. Candow DG, Little JP, Chilibeck PD, Abeysekara S, Zello GA, Kazachkov M, Cornish SM, Yu PH (2008) Low-dose creatine combined with protein during resistance training in older men. Med Sci Sports Exerc (Epub ahead of print)Google Scholar
  21. Chilibeck PD, Chrusch MJ, Chad KE, Shawn Davison K, Burke DG (2005) Creatine monohydrate and resistance training increase bone mineral content and density in older men. J Nutr Health Aging 9:352–353PubMedGoogle Scholar
  22. Chung YL, Alexanderson H, Pipitone N, Morrison C, Dastmalchi M, Stahl-Hallengren C, Richards S, Thomas EL, Hamilton G, Bell JD, Lundberg IE, Scott DL (2007) Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: 6-month, double-blind, randomized, placebo-controlled trial. Arthritis Rheum 57:694–702. doi: 10.1002/art.22687 PubMedGoogle Scholar
  23. Coplan JD, Mathew SJ, Mao X, Smith EL, Hof PR, Coplan PM, Rosenblum LA, Gorman JM, Shungu DC (2006) Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: relationship to IQ and early trauma. Psychiatry Res 147:27–39. doi: 10.1016/j.pscychresns.2005.12.011 PubMedGoogle Scholar
  24. De Deyn PP, Macdonald RL (1990) Guanidino compounds that are increased in cerebrospinal fluid and brain of uremic patients inhibit GABA and glycine responses on mouse neurons in cell culture. Ann Neurol 28:627–633. doi: 10.1002/ana.410280505 PubMedGoogle Scholar
  25. De Deyn PP, Wirshing WC (2001) Scales to assess efficacy and safety of pharmacologic agents in the treatment of behavioral and psychological symptoms of dementia. J Clin Psychiatry 62(Suppl 21):19–22PubMedGoogle Scholar
  26. Deacon SJ, Vincent EE, Greenhaff PL, Fox J, Steiner MC, Singh SJ, Morgan MD (2008) Randomized controlled trial of dietary creatine as an adjunct therapy to physical training in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 178:233–239. doi: 10.1164/rccm.200710-1508OC PubMedGoogle Scholar
  27. Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie MJ, Francaux M (2008) Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. J Appl Physiol 104:371–378. doi: 10.1152/japplphysiol.00873.2007 PubMedGoogle Scholar
  28. Dempsey RL, Mazzone MF, Meurer LN (2002) Does oral creatine supplementation improve strength? A meta-analysis. J Fam Pract 51:945–951PubMedGoogle Scholar
  29. Drory VE, Gross D (2002) No effect of creatine on respiratory distress in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 3:43–46. doi: 10.1080/146608202317576534 PubMedGoogle Scholar
  30. Dupuis L, Oudart H, Rene F, Gonzalez de Aguilar JL, Loeffler JP (2004) Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci USA 101:11159–11164. doi: 10.1073/pnas.0402026101 PubMedGoogle Scholar
  31. Earnest CP, Almada AL, Mitchell TL (1996) High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci (Lond) 91:113–118Google Scholar
  32. Escolar DM, Buyse G, Henricson E, Leshner R, Florence J, Mayhew J, Tesi-Rocha C, Gorni K, Pasquali L, Patel KM, McCarter R, Huang J, Mayhew T, Bertorini T, Carlo J, Connolly AM, Clemens PR, Goemans N, Iannaccone ST, Igarashi M, Nevo Y, Pestronk A, Subramony SH, Vedanarayanan VV, Wessel H (2005) CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy. Ann Neurol 58:151–155. doi: 10.1002/ana.20523 PubMedGoogle Scholar
  33. Faager G, Soderlund K, Skold CM, Rundgren S, Tollback A, Jakobsson P (2006) Creatine supplementation and physical training in patients with COPD: a double blind, placebo-controlled study. Int J Chron Obstruct Pulmon Dis 1:445–453. doi: 10.2147/copd.2006.1.4.445 PubMedGoogle Scholar
  34. Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF (2000) Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J Neurosci 20:4389–4397PubMedGoogle Scholar
  35. Francaux M, Poortmans JR (1999) Effects of training and creatine supplement on muscle strength and body mass. Eur J Appl Physiol Occup Physiol 80:165–168. doi: 10.1007/s004210050575 PubMedGoogle Scholar
  36. Fuld JP, Kilduff LP, Neder JA, Pitsiladis Y, Lean ME, Ward SA, Cotton MM (2005) Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease. Thorax 60:531–537. doi: 10.1136/thx.2004.030452 PubMedGoogle Scholar
  37. Funanage VL, Carango P, Shapiro IM, Tokuoka T, Tuan RS (1992) Creatine kinase activity is required for mineral deposition and matrix synthesis in endochondral growth cartilage. Bone Miner 17:228–236. doi: 10.1016/0169-6009(92)90742-V PubMedGoogle Scholar
  38. Galbraith RA, Furukawa M, Li M (2006) Possible role of creatine concentrations in the brain in regulating appetite and weight. Brain Res 1101:85–91. doi: 10.1016/j.brainres.2006.05.032 PubMedGoogle Scholar
  39. Gerber I, ap Gwynn I, Alini M, Wallimann T (2005) Stimulatory effects of creatine on metabolic activity, differentiation and mineralization of primary osteoblast-like cells in monolayer and micromass cell cultures. Eur Cell Mater 10:8–22PubMedGoogle Scholar
  40. Gordon A, Hultman E, Kaijser L, Kristjansson S, Rolf CJ, Nyquist O, Sylven C (1995) Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 30:413–418PubMedGoogle Scholar
  41. Green HJ, Burnett ME, D’Arsigny CL, O’Donnell DE, Ouyang J, Webb KA (2008) Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease. J Appl Physiol 105:879–886. doi: 10.1152/japplphysiol.90458.2008 PubMedGoogle Scholar
  42. Greenhaff PL (2001) The creatine–phosphocreatine system: there’s more than one song in its repertoire. J Physiol 537:657. doi: 10.1113/jphysiol.2001.013478 PubMedGoogle Scholar
  43. Groeneveld GJ, Veldink JH, van der Tweel I, Kalmijn S, Beijer C, de Visser M, Wokke JH, Franssen H, van den Berg LH (2003) A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann Neurol 53:437–445. doi: 10.1002/ana.10554 PubMedGoogle Scholar
  44. Grunewald T, Beal MF (1999) Bioenergetics in Huntington’s disease. Ann N Y Acad Sci 893:203–213. doi: 10.1111/j.1749-6632.1999.tb07827.x PubMedGoogle Scholar
  45. Gualano B, Novaes RB, Artioli GG, Freire TO, Coelho DF, Scagliusi FB, Rogeri PS, Roschel H, Ugrinowitsch C, Lancha AH Jr (2008a) Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training. Amino Acids 34:245–250. doi: 10.1007/s00726-007-0508-1 PubMedGoogle Scholar
  46. Gualano B, Ugrinowitsch C, Artioli GG, Benatti FB, Scagliusi FB, Harris RC, Lancha AH Jr (2008b) Does creatine supplementation improve the plasma lipid profile in healthy male subjects undergoing aerobic training? J Int Soc Sports Nutr 5:16. doi: 10.1186/1550-2783-5-16 PubMedGoogle Scholar
  47. Gualano B, Ugrinowitsch C, Novaes RB, Artioli GG, Shimizu MH, Seguro AC, Harris RC, Lancha AH Jr (2008c) Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial. Eur J Appl Physiol 103:33–40. doi: 10.1007/s00421-007-0669-3 PubMedGoogle Scholar
  48. Guerrero-Ontiveros ML, Wallimann T (1998) 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 184:427–437. doi: 10.1023/A:1006895414925 PubMedGoogle Scholar
  49. Harris RC, Soderlund K, Hultman E (1992) Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 83:367–374Google Scholar
  50. Hass CJ, Collins MA, Juncos JL (2007) Resistance training with creatine monohydrate improves upper-body strength in patients with Parkinson disease: a randomized trial. Neurorehabil Neural Repair 21:107–115. doi: 10.1177/1545968306293449 PubMedGoogle Scholar
  51. Hausmann ON, Fouad K, Wallimann T, Schwab ME (2002) Protective effects of oral creatine supplementation on spinal cord injury in rats. Spinal Cord 40:449–456. doi: 10.1038/sj.sc.3101330 PubMedGoogle Scholar
  52. Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, Como P, Zimmerman C, Lin M, Zhang L, Ulug AM, Beal MF, Matson W, Bogdanov M, Ebbel E, Zaleta A, Kaneko Y, Jenkins B, Hevelone N, Zhang H, Yu H, Schoenfeld D, Ferrante R, Rosas HD (2006) Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2’dG. Neurology 66:250–252. doi: 10.1212/01.wnl.0000194318.74946.b6 PubMedGoogle Scholar
  53. Hobson GM, Funanage VL, Elsemore J, Yagami M, Rajpurohit R, Perriard JC, Hickok NJ, Shapiro IM, Tuan RS (1999) Developmental expression of creatine kinase isoenzymes in chicken growth cartilage. J Bone Miner Res 14:747–756. doi: 10.1359/jbmr.1999.14.5.747 PubMedGoogle Scholar
  54. in‘t Zandt HJ, Renema WK, Streijger F, Jost C, Klomp DW, Oerlemans F, Van der Zee CE, Wieringa B, Heerschap A (2004) Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: a quantitative in vivo 1H and 31P magnetic resonance study. J Neurochem 90:1321–1330Google Scholar
  55. Item CB, Stockler-Ipsiroglu S, Stromberger C, Muhl A, Alessandri MG, Bianchi MC, Tosetti M, Fornai F, Cioni G (2001) Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet 69:1127–1133PubMedGoogle Scholar
  56. Kaldis P, Hemmer W, Zanolla E, Holtzman D, Wallimann T (1996) ‘Hot spots’ of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus. Dev Neurosci 18:542–554PubMedGoogle Scholar
  57. Kley RA, Vorgerd M, Tarnopolsky MA (2007) Creatine for treating muscle disorders. Cochrane Database Syst Rev CD004760Google Scholar
  58. Klopstock T, Querner V, Schmidt F, Gekeler F, Walter M, Hartard M, Henning M, Gasser T, Pongratz D, Straube A, Dieterich M, Muller-Felber W (2000) A placebo-controlled crossover trial of creatine in mitochondrial diseases. Neurology 55:1748–1751PubMedGoogle Scholar
  59. Koga Y, Takahashi H, Oikawa D, Tachibana T, Denbow DM, Furuse M (2005) Brain creatine functions to attenuate acute stress responses through GABAnergic system in chicks. Neuroscience 132:65–71PubMedGoogle Scholar
  60. Kornblum C, Schroder R, Muller K, Vorgerd M, Eggers J, Bogdanow M, Papassotiropoulos A, Fabian K, Klockgether T, Zange J (2005) Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. Eur J Neurol 12:300–309PubMedGoogle Scholar
  61. Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, Milnor P, Almada AL (2003) Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem 244:95–104PubMedGoogle Scholar
  62. Kuehl K, Goldberg L, Elliot D (1998) Renal insufficiency after creatine supplementation in a college football athlete (abstract). Med Sci Sports Exerc 30:S235Google Scholar
  63. Kuethe F, Krack A, Richartz BM, Figulla HR (2006) Creatine supplementation improves muscle strength in patients with congestive heart failure. Pharmazie 61:218–222PubMedGoogle Scholar
  64. Lensman M, Korzhevskii DE, Mourovets VO, Kostkin VB, Izvarina N, Perasso L, Gandolfo C, Otellin VA, Polenov SA, Balestrino M (2006) Intracerebroventricular administration of creatine protects against damage by global cerebral ischemia in rat. Brain Res 1114:187–194PubMedGoogle Scholar
  65. Louis M, Lebacq J, Poortmans JR, Belpaire-Dethiou MC, Devogelaer JP, Van Hecke P, Goubel F, Francaux M (2003a) Beneficial effects of creatine supplementation in dystrophic patients. Muscle Nerve 27:604–610PubMedGoogle Scholar
  66. Louis M, Poortmans JR, Francaux M, Berre J, Boisseau N, Brassine E, Cuthbertson DJ, Smith K, Babraj JA, Waddell T, Rennie MJ (2003b) No effect of creatine supplementation on human myofibrillar and sarcoplasmic protein synthesis after resistance exercise. Am J Physiol Endocrinol Metab 285:E1089–E1094PubMedGoogle Scholar
  67. Mancini DM, Ferraro N, Tuchler M, Chance B, Wilson JR (1988) Detection of abnormal calf muscle metabolism in patients with heart failure using phosphorus-31 nuclear magnetic resonance. Am J Cardiol 62:1234–1240PubMedGoogle Scholar
  68. Marquis K, Debigare R, Lacasse Y, LeBlanc P, Jobin J, Carrier G, Maltais F (2002) Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 166:809–813PubMedGoogle Scholar
  69. Mazzini L, Balzarini C, Colombo R, Mora G, Pastore I, De Ambrogio R, Caligari M (2001) Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results. J Neurol Sci 191:139–144PubMedGoogle Scholar
  70. McMorris T, Harris RC, Swain J, Corbett J, Collard K, Dyson RJ, Dye L, Hodgson C, Draper N (2006) Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology (Berl) 185:93–103Google Scholar
  71. McMorris T, Harris RC, Howard AN, Langridge G, Hall B, Corbett J, Dicks M, Hodgson C (2007a) Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiol Behav 90:21–28PubMedGoogle Scholar
  72. McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A (2007b) Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 14:517–528PubMedGoogle Scholar
  73. Menezes LG, Sobreira C, Neder L, Rodrigues-Junior AL, Martinez JA (2007) Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats. J Appl Physiol 102:698–703PubMedGoogle Scholar
  74. NET-PD N (2006) A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology 66:664–671Google Scholar
  75. Nissen SL, Sharp RL (2003) Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis. J Appl Physiol 94(2):651–659PubMedGoogle Scholar
  76. Olsen S, Aagaard P, Kadi F, Tufekovic G, Verney J, Olesen JL, Suetta C, Kjaer M (2006) Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol 573:525–534PubMedGoogle Scholar
  77. Op‘t Eijnde B, Richter EA, Henquin JC, Kiens B, Hespel P (2001) Effect of creatine supplementation on creatine and glycogen content in rat skeletal muscle. Acta Physiol Scand 171:169–176Google Scholar
  78. Op’t Eijnde B, Jijakli H, Hespel P, Malaisse WJ (2006) Creatine supplementation increases soleus muscle creatine content and lowers the insulinogenic index in an animal model of inherited type 2 diabetes. Int J Mol Med 17:1077–1084PubMedGoogle Scholar
  79. Ozkan O, Duman O, Haspolat S, Ozgentas HE, Dikici MB, Gurer I, Gungor HA, Guzide Gokhan A (2005) Effect of systemic creatine monohydrate supplementation on denervated muscle during reinnervation: experimental study in the rat. J Reconstr Microsurg 21:573–579PubMedGoogle Scholar
  80. Parise G, Mihic S, MacLennan D, Yarasheski KE, Tarnopolsky MA (2001) Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol 91:1041–1047PubMedGoogle Scholar
  81. Passaquin AC, Renard M, Kay L, Challet C, Mokhtarian A, Wallimann T, Ruegg UT (2002) Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Neuromuscul Disord 12:174–182PubMedGoogle Scholar
  82. Pedersen BK, Saltin B (2006) Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports 16(Suppl 1):3–63PubMedGoogle Scholar
  83. Poortmans JR (1998) Renal dysfunction accompanying oral creatine supplements: reply. Lancet 352:234PubMedGoogle Scholar
  84. Poortmans JR, Francaux M (1999) Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 31:1108–1110PubMedGoogle Scholar
  85. Poortmans JR, Francaux M (2000) Adverse effects of creatine supplementation: fact or fiction? Sports Med 30:155–170PubMedGoogle Scholar
  86. Poortmans JR, Francaux M (2008) Creatine consumption in health. In: Stout JR, Antonio J, Kalman D (eds) Essentials of creatine in sports and health. Humana Press, Totawa, pp 127–172CrossRefGoogle Scholar
  87. Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR (1997) Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol 76:566–567PubMedGoogle Scholar
  88. Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux M (2005) Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Med Sci Sports Exerc 37:1717–1720PubMedGoogle Scholar
  89. Pritchard NR, Kalra PA (1998) Renal dysfunction accompanying oral creatine supplements. Lancet 351:1252–1253PubMedGoogle Scholar
  90. Rabchevsky AG, Sullivan PG, Fugaccia I, Scheff SW (2003) Creatine diet supplement for spinal cord injury: influences on functional recovery and tissue sparing in rats. J Neurotrauma 20:659–669PubMedGoogle Scholar
  91. Rawson ES, Clarkson PM, Price TB, Miles MP (2002) Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects. Acta Physiol Scand 174:57–65PubMedGoogle Scholar
  92. Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL (2000) Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med 34:284–288PubMedGoogle Scholar
  93. Ryu H, Rosas HD, Hersch SM, Ferrante RJ (2005) The therapeutic role of creatine in Huntington’s disease. Pharmacol Ther 108:193–207PubMedGoogle Scholar
  94. Safdar A, Yardley NJ, Snow R, Melov S, Tarnopolsky MA (2008) Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics 32:219–228PubMedGoogle Scholar
  95. Sakellaris G, Kotsiou M, Tamiolaki M, Kalostos G, Tsapaki E, Spanaki M, Spilioti M, Charissis G, Evangeliou A (2006) Prevention of complications related to traumatic brain injury in children and adolescents with creatine administration: an open label randomized pilot study. J Trauma 61:322–329PubMedGoogle Scholar
  96. Salomons GS, van Dooren SJ, Verhoeven NM, Cecil KM, Ball WS, Degrauw TJ, Jakobs C (2001) X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. Am J Hum Genet 68:1497–1500PubMedGoogle Scholar
  97. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54:823–827PubMedGoogle Scholar
  98. Scheff SW, Dhillon HS (2004) Creatine-enhanced diet alters levels of lactate and free fatty acids after experimental brain injury. Neurochem Res 29:469–479PubMedGoogle Scholar
  99. Schneider-Gold C, Beck M, Wessig C, George A, Kele H, Reiners K, Toyka KV (2003) Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Neurology 60:500–502PubMedGoogle Scholar
  100. Schulze A (2003) Creatine deficiency syndromes. Mol Cell Biochem 244:143–150PubMedGoogle Scholar
  101. Sewell DA, Harris RC (1995) Effect of creatine supplementation in the thoroughbred horse. Equine Vet J 18:239–242Google Scholar
  102. Shefner JM, Cudkowicz ME, Schoenfeld D, Conrad T, Taft J, Chilton M, Urbinelli L, Qureshi M, Zhang H, Pestronk A, Caress J, Donofrio P, Sorenson E, Bradley W, Lomen-Hoerth C, Pioro E, Rezania K, Ross M, Pascuzzi R, Heiman-Patterson T, Tandan R, Mitsumoto H, Rothstein J, Smith-Palmer T, MacDonald D, Burke D (2004) A clinical trial of creatine in ALS. Neurology 63:1656–1661PubMedGoogle Scholar
  103. Smith CA, Chetlin RD, Gutmann L, Yeater RA, Alway SE (2006) Effects of exercise and creatine on myosin heavy chain isoform composition in patients with Charcot-Marie-Tooth disease. Muscle Nerve 34:586–594PubMedGoogle Scholar
  104. Somjen D, Kaye AM (1994) Stimulation by insulin-like growth factor-I of creatine kinase activity in skeletal-derived cells and tissues of male and female rats. J Endocrinol 143:251–259PubMedGoogle Scholar
  105. Somjen D, Kaye AM, Rodan GA, Binderman I (1985) Regulation of creatine kinase activity in rat osteogenic sarcoma cell clones by parathyroid hormone, prostaglandin E2, and vitamin D metabolites. Calcif Tissue Int 37:635–638PubMedGoogle Scholar
  106. Stockler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M, Hanicke W, Frahm J (1994) Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 36:409–413PubMedGoogle Scholar
  107. Stockler S, Hanefeld F, Frahm J (1996) Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 348:789–790PubMedGoogle Scholar
  108. Stout JR, Sue Graves B, Cramer JT, Goldstein ER, Costa PB, Smith AE, Walter AA (2007) Effects of creatine supplementation on the onset of neuromuscular fatigue threshold and muscle strength in elderly men and women (64–86 years). J Nutr Health Aging 11:459–464PubMedGoogle Scholar
  109. Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AH, Warner TT (2003) Creatine therapy for Huntington’s disease: clinical and MRS findings in a 1-year pilot study. Neurology 61:141–142PubMedGoogle Scholar
  110. Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AH, Warner TT (2005) High-dose creatine therapy for Huntington disease: a 2-year clinical and MRS study. Neurology 64:1655–1656PubMedGoogle Scholar
  111. Tarnopolsky MA (2007) Clinical use of creatine in neuromuscular and neurometabolic disorders. Subcell Biochem 46:183–204PubMedGoogle Scholar
  112. Tarnopolsky M, Martin J (1999) Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology 52:854–857PubMedGoogle Scholar
  113. Tarnopolsky MA, Parise G (1999) Direct measurement of high-energy phosphate compounds in patients with neuromuscular disease. Muscle Nerve 22:1228–1233PubMedGoogle Scholar
  114. Tarnopolsky MA, Roy BD, MacDonald JR (1997) A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve 20:1502–1509PubMedGoogle Scholar
  115. Tarnopolsky MA, Parise G, Yardley NJ, Ballantyne CS, Olatinji S, Phillips SM (2001) Creatine-dextrose and protein-dextrose induce similar strength gains during training. Med Sci Sports Exerc 33:2044–2052PubMedGoogle Scholar
  116. Tarnopolsky MA, Bourgeois JM, Snow R, Keys S, Roy BD, Kwiecien JM, Turnbull J (2003) Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats. Am J Physiol Regul Integr Comp Physiol 285:R762–R769PubMedGoogle Scholar
  117. Tarnopolsky M, Mahoney D, Thompson T, Naylor H, Doherty TJ (2004a) Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Muscle Nerve 29:51–58PubMedGoogle Scholar
  118. Tarnopolsky MA, Mahoney DJ, Vajsar J, Rodriguez C, Doherty TJ, Roy BD, Biggar D (2004b) Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy. Neurology 62:1771–1777PubMedGoogle Scholar
  119. Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, Kraemer WJ, Meyer RA, Spriet LL, Tarnopolsky MA, Wagenmakers AJ, Williams MH (2000) American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 32:706–717PubMedGoogle Scholar
  120. Thorsteinsdottir B, Grande JP, Garovic VD (2006) Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate. J Ren Nutr 16:341–345PubMedGoogle Scholar
  121. Verbessem P, Lemiere J, Eijnde BO, Swinnen S, Vanhees L, Van Leemputte M, Hespel P, Dom R (2003) Creatine supplementation in Huntington’s disease: a placebo-controlled pilot trial. Neurology 61:925–930PubMedGoogle Scholar
  122. Volaklis KA, Tokmakidis SP (2005) Resistance exercise training in patients with heart failure. Sports Med 35:1085–1103PubMedGoogle Scholar
  123. Vorgerd M, Grehl T, Jager M, Muller K, Freitag G, Patzold T, Bruns N, Fabian K, Tegenthoff M, Mortier W, Luttmann A, Zange J, Malin JP (2000) Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Arch Neurol 57:956–963PubMedGoogle Scholar
  124. Vorgerd M, Zange J, Kley R, Grehl T, Husing A, Jager M, Muller K, Schroder R, Mortier W, Fabian K, Malin JP, Luttmann A (2002) Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Arch Neurol 59:97–101PubMedGoogle Scholar
  125. Wallimann T, Hemmer W (1994) Creatine kinase in non-muscle tissues and cells. Mol Cell Biochem 133–134:193–220PubMedGoogle Scholar
  126. Walter MC, Lochmuller H, Reilich P, Klopstock T, Huber R, Hartard M, Hennig M, Pongratz D, Muller-Felber W (2000) Creatine monohydrate in muscular dystrophies: a double-blind, placebo-controlled clinical study. Neurology 54:1848–1850PubMedGoogle Scholar
  127. Walter MC, Reilich P, Lochmuller H, Kohnen R, Schlotter B, Hautmann H, Dunkl E, Pongratz D, Muller-Felber W (2002) Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurol 249:1717–1722PubMedGoogle Scholar
  128. Watanabe A, Kato N, Kato T (2002) Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res 42:279–285PubMedGoogle Scholar
  129. Weiss RG, Gerstenblith G, Bottomley PA (2005) ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci USA 102:808–813PubMedGoogle Scholar
  130. Wendt S, Dedeoglu A, Speer O, Wallimann T, Beal MF, Andreassen OA (2002) Reduced creatine kinase activity in transgenic amyotrophic lateral sclerosis mice. Free Radic Biol Med 32:920–926PubMedGoogle Scholar
  131. Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80:1107–1213PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Bruno Gualano
    • 1
    • 2
    • 4
    Email author
  • Guilherme Giannini Artioli
    • 1
    • 2
  • Jacques R. Poortmans
    • 3
  • Antonio Herbert Lancha Junior
    • 1
  1. 1.Laboratory of Applied Nutrition and Metabolism, School of Physical Education and SportUniversity of São PauloSão PauloBrazil
  2. 2.Laboratory of Rheumatology Assessment and Conditioning, Division of Rheumatology, School of MedicineUniversity of São PauloSão PauloBrazil
  3. 3.Laboratory for Sport Nutrition, Institute of Motor SciencesFree University of BrusselsBrusselsBelgium
  4. 4.São PauloBrazil

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