Intervention Review

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Creatine for treating muscle disorders

  1. Rudolf A Kley1,*,
  2. Mark A Tarnopolsky2,
  3. Matthias Vorgerd3

Editorial Group: Cochrane Neuromuscular Disease Group

Published Online: 5 JUN 2013

Assessed as up-to-date: 11 SEP 2012

DOI: 10.1002/14651858.CD004760.pub4


How to Cite

Kley RA, Tarnopolsky MA, Vorgerd M. Creatine for treating muscle disorders. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD004760. DOI: 10.1002/14651858.CD004760.pub4.

Author Information

  1. 1

    University Hospital Bergmannsheil, Ruhr University Bochum, Department of Neurology, Bochum, Germany

  2. 2

    McMaster University, Department of Neurology and Rehabilitation, Hamilton, Ontario, Canada

  3. 3

    Kliniken Bergmannsheil, Ruhr University Bochum, Department of Neurology, Bochum, Germany

*Rudolf A Kley, Department of Neurology, University Hospital Bergmannsheil, Ruhr University Bochum, Buerkle-de-la-Camp-Platz 1, Bochum, 44789, Germany. rudolf.kley@rub.de.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 5 JUN 2013

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Banerjee 2010 {published data only}
  • Banerjee B, Sharma U, Balasubramanian K, Kalaivani M, Kalra V, Jagannathan NR. Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized, placebo-controlled 31P MRS study. Magnetic Resonance Imaging 2010;28(5):698-707. [PUBMED: 20395096]
Chung 2007 {published and unpublished data}
  • Chung YL, Alexanderson H, Pipitone N, Morrison C, Dastmalchi M, Stahl-Hallengren C, et al. Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: Six-month, double-blind, randomized, placebo-controlled trial. Arthritis and Rheumatism 2007;57(4):694-702. [PUBMED: 17471547]
Escolar 2005 {published data only}
Klopstock 2000 {published and unpublished data}
  • Klopstock T, Querner V, Schmidt F, Gekeler F, Walter M, Hartard M, et al. A placebo-controlled crossover trial of creatine in mitochondrial diseases. Neurology 2000;55(11):1748-51. [PUBMED: 11113239]
Kornblum 2005 {published and unpublished data}
Louis 2003 {published and unpublished data}
Schneider-Gold 2003 {published and unpublished data}
  • Schneider-Gold C, Beck M, Wessig C, George A, Kele H, Reiners K, et al. Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Neurology 2003;60(3):500-2. [PUBMED: 12578937]
Tarnopolsky 1997 {published and unpublished data}
Tarnopolsky 2004a {published and unpublished data}
  • Tarnopolsky MA, Mahoney DJ, Vajsar J, Rodriguez C, Doherty TJ, Roy BD, et al. Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy. Neurology 2004;62(10):1771-7. [PUBMED: 15159476]
Tarnopolsky 2004b {published and unpublished data}
Vorgerd 2000 {published and unpublished data}
  • Vorgerd M, Grehl T, Jager M, Muller K, Freitag G, Patzold T, et al. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled cross-over trial. Archives of Neurology 2000;57(7):956-63. [PUBMED: 10891977]
Vorgerd 2002 {published and unpublished data}
  • Vorgerd M, Zange J, Kley R, Grehl T, Husing A, Jager M, et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled cross-over study. Archives of Neurology 2002;59(1):97-101. [PUBMED: 11790236]
Walter 2000 {published and unpublished data}
  • Walter MC, Lochmuller H, Reilich P, Klopstock T, Huber R, Hartard M, et al. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study. Neurology 2000;54(9):1848-50. [PUBMED: 10802796]
Walter 2002 {published and unpublished data}
  • Walter MC, Reilich P, Lochmuller H, Kohnen R, Schlotter B, Hautmann H, et al. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. Journal of Neurology 2002;249(12):1717-22. [PUBMED: 12529796]

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Barisic 2002 {published data only}
  • Barisic N, Bernert G, Ipsiroglu O, Stromberger C, Muller T, Gruber S, et al. Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy. Neuropediatrics 2002;33(3):157-61. [PUBMED: 1220074]
Beurey 1967 {published data only}
  • Beurey J, Duc M, Weber M, Gurecki H, Perello R. Trial therapy of acute polymyositis with phosphocreatine. [Essai de traitement de polymyosite aigue par phosphocreatine.]. Bulletin de la Societe Francaise de Dermatologie et de Syphiligraphie 1967;74(2):276-80.
Borchert 1999 {published data only}
Duperrat 1972 {published data only}
  • Duperrat B, Puissant A, Mallard D, Jourdain JC, Thomas D. Dermatomyositis with cardiac involvement and trial treatment with phosphocreatine [Dermatomyosite avec atteinte cardiaque et essai de traitement par la phosphocréatine]. Bulletin de la Societe Francaise de Dermatologie et de Syphiligraphie 1972;79(3):208-10.
Felber 2000 {published data only}
  • Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W. Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Neurological Research 2000;22(2):145-50.
Freddi 1979 {published data only}
Hagenfeldt 1994 {published data only}
Komura 2003 {published data only}
Matsumura 2004 {published data only}
  • Matusmura T, Yokoe M, Nakamori M, Hattori N, Saito T, Nozaki S, et al. A clinical trial of creatine monohydrate in muscular dystrophy patients. Rinsho Shinkeigaku 2004;44(10):661-6.
Rodriguez 2007 {published data only}
Sejersen 2000 {published and unpublished data}
  • Sejersen T, Hovmoller M, Hok L, Nordmark-Andersson E, Winberg P, Nylander E, et al. Lack of detectable effect of creatine supplementation on skeletal muscle or cardiac function in Duchenne muscular dystrophy. Neuromuscular Disorders 2000;10:375.
Stout 2001 {published data only}
  • Stout JR, Eckerson JM, May E, Coulter C, Bradley-Popovich GE. Effects of resistance exercise and creatine supplementation on myasthenia gravis: a case study. Medicine and Science in Sports and Exercise 2001;33(6):869-72.
Tarnopolsky 1999 {published data only}
Tarnopolsky 2004 {published data only}

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
NCT01217320 {published data only}
  • NCT01217320. Creatine supplementation in pediatric rheumatology. http://www.clinicaltrials.gov/ct2/show/NCT01217320 (accessed 26 April 2013).

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Andreassen 2001
  • Andreassen OA, Dedeoglu A, Ferrante RJ, Jenkins BG, Ferrante KL, Thomas M, et al. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiology of Disease 2001;8(3):479-91.
Brose 2003
  • Brose A, Parise G, Tarnopolsky MA. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. Journals of Gerontology. Series B, Psychological Sciences and Social Sciences 2003;58(1):11-9.
Burke 2003
  • Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Medicine and Science in Sports and Exercise 2003;35(11):1946-55.
Casey 1996
  • Casey A, Constantin-Teodosiu D, Howell S, Hultman E, Greenhaff PL. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. American Journal of Physiology 1996;271(1 Pt 1):E31-7.
Chetlin 2004
Chilibeck 2004
  • Chilibeck PD, Stride D, Farthing JP, Burke DG. Effect of creatine ingestion after exercise on muscle thickness in males and females. Medicine and Science in Sports and Exercise 2004;36(10):1781-8.
Chilibeck 2005
  • Chilibeck PD, Chrusch MJ, Chad KE, Shawn Davison K, Burke DG. Creatine monohydrate and resistance training increase bone mineral content and density in older men. Journal of Nutrition, Health and Aging 2005;9(5):352-3.
Chrusch 2001
  • Chrusch MJ, Chilibeck PD, Chad KE, Davison KS, Burke DG. Creatine supplementation combined with resistance training in older men. Medicine and Science in Sports and Exercise 2001;33(12):2111-7.
Dechent 1999
  • Dechent P, Pouwels PJ, Wilken B, Hanefeld F, Frahm J. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology 1999;277(3 Pt 2):R698-704.
Dedeoglu 2003
Deldicque 2008
  • Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie MJ, Francaux M. Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. Journal of Applied Physiology 2008;104(2):371-8.
Fenichel 2001
  • Fenichel GM, Griggs RC, Kissel J, Kramer TI, Mendell JR, Moxley RT, et al. A randomized efficacy and safety trial of oxandrolone in the treatment of Duchenne dystrophy. Neurology 2001;56(8):1075-9. [PUBMED: 11320181]
Ferrante 2000
  • Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. Journal of Neuroscience 2000;20(12):4389-97.
Greenwood 2003
  • Greenwood M, Kreider RB, Melton C, Rasmussen C, Lancaster S, Cantler E, et al. Creatine supplementation during college football training does not increase the incidence of cramping or injury. Molecular and Cellular Biochemistry 2003;244(1-2):83-8.
Groeneveld 2005
  • Groeneveld GJ, Beijer C, Veldink JH, Kalmijn S, Wokke JH, van den Berg LH. Few adverse effects of long-term creatine supplementation in a placebo-controlled trial. International Journal of Sports Medicine 2005;26(4):307-313.
Gualano 2010
Guimbal 1993
  • Guimbal C, Kilimann MW. A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. Journal of Biological Chemistry 1993;268(12):8418-21.
Guthmiller 1994
  • Guthmiller P, van Pilsum JF, Boen JR, McGuire DM. Cloning and sequencing of rat kidney L-arginine: glycine amidinotransferase. Studies on the mechanism of regulation by growth hormone and creatine. Journal of Biological Chemistry 1994;269(26):17556-60.
Harris 1992
  • Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science 1992;83(3):367-74.
Hersch 2006
  • Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, et al. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG. Neurology 2006;66(2):250-2.
Higgins 2011
  • Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Hultman 1996
Josefson 1996
Klivenyi 1999
  • Klivenyi P, Ferrante RJ, Matthews RT, Bogdanov MB, Klein AM, Andreassen OA, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nature Medicine 1999;5(3):347-50.
Klivenyi 2004
  • Klivenyi P, Calingasan NY, Starkov A, Stavrovskaya IG, Kristal BS, Yang L, et al. Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Neurobiology of Disease 2004;15(3):610-7.
Kreider 2003
  • Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Molecular and Cellular Biochemistry 2003;244(1-2):95-104.
Malcon 2000
Manzur 2004
  • Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database of Systematic Reviews 2004, Issue 2. [DOI: 10.1002/14651858.CD003725.pub3]
Matthews 1990
Matthews 1991
  • Matthews PM, Allaire C, Shoubridge EA, Karpati G, Carpenter S, Arnold DL. In vivo muscle magnetic resonance spectroscopy in the clinical investigation of mitochondrial disease. Neurology 1991;41(1):114-20.
Matthews 1998
  • Matthews RT, Yang L, Jenkins BG, Ferrante RJ, Rosen BR, Kaddurah-Daouk R, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington´s disease. Journal of Neuroscience 1998;18(1):156-63.
Mihic 2000
  • Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medicine and Science in Sports and Exercise 2000;32(2):291-6.
Parise 2001
  • Parise G, Mihic S, MacLennan D, Yarasheski KE, Tarnopolsky MA. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. Journal of Applied Physiology 2001;91(3):1041-7.
Park 1994
  • Park JH, Vital TL, Ryder NM, Hernanz-Schulman M, Partain CL, Price RR, et al. Magnetic resonance imaging and P-31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal management of patients with dermatomyositis. Arthritis and Rheumatism 1994;37(5):736-46.
Park 1995
  • Park JH, Olsen NJ, King L, Jr, Vital T, Buse R, Kari S, et al. Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to detect and quantify muscle dysfunction in the amyopathic and myopathic variants of dermatomyositis. Arthritis and Rheumatism 1995;38(1):68-77.
Passaquin 2002
  • Passaquin AC, Renard M, Kay L, Challet C, Mokhtarian A, Wallimann T, et al. Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Neuromuscular Disorders 2002;12(2):172-82.
Persky 2003
Poortmans 1999
Poortmans 2000
Poortmans 2005
  • Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux M. Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Medicine and Science in Sports and Exercise 2005;37(10):1717-20.
Pulido 1998
  • Pulido SM, Passaquin AC, Leijendekker WJ, Challet C, Wallimann T, Ruegg UT. Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells. FEBS Letters 1998;439(3):357-62.
Rawson 2004
  • Rawson ES, Persky AM, Price TB, Clarkson PM. Effects of repeated creatine supplementation on muscle, plasma, and urine creatine levels. Journal of Strength and Conditioning Research 2004;18(1):162-7.
RevMan 2012
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Rose 2004
Roy 2002
  • Roy BD, Bourgeois JM, Mahoney DJ, Tarnopolsky MA. Dietary supplementation with creatine monohydrate prevents corticosteroid-induced attenuation of growth in young rats. Canadian Journal of Physiology and Pharmacology 2002;80(10):1008-14.
Safdar 2008
  • Safdar A, Yardley NJ, Snow R, Melov S, Tarnopolsky MA. Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiological Genomics 2008;32:219-28.
Scott 1982
Shao 2006
Shefner 2004
Soueidan 1993
Sullivan 2000
Tarnopolsky 1999a
Tarnopolsky 1999b
Tarnopolsky 2000
  • Tarnopolsky MA, MacLennan DP. Creatine monohydrate supplementation enhances high-intensity exercise performance in males and females. International Journal of Sport Nutrition and Exercise Metabolism 2000;10(4):452-63.
Tarnopolsky 2001
Terjung 2000
  • Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, et al. American College of Sports Medicine round table. The physiological and health effects of oral creatine supplementation. Medicine and Science in Sports and Exercise 2000;32(3):706-17.
Verbessem 2003
  • Verbessem P, Lemiere J, Eijnde BO, Swinnen S, Vanhees L, Van Leemputte M, et al. Creatine supplementation in Huntington's disease: a placebo-controlled pilot trial. Neurology 2003;61(7):925-30.
Wyss 1992
  • Wyss M, Smeitink J, Wevers RA, Wallimann T. Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism. Biochimica et Biophysica Acta 1992;1102(2):119-66.
Wyss 1998
  • Wyss M, Felber S, Skladal D, Koller A, Kremser C, Sperl W. The therapeutic potential of oral creatine supplementation in muscle disease. Medical Hypotheses 1998;51(4):333-6. [PUBMED: 9824841]
Wyss 2000
Zhu 2004
  • Zhu S, Li M, Figueroa BE, Liu A, Stavrovskaya IG, Pasinelli P, et al. Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice. Journal of Neuroscience 2004;24(26):5909-12.

References to other published versions of this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Kley 2004
  • Kley RA, Vorgerd M, Tarnopolsky MA. Creatine for treating muscle disorders. Cochrane Database of Systematic Reviews 2004, Issue 2. [DOI: 10.1002/14651858.CD004760]
Kley 2007
Kley 2011