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CNS Drugs
Published in: CNS Drugs 14/2004

01-12-2004 | Leading Article

The Role of Creatine in the Management of Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disorders

Authors: Amy Cameron Ellis, Jeffrey Rosenfeld

Published in: CNS Drugs | Issue 14/2004

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Abstract

Creatine is consumed in the diet and endogenously synthesised in the body. Over the past decade, the ergogenic benefits of synthetic creatine monohydrate have made it a popular dietary supplement, particularly among athletes. The anabolic properties of creatine also offer hope for the treatment of diseases characterised by weakness and muscle atrophy. Moreover, because of its cellular mechanisms of action, creatine offers potential benefits for diseases involving mitochondrial dysfunction. Recent data also support the hypothesis that creatine may have a neuroprotective effect.
Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of motor neurons, resulting in weakening and atrophy of skeletal muscles. In patients with this condition, creatine offers potential benefits in terms of facilitating residual muscle contractility as well as improving neuronal function. It may also help stabilise mitochondrial dysfunction, which plays a key role in the pathogenesis of ALS. Indeed, the likely multifactorial aetiology of ALS means the combined pharmacodynamic properties of creatine offer promise for the treatment of this condition.
Evidence from available animal models of ALS supports the utility of treatment with creatine in this setting. Limited data available in other neuromuscular and neurodegenerative diseases further support the potential benefit of creatine monohydrate in ALS. However, few randomised, controlled trials have been conducted. To date, two clinical trials of creatine monohydrate in ALS have been completed without demonstration of significant improvements in overall survival or a composite measure of muscle strength. These trials have also posed unanswered questions about the optimal dosage of creatine and its beneficial effects on muscle fatigue, a measure distinct from muscle strength. A large, multicentre, clinical trial is currently underway to further investigate the efficacy of creatine monohydrate in ALS and address these unresolved issues. Evidence to date shows that creatine supplementation has a good safety profile and is well tolerated by ALS patients.
The purpose of this article is to provide a short, balanced review of the literature concerning creatine monohydrate in the treatment of ALS and related neurodegenerative diseases. The pharmacokinetics and rationale for the use of creatine are described along with available evidence from animal models and clinical trials for ALS and related neurodegenerative or neuromuscular diseases.
Literature
1.
Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med 2001; 344(22): 1688–700PubMed
2.
Cluskey S, Ramsden DB. Mechanisms of neurodegeneration in amyotrophic lateral sclerosis. Mol Pathol 2001; 54(6): 386–92PubMed
3.
Rosen DR. Mutations in Cu/Zn superoxide dismutase are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59–62PubMed
4.
Ferrante RJ, Shinobu LA, Schulz JB, et al. Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. Ann Neurol 1997; 42(3): 326–34PubMed
5.
Andersen P, Morita M, Brown R. Genetics of amyotrophic lateral sclerosis: an overview. In: Brown R, Meininger V, Swash M, editors. Amyotrophic lateral sclerosis. London: Martin-Dunitz, 2000
6.
Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem 1992; 59(5): 1609–23PubMed
7.
Halliwell B. Oxygen radicals as key mediators in neurological disease: fact or fiction? Ann Neurol 1992; 32 Suppl.: S10–15PubMed
8.
Beckman JS, Estevez AG, Crow JP, et al. Superoxide dismutase and the death of motoneurons in ALS. Trends Neurosci 2001; 24(11 Suppl.): S15–20PubMed
9.
Brown RH. Superoxide dismutase and familial amyotrophic lateral sclerosis: new insights into mechanisms and treatments. Ann Neurol 1996; 39(2): 145–6PubMed
10.
Menzies FM, Cookson MR, Taylor RW, et al. Mitochondrial dysfunction in a cell culture model of familial amyotrophic lateral sclerosis. Brain 2002; 125 (Pt 7): 1522–33PubMed
11.
Menzies FM, Ince PG, Shaw PJ. Mitochondrial involvement in amyotrophic lateral sclerosis. Neurochem Int 2002; 40(6): 543–51PubMed
12.
Jung C, Higgins CM, Xu Z. Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis. J Neurochem 2002; 83(3): 535–45PubMed
13.
Kaal EC, Vlug AS, Versleijen MW, et al. Chronic mitochondrial inhibition induces selective motoneuron death in vitro: a new model for amyotrophic lateral sclerosis. J Neurochem 2000; 74(3): 1158–65PubMed
14.
Bowling AC, Schulz JB, Brown RH, et al. Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem 1993; 61(6): 2322–5PubMed
15.
Beal MF. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 1992; 31(2): 119–30PubMed
16.
Fosslien E. Mitochondrial medicine: molecular pathology of defective oxidative phosphorylation. Ann Clin Lab Sci 2001; 31(1): 25–67PubMed
17.
Martin LJ. Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J Neuropathol Exp Neurol 1999; 58(5): 459–71PubMed
18.
Rothstein JD, Kuncl R, Chaudhry V, et al. Excitatory amino acids in amyotrophic lateral sclerosis: an update. Ann Neurol 1991; 30(2): 224–5PubMed
19.
Rothstein JD. Therapeutic horizons for amyotrophic lateral sclerosis. Curr Opin Neurobiol 1996; 6(5): 679–87PubMed
20.
Kruman II, Pedersen WA, Springer JE, et al. ALS-linked Cu/ Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis. Exp Neurol 1999; 160(1): 28–39PubMed
21.
Carri MT, Ferri A, Battistoni A, et al. Expression of a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells. FEBS Lett 1997; 414(2): 365–8PubMed
22.
Canton T, Pratt J, Stutzmann JM, et al. Glutamate uptake is decreased tardively in the spinal cord of FALS mice. Neuroreport 1998; 9(5): 775–8PubMed
23.
Trotti D, Rolfs A, Danbolt NC, et al. SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter [published erratum appears in Nat Neurosci 1999 Sep; 2(9): 848]. Nat Neurosci 1999; 2(5): 427–33PubMed
24.
Howland DS, Liu J, She Y, et al. Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci U S A 2002; 99(3): 1604–9PubMed
25.
Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 2000; 130(4S Suppl.): 1007–1015S
26.
Schulz JB, Lindenau J, Seyfried J, et al. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 2000; 267(16): 4904–11PubMed
27.
Campiani G, Fattorusso C, De Angelis M, et al. Neuronal high-affinity sodium-dependent glutamate transporters (EAATs): targets for the development of novel therapeutics against neurodegenerative diseases. Curr Pharm Des 2003; 9(8): 599–625PubMed
28.
Pearson AM, Young RB. Diseases and disorders of muscle. Adv Food Nutr Res 1993; 37: 339–423PubMed
29.
Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev 2001; 53(2): 161–76PubMed
30.
Jacobs I. Dietary creatine monohydrate supplementation. Can J Appl Physiol 1999; 24(6): 503–14PubMed
31.
Greenhaff PL. Creatine and its application as an ergogenic aid. Int J Sport Nutr 1995; 5 Suppl.: S100–110PubMed
32.
Greenhaff PL, Bodin K, Soderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994; 266 (5 Pt 1): E725–730PubMed
33.
Bogdanis GC, Nevill ME, Boobis LH, et al. Contribution of phosphocreatine and aerobic metabolism to energy supply during repeated sprint exercise. J Appl Physiol 1996; 80(3): 876–84PubMed
34.
Benzi G, Ceci A. Creatine as nutritional supplementation and medicinal product. J Sports Med Phys Fitness 2001; 41(1): 1–10PubMed
35.
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): 427–37PubMed
36.
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(4): 387–95PubMed
37.
Hultman E, Soderlund K, Timmons JA, et al. Muscle creatine loading in men. J Appl Physiol 1996; 81(1): 232–7PubMed
38.
Tarnopolsky MA, MacLennan DP. Creatine monohydrate supplementation enhances high-intensity exercise performance in males and females. Int J Sport Nutr Exerc Metab 2000; 10(4): 452–63PubMed
39.
Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992; 83(3): 367–74PubMed
40.
Casey A, Greenhaff PL. Does dietary creatine supplementation play a role in skeletal muscle metabolism and performance? Am J Clin Nutr 2000; 72(2 Suppl.): 607–617S
41.
Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Curr Opin Clin Nutr Metab Care 2000; 3(6): 497–502PubMed
42.
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
43.
Tarnopolsky MA, Roy BD, MacDonald JR. A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve 1997; 20(12): 1502–9PubMed
44.
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): 357–62PubMed
45.
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): 145–50PubMed
46.
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): 147–51PubMed
47.
Haugland RB, Chang DT. Insulin effect on creatine transport in skelatal muscle (38464). Proc Soc Exp Biol Med 1975; 148(1): 1–4PubMed
48.
Koszalka TR, Andrew CL, Brent RL. Effect of insulin on the uptake of creatine-1-14 C by skeletal muscle in normal and x-irradiated rats. Proc Soc Exp Biol Med 1972; 139(4): 1265–71PubMed
49.
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): E974–979PubMed
50.
Steenge GR, Simpson EJ, Greenhaff PL. Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. J Appl Physiol 2000; 89(3): 1165–71PubMed
51.
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): E821–826PubMed
52.
Vandenberghe K, Gillis N, Van Leemputte M, et al. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996; 80(2): 452–7PubMed
53.
Doherty M, Smith PM, Davison RC, et al. Caffeine is ergogenic after supplementation of oral creatine monohydrate. Med Sci Sports Exerc 2002; 34(11): 1785–92PubMed
54.
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(1): 73–82PubMed
55.
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): 2055–63PubMed
56.
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 Occup Physiol 1994; 69(3): 268–76PubMed
57.
Bosco C, Tihanyi J, Pucspk J, et al. Effect of oral creatine supplementation on jumping and running performance. Int J Sports Med 1997; 18(5): 369–72PubMed
58.
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(3): 56–61PubMed
59.
Engelhardt M, Neumann G, Berbalk A, et al. Creatine supplementation in endurance sports. Med Sci Sports Exerc 1998; 30(7): 1123–9PubMed
60.
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(4): 330–46PubMed
61.
Maganaris CN, Maughan RJ. Creatine supplementation enhances maximum voluntary isometric force and endurance capacity in resistance trained men. Acta Physiol Scand 1998; 163(3): 279–87PubMed
62.
McNaughton LR, Dalton B, Tarr J. The effects of creatine supplementation on high-intensity exercise performance in elite performers. Eur J Appl Physiol Occup Physiol 1998; 78(3): 236–40PubMed
63.
Prevost MC, Nelson AG, Morris GS. Creatine supplementation enhances intermittent work performance. Res Q Exerc Sport 1997; 68(3): 233–40PubMed
64.
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(3): 65–8PubMed
65.
Smith JC, Stephens DP, Hall EL, et al. Effect of oral creatine ingestion on parameters of the work rate-time relationship and time to exhaustion in high-intensity cycling. Eur J Appl Physiol Occup Physiol 1998; 77(4): 360–5PubMed
66.
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): E31–37PubMed
67.
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(2): 207–9PubMed
68.
Juhn MS, Tarnopolsky M. Oral creatine supplementation and athletic performance: a critical review [published erratum appears in Clin J Sport Med 1999 Apr; 9 (2): 62]. Clin J Sport Med 1998; 8(4): 286–97PubMed
69.
Van Schuylenbergh R, Van Leemputte M, Hespel P. Effects of oral creatine-pyruvate supplementation in cycling performance. Int J Sports Med 2003; 24(2): 144–50PubMed
70.
Snow RJ, Turnbull J, da Silva S, et al. Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice. Neuroscience 2003; 119(3): 661–7PubMed
71.
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(2): 216–9PubMed
72.
Barnett C, Hinds M, Jenkins DG. Effects of oral creatine supplementation on multiple sprint cycle performance. Aust J Sci Med Sport 1996; 28(1): 35–9PubMed
73.
Preen D, Dawson B, Goodman C, et al. Pre-exercise oral creatine ingestion does not improve prolonged intermittent sprint exercise in humans. J Sports Med Phys Fitness 2002; 42(3): 320–9PubMed
74.
Lemon PW. Dietary creatine supplementation and exercise performance: why inconsistent results? Can J Appl Physiol 2002; 27(6): 663–81PubMed
75.
Wyss M, Wallimann T. Creatine metabolism and the consequences of creatine depletion in muscle. Mol Cell Biochem 1994; 133-134: 51–66
76.
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(4): 489–95PubMed
77.
Balsom PD, Harridge SD, Soderlund K, et al. Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993; 149(4): 521–3PubMed
78.
Bemben MG, Bemben DA, Loftiss DD, et al. Creatine supplementation during resistance training in college football athletes. Med Sci Sports Exerc 2001; 33(10): 1667–73PubMed
79.
Clarkson PM, Rawson ES. Nutritional supplements to increase muscle mass. Crit Rev Food Sci Nutr 1999; 39(4): 317–28PubMed
80.
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): 347–50PubMed
81.
Dolder M, Wendt S, Wallimann T. Mitochondrial creatine kinase in contact sites: interaction with porin and adenine nucleotide translocase, role in permeability transition and sensitivity to oxidative damage. Biol Signals Recept 2001; 10(1–2): 93–111PubMed
82.
WallimannT, 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 (Pt 1): 21–40
83.
Fontaine E, Bernardi P. Progress on the mitochondrial permeability transition pore: regulation by complex I and ubiquinone analogs. J Bioenerg Biomembr 1999; 31(4): 335–45PubMed
84.
Tarnopolsky MA, Beal MF. Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 2001; 49(5): 561–74PubMed
85.
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): 4389–97PubMed
86.
Steeghs K, Benders A, Oerlemans F, et al. Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. Cell 1997; 89(1): 93–103PubMed
87.
de Groof AJ, Fransen JA, Errington RJ, et al. The creatine kinase system is essential for optimal refill of the sarcoplasmic reticulum Ca2+ store in skeletal muscle. J Biol Chem 2002; 277(7): 5275–84PubMed
88.
Andreassen OA, Jenkins BG, Dedeoglu A, et al. Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J Neurochem 2001; 77(2): 383–90PubMed
89.
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(23): 13435–40PubMed
90.
Brewer GJ, Wallimann TW. Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons. J Neurochem 2000; 74(5): 1968–78PubMed
91.
Lawler JM, Barnes WS, Wu G, et al. Direct antioxidant properties of creatine. Biochem Biophys Res Commun 2002; 290(1): 47–52PubMed
92.
Derave W, Van Den Bosch L, Lemmens G, et al. Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment. Neurobiol Dis 2003 Aug; 13(3): 264–72PubMed
93.
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): 156–63PubMed
94.
Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol 2003; 53(2): 267–70PubMed
95.
Klivenyi P, Kiaei M, Gardian G, et al. Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem 2004; 88(3): 576–82PubMed
96.
Shefner J, Cudkowicz M, Shchoenfeld D, et al. A clinical trial of creatine in patients with amyotrophic lateral sclerosis. Abstracts from the 14th International Symposium on ALS/MND. Amyotroph Lateral Scler Other Motor Neuron Disord 2003; 4Suppl. 1: 28–9
97.
Groeneveld GJ, Veldink JH, van der Tweel I, et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann Neurol 2003; 53(4): 437–45PubMed
98.
Drory VE, Gross D. No effect of creatine on respiratory distress in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2002; 3(1): 43–6PubMed
99.
Mazzini L, Balzarini 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): 139–44PubMed
100.
Rosenfeld J, Jackson C, Smith J, et al. A pilot trial of ultrapure creatine in amyotrophic lateral sclerosis [abstract]. Amyotroph Lateral Scler Other Motor Neuron Disord 2001; 2Suppl 2 (1466-0822): 20
101.
Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol 1999; 157(1): 142–9PubMed
102.
Shear DA, Haik KL, Dunbar GL. Creatine reduces 3-nitropropionic-acid-induced cognitive and motor abnormalities in rats. Neuroreport 2000; 11(9): 1833–7PubMed
103.
Dedeoglu A, Kubilus JK, Yang L, et al. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington’s disease transgenic mice. J Neurochem 2003; 85(6): 1359–67PubMed
104.
Walter MC, Reilich P, Lochmuller H, et al. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurol 2002; 249(12): 1717–22PubMed
105.
Doherty TJ, Lougheed K, Markez J, et al. Creatine monohydrate does not increase strength in patients with hereditary neuropathy. Neurology 2001; 57(3): 559–60PubMed
106.
Tarnopolsky M, Martin J. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology 1999; 52(4): 854–7PubMed
107.
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): 174–82PubMed
108.
Walter MC, Lochmuller H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: a double-blind, placebo-controlled clinical study. Neurology 2000; 54(9): 1848–50PubMed
109.
Louis M, Lebacq J, Poortmans JR, et al. Beneficial effects of creatine supplementation in dystrophic patients. Muscle Nerve 2003; 27(5): 604–10PubMed
110.
Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review [published erratum appears in Clin J Sport Med 1999 Apr; 9 (2): 62]. Clin J Sport Med 1998; 8(4): 298–304PubMed
111.
Schilling BK, Stone MH, Utter A, et al. Creatine supplementation and health variables: a retrospective study. Med Sci Sports Exerc 2001; 33(2): 183–8PubMed
112.
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(12): 2044–52PubMed
113.
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(8): 2250–3PubMed
114.
Ingwall JS, Weiner CD, Morales MF, et al. Specificity of creatine in the control of muscle protein synthesis. J Cell Biol 1974; 62(1): 145–51PubMed
115.
Ingwall JS, Morales MF, Stockdale FE, et al. Creatine: a possible stimulus skeletal cardiac muscle hypertrophy. Recent Adv Stud Cardiac Struct Metab 1975; 8: 467–81PubMed
116.
Ingwall JS. Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res 1976; 38(5 Suppl. 1): I115–123
117.
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(3): 1041–7PubMed
118.
Vierck JL, Icenoggle DL, Bucci L, et al. The effects of ergogenic compounds on myogenic satellite cells. Med Sci Sports Exerc 2003; 35(5): 769–76PubMed
119.
Dangott B, Schultz E, Mozdziak PE. Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med 2000; 21(1): 13–6PubMed
120.
Wyss M, Felber S, Skladal D, et al. The therapeutic potential of oral creatine supplementation in muscle disease. Med Hypotheses 1998; 51(4): 333–6PubMed
121.
Tarnopolsky M, Parise G, Fu MH, et al. Acute and moderateterm creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans. Mol Cell Biochem 2003; 244(1–2): 159–66PubMed
122.
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): 291–6PubMed
Metadata
Title
The Role of Creatine in the Management of Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disorders
Authors
Amy Cameron Ellis
Jeffrey Rosenfeld
Publication date
01-12-2004
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 14/2004
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/00023210-200418140-00002

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