Creatine for Muscular Dystrophy
July 1, 2000 2 minutes read
Creatine for Muscular Dystrophy
Abstract & Commentary
Source: Walter MC, et al. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study. Neurology 2000;54:1848-1850.
Thirty-six muscular dystrophy (md) patients, including facioscapulohumeral (n = 12), Becker (n = 10), Duchenne (n = 8), and sarcoglycan-deficient (n = 6) MD, were enrolled in an eight-week, double-blind, placebo-controlled, crossover study of creatine monohydrate (CREAPURE; Cr), followed by a three-week washout period, to determine safety and efficacy of 5 g/d or 10 g/d, for children and adults, respectively. Medical Research Council (MRC) scale, Neuromuscular Symptoms Score ([NSS] Soueidan SA, Dalakas MC. Neurology 1993;43:876-879), vital capacity (VC), and patient self-rating were primary end points, and standard statistical analyses, including Wilcoxon’s and Fisher’s exact tests, were used to assess results.
Muscle strength significantly improved by 3%, and NSS by 10%, on Cr, compared to a declining trend on placebo, with improvement seen in all forms of MD, in both mildly and severely affected muscles, more so in children than adults. Twenty-one of the 36 patients self-reported improvement by Cr vs. no improvement by placebo. VC did not change, serum creatine kinase levels did not rise, and side effects were absent in all patients. Oral Cr is safe, well tolerated, and mildly efficacious. Further larger scale studies are warranted to determine its efficacy in specific MDs as well as in other neuromuscular conditions.
Commentary
Cr may also be beneficial for neurogenic neuromuscular disorders, acting through several potential mechanisms. First, calcium is cytotoxic in certain clinical situations (e.g., cerebral ischemia) and creatine kinase deficiency results in impaired calcium buffering. Cr regenerates adenosine triphosphate (ATP), which is then used by calcium adenosine triphosphatase (ATPase) for calcium buffering, thus inhibiting its cytotoxic effect. Second, in animal models of Huntington’s disease, Cr supplementation protects against striatal damage produced by 3-nitroproprionic acid (3-NPA) by attenuating lactate increases, as well as ATP and phosphocreatine decreases, induced by 3-NPA (Matthews RT, et al. J Neurosci 1998;18:156-163). Lastly, Cr blocks the mitochondrial transition pore, an opening in the inner mitochondrial membrane that occurs as a result of various stimuli, including excess calcium, and which is linked to excitotoxic and apoptotic cell death (White RJ, Reynolds IJ; Schinder AF, et al. J Neurosci 1996;16:5688-5697; 6125-6133). Cr inhibits mitochondrial pore opening by stabilizing mitochondrial creatine kinase. Cr supplementation appears to show promise for the treatment of neuromuscular disease and also is being evaluated in a multicenter trial for amyotrophic lateral sclerosis. We await the results with interest. —mr
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