Many of the neuromuscular (e.g.,
muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by
creatine monohydrate (CrM) supplementation. Studies using the mdx model of
Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular
calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and
Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in
myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with
mitochondrial cytopathy. Lower-dose CrM supplementation in patients with
McArdle's disease (
myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with
steroid myopathy, inflammatory myopathy,
myoadenylate deaminase deficiency, and
fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether
creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use
surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns.