Clinicacl use of creatine in neuromuscular and neurometabolic disorders

[Guest guest]

Subcell Biochem. 2007;46:183-204.

Clinical use of creatine in neuromuscular and neurometabolic

disorders.

Tarnopolsky MA.

Department of Pediatrics and Medicine (Neurology and Rehabilitation),

Neuromuscular and Neurometabolic Clinic, Rm 2H26, McMaster University

Medical Center, 1200 Main St. W., Hamilton, Ontario, Canada, L8N 3Z5.

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.