Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study.

Abstract

BACKGROUND:

In a recent study, we showed that administration of low-dose creatine (Cr) (60 mg/kg daily) improved work capacity in patients with McArdle disease.

OBJECTIVE:

To assess the efficacy of high-dose Cr therapy in McArdle disease.

DESIGN:

Randomized, double-blind, placebo-controlled crossover study.

PATIENTS:

Nineteen patients with McArdle disease.

INTERVENTION:

Treatment with Cr, 150 mg/kg daily. Each treatment phase with Cr or placebo lasted 5 weeks.

MAIN OUTCOME MEASURES:

The patient's daily rating of symptoms of exercise intolerance. At the end of each treatment phase, serum creatine and serum creatine kinase levels, phosphorus 31 magnetic resonance spectroscopy, and surface electromyograms were assessed.

RESULTS:

Clinical end points revealed increases in the intensity of exercise-induced pain in working muscles (mean treatment-induced difference [d], 0.30 in log(score); 95% confidence interval [CI], 0.05-0.55; P =.02), the limitation of daily activities (d, 0.59; 95% CI, 0.22-0.97;P =.005), and body mass index (d, 0.33 kg/m2, 95% CI, 0.10-0.56 kg/m2; P =.008) with Cr use. Surface electromyograms revealed a smaller increase in the electromyographic amplitude over time during muscle contraction with Cr use (d, -13.52%/min; 95% CI, -23.71%/min to -3.34%/min; P =.01). There were no significant changes in phosphorus 31 magnetic resonance spectroscopy variables.

CONCLUSIONS:

Administration of high-dose Cr worsened the main clinical symptoms of exercise intolerance in McArdle disease. These neurologic adverse effects represent a major dose-limiting factor in Cr therapy for McArdle disease. Taken together with results of a previous study, the indication for symptomatic therapy with Cr needs to be clarified. An effective Cr dosage without adverse effects may be between 60 and 150 mg/kg daily.

• Authors: Matthias Vorgerd, Jochen Zange, Rudolf Kley, T Grehl, Anika Hüsing, Matthias Jäger, Klaus Müller, Rolf Schröder, Wilhelm Mortier, Klaus Fabian, Jean-Pierre Malin, Alwin Luttmann
• Journal: Archives of neurology (Arch Neurol) Vol. 59 Issue 1 Pg. 97-101 (Jan 2002) ISSN: 0003-9942 [Print] United States
• PMID: 11790236 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphorus Isotopes
• Creatine

Topics

• Adolescent
• Adult
• Child
• Creatine (administration & dosage, adverse effects)
• Cross-Over Studies
• Double-Blind Method
• Electromyography
• Exercise
• Female
• Glycogen Storage Disease Type V (diagnosis, drug therapy, physiopathology)
• Humans
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Muscle Fatigue (drug effects)
• Phosphorus Isotopes
• Treatment Failure