Effect of High-Dose Creatine Therapy on Symptoms of Exercise Intolerance in McArdle Disease Double-blind, Placebo-Controlled Crossover Study

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/m 2 , 95% CI, 0.10-0.56 kg/m 2 ; 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.