Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study
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Published on: July 5, 2017
Matthias Vorgerd1, Jochen Zange, Rudolf Kley
1Department of Neurology, Ruhr-University Bochum, Kliniken Bergmannsheil, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. matthias.vorgerd@ruhr-uni-bochum.de
Insights
High-dose creatine (Cr) therapy worsened exercise intolerance symptoms in patients with McArdle disease, indicating a potential dose-limiting factor for treatment. Further research is needed to clarify the effective and safe dosage of Cr for symptom management.
Area of Science:
- Neurology
- Metabolic disorders
- Exercise physiology
Background:
- McArdle disease is a glycogen storage disease affecting muscle energy metabolism.
- Previous studies indicated low-dose creatine (Cr) supplementation may improve work capacity in these patients.
- High-dose Cr therapy efficacy and safety in McArdle disease require further investigation.
Purpose of the Study:
- To evaluate the efficacy of high-dose creatine (150 mg/kg daily) in patients with McArdle disease.
- To assess the impact of high-dose Cr on exercise intolerance and related clinical parameters.
- To identify potential adverse effects and dose-limiting factors of Cr therapy.
Main Methods:
- A randomized, double-blind, placebo-controlled crossover study was conducted.
- Nineteen patients diagnosed with McArdle disease participated in the study.
- Interventions included 5-week treatment phases with either Cr (150 mg/kg daily) or placebo.
Main Results:
- High-dose Cr administration led to increased exercise-induced muscle pain and limitation in daily activities.
- Body mass index also increased with Cr treatment.
- Surface electromyography showed a smaller increase in electromyographic amplitude during muscle contraction with Cr, while phosphorus 31 magnetic resonance spectroscopy revealed no significant changes.
Conclusions:
- High-dose creatine (150 mg/kg daily) exacerbates exercise intolerance symptoms in McArdle disease.
- Neurologic adverse effects associated with high-dose Cr are a significant dose-limiting factor.
- The optimal therapeutic dosage for Cr in McArdle disease may lie between 60 and 150 mg/kg daily, warranting further clarification.
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.
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