Background: Progressive muscle weakness is a main symptom of most hereditary muscle diseases. Creatine is a popular nutritional supplement among athletes. It improves muscle performance in healthy individuals and might be helpful for treating myopathies.
Objectives: To evaluate the efficacy of oral creatine supplementation in muscle diseases.
Search strategy: We searched the Cochrane Neuromuscular Disease Group Register in May 2004 for randomised trials using the search term 'creatine'. We also searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2005) using the same search term. We adapted this strategy to search MEDLINE (PubMed, from January 1966 to September 2005) and EMBASE (from January 1980 to May 2004). We reviewed the bibliographies of the randomised trials identified, contacted the authors and known experts in the field and approached pharmaceutical companies to identify additional published or unpublished data.
Selection criteria: Types of studies: randomised or quasi-randomised controlled trials.
Types of participants: people of all ages with hereditary muscle disease. Types of intervention: any creatine supplementation of at least 0.03 g/kg body weight/day.
Primary outcome measure: change in muscle strength measured by quantitative muscle testing.
Secondary outcome measures: change in muscle strength measured by manual muscle testing, change in energy parameters assessed by 31 phosphorous spectroscopy, change in muscle mass or a surrogate for muscle mass, adverse events.
Data collection and analysis: Two authors independently applied the selection criteria, assessed trial quality and extracted data. Some missing data were obtained from investigators.
Main results: Twelve trials, including 266 participants, met the selection criteria. One trial compared creatine and glutamine treatment with placebo. In trials with 138 participants with muscular dystrophies treated with creatine, there was a significant increase in maximum voluntary contraction in the creatine group compared to placebo, with a weighted mean difference of 8.47% (95% confidence intervals 3.55 to 13.38). There was also an increase in lean body mass during creatine treatment compared to placebo (weighted mean difference 0.63 kg, 95% confidence intervals 0.02 to 1.25). No trial reported any clinically relevant adverse event. In trials with 33 participants with metabolic myopathies treated with creatine, there was no significant difference in maximum voluntary contraction between the creatine and placebo group (weighted mean difference -2.26%, confidence intervals -6.29 to 1.78). One trial reported a significant increase in muscle pain during high-dose creatine treatment (150 mg/kg body weight) in glycogen storage disease type V.
Authors' conclusions: Evidence from randomised controlled trials shows that short- and medium-term creatine treatment improves muscle strength in people with muscular dystrophies, and is well-tolerated. Evidence from randomised controlled trials does not show significant improvement in muscle strength in metabolic myopathies. High-dose creatine in glycogenosis type V increased muscle pain.