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Effects of creatine supplementation in Rett syndrome: a randomized, placebo-controlled trial
Michael Freilinger1, Daniela Dunkler, Ines Lanator
1Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. michael.freilinger@meduniwien.ac.at
Objective:
To evaluate the effects of creatine monohydrate (CMH) supplementation on global DNA methylation and disease-specific clinical symptoms in female patients with Rett syndrome (RTT).
Methods:
Double-blind, randomized, placebo-controlled crossover trial of female patients with RTT. Participants received 200 mg/kg of either CMH or placebo daily for 6 months and switched following a 4-week washout period. Primary endpoints were change in global DNA methylation and in a RTT-specific symptom score as defined by medical history and clinical evaluation with Rett Syndrome Motor and Behavioral Assessment. Secondary endpoints were changes in biochemical markers of methionine metabolism.
Results:
Eighteen female patients aged 3 to 25 years with clinically diagnosed typical RTT and MECP2 mutation at clinical Stages III or IV were studied. CMH supplementation resulted in a statistically significant increase of global methylation by 0.11 (95% confidence interval 0.03-0.19, p = .009) compared with placebo. Total and subscores of Rett Syndrome Motor and Behavioral Assessment tended to improve but without statistical significance.
Conclusion:
CMH supplementation increases global DNA methylation statistically significantly. Scores were lower for creatine than for placebo reflecting clinical improvement but not reaching statistical significance. Biochemical variables of methionine-homocysteine remethylation are unaffected. Multicenter studies are urgently warranted to evaluate the long-term effects of CMH supplementation in an optimally homogenous RTT population over a prolonged period.
