Literature Review

Creatine Does Not Slow Rate of Parkinson’s Disease Progression



Treatment with creatine monohydrate for at least five years, compared with placebo, did not improve clinical outcome in patients with early and treated Parkinson’s disease, according to a study in the February 10 issue of JAMA. “Creatine was initially considered because of evidence that it plays an important role in cellular energy production, which may be impaired in Parkinson’s disease,” the research team wrote. “Yet despite the available preclinical and clinical evidence, creatine failed to slow the clinical progression of Parkinson’s disease, as measured across five domains of Parkinson’s disease measured in the long-term clinical trial.”

To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in patients with Parkinson’s disease, Karl Kieburtz, MD, MPH, Senior Associate Dean of Clinical Research at the University of Rochester in New York, and colleagues conducted a long-term, multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1,741 men and women with early (ie, within five years of diagnosis) and treated (ie, receiving dopaminergic therapy) Parkinson’s disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.

Participants were randomized to receive placebo or creatine monohydrate (10 g/day) for a minimum of five years (maximum follow-up, eight years). The primary outcome measure was a difference in clinical decline from baseline to five-year follow-up, compared between the two groups using a global statistical test. Clinical status was defined by modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity.

The trial was terminated early for futility, based on the results of a planned interim analysis of participants enrolled at least five years prior to the date of the analysis (n = 955). The median follow-up time was four years. Using several measures of Parkinson’s disease progression, the researchers found that treatment with creatine, compared with placebo, did not improve clinical outcomes. Of the 955 participants, the means of the summed ranks were 2,360 for placebo and 2,414 for creatine. There were no detectable differences in adverse and serious adverse events by body system.

“These findings do not support the use of creatine monohydrate in patients with Parkinson’s disease,” the authors concluded.

Glenn S. Williams

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