A Cochrane review included 3 RCTs with a total of 386 patients with amyotrophic lateral sclerosis (ALS). The patients were randomized to either creatine 5 to 10 g per day or placebo. There was no statistical difference in survival between the creatine and placebo groups across all 3 studies (Chi2 = 0.09, p = 0.76). In addition, there was no statistical difference in ALS functional rating revised scores (ALSFRS-R) slopes between the groups in any studies (slope difference of +0.03 ALSFRS-R/month in the creatine group; p = 0.76). Interestingly, there was a trend towards slightly worsened forced vital capacity (FVC) slope in the creatine group (slope difference of -0.63 FVC/month in the creatine group) in 2 studies which included FVC as an outcome, but this difference was not statistically significant (p = 0.054). Creatine was well-tolerated in all studies, with no evidence of renal failure or serious adverse events specifically attributable to creatine.
Comment: The quality of the evidence is downgraded by indirectness of evidence (differences in studied patients).