Abstract

Our objective was to determine the effect of creatine monohydrate on disease progression in patients with amyotrophic lateral sclerosis (ALS). One hundred and seven patients with the diagnosis of probable or definite ALS, of less than five years duration from symptom onset, were randomized to either treatment with daily creatine monohydrate (5 g/d) or placebo. In this multicenter, double-blinded study we followed changes in disease progression: using quantitative measures of strength via maximal isometric voluntary contraction, forced vital capacity, ALSFRS, quality of life, fatigue and survival. Patients were followed for nine months. The results showed that creatine monohydrate did not significantly improve motor, respiratory or functional capacity in this patient population. The drug was well tolerated and the study groups well balanced, especially considering the absence of forced vital capacity criteria for entrance into the study. There was a trend toward improved survival in patients taking daily creatine monohydrate and this was identical to the trend seen in another recently published report of creatine in ALS patients . In conclusion, creatine monohydrate (5 g/d) did not have an obvious benefit on the multiple markers of disease progression measured over nine months. We measured fatigue during isometric contraction and found no significant improvement despite anecdotal patient reports prior to and during the study. The trend toward improved survival was also found in another recently completed blinded trial using creatine monohydrate. Further investigation on the possible survival benefit of creatine in this patient population is ongoing.

Highlights

  • The mechanism of amyotrophic lateral sclerosis (ALS) involves a complex inter-relationship of various biochemical processes

  • The enzyme creatine kinase catalyzes the phosphorylation of creatine and the dephosphorylation of phosphocreatine

  • All serious adverse events were reported to an independent Data Safety Monitoring Board (DSMB) twice yearly

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Summary

Introduction

The mechanism of amyotrophic lateral sclerosis (ALS) involves a complex inter-relationship of various biochemical processes. Glutamate homeostasis, calcium metabolism and the immune system can all contribute [2]. Mitochondrial dysfunction has been implicated as a pivotal component in several parallel pathways [3]. Attempts to enhance mitochondrial function have, generated significant interest as potential therapy for patients with ALS. Creatine is a naturally occurring guanidinederived compound that is synthesized endogenously in humans in the liver and is found predominantly in muscle and brain (4Á6). The enzyme creatine kinase catalyzes the phosphorylation of creatine and the dephosphorylation of phosphocreatine

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