Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS

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 1. 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.

Figure 1.

Slope of decline in MVIC in patients taking creatine and those taking placebo over the nine-month study period.

Figure 2.

Survival.

Figure 3.

Compliance testing via 24-h urine-creatine measures.Creatine was measured in 24-hour urine collections at baseline, three and nine months. The creatine treatment group had a significant increase in measured creatine, as expected, compared with the placebo group. This indicator of compliance with assigned treatment group revealed significant compliance to the protocol, despite the availability of creatine in the community (see text). Creatine vs. placebo at baseline, p=0.367 Creatine vs. placebo at three months, p<0.00001 Creatine vs. placebo at nine months, p<0.00001