Free radical accumulation and oxidative stress have been proposed as contributing to the progression of
amyotrophic lateral sclerosis (
motor neuron disease). A range of
antioxidant medications is available, and has been studied. We aimed to examine the effects of
antioxidant medication in the treatment of people with
amyotrophic lateral sclerosis, and searched the Cochrane
Neuromuscular Disease Group Trials register (August 2005), MEDLINE (January 1966 to August 2005), EMBASE (January 1980 to August 2005) and other sources. Selection criteria were all randomized or quasi-randomized controlled trials of
antioxidant treatment for
amyotrophic lateral sclerosis. The authors independently applied the selection criteria, assessed study quality and two authors performed independent data extraction. The search identified 23 studies for consideration but only nine studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure as the primary outcome measure (survival at 12 months treatment). However, sufficient data were available from four studies to allow analysis of this outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed for
vitamin E 500 mg twice daily;
vitamin E 1 g five times daily;
acetylcysteine 50 mg/kg daily
subcutaneous infusion; or a combination of
L-methionine 2 g,
vitamin E 400 International Units, and
selenium 0.03 mg three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta analysis of all
antioxidants combined. No significant differences were demonstrated in any of the secondary outcome measures. In the opinion of the reviewers, there is insufficient evidence of efficacy of individual
antioxidants, or
antioxidants in general, in the treatment of people with
amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally, the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as
vitamin C and E are unlikely to be performed. If future trials of
antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of
vitamins C and E, and other considerations related to the lack of other effective treatments for
amyotrophic lateral sclerosis, explain the continuing use of these
vitamins by physicians and people with
amyotrophic lateral sclerosis. While there is no substantial clinical trial evidence to support their clinical use, there is no clear
contraindication.