A systematic review of antioxidant treatment for amyotrophic lateralsclerosis/motor neuron disease

摘要

Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateralsclerosis (motor neuron disease). A range of antioxidant medications is available, and has been studied. We aimed toexamine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis, and searched theCochrane 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-randomizedcontrolled trials of antioxidant treatment for amyotrophic lateral sclerosis. The authors independently applied the selectioncriteria, assessed study quality and two authors performed independent data extraction. The search identified 23 studies forconsideration but only nine studies met the inclusion criteria. Only two studies used our predetermined primary outcomemeasure as the primary outcome measure (survival at 12 months treatment). However, sufficient data were available fromfour studies to allow analysis of this outcome measure, and a meta-analysis was performed. In the individual studies nosignificant effect was observed for vitamin E 500 mg twice daily; vitamin E 1 g five times daily; acetylcysteine 50 mg/kg dailysubcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 0.03 mgthree times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta analysis of allantioxidants combined. No significant differences were demonstrated in any of the secondary outcome measures. In theopinion of the reviewers, there is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in thetreatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supportedby the analysis we used. Generally, the studies were poorly designed, and underpowered, with low numbers of participantsand of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. Iffuture 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 otherconsiderations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use ofthese vitamins by physicians and people with amyotrophic lateral sclerosis. While there is no substantial clinical trialevidence to support their clinical use, there is no clear contraindication.