There is no cure for amyotrophic lateral sclerosis, also known as motor neuron disease, a progressively disabling and ultimately fatal disease. Antioxidants, including vitamins C, E, selegiline, selenium, methionine and acetylcysteine, have been suggested as possible treatments and some of these are commonly advised by physicians treating people with amyotrophic lateral sclerosis. We identified nine studies involving a total of 830 participants. We did not find any well-designed randomized controlled trial evidence to support the use of these medications. Trials of antioxidants identified in this review were generally of poor methodological quality and lacked statistical power. However, antioxidants are generally well tolerated without serious adverse effects.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 7, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Orrell RW, Lane RJM, Ross M. Antioxidant treatment for amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD002829. DOI: 10.1002/14651858.CD002829.pub4

Editorial Group: Neuromuscular Disease Group

This version first published online: October 18. 2004
Last assessed as up-to-date: January 1. 2008

Abstract

Background

Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications have been studied.

Objectives

To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis.

Search strategy

We searched the Cochrane Neuromuscular Disease Group Trials Register (December 2007), MEDLINE (from January 1966 to December 2007), EMBASE (from January 1980 to December 2007) and other sources.

Selection criteria

All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis.

Data collection and analysis

The authors independently applied the selection criteria, assessed study quality and two authors performed independent data extraction.

Main results

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 0.03mg 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.

Authors' conclusions

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.

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