Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease

  • Review
  • Intervention


  • RW Orrell,

    Corresponding author
    1. Royal Free and University College Medical School, Department of Clinical Neurosciences, London, UK
    • RW Orrell, Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London (Royal Free Campus), Rowland Hill Street, London, NW3 2QG, UK.

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  • JM Lane,

  • MA Ross



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 are available, and have been studied.


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 (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources.

Selection criteria

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

Data collection and analysis

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

Main results

The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed.
In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures.

Reviewers' 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 patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Plain language summary


There is a lack of evidence of efficacy for antioxidants in treating amyotrophic lateral sclerosis

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 did not find any evidence to support the use of these medications on the basis of well-designed randomized controlled trials. Trials of antioxidants were generally of poor methodological quality and lacked statistical power. However, antioxidants are generally well tolerated without serious adverse effects.