Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration

Cochrane Database Syst Rev. 2012 Nov 14:11:CD000254. doi: 10.1002/14651858.CD000254.pub3.


Background: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of age-related macular degeneration (AMD).

Objectives: The objective of this review was to assess the effects of antioxidant vitamin or mineral supplementation on the progression of AMD in people with AMD.

Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Allied and Complementary Medicine Database (AMED) (January 1985 to August 2012), OpenGrey (System for Information on Grey Literature in Europe) (, the metaRegister of Controlled Trials (mRCT) (, ( and the WHO International Clinical Trials Registry Platform (ICTRP) ( We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 20 August 2012. We searched the reference lists of identified reports and the Science Citation Index. We contacted investigators and experts in the field for details of unpublished studies. We also searched for systematic reviews of harms of vitamin supplements.

Selection criteria: We included randomised trials comparing antioxidant vitamin or mineral supplementation (alone or in combination) to placebo or no intervention in people with AMD.

Data collection and analysis: Two authors assessed risk of bias and extracted data from the included trials. Where appropriate, we pooled data using a random-effects model unless three or fewer trials were available in which case we used a fixed-effect model.

Main results: Thirteen trials (6150 participants) were included in this review. Over half the participants (3640) were randomised in one trial (AREDS in the USA), which found a beneficial effect of antioxidant (beta-carotene, vitamin C and vitamin E) and zinc supplementation on progression to advanced AMD (adjusted odds ratio (OR) 0.68, 95% confidence interval (CI) 0.53 to 0.87) over an average of 6.3 years. People taking supplements were less likely to lose 15 or more letters of visual acuity (adjusted OR 0.77, 95% CI 0.62 to 0.96). The other trials, in general, had shorter follow-up (less than two years). No evidence for an effect of supplementation was seen in these smaller trials of shorter duration. Overall we considered the strength of the evidence to be moderate. We did not consider included trials, in general, to be at risk of bias, although we found it difficult to assess reporting biases. The main reason for downgrading the strength of the evidence was because, for several analyses, only one trial was included and therefore consistency of the findings could not be assessed. The included trials reported the following adverse effects: hospitalisation for genito-urinary problems was more common in people taking zinc and yellowing of skin was more common in people taking antioxidants. Systematic searching of the literature identified other potential harms of vitamin supplementation, in particular an increased risk of lung cancer in smokers associated with beta-carotene supplements, but we were unable to identify a good systematic review of the evidence for harms of nutritional supplementation.

Authors' conclusions: People with AMD may experience delay in progression of the disease with antioxidant vitamin and mineral supplementation. This finding is drawn from one large trial conducted in a relatively well-nourished American population. The generalisability of these findings to other populations is not known. Although generally regarded as safe, vitamin supplements may have harmful effects. A systematic review of the evidence on harms of vitamin supplements is needed.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Antioxidants / therapeutic use*
  • Dietary Supplements
  • Humans
  • Macular Degeneration / prevention & control*
  • Minerals / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Vitamins / therapeutic use*


  • Antioxidants
  • Minerals
  • Vitamins