Vitamins for age-related macular degeneration.

The Problem

A 68-year-old woman presents to you for evaluation of low back pain. She has a history of hypertension, hyperlipidemia, and atrial fibrillation. She is deeply concerned about her husband who was recently seen by an ophthalmologist and diagnosed with age-related macular degeneration (AMD). The patient herself had been seen by an ophthalmologist 6 months ago and received a new prescription for corrective lenses and had an otherwise unremarkable exam. She reports to you that her husband has received a prescription for "vision vitamins" to prevent the progression of his disease. She asks you whether she should take vitamins like his to prevent the development of the disease. She says that if you think they will help her, she would like a prescription for them. You diagnose her with musculoskeletal low back pain, recommend rehabilitation exercises, and promise to investigate the utility of these supplements for preventing AMD.

The Question

Do vitamin supplements prevent the development of age-related macular degeneration, compared with placebo?

The Search

You log on to PubMed (www.pubmed.gov), enter "macular degeneration AND vitamins," and limit the search to "meta-analysis." You identify a relevant study. (See box at right.)

Our Critique

This was a well-conducted systematic review, leaving it unlikely that important studies were missed. The included studies were of high quality and involved a large number of patients. If supplementation does help prevent or delay AMD, it is likely a small benefit, with confidence intervals compatible with a protective effect not exceeding 10% for preventing age-related maculopathy (ARM) and 25% for preventing AMD (i.e., advanced ARM). Careful attention should be paid to the fact that supplementation could be associated with potential harm. With the emergence of compelling evidence that [beta]-carotene supplementation increases the risk for lung cancer among cigarette smokers, we have learned that vitamin supplementation is not without potential attendant risks. With the probable exception of vitamin D and calcium supplementation, it has not been convincingly demonstrated that vitamin and/or mineral supplementation in addition to a well-balanced diet does much more for our patients than create "expensive urine."

Clinical Decision

You inform your patient that you do not believe that vitamin or mineral supplementation will prevent the development of ARM or AMD. You encourage her to eat a well-balanced diet and continue to take calcium and vitamin D supplementation for her bones.

J.R. Evans and K. Henshaw

Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst.

Rev. 2008;1:CD000253.

* Criteria for Study Inclusion: For the purposes of this systematic review, the term age-related maculopathy (ARM) was used as an overall term and AMD was used to describe late-stage disease. Antioxidants were defined as any vitamin or mineral known to have an antioxidant effect or known to be an important component of an antioxidant enzyme in the retina, and included vitamin C, vitamin E, carotenoids, selenium, and zinc. Randomized trials comparing antioxidant vitamin and/or mineral supplementation, alone or in combination, with a control given for at least 1 year were included. Study participants included the general population without AMD and excluded studies in which participants exclusively had AMD.

* Study Identification: Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Group Trials Register, MEDLINE, EMBASE, SIGLE, National Research Register, PubMed, and AMED.

* Study Selection: The authors assessed titles and abstracts resulting from the searches and selected studies according to selection criteria. Full copies of all reports referring to controlled trials that definitely or potentially met the inclusion criteria were obtained. Investigators of original studies were contacted for unpublished data. Quality of the studies was independently assessed by the authors of the current study.

* Outcomes: Primary outcomes included number of subjects developing AMD, number of subjects with visual loss due to AMD, quality of life measures, and adverse events.

* Results: The authors identified three primary prevention trials of antioxidant or mineral supplements for ARM that took place in Australia, Finland, or the United States. A total of 23,099 subjects were randomized. Duration of supplementation ranged from 4 to 12 years. Studies evaluated alpha-tocopherol, [beta]-carotene, and vitamin E and were of high methodologic quality. No evidence of an overall effect of antioxidant supplementation was observed for the prevention of ARM (relative risk 1.04; 95% confidence interval: 0.92-1.18) or for AMD (RR 1.03; 95% CI: 0.74-1.43). For the specific supplements, no evidence of an effect was observed for the prevention of ARM with alpha-tocopherol (RR 1.11; 95% CI: 0.91-1.36) or with [beta]-carotene (RR = 1.03; 95% CI: 0.98-1.19). In addition, no benefit of either supplement for preventing the development of late-stage ARM was observed.

Dr. EBBERT and DR. TANGALOS are with the Mayo Clinic in Rochester, Minn. They have no conflict of interest to report. To respond to this column or suggest topics for consideration, write to Dr. Ebbert and Dr. Tangalos at our editorial offices or e-mail them at imnews@elsevier.com.

BY JON O. EBBERT, M.D., AND ERIC G. TANGALOS,M.D.