Cochrane Briefs


Am Fam Physician. 2006 Sep 1;74(5):750.

Antioxidants and Minerals for Age-Related Macular Degeneration

Clinical Question

Does supplementation with high doses of antioxidant vitamins and minerals slow the progression of age-related macular degeneration (ARMD)?

Evidence-Based Answer

Supplementation with a combination of vitamin C, vitamin E, beta-carotene, and zinc modestly reduces the progression of ARMD in patients with disease in one or both eyes. High-dose vitamin supplements should not be recommended for patients without ARMD because of the possible harmful effects of vitamin E and beta-carotene at high doses.

Practice Pointers

ARMD is the most common cause of blindness in industrialized countries, with up to one third of adults older than 75 years showing at least early signs of the disease. High doses of vitamin C, vitamin E, carotenoids, lutein, selenium, and zinc are increasingly being recommended to prevent or treat ARMD. However, some studies have shown that high doses of vitamin E and beta-carotene may increase all-cause mortality.1,2

Evans reviewed any randomized trial comparing antioxidant vitamins with placebo in patients with ARMD in one or both eyes. The primary outcome was visual acuity. Eight studies were included in the systematic review. Patients had a mean age of 70 years. Three of the trials studied zinc alone, two studied an antioxidant combination, one studied lutein, and one vitamin E. The vitamin E trial (Vitamin E, Cataract and Age-related maculopathy study [VECAT]) had 1,204 participants and followed patients for four years. The largest study (Age-Related Eye Disease Study [AREDS]), which compared zinc alone, an antioxidant combination, or both, with placebo, included 3,640 patients and lasted six years.3 The other six studies each had fewer than 200 patients and lasted for no more than two years; thus, most of the data come from the VECAT and AREDS trials.

The AREDS trial found that supplementation with vitamin C, vitamin E, zinc, and beta-carotene slows the progression of disease in patients with ARMD (relative risk = 0.68; 99% confidence interval, 0.49 to 0.93).3 The VECAT study included healthy older patients and found no visual benefit to supplementation with vitamin E (500 IU per day) after four years. Given the potential risks of vitamin E, it cannot be recommended to protect vision in patients without ARMD. The single study of lutein included 52 patients and found no effect on visual acuity.

Vitamin supplements for “eye health” are increasingly used by patients who may have a family history of ARMD but who do not have macular degeneration. It is important to warn patients about the potential harms of these supplements and the lack of known benefit.


Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2006;(2):CD000254.


1. Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37–46.

2. Albanes D, Heinonen OP, Huttunen JK, Taylor PR, Virtamo J, Edwards BK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 1995;62(6 suppl):1427S–30S.

3. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417–36.

The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family and Community Medicine, University of California, San Francisco.



Copyright © 2006 by the American Academy of Family Physicians.
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