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Antioxidants for macular degeneration

Clinical bottom line

In older people with age-related macular degeneration, the use of antioxidant supplements plus zinc results in a small but useful reduction in risk of worsening vision over five years


AREDS. 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. Archives of Ophthalmology 2001 119: 1417-1436.


This large (3,640 patients) study randomised patients with age-related macular degeneration to placebo, antioxidants, zinc, or antioxidants plus zinc for five years. All patients had best-eye visual acuity of 20/32 or better in at least one eye. They had category 2, 3 or 4 disease, meaning that they had to have small drusen to intermediate drusen.

The treatment interventions were identical in appearance. The antioxidants comprised 500 mg vitamin C, 400 IU of vitamin E, and 15 mg beta-carotene, or zinc (80 mg as zinc oxide), or both together. Treatment was for five years.

The main outcome was progression to advanced macular degeneration (AMD event) for a study eye, defined as photocoagulation or other treatment for neovascularisation, or documentation of progression with pre-set criteria. A second outcome was a decrease in best-corrected visual acuity score from baseline of 15 or more letters in a study eye.


Over 90% of patients attended for assessment over the period, and tablet counts suggested that over 70-% of patients took more than 75% of their study tablets.

Progression to an AMD event was more likely for people with more advanced eye disease. For those in category 2, only about 2% had an event by two years. For those with category 3 it was 18%, and for those with category 4 it was 43% (Figure 1). Analysis of the effect of the treatments was very extensive, but the main interest was for those with category 3 and 4 eye disease initially (70% of the patients).

Figure 1: Development of AMD event by initial category of disease

Antioxidants and zinc were associated with lower rates of development of an AMD event or loss of visual acuity. For AMD, the approximate NNT to prevent one event over five years are shown in Table 1. For loss of visual acuity, only patients in category 4 initially had a significantly reduced rate of events compared with placebo. Antioxidants plus zinc was better then either alone.

Table 1: ANMD events in patients with initial category 3 and 4

Percent with outcome at five years
Odds ratio
(95% CI)
Approximate NNTp
AMD event
0.8 (0.6 to 1.1)
0.7 (0.5 to 1.0)
Antioxidant + zinc
0.7 (0.5 to 0.9)


There were no serious adverse events of note.


This is a terrific trial. It was large and well conducted, and in an important disease area. It showed that the combination of antioxidants plus zinc was worthwhile in people with extant macular degeneration to prevent or slow further advancement in some of them.