AREDS offers evidence of micronutrients' role in AMD

"Although the pathogenesis of AMD is not well known, oxidative stress may be an important factor, which is the basis for the use of micronutrients to relieve oxidative stress," she said.

Dr. Chew reviewed the randomized Age-Related Eye Disease Study (AREDS), in which 25% of the patients received placebo, antioxidants (beta-carotene, vitamin C, and vitamin E), zinc and copper, or a combination of antioxidants and zinc.

In addition to the effect of the combination treatment, she pointed out, the natural history data are also important. The results showed that 1.3% of patients with small to moderate drusen (category 2 disease) develop advanced AMD at 5 years compared with 18% of patients who had intermediate to large drusen (category 3 disease). The group with the highest rate (43%) were those patients with advanced AMD in one eye and good vision in the fellow eye.

"This information is important because patients in category 2 would not benefit from any treatment because of the low rate of progression to advanced AMD. Therefore, antioxidants and zinc can be considered for patients with categories 3 to 4 disease," she said.

In patients with small drusen, there was little change in the progression of increasing drusen size or area when the AREDS supplement was given. Therefore the supplement is not recommended for AMD less severe than the intermediate risk (category 3).

In patients with advanced AMD who received the AREDS supplement and had 20/100 or better vision at baseline, the rate of vision loss was less compared with the placebo group.

"The combination treatment has a protective effect against vision loss. For patients with 20/100 or better vision, it may be important that they received combination of antioxidant vitamins and mineral therapy," she said.

The treatment does not come without a price, however, and adverse events have been reported with beta-carotene, namely a higher risk of lung cancer in patients who are smokers. Beta-carotene is not recommended for patients who are smokers.

Vitamin E and mortality

A meta-analysis of 19 trials that considered the question, "Does vitamin E supplementation increase the risk of mortality in adults?" The doses of vitamin E evaluated in this meta-analysis ranged from 16 to 2,000 international units (IU). The results showed that a dose of vitamin E of 400 IU or higher was considered to be associated with a higher risk of mortality because of cardiovascular disease. The dose of vitamin E used in the AREDS was 400 IU.

A limited meta-analysis conducted by the AREDS investigators on the three studies, which used the doses of 400 to 440 IU of vitamin E, did not show an increased risk of mortality. In fact, they found that patients who received vitamin E when compared with the placebo group actually enjoyed a protective effect. Vitamin E therefore does not seem to have an adverse effect at the dose used in the AREDS.