Antioxidants Don't Prevent Macular Degeneration

MELBOURNE, Australia, Oct. 9 -- A diet rich in antioxidant vitamins and minerals (vitamins A, C, and E, various carotenoids, and zinc) did nothing to prevent age-related macular degeneration, according to a large review and meta-analysis.

Moreover, antioxidant supplements, mainly vitamin E and beta-carotene, also missed the mark, Tien Y. Wong, M.D., Ph.D., of the University of Melbourne, and colleagues reported in BMJ Online First.

The retina, with its high oxygen content and constant exposure to light, is particularly susceptible to oxidative damage. Thus, it has long been suggested that antioxidants found in fruits and vegetables could be useful for preventing the development and progression of the eye disorder, the researchers wrote.

Randomized controlled trials and observational studies have focused on the role of antioxidants and supplements in the secondary prevention of progression to late disease, but the evidence of dietary antioxidants as a primary preventive measure remains unclear, the researchers wrote.

To evaluate antioxidants as primary prevention, the researchers undertook a systematic review and meta-analysis of randomized clinical trials and prospective cohort studies.

Results were pooled quantitatively using meta-analytic methods. All the studies adjusted for age and smoking in their analyses.

Nine prospective cohort studies and three randomized clinical trials met the selection criteria.

The cohort studies included 149,203 people, with 1,878 incident cases of early age-related macular degeneration. Participants had been recruited from 1980 through 1994, and all the studies were conducted in the U.S. or other Western countries among well-nourished individuals.

Mean follow-up was nine years, and most participants were 49 years or older, although two studies included individuals in their early 40s.

The dietary antioxidants differed across the studies, and not all studies contributed to the meta-analysis of each antioxidant.

However, when the results were pooled, the researchers found that a range of dietary antioxidants -- including vitamins A, C, and E; zinc; lutein and zeaxanthin; ?- carotene; ?-carotene; ?-cryptoxanthin; and lycopene -- had little or no effect in the primary prevention of early age-related macular degeneration.

Pooled odds ratios ranged from 0.91 to 1.11, with the exception of vitamin E, which had a modest borderline protective effect of almost 20% (odds ratio 0.83, 95% confidence interval 0.69 to 1.01).

In addition, antioxidant supplements were analyzed in three randomized controlled clinical trials (including one abstract).

One trial evaluated vitamin E versus placebo supplementation in the Australian population, and a second trial evaluated ?-tocopherol and ?-carotene versus placebo in Finland. Neither of these trials found the supplements effective for primary prevention.

Discussing the possibility of a borderline effect for dietary vitamin E, Dr. Wong and colleagues noted that the results from these two randomized controlled trials of vitamin E supplements given in doses 2.5-fold to 15-fold higher than the highest dietary range did not support a vitamin E benefit.

The researchers listed important study imitations. Few randomized controlled trials were found, they said, and it was not possible to evaluate the effect of potential antioxidant synergism, including various combinations or ratios.

Some of the studies may not have represented the wider community. Also, all studies were conducted in relatively well-nourished populations, and results therefore may not have been generalizable.

The assessment and definition of the eye disorder also varied from study to study.

Finally, they noted, dietary intake is difficult to measure, and most studies used food-frequency questionnaires, given only once at baseline, thus misclassification may have occurred.

"There is insufficient evidence to support the role of dietary antioxidants, including the use of antioxidant supplements, for the primary prevention of early age-related macular degeneration," the researchers said.

Cigarette smoking remains the only widely accepted modifiable risk factor for primary prevention, they added, and patients seeking advice should be encouraged to stop smoking,

In an accompanying editorial Jennifer Evans, M.Sc., of the London School of Hygiene and Tropical Medicine International, noted that this is the first review of usual dietary intake for primary prevention. Previous reviews, she said, have studied supplements.

The prospective studies found that people with relatively high dietary intakes of antioxidant nutrients were no more or less likely to develop the condition than those with relatively low intakes.

However, she noted, a diet high in fruits and vegetables has many other health benefits, and should still be recommended.

Ms. Evans did note a possible exception to the findings: a high dietary intake of vitamin E was associated with a 20% reduced odds of age-related macular degeneration.

The significance of this finding, however, depended on which studies were included in the meta-analysis, and further studies are needed to confirm the relevance of this finding.

Currently, she said, reducing the prevalence of smoking is probably the most effective way of reducing the population burden of this common cause of visual loss in older people.

Co-author Elaine W-T Chong MBBS, received a National Health and Medical Research Council public health scholarship, funded by the Federal Government of Australia. Dr. Wong and co-author Robin H. Guymer, M.D., Ph.D., are on advisory boards of Pfizer and Novartis and have received grants, honoraria, and traveling fees from these companies.