Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

Authors: CHIU, CHUNG-JUNG - JM USDA HNRCA @ TUFTS; MILTON, ROY - AREDS COORDINATING CENTER; KLEIN, RONALD - UNIV OF WISC SCH OF MED; GENSLER, GARY - AREDS COORDINATING CENTER; Taylor, Allen

Submitted to: Ophthalmology: Journal of The American Academy of Ophthalmology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/1/2009
Publication Date: 5/1/2009
Citation: Chiu, C., Milton, R.C., Klein, R., Gensler, G., Taylor, A. 2009. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study. Ophthalmology: Journal of The American Academy of Ophthalmology. 116(5):939-946.

Interpretive Summary: Previous studies, including our recent studies on dietary patterns and carbohydrate, have accumulated a firm body of evidence supporting the idea that diet can be optimized to prevent the progression of age-related macular degeneration (AMD). Although many 'one-at-a-time' studies, which evaluate only one nutrient at a time, have identified the key nutrients which are responsible for the protection, such as vitamins C, E, zinc, and lutein/zeaxanthin, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and glycemic index (GI), few have studied the combined effects of more than two of these nutrients at the same time, not to mention considering all of these nutrients together. This is because the current available method has its limitations. In order to overcome this impediment, we developed a scoring system to summarize the jointed effect of the above-mentioned nutrients and related the compound score to AMD risk. Our results showed that people can benefit most from consuming a diet rich in low-GI foods (such as whole grains) and the above-mentioned nutrients. Beta-carotene intake was previously considered beneficial in 'one-at-a-time' studies, but has raised concerns about increasing lung cancer risk in smokers. We have found no evidence that higher beta-carotene intake accrues more benefit to the disease. Therefore, our data suggests that it is unnecessary to promote beta-carotene consumption to achieve an optimal diet for AMD prevention.

Technical Abstract: Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. This has not been done previously. Design: Cross-sectional study. Participants: 4,003 participants of the Age-Related Eye Disease Study (AREDS) contributed 7,934 eyes. Methods: Considering dietary intakes of vitamins C and E, zinc, lutein/zeaxanthin, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and low-dietary glycemic index (dGI) from the AREDS baseline information, we assigned each nutrient a percentile rank score then summed them into a Compound score for each participant. Using eye as the unit of analysis, we evaluated the association between the Compound score and risk of prevalent AMD. Validation, fitness, and performance of the model were evaluated using bootstrapping techniques, adjusted quasilikelihood under the independence model criterion (QICu), and the c-index, respectively. Main Outcome Measures: Stereoscopic fundus photographs of the macula were taken and graded at baseline using the AREDS protocol and AMD Classification System. Results: Our results showed that higher Compound scores were associated with lower risk for early AMD, indicated by drusen, and advanced AMD. Validation analyses indicated that these relationships are robust (the average 50-time bootstrapping per quartile odds ratios [ORs] = 0.727, 0.827, and 0.753, respectively, for drusen, and 0.616, 0.536, and 0.572, respectively, for advanced AMD). Model selection analyses suggested that the Compound score should be included, but that measures of dietary beta-carotene should not be included. Conclusion: We found that consuming diets which provide low dGI and higher intakes of the above-mentioned nutrients were associated with the greatest reduction in risk for prevalent drusen and advanced AMD, while dietary beta-carotene did not affect these relationships. These findings warrant further prospective studies.