Diet and age-related macular degeneration: expanding our view.

In the current issue of the Journal (1), Chiu et al describe their observations of a new aspect of diet that may be related to one type and stage of age-related macular degeneration (AMD) of the eye: a diet that is high in foods with a high glycemic index. This aspect of the diet adds to the long and growing list of dietary attributes that have been related to early and later stages of AMD in different study samples over the past 15 y. Because there is no cure and limited treatments for the end-stage condition of AMD, it is the leading cause of blindness in persons older than 50 y in developed countries. Diet is potentially one of the most costeffective strategies to prevent the development of AMD, the incidence of which is expected to increase by 50% by 2030 in the United States. The scope of dietary-related degenerative conditions such as AMD may not only increase in the near future in the United States, but may become an increasing concern in the developing world as a result of sweeping social, economic, and dietary changes that accompany the economic development of these areas (2). The results of several previous epidemiologic studies and clinical trials suggest that diets high in antioxidant nutrients (vitamins C and E, carotenoids such as lutein and zeaxanthin, fruit and vegetables that contain these nutrients, and nonnutritive antioxidants) or zinc are associated with a decreased occurrence of early or late AMD (3). A high dietary intake of fat was associated with a higher prevalence or incidence of early or late AMD in numerous studies (4), whereas higher intakes of fish or n 3 fatty acids were associated with lower rates of AMD (4). Because of evidence that the pathogenesis of AMD likely involves a complex interaction of cellular and vascular factors, which may be promoted by light damage, oxidative stress, and inflammation, it comes as no surprise that numerous nutrients and other dietary components may play several different roles that could be additive or complementary. A substantial body of experimental data in animals and clinical and pathologic studies in humans support the biological plausibility that the several dietary attributes discussed above may be protective. The authors of the present study cite several potential biological mechanisms by which the glycemic index might also be related to AMD. Although advanced glycation end products have been found in drusen, it is not yet known whether they are a cause or a consequence of degenerative changes. Degeneration of the retinal vasculature is a well-known complication of diabetes mellitus. Yet, the presence of diabetes has not often been related to AMD in previous epidemiologic studies. The biological plausibility that elevations in blood sugar promote AMD, particularly in the absence of diabetes, remains untested. As is common in most of the published investigations of the relation between diet and AMD, this editorial describes the degree to which this one dimension of diet, ie, glycemic index, is related to AMD. It may be that a low glycemic index score is a marker for other combined aspects of diet that could protect against AMD. Diets with a low glycemic index often include plenty of fruit, vegetables, whole grains, legumes, and milk and few refined grains and sugars. Obviously, such diets are richer in a variety of nutritive and nonnutritive antioxidants. Diets with a high glycemic index, like high-fat diets, may be associated with higher rates of AMD because they are simply poorer in a wide variety of protective nutrients and other dietary components. Having a diet with a low glycemic index score might also be related to health-conscious fat choices that might also protect against AMD, such as low or moderate intakes of saturated and polyunsaturated fats and high intakes of fish and n 3 fats from nuts, seeds, and whole grains. Unfortunately, we have no simple way of accounting for these multiple simultaneous aspects of diet that may be related to AMD. As did these investigators, we assume that we account for all other aspects of diet by adding the level of consumption of other dietary components to the regression model. When risk estimates do not change, we discount their influence on the observed association. Because our measures of specific diet attributes are imprecise with regard to the level and timing of diet exposure, residual confounding makes the approach of adding individual estimates of numerous other nutrients (that are often highly correlated) insufficient for completely removing this influence. Moreover, persons with low glycemic index scores may have slightly or moderately higher intakes of a broad array of micronutrients that would be harder to statistically adjust for than would be larger intakes of a few nutrients. It may be that the glycemic index score reflects a broader diet pattern that protects against AMD. No studies of the relations of diet patterns with AMD have been published. In the past decade, increasing numbers of studies have found that overall diet patterns are related to the slower development of chronic conditions, such as hypertension and cardiovascular diseases. Because these conditions may be risk factors for AMD, patterns that slow these