Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in older Americans. There has been a long standing interest in the role of diet in the development of AMD. As early as the first National Health and Nutrition Examination Survey in the 1970s, higher intakes of fruits and vegetables were inversely correlated with the prevalence of AMD. Carotenoids and omega3 fatty acids are the most studied dietary factors due to strong biological plausibility. However, evidence from epidemiologic studies and clinical trials on the relations has been inconsistent.

Chapter I prospectively examined the intakes of lutein/zeaxanthin and other common carotenoids in relation to the risk of AMD over more than two decades of follow-up among two large US cohorts, the Nurses’ Health Study and Health Professionals Follow-Up Study. We assessed nutrient intakes by repeated food frequency questionnaires. We also computed bioavailable plasma carotenoid scores directly from food intake using validated regression models. Cox proportional hazards models were used to compute the associations. Higher intakes of bioavailable carotenoids (except lycopene) were inversely associated with advanced AMD but not intermediate AMD. Analyses based on bioavailable intakes resulted in stronger associations than conventional nutrient intakes.

Chapter II prospectively evaluated the marine long-chain omega3 fatty acids. We found that long-chain omega3 fatty acids were inversely associated with visually significant intermediate AMD. There was no association with advanced AMD; however, the totality of current evidence for advanced AMD is also discordant.

Chapter III further investigated the plant-derived omega3 fatty acids, α-linolenic acid (ALA). We found that higher intake of ALA was associated with intermediate AMD before 2002 but not after. This coincides with the same time period when trans ALA was found in our participants’ blood and in mayonnaise, a primary food source of ALA. Whether trans ALA mediates this positive association warrants further studies.

Although randomized trials are usually believed as the “gold standard”, dietary factors are hard to be adequately studied by randomized trials due to the complexities of diet and disease relations. Thus, findings in this thesis from large long-term prospective cohort studies provide the next best form of evidence.