Dietary nutrient intake and progression to late age-related macular degeneration in the Age-Related Eye Disease Studies 1 and 2

Purpose: To analyze associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration (AMD) and its subtypes. Additional objectives were to analyze progression to large drusen and interactions with AMD genotype.

Design: Post hoc analysis of two controlled clinical trial cohorts: Age-Related Eye Disease Study (AREDS; recruitment 1992-8) and AREDS2 (recruitment 2006-8).

Participants: Eyes with no late AMD at baseline in AREDS participants (n=4,504) and AREDS2 participants (n=3,738): total of 14,135 eyes. Mean age was 71.0 years (SD 6.7); 56.5% were female.

Methods: Fundus photographs were collected at annual study visits and graded centrally for late AMD. Dietary intake of multiple nutrients was calculated for each participant from food frequency questionnaires.

Main outcome measures: Progression to late AMD, geographic atrophy (GA), neovascular AMD, and (separate analyses) large drusen.

Results: Over median follow-up of 10.2 years, of the 14,135 eyes, 32.7% progressed to late AMD. For nine nutrients, intake quintiles 4 or 5 (versus 1) were significantly (P≤0.0005) associated with decreased risk of late AMD: vitamins A, B6, and C, folate, β-carotene, lutein/zeaxanthin, magnesium, copper, and alcohol. For three nutrients, quintiles 4 or 5 were significantly associated with increased risk: saturated fatty acid, monounsaturated fatty acid, and oleic acid. Similar results were observed for GA. Regarding neovascular AMD, nine nutrients were nominally associated with decreased risk (vitamins A and B6, β-carotene, lutein/zeaxanthin, magnesium, copper, docosahexaenoic acid, omega-3 fatty acid, and alcohol) and three with increased risk (saturated fatty acid, monounsaturated fatty acid, and oleic acid). In separate analyses (n=5,399 eyes of 3,164 AREDS participants), 12 nutrients were nominally associated with decreased risk of large drusen.

Conclusions: Higher dietary intake of multiple nutrients, including minerals, vitamins, and carotenoids, is associated with decreased risk of progression to late AMD. These associations are stronger for GA, for which no treatments are available, than for neovascular AMD. The same nutrients tend also to have protective associations against large drusen development. Strong genetic interactions exist for some nutrient-genotype combinations, particularly omega-3 fatty acids and CFH. These data may justify further research into underlying mechanisms and randomized trials of supplementation.