BACKGROUND: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and reducing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD).

METHODS: Dietary information was collected at baseline and fundus photograph grades were obtained during the 8-y trial period from 2,924 eligible AREDS AMD trial participants. Using eye as the unit of analysis and multi-failure Cox proportional-hazards regression, we related the risk of AMD progression to dietary intake in the four arms of the trial.

RESULTS: Independent of AREDS supplementation, higher intakes of DHA (>/= 64.0 vs. < 26.0 mg/d) (hazard ratio [HR] = 0.73, 95% confidence interval [CI], 0.57, 0.94), EPA (>/= 42.3 vs. < 12.7 mg/d) (HR = 0.74, 95% CI, 0.59, 0.94), and lower dGI (dGI, < 75.2 vs. >/= 81.5) (HR = 0.76, 95% CI, 0.60, 0.96) were associated with lower risk for progression to advanced AMD. Participants consuming lower dGI and higher DHA or EPA had the lowest risk (P for synergistic interaction < 0.001). Only participants in the ''placebo'' (P for antagonistic interaction = 0.006) benefited from higher DHA intake against early AMD progression (HR = 0.58, 95% CI, 0.37, 0.92; Ptrend = 0.01).

CONCLUSIONS: Our findings show an association of consuming a diet rich in DHA with lower progression of early AMD. In addition to the AREDS supplement, lower dGI with higher intakes of DHA and EPA was associated with reduced progression to advanced AMD.