Association of Dietary Nitrate and a Mediterranean Diet With Age-Related Macular Degeneration Among US Adults: The Age-Related Eye Disease Study (AREDS) and AREDS2.

Importance: Low dietary nitrate intake has previously been suggested to be a risk factor for age-related macular degeneration (AMD) progression; however, this finding has not been replicated in other cohorts or adjusted for dietary patterns. Objective: To determine whether there is an association between dietary nitrate intake and AMD progression. Design, Setting, and Participants: This cohort study analyzed data from the prospective Age-Related Eye Disease Study (AREDS) and AREDS2 randomized clinical trial cohorts and their extended follow-up studies, which were conducted in multicenter outpatient retinal practices. Participants in both trials had non-late AMD in at least 1 eye. Data were analyzed from March 1, 2020, to September 30, 2022. Exposure: Dietary nitrate intake. Main Outcomes and Measures: Association between dietary nitrate intake and development of late AMD (neovascular AMD [nAMD] or geographic atrophy [GA]) or large drusen. The interactions of dietary patterns, with common at-risk single-nucleotide polymorphisms, were also assessed. Results: In the combined AREDS/AREDS2 cohort of 7788 participants (4288 AREDS participants and 3610 AREDS2 participants [110 of whom participated in both studies]), there were 13 511 eligible eyes. The combined cohort comprised 4396 women (56%) and 3392 men (44%), and the combined mean (SD) age was 71.1 (6.6) years. Dietary nitrate intake was associated with a decreased risk of progression to late AMD in the combined AREDS/AREDS2 cohort (hazard ratio [HR], 0.77 [95% CI, 0.69-0.86] for quartile 4 vs quartile 1 of intake) and a decreased risk of GA (HR, 0.71 [95% CI, 0.61-0.83]) and nAMD (HR, 0.85 [95% CI, 0.73-0.99]). In AREDS, increased nitrate intake (quartile 4 vs quartile 1) was associated with a decreased risk of late AMD (HR, 0.77 [95% CI, 0.65-0.91]) and GA (HR, 0.80 [95% CI, 0.65-0.97]) but not nAMD; in AREDS2, there was no association between nitrate intake (quartile 4 vs quartile 1) and late AMD (HR, 0.90 [95% CI, 0.80-1.02]) or nAMD (HR, 0.93 [95% CI, 0.78-1.11]). There was a correlation between Mediterranean dietary patterns and dietary nitrate intake (r = 0.52, P < .001). Conclusions and Relevance: The findings of this cohort study suggest that dietary nitrate intake was associated with lower AMD risk. However, this association disappeared after adjusting for Mediterranean dietary patterns. These results are subject to potential bias and are hypothesis-generating in nature; therefore, they are insufficient to support new clinical recommendations. Previously described associations between dietary nitrate intake and AMD may in fact represent overall dietary patterns. Further research is needed before dietary nitrate intake can be recommended as a therapy for AMD.