Association of Dietary Nitrate Intake with the 15-Year Incidence of Age-Related Macular Degeneration

Background Dietary nitrate, found predominantly in green leafy vegetables and beetroot, is a precursor of nitric oxide. Under- or overproduction of nitric oxide is implicated in the etiology of several eye diseases. However, the potential influence of dietary nitrate intake on age-related macular degeneration (AMD) risk has not been assessed. Objective To investigate the temporal association between dietary nitrate intake (from both vegetable and nonvegetable sources) and the 15-year incidence of AMD, independent of potential confounders. Design A longitudinal cohort study conducted from 1992-1994 to 2007-2009. Participants/setting The Blue Mountains Eye Study is a population-based study of adults aged 49+ at baseline, from a region west of Sydney, Australia. At baseline, 2,856 participants with complete dietary data and AMD information were examined, and of these, 2,037 participants were re-examined 15 years later and thus included in incidence analysis. Main outcomes measured Incidence of AMD (main outcome) was assessed from retinal photographs. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. Nitrate intake from vegetables and nonvegetable sources was calculated by use of a validated comprehensive database. Results After adjusting for age, sex, smoking, energy intake, fish consumption, and AMD risk alleles (complement factor H and age-related maculopathy susceptibility-2 single nucleotide polymorphisms), participants in the third quartile compared with those in the first quartile (reference group) of total nitrate and total vegetable nitrate intake had reduced risk of incident early AMD: odds ratio (OR) 0.61 (95% CI 0.41 to 0.90) and OR 0.65 (95% CI 0.44 to 0.96), respectively. Significant associations were not observed between the fourth vs first quartile of total nitrate and vegetable nitrate intake with incident early AMD: OR 0.74 (95% CI 0.51 to 1.08) and OR 0.69 (95% CI 0.47 to 1.00), respectively. Nonsignificant associations were also observed with 15-year incidence of late AMD and total nonvegetable nitrate intake. Conclusions These novel findings could have important implications, if the association between total nitrate intake and vegetable nitrate intake and 15-year incidence of early AMD is confirmed in other observational or intervention studies.