Dietary nitrate intake associated with lower Age-Related Macular Degeneration risk
Age-related macular degeneration (AMD) is a leading cause of vision loss in high-income nations. Although the exact pathogenesis remains unknown, alterations in blood flow and inflammation have been implicated as possible mechanisms in AMD pathogenesis. Both nitric oxide (NO) and nitric oxide synthase (NOS) are involved in these processes, and altered levels of NO and NOS have been reported in cases of AMD. This raises the possibility that dietary intake of nitrates, which are the precursors for NO, may influence AMD development or progression.
Dietary nitrate is obtained predominantly from vegetables, particularly leafy green vegetables. Leafy green vegetable intake has previously been associated with lower risk of AMD. Given the potential role of NO in mediating inflammation and vascular function, it is possible that nitrate intake contributes to the benefit associated with leafy green vegetable intake.
Geoffrey K. Broadhead and team assessed the association between dietary nitrate intake and the progression to intermediate and late AMD in a large prospective study comprising 2 randomized clinical trial (RCT) cohorts. They also explored potential confounding and interactions between dietary nitrate intake and lutein intake.
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. 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.
In the combined AREDS/AREDS2 cohort of 7788 participants (4288 AREDS participants and 3610 AREDS2 participants), 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 and a decreased risk of GA and nAMD. In AREDS, increased nitrate intake (quartile 4 vs quartile 1) was associated with a decreased risk of late AMD and GA but not nAMD; in AREDS2, there was no association between nitrate intake (quartile 4 vs quartile 1) and late AMD or nAMD. There was a correlation between Mediterranean dietary patterns and dietary nitrate intake (r = 0.52, P < .001).
Dietary nitrates have been suggested as possible contributors to the cardioprotective effect of fruit and vegetable–rich diets but have not been studied in relation to AMD until recently. In the AREDS/AREDS2 combined cohort, dietary nitrate intake was associated with a reduced risk of progression to late AMD, including its subtypes. The findings of this cohort study suggest that nitrate intake was associated with a decreased risk of progression to late AMD, including both late AMD subtypes. This association persisted even after accounting for lutein and zeaxanthin intake as a potential confounder and was strongest among individuals with lower adherence to a fruit and vegetable–rich diet pattern. A protective association was also seen against the development of large drusen, suggesting that the benefit of dietary nitrates may extend across a wide spectrum of AMD severities; however, no evidence was seen to support recommending additional nitrate supplementation. These results are from post hoc analyses and are therefore hypothesis-generating in nature. Much of the outcome associated with nitrate intake can be attributed to plant-based dietary patterns in general, such as a Mediterranean diet. Further research, including potential randomized clinical trials, may be warranted to further assess the role of dietary nitrate in reducing the risk of AMD progression.
Source: Geoffrey K. Broadhead, Elvira Agrón, David Peprah; JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2022.5404
