Cohort study2023

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

Broadhead GK, Agrón E, Peprah D, Keenan TDL, Lawler TP, Mares J, Chew EY, AREDS/AREDS2 Investigators

JAMA ophthalmology · 14 citations

Review labels

No stated lifestyle adjustment

Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.

How it was studied

Design
Cohort study (indexed by PubMed)
Studied in
People
Main outcome
Clinical events such as disease or death
Intake measured by
Not stated

Who paid for it

Funding
Independent funding
Government
National Eye Institute
Government
NEI NIH HHS
Grants
National Eye Institute (N01-EY-5-0007)

Based on 2 listed funder(s).

Publication

Published
2022-12-22 · JAMA Ophthalmol · vol. 141 · issue 2 · p. 130
Publisher
American Medical Association
Cited
18 citations · more than 92% of similar papers · 2.9× the field average
Impact
Top 10% most cited in its field
References
30 works
Access
Open access (repository copy)
Research areas
Retinal Diseases and Treatments · Glaucoma and retinal disorders · Ophthalmology and Visual Impairment Studies
Keywords
Medicine, Macular degeneration, Cohort, Cohort study, Quartile, Hazard ratio, Prospective cohort study, Internal medicine, Odds ratio, Drusen, Ophthalmology, Confidence interval
MeSH
humans, nitrates, angiogenesis inhibitors, vascular endothelial growth factor a, cohort studies, prospective studies, diet, mediterranean, visual acuity, adult, aged, female, male, geographic atrophy, wet macular degeneration

96 authors

From AU, US

  • Geoffrey BroadheadThe University of Sydney; National Institutes of Health; National Eye Institute
  • Elvira AgrónNational Institutes of Health; National Eye Institute
  • David PeprahNational Institutes of Health; National Eye Institute
  • Tiarnán D L KeenanNational Institutes of Health; National Eye Institute
  • Thomas P. LawlerUniversity of Wisconsin–Madison; University of Wisconsin Carbone Cancer Center
  • Julie A. MaresUniversity of Wisconsin–Madison

Abstract

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.

Abstract via Europe PMC. Copyright remains with the authors or publisher.

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