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Original Investigation
October 29, 2020

Effect of Vitamin D and ω-3 Fatty Acid Supplementation on Risk of Age-Related Macular Degeneration: An Ancillary Study of the VITAL Randomized Clinical Trial

Author Affiliations
  • 1Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
JAMA Ophthalmol. 2020;138(12):1280-1289. doi:10.1001/jamaophthalmol.2020.4409
Key Points

Question  Can daily supplementation with vitamin D3 and marine ω-3 fatty acids prevent the development or progression of age-related macular degeneration (AMD)?

Findings  In this randomized clinical trial of 25 871 adult US men and women, daily supplementation with vitamin D3, 2000 IU, and marine ω-3 fatty acids, 1 g, for a median of 5.3 years had no overall effect on the primary vision end point of total AMD events, a composite of incident AMD and progression to advanced AMD.

Meaning  Neither vitamin D3 nor marine ω-3 fatty acid supplementation had a significant overall effect on AMD incidence or progression.

Abstract

Importance  Observational studies suggest that higher intake or blood levels of vitamin D and marine ω-3 fatty acids may be associated with lower risks of age-related macular degeneration (AMD). However, evidence from randomized trials is limited.

Objective  To evaluate whether daily supplementation with vitamin D3, marine ω-3 fatty acids, or both prevents the development or progression of AMD.

Design, Setting, and Participants  This was a prespecified ancillary study of the Vitamin D and Omega-3 Trial (VITAL), a nationwide, placebo-controlled, 2 × 2 factorial design randomized clinical trial of supplementation with vitamin D and marine ω-3 fatty acids for the primary prevention of cancer and cardiovascular disease. Participants included 25 871 men and women in the US. Randomization was from November 2011 to March 2014, and study pill-taking ended as planned on December 31, 2017.

Interventions  Vitamin D3 (cholecalciferol), 2000 IU per day, and marine ω-3 fatty acids, 1 g per day.

Main Outcomes and Measures  The primary end point was total AMD events, a composite of incident cases of AMD plus cases of progression to advanced AMD among participants with AMD at baseline, based on self-report confirmed by medical record review. Analyses were conducted using the intention-to-treat population.

Results  In total, 25 871 participants with a mean (SD) age of 67.1 (7.0) years were included in the trial. Of them, 50.6% were women, 71.3% were self-declared non-Hispanic White participants, and 20.2% were Black participants. During a median (range) of 5.3 (3.8-6.1) years of treatment and follow-up, 324 participants experienced an AMD event (285 incident AMD and 39 progression to advanced AMD). For vitamin D3, there were 163 events in the treated group and 161 in the placebo group (hazard ratio [HR], 1.02; 95% CI, 0.82-1.27). For ω-3 fatty acids, there were 157 events in the treated group and 167 in the placebo group (HR, 0.94; 95% CI, 0.76-1.17). In analyses of individual components for the primary end point, HRs comparing vitamin D3 groups were 1.09 (95% CI, 0.86-1.37) for incident AMD and 0.63 (95% CI, 0.33-1.21) for AMD progression. For ω-3 fatty acids, HRs were 0.93 (95% CI, 0.73-1.17) for incident AMD and 1.05 (95% CI, 0.56-1.97) for AMD progression.

Conclusion and Relevance  Neither vitamin D3 nor marine ω-3 fatty acid supplementation had a significant overall effect on AMD incidence or progression.

Trial Registration  ClinicalTrials.gov Identifier: NCT01782352

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