Vitamin D, Marine ω-3 Fatty Acid Supplementations Have No Impact on AMD

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Results from a prespecified ancillary study show neither vitamin D3 nor marine ω-3 fatty acid supplementation had a significant overall effect on age-related macular degeneration (AMD) incidence or progression.

Results from a prespecified ancillary study show neither vitamin D3 nor marine ω-3 fatty acid supplementation had a significant overall effect on age-related macular degeneration (AMD) incidence or progression. Findings1 were published in JAMA Ophthalmology.

AMD is the leading cause of severe, irreversible vision loss in US adults while for those with advanced, neovascular AMD, treatment is currently available in the form of anti-vascular endothelial growth factor therapy. For individuals with intermediate to advanced forms of the disease, supplements of antioxidants plus zinc is recommended.

Thus, “for the large majority of people with early or no AMD, there is no effective intervention other than lifestyle modifications, such as avoidance of cigarette smoking,” authors wrote.

Previous observational studies have suggested higher intake or blood levels of vitamin D and marine ω-3 fatty acids may be associated with lower risks of the disease.


In the current study, researchers analyzed data from the Vitamin D and Omega-3 Trial (VITAL), a double-blind, placebo-controlled randomized clinical trial initially designed to analyze the supplements’ association with prevention of cancer and cardiovascular disease among US men and women.

Between November 2011 and March 2014, a total of 25,871 participants with a mean (SD) age of 67.1 (7) years were randomized to receive 2000 IU of vitamin D3 (cholecalciferol) or 1 g of marine ω-3 fatty acids per day. Pill taking ended on December 31, 2017, yielding a median (range) treatment window of 5.3 (3.8-6.1) years.

At baseline, each participant completed a questionnaire asking if they had ever been diagnosed with macular degeneration. Subsequent annual questionnaires also included the question. Following an affirmative answer, “ophthalmologists and optometrists were contacted by mail and asked to complete an AMD questionnaire that requested information on the date of initial diagnosis, best-corrected visual acuity at the time of diagnosis, and date when best-corrected visual acuity reached 20/30 or worse.”

Some participants also gave annual blood samples which showed a mean rise of 40% in vitamin D level and 54.7% in ω-3 level over the course of the trial.

The final study cohort included 71.3% non-Hispanic White participants and 20.2% Black participants. Analyses revealed:

  • 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)
  • 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

Average rate of response to study questionaries was 93.1% and adherence to the pill regimen was high, as more than 80% of participants reported taking at least two-thirds of the capsules during the 5 years of follow-up.

Because the AMD end point was based on participant reports followed by medical record review, researchers noted some underascertainment of AMD is likely.

“These negative results of a large, well-designed, and well conducted clinical trial, performed by highly experienced investigators, is discouraging,” wrote Robert N. Frank, MD, in an accompanying editorial.2 He continued, “although the present study yielded negative results, it has been abundantly clear over the last number of years that overall progress in other areas of research in the causes and treatment of AMD remains considerable.”


  1. Christen WG, Cook NR, Manson JE, et al. Effect of vitamin D and ω-3 fatty acid supplementation on risk of age-related macular degeneration. JAMA Ophthalmol. Published online October 29, 2020. doi: 10.1001/jamaophthalmol.2020.4409
  2. Frank, RN. Of age-related macular degeneration and vitamins. JAMA Ophthalmol. Published online October 29, 2020. doi:10.1001/jamaophthalmol.2020.4417