Neither vitamin D3 nor marine omega 3 fatty acid supplementation has a significant overall effect on age-related macular degeneration (AMD) incidence or progression, according to researchers from Harvard Medical School and Harvard T.H. Chan School of Public Health.

For most people with early or no AMD, there is no effective intervention other than lifestyle modifications. While observational evidence has suggested that people with higher dietary intake or blood levels of vitamin D or marine omega 3 fatty acids (docosahexanoic acid and eicosapentaenoic acid) may have lower rates of AMD, randomized trial data of the use of these nutrients for AMD has been limited.

To evaluate whether daily supplementation with vitamin D3, marine omega 3 fatty acids, or both, prevents the development or progression of AMD, researchers conducted a prespecified ancillary study of Vitamin D and Omega-3 Trial (VITAL), a nationwide double-blind, placebo-controlled randomized clinical trial. VITAL examined the use of Vitamin D and marine omega 3 fatty acids for preventing cancer and cardiovascular disease.


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In total, 25,871 participants with a mean (SD) age of 67.1 (7.0) years were included in the trial. The demographic breakdown included 50.6% women, 71.3% self-declared non-Hispanic White participants, and 20.2% Black participants. Baseline characteristics of study participants were distributed equally between active and placebo treatment groups.

In this ancillary trial of initially healthy men and women, daily supplementation with vitamin D3 (2000 IU/d) and marine omega 3 fatty acids (1 g/d) for a median of 5.3 years had no overall effect on the primary vision endpoint of total AMD events, according to the researchers. Total AMD events are defined as a composite of incident AMD and progression to advanced AMD. While the progression of AMD was less common in the vitamin D3 group, the difference was not statistically significant, according to the investigators.

Specifically, 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 progressions 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 omega 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 endpoint, 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.

This trial had several limitations, according to the researchers. First, the median duration of the trial intervention was 5.3 years, and detection of supplement-related benefits, if present, may require longer follow-up. Second, no adjustment was made for multiple comparisons, and some subgroup analyses were based on small numbers of events. Third, the sub-additive interaction the team observed, if real, may have influenced the power of the primary analyses, which did not take this interaction into account. Lastly, the AMD endpoint was based on participant reports followed by medical record review. As a result, some under ascertainment is likely, according to the researchers.

References

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: an ancillary study of the vital randomized clinical trial. JAMA Ophthalmol. Published online October 29, 2020. doi:10.1001/jamaophthalmol.2020.4409