Written by Angeline A. De Leon, Staff Writer. This study found that neither vitamin D3 nor marine ω-3 fatty acid supplementation significantly influenced the overall effect on age-related macular degeneration (AMD) incidence or progression.
AMD is a progressive eye disease that represents the leading cause of vision loss in the U.S. 1. Early stages of AMD do not usually involve significant changes in eye sight, but advanced stages of the disease result in severe and irreversible loss of vision 2. For patients with more advanced forms of the disease, increased dietary intake of vitamin D and omega-3 fatty acids has been shown to be associated with reduced prevalence of AMD 3. An inverse association between vitamin D intake and AMD risk has previously been suggested 4, however, corroborating evidence from randomized controlled trials is still lacking. One of the few randomized trials on nutrient supplementation and AMD prevention actually reports contradicting findings, suggesting that consumption of omega-3 fatty acids and high-dose antioxidants like vitamin D has no meaningful impact on AMD progression 5. To clarify the potential prophylactic role of vitamin D and omega-3 fatty acids in AMD, a research team at Harvard University investigated the respective effects of vitamin D3 and omega-3 fatty acids supplementation on the development of AMD.
The current study 6 represents a prespecified ancillary study of a randomized, double-blind, placebo-controlled trial investigating the effects of vitamin D3 and omega-3 fatty acids supplementation on cancer and CVD prevention. A total of 25,871 subjects (mean age = 67.1 years) were randomized to consume 2,000 IU vitamin D3,, 1g marine omega-3 fatty acids, both vitamin D3 and omega-3 fatty acids together, or placebo once daily for a median treatment period of 5.3 years. At baseline and for every following year of treatment, total AMD events (composite of incident AMD cases + cases of progression to advanced AMD among subjects with AMD at baseline) were ascertained based on self-report questionnaires that were confirmed by medical record review. Hazard Ratio (HR) estimates of AMD were then respectively calculated for subjects in the vitamin D3 group and for those in the omega-3 fatty acids group, relative to placebo.
Over a median follow-up period of 5.3 years, 324 subjects reported an AMD event (285 incident cases and 39 cases of progression to advanced AMD). Within the vitamin D3 group, 163 total AMD events occurred (HR = 1.02, 95% Confidence Interval: 0.82 to 1.27, p = 0.86), with 148 cases of incident AMD (HR = 1.09, 95% CI: 0.86 to 1.37, p = 0.48) and 15 cases of AMD progression (HR = 0.63, 95% CI: 0.33 to 1.21, p = 0.17). For the omega-3 group, 157 total AMD events were recorded (HR = 0.94, 95% CI: 0.76 to 1.17, p = 0.57), with 137 cases of incident AMD (HR = 0.93, 95% CI: 0.73 to 1.17, p = 0.52) and 20 cases of AMD progression (HR = 1.05, 95% CI: 0.56 to 1.97, p = 0.88).
Overall, findings from this ancillary study do not suggest a significant overall effect of supplementation with either vitamin D3 or omega-3 fatty acids on the development of AMD. Neither intervention appeared to significantly impact AMD incidence or AMD progression. Given that only 12.7% of subjects had low levels of circulating 25-hydroxyvitamin D concentrations (levels below 25 ng/mL, associated with increased AMD risk 7, one possibility is that null findings may be related to the fact that vitamin D requirements for AMD prevention were already sufficiently met for the majority of subjects. Regarding omega-3 fatty acids, present findings are in line with prior research reporting a non-significant relationship between supplementation with EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) for 3 years and AMD progression 8. Prospective studies are crucial in reconciling these discrepant findings in the literature. Major limitations of the current study pertain to the failure to adjust for multiple comparisons in analyses and the measurement of AMD events based on self-report accounts followed by medical verification, which may have caused an underestimation of AMD rates.
Source: Christen WG, Cook NR, Manson JE, et al. Effect of vitamin D and omega-3 fatty acid supplementation on risk of age-related macular degeneration: an ancillary study of the VITL randomized clinical trial. JAMA Ophthalmology. 2020; 138(12): 1280-1289. DOI: 10.1001/jamaopthalmol.2020.4409.
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Posted March 5, 2021.
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- 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. 2020;138(12):1280-1289.
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- Souied EH, Delcourt C, Querques G, et al. Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study. Ophthalmology. 2013;120(8):1619-1631.