Effect of Antioxidant Supplementation on Macular Pigment Optical Density and Visual Functions: A systematic review and network meta-analysis of randomized controlled trials

Context Antioxidants are bioactive molecules that function to scavenge free radicals and balance oxidative stress. While all antioxidants can act as reactive oxygen species scavengers, their efficacy on eye health may vary. Moreover, the comparative effectiveness and potential additive effect among groups of antioxidants, hitherto, have not been systematically studied. Objective A systematic review and network meta-analysis was conducted to investigate the comparative or additive effect of dietary antioxidant supplements on eye health. Methods Four databases (PubMed, Embase, CINAHL and Cochrane) were searched and relevant randomized controlled trials were identified. Results Out of 60 articles selected for systematic review, 38 were included in the network meta-analysis, categorized into eight distinct antioxidant-supplemented groups and placebo. All groups significantly increased macular pigment optical density (MPOD) and contrast sensitivity at low spatial frequency while only the antioxidant mixture + lutein + fatty acid combination exhibited significant improvements for visual acuity (hazard ratio= -0.15; 95% Confidence Interval, CI: -0.28, -0.02) and lutein + zeaxanthin combination for photostress recovery time (hazard ratio = -5.75; 95% CI: -8.80, -1.70). Especially, the lutein + zeaxanthin + fatty acid combination was ranked best for MPOD (Surface Under the Cumulative Ranking, SUCRA: 99.3%) and second-best for contrast sensitivity at low spatial frequency (67.7%). However, these findings should be interpreted with caution due to low quality of evidence, primarily influenced by indirectness and potential publication bias. Conclusion Overall antioxidant supplementation was estimated to improve eye health parameters on average while different combinations of antioxidants may also have varying effects on improving visual health from multiple perspectives.