Effect of Antioxidant Supplementation on Macular Pigment Optical Density and Visual Functions: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Abstract

Effect of Antioxidant Supplementation on Macular Pigment Optical Density and Visual Functions: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Weili Hu, Vernice Seah, Vanessa Huang, Jung Eun Kim * Department of Food Science and Technology, National University of Singapore, Singapore ABSTRACT Antioxidants are bioactive molecules that function to scavenge free radicals and balance oxidative stress. Although all antioxidants can act as reactive oxygen species scavengers, their efficacy on eye health may vary. Moreover, the comparative effectiveness and potential additive effect between groups of antioxidants, hitherto, have not been systematically studied. A systematic review and network meta-analysis were conducted to investigate the comparative or additive effect of dietary antioxidant supplements on eye health. Four databases (PubMed, Embase, CINAHL, and Cochrane) were searched, and relevant randomized controlled trials were identified. Out of 60 articles selected for systematic review, 38 were included in the network meta-analysis, categorized into 8 distinct antioxidant-supplemented groups and placebo. All groups significantly increased macular pigment optical density and contrast sensitivity at low spatial frequency, whereas only the antioxidant mixture þ lutein (L) þ fatty acid combination exhibited significant improvements in visual acuity (hazard ratio ¼ –0.15; 95% confidence interval: –0.28, –0.02) and L þ zeaxanthin combination for photostress recovery time (hazard ratio ¼ –5.75; 95% confidence interval: –8.80, –1.70). Especially, the L þ zeaxanthin þ fatty acid combination was ranked best for macular pigment optical density (surface under the cumulative ranking: 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. Overall, antioxidant supplementation was estimated to improve eye health parameters, whereas different combinations of antioxidants may also have varying effects on improving visual health from multiple perspectives. This study was registered at PROSPERO as CRD42022369250. Keywords: antioxidants, xanthophyll, fatty acid, vitamin, macular pigment optical density, visual acuity, contrast sensitivity, photostress recovery time