Deciphering the macular pigment–cognition axis through a systems biology and multi-omics lens for precision nutrition

Background Macular pigment optical density (MPOD) is a robust, non-invasive biomarker of retinal and brain carotenoid status, reflecting tissue levels of the dietary xanthophylls lutein and zeaxanthin, which are essential for visual and cognitive health. Higher macular carotenoids consistently associate with superior cognitive performance across the lifespan, yet the biological mechanisms underlying this relationship remain poorly defined. Here, I argue that addressing this gap requires a systems biology framework integrating in vivo MPOD imaging with multi-omics technologies, nutritional profiling, and artificial intelligence–enabled analytics within a precision nutrition paradigm. Genomic, transcriptomic, proteomic, lipidomic, metabolomic, epigenomic, and microbiome data will provide complementary insights into carotenoid absorption, transport, tissue distribution, and molecular action in the brain. Integrating these layers with longitudinal cognitive and neuroimaging measures will enable causal inference, identify molecular mediators, and predict individual responsiveness to dietary interventions. Conclusions Taken together, this multi-omics framework promises to translate macular pigment research from associative observations into mechanistically informed, personalized strategies to support cognitive resilience across the lifespan.