Why Skin Carotenoid Measurements Cannot Serve as a Proxy for Macular Pigment Optical Density (MPOD): A Biochemical, Anatomical, Optical, and Statistical Review.

Carotenoids accumulate in both the skin and the macula, but their biochemical specificity, anatomical localization, optical environments, and temporal kinetics differ fundamentally. Despite superficial similarities, these distinctions raise questions about whether non-invasive skin carotenoid measurements, which are obtained using reflection spectroscopy or resonance Raman spectroscopy, can meaningfully reflect macular pigment optical density (MPOD), a retina-specific biomarker associated with visual performance and neuroprotective function. This review synthesizes evidence across biochemistry, tissue distribution, optical pathways, kinetic behavior, and statistical correlations to evaluate this proposed relationship. Skin carotenoid measurements capture a broad mixture of dietary carotenoids, which are dominated by β-carotene and lycopene, that accumulate superficially within the epidermis and dermis and respond rapidly to short-term dietary and environmental changes. In contrast, MPOD reflects only lutein, zeaxanthin, and meso-zeaxanthin, which are selectively transported into the foveal neurosensory retina and change slowly through regulated retinal uptake and deposition. Across human studies, correlations between skin carotenoids and MPOD are weak, inconsistent, and biologically implausible, with large cohort analyses demonstrating near-zero associations. Collectively, evidence across biochemical, anatomical, optical, physiological, and statistical domains shows that skin carotenoid values encode general systemic antioxidant exposure, whereas MPOD reflects a highly localized, retina-specific carotenoid reservoir. Therefore, skin carotenoid measurements cannot be used to estimate, substitute for, or infer macular pigment levels. Accurate assessment of MPOD requires direct retinal imaging technologies.