{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T03:40:04Z","timestamp":1770090004670,"version":"3.49.0"},"reference-count":21,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u03b2-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.<\/jats:p>","DOI":"10.3390\/nu18030492","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:38:12Z","timestamp":1770046692000},"page":"492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Why Skin Carotenoid Measurements Cannot Serve as a Proxy for Macular Pigment Optical Density (MPOD): A Biochemical, Anatomical, Optical, and Statistical Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4761-1990","authenticated-orcid":false,"given":"Mohsen","family":"Sharifzadeh","sequence":"first","affiliation":[{"name":"Electrical & Computer Engineering Department, Brigham Young University (BYU), Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1364\/JOSAA.23.002373","article-title":"Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions","volume":"23","author":"Sharifzadeh","year":"2006","journal-title":"J. Opt. Soc. Am. A"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hwang, J.-E., Park, J.-Y., Jung, M.H., Eom, K., Moon, H.S., Joung, H., and Kim, Y.J. (2023). Evaluation of a commercial device based on reflection spectroscopy as an alternative to resonance Raman spectroscopy in measuring skin carotenoid levels: Randomized controlled trial. Sensors, 23.","DOI":"10.3390\/s23177654"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.abb.2018.03.033","article-title":"Optical assessment of skin carotenoid status as a biomarker of vegetable and fruit intake","volume":"646","author":"Ermakov","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1039\/c0pp00126k","article-title":"Human ocular carotenoid-binding proteins","volume":"9","author":"Li","year":"2010","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kunceviciene, E., Mockute, R., Petrauskaite, A., Budiene, B., Smalinskiene, A., Zvykaite, I., and Liutkeviciene, R. (2023). Twins\u2019 macular pigment optical density assessment and relation with SCARB1 gene polymorphism. Genes, 14.","DOI":"10.3390\/genes14010125"},{"key":"ref_6","first-page":"564738","article-title":"Effect of supplemental lutein and zeaxanthin on serum, macular pigmentation, and visual performance in patients with early age-related macular degeneration","volume":"2015","author":"Huang","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10262","DOI":"10.1038\/s41598-020-66962-2","article-title":"Effect of an antioxidant supplement containing high-dose lutein and zeaxanthin on macular pigment and skin carotenoid levels","volume":"10","author":"Obana","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1016\/j.visres.2007.09.002","article-title":"Macular pigment, photopigments, and melanin: Distributions in young subjects determined by four-wavelength reflectometry","volume":"47","author":"Bone","year":"2007","journal-title":"Vis. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1016\/j.tjnut.2023.06.006","article-title":"Macular pigment optical density and skin carotenoids in a childhood sample","volume":"153","author":"Cannavale","year":"2023","journal-title":"J. Nutr."},{"key":"ref_10","first-page":"1324","article-title":"The relation between carotenoids measured in the skin and eye","volume":"155","author":"Smith","year":"2025","journal-title":"Nutr. Methodol. Math. Model."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9318","DOI":"10.1038\/s41598-019-45751-6","article-title":"Skin carotenoid index in a large Japanese population sample","volume":"9","author":"Obana","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1167\/iovs.17-21818","article-title":"Correlations between macular, skin, and serum carotenoids","volume":"58","author":"Conrady","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1167\/iovs.06-0864","article-title":"The relationships between macular pigment optical density and its constituent carotenoids in diet and serum","volume":"48","author":"Nolan","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, P.Y., Cripps, A.W., West, N.P., Cox, A.J., and Zhang, P. (2019). A correlation-based network for biomarker discovery in obesity with metabolic syndrome. BMC Bioinform., 20.","DOI":"10.1186\/s12859-019-3064-2"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41598-019-57247-4","article-title":"Corruption of the Pearson correlation coefficient by measurement error and its estimation, bias, and correction under different error models","volume":"10","author":"Saccenti","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1167\/iovs.13-11891","article-title":"Blue-light reflectance imaging of macular pigment in infants and children","volume":"54","author":"Bernstein","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/1028415X.2024.2370175","article-title":"Skin and macular carotenoids and relations to academic achievement among school-aged children","volume":"28","author":"Rosok","year":"2025","journal-title":"Nutr. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.jand.2014.04.026","article-title":"Skin carotenoids: A biomarker of fruit and vegetable intake in children","volume":"114","author":"Aguilar","year":"2014","journal-title":"J. Acad. Nutr. Diet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/ejcn.2012.31","article-title":"eSkin carotenoid status measured by resonance Raman spectroscopy as a biomarker of fruit and vegetable intake in preschool children","volume":"66","author":"Scarmo","year":"2012","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1017\/S000711451200582X","article-title":"Single vs. multiple measures of skin carotenoids by resonance Raman spectroscopy as a biomarker of usual carotenoid status","volume":"110","author":"Scarmo","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.3390\/nu5061962","article-title":"Macular pigment and its contribution to vision","volume":"5","author":"Loskutova","year":"2013","journal-title":"Nutrients"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/3\/492\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:44:53Z","timestamp":1770047093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/3\/492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["nu18030492"],"URL":"https:\/\/doi.org\/10.3390\/nu18030492","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]}}}