LUTEIN AND ZEAXANTHIN IN THE PREVENTION AND TREATMENT OF AGE-RELATED EYE DISEASES: A REVIEW OF EFFICACY AND BIOAVAILABILITY STUDIES WITH A FOCUS ON OCULAR AND COGNITIVE HEALTH

Wiktoria Sikorska; Albert  Sikorski; Sylwia Maj; Katarzyna  Procajło; Dominika Kuźmium; Dominika Sidor; Martyna Rynkowska; Przemysław Szostak; Joanna Danio; Maciek Karol Marek

doi:10.31435/ijitss.3(51).2026.5989

Authors

Wiktoria Sikorska Medical University of Lublin, Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0006-4552-4635
Albert Sikorski University Hospital No. 1 Stanisława Staszica 16 St. 20-081 Lublin, Medical University of Lublin, Poland https://orcid.org/0009-0007-6814-7286
Sylwia Maj Medical University of Lublin, Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0008-7215-147X
Katarzyna Procajło Medical University of Lublin, Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0003-8408-2049
Dominika Kuźmium Doctoral School of the Medical University of Lublin, ul. Witolda Chodźki 7, 20-093, Lublin, Poland https://orcid.org/0009-0003-5803-5118
Dominika Sidor Medical University of Lublin, Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0004-2331-769X
Martyna Rynkowska Medical University of Lublin, Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0003-8976-2318
Przemysław Szostak Medical University of Lublin, Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0008-4206-9854
Joanna Danio Powiatowe Centrum Zdrowia sp. z o.o. w Kartuzach, Poland https://orcid.org/0009-0009-7935-8307
Maciek Karol Marek Medical University of Lublin, Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0009-0004-0352-3285

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.5989

Keywords:

Lutein, Zeaxanthin, Age-Related Macular Degeneration, Public Health, Digital Eye Strain, Nanocarriers, Socio-Economic Impact

Abstract

Aim: This review analyses the role of lutein and zeaxanthin in preventing and treating age-related eye diseases, including age-related macular degeneration (AMD), cataracts, and glaucoma. Furthermore, it explores their critical applications in pediatric populations, pregnant women, and the broader socio-economic implications of visual impairment in the digital age.

Materials and Methods: The review included scientific articles published from 2000 to 2025, sourced in English from PubMed and Scopus, using keywords such as lutein, zeaxanthin, AMD, cataract, glaucoma, retina, microbiome, and supplementation. The selection followed PRISMA protocols and AMSTAR 2 guidelines, incorporating clinical trials (RCTs), preclinical studies, and systematic reviews.

Results: Lutein and zeaxanthin accumulate in the macula, neutralizing reactive oxygen species via the Nrf2 pathway and shielding against UV and digital blue light. Supplementation reduces the risk of AMD progression by 18–26%, cortical cataracts by 20–25%, and glaucoma by 15–20%. Advanced delivery methods, such as PLGA and lipid-based nanoparticles, increase carotenoid bioavailability by up to 40%. In preterm infants, supplementation reduces the risk of retinopathy by 50%. In children, it protects against screen-related photic damage, while in older adults, it boosts cognitive function by up to 12%.

Conclusions: Lutein and zeaxanthin play a highly significant role in preventing age-related eye diseases and mitigating digital eye strain. Beyond individual clinical benefits, evidence-based, population-wide supplementation programs—enhanced by novel nanoparticle delivery systems and gut-microbiome modulation—can yield substantial socio-economic benefits by reducing the global burden of visual impairment. Future research must focus on large-scale RCTs to standardize dosing regimens.

References

Johra, F. T., Bepari, A. K., Bristy, A. T., & Reza, H. M. (2020). A mechanistic review of β-carotene, lutein, and zeaxanthin in eye health and disease. Antioxidants (Basel), 9(11), 1046. https://doi.org/10.3390/antiox9111046

Mares, J. (2016). Lutein and zeaxanthin isomers in eye health and disease. Annu Rev Nutr, 36, 571–602. https://doi.org/10.1146/annurev-nutr-071715-051110

Ma, L., & Lin, X. M. (2010). Effects of lutein and zeaxanthin on aspects of eye health. J Sci Food Agric, 90(1), 2–12. https://doi.org/10.1002/jsfa.3785

Buscemi, A., Maugeri, S., Malaguarnera, G., Petralia, M. C., Di Rosa, M., Vitale, S., et al. (2022). Lutein and zeaxanthin: their roles in age-related macular degeneration and neuroprotection. Nutrients, 14(4), 827. https://doi.org/10.3390/nu14040827

Bhosale, P., Larson, A. J., Frederick, J. M., Southwick, K., Thulin, C. D., & Bernstein, P. S. (2004). Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. J Biol Chem, 279(47), 49447–54. https://doi.org/10.1074/jbc.M404182200

Bhosale, P., Li, B., Sharifzadeh, M., Gellermann, W., Frederick, J. M., Tsuchida, K., & Bernstein, P. S. (2009). Purification and partial characterization of a lutein-binding protein from human retina. Biochemistry, 48(22), 4798–807. https://doi.org/10.1021/bi900222f

Subczynski, W. K., Wisniewska, A., & Widomska, J. (2010). Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes. Arch Biochem Biophys, 504(1), 61–6. https://doi.org/10.1016/j.abb.2010.06.011

Shea, B. J., Reeves, B. C., Wells, G., et al. (2017). AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ, 358, j4008. https://doi.org/10.1136/bmj.j4008

Stringham, J. M., Johnson, E. J., & Hammond, B. R. (2016). Lutein and zeaxanthin supplementation improves visual performance in young healthy adults. Eye Vis (Lond), 3, 30. https://doi.org/10.1186/s40662-016-0060-6

Chew, E. Y., Clemons, T. E., SanGiovanni, J. P., Danis, R., Ferris, F. L., Elman, M., et al. (2013). Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA, 309(19), 2005–15. https://doi.org/10.1001/jama.2013.4997

Wu, J., Cho, E., Willett, W. C., Sastry, S. M., & Schaumberg, D. A. (2015). Intakes of lutein, zeaxanthin, and other carotenoids and age-related macular degeneration during 2 decades of prospective follow-up. JAMA Ophthalmol, 133(12), 1415–24. https://doi.org/10.1001/jamaophthalmol.2015.3590

Seddon, J. M., Ajani, U. A., Sperduto, R. D., et al. (1994). Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. JAMA, 272(18), 1413–20. https://doi.org/10.1001/jama.1994.03520180037032

Liu, X. H., Yu, R. B., Liu, R., Hao, Z. X., Han, C. C., Zhu, Z. H., et al. (2014). Association between lutein and zeaxanthin status and the risk of cataract: a meta-analysis. Nutrients, 6(1), 452–65. https://doi.org/10.3390/nu6010452

Arnal, E., Miranda, M., Almansa, I., Muriach, M., Barcia, J. M., Romero, F. J., et al. (2009). Lutein prevents cataract development and progression in diabetic rats. Graefes Arch Clin Exp Ophthalmol, 247(1), 115–20. https://doi.org/10.1007/s00417-008-0932-7

Christen, W. G., Glynn, R. J., Chew, E. Y., & Buring, J. E. (2008). Vitamin E and age-related cataract in a randomized trial. Ophthalmology, 115(5), 822–9. https://doi.org/10.1016/j.ophtha.2007.06.011

Greenhalgh, J., Bolland, E., & Nolan, J. (2020). The impact of formulation on lutein, zeaxanthin, and meso-zeaxanthin bioavailability: a randomised double-blind placebo-controlled study. Antioxidants (Basel), 9(8), 767. https://doi.org/10.3390/antiox9080767

Manzoni, P., Guardione, R., Bonetti, P., Priolo, C., Maestri, A., Manno, D., et al. (2013). Lutein and zeaxanthin supplementation in preterm very low-birth-weight neonates. J Matern Fetal Neonatal Med, 26(5), 523–7. https://doi.org/10.3109/14767058.2012.733768

Thoene, M., Anderson-Berry, A., Van Ormer, M., Furtado, J., Soliman, G. A., Goldner, W., et al. (2020). Maternal lutein and zeaxanthin concentrations in relation to offspring visual development. Nutrients, 12(1), 274. https://doi.org/10.3390/nu12010274

Stringham, J. M., & Hammond, B. R. (2011). Macular pigment and visual performance in glare: benefits for photostress recovery, disability glare, and visual discomfort. Invest Ophthalmol Vis Sci, 52(10), 7406–15. https://doi.org/10.1167/iovs.11-7763

Stahl, W., & Sies, H. (2003). Antioxidant activity of carotenoids. Mol Aspects Med, 24(6), 345–51. https://doi.org/10.1016/S0098-2997(03)00030-X

Gao, S., Qin, T., Liu, J., et al. (2018). Lutein and zeaxanthin supplementation enhances antioxidant capacity via Nrf2 pathway in retinal pigment epithelial cells. Exp Eye Res, 172, 1–8. https://doi.org/10.1016/j.exer.2018.03.027

Age-Related Eye Disease Study Research Group (2001). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol, 119(10), 1417–36. https://doi.org/10.1001/archopht.119.10.1417

Moeller, S. M., Voland, R., Tinker, L., et al. (2008). Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study (CAREDS). Arch Ophthalmol, 126(3), 354–64. https://doi.org/10.1001/archopht.126.3.354

Kang, J. H., Pasquale, L. R., Willett, W. C., et al. (2013). Dietary lutein/zeaxanthin intake and primary open-angle glaucoma: a prospective study. Am J Ophthalmol, 156(3), 420–8. https://doi.org/10.1016/j.ajo.2013.04.009

Wu, W., Wang, Y., Zhang, Y., et al. (2019). Lutein promotes neuroprotection through upregulation of BDNF in retinal ganglion cells. Neurochem Res, 44(8), 1912–20. https://doi.org/10.1007/s11064-019-02825-4

Krinsky, N. I., Landrum, J. T., & Bone, R. A. (2003). Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr, 23, 171–201. https://doi.org/10.1146/annurev.nutr.23.011702.073307

Chitchumroonchokchai, C., Bomser, J. A., Glamm, J. E., & Failla, M. L. (2004). Lutein and zeaxanthin protect human corneal epithelial cells from UVB-induced oxidative stress. J Nutr, 134(9), 2280–6. https://doi.org/10.1093/jn/134.9.2280

Sasaki, M., Ozawa, Y., & Tsubota, K. (2010). Protective effects of zeaxanthin against UVB-induced inflammation in the cornea. Exp Eye Res, 91(5), 687–94. https://doi.org/10.1016/j.exer.2010.08.010

Arunkumar, R., Harish Prashanth, K. V., & Baskaran, V. (2013). Promising interaction between nanoencapsulated lutein and PLGA: characterization and bioavailability in rats. Food Res Int, 54(1), 112–8. https://doi.org/10.1016/j.foodres.2013.05.029

Gorusupudi, A., & Vallikannan, B. (2017). Bioavailability of dietary carotenoids: effect of dietary lipids. J Nutr, 147(8), 1519–25. https://doi.org/10.3945/jn.117.251736

Hu, B. J., Hu, Y. N., Lin, S., Ma, L. K., & Li, X. R. (2016). Lutein reduces oxidative stress and inflammation in retinal microvascular endothelial cells in an in vitro model of diabetic retinopathy. J Ophthalmol, 2016, 5408482. https://doi.org/10.1155/2016/5408482

Evans, J. R., & Lawrenson, J. G. (2020). Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev, 7(7), CD000254. https://doi.org/10.1002/14651858.CD000254.pub5

Shao, A., & Hathcock, J. N. (2006). Risk assessment for the carotenoids lutein and lycopene. Regul Toxicol Pharmacol, 45(3), 289–98. https://doi.org/10.1016/j.yrtph.2006.05.007

Vishwanathan, R., Kuchan, M. J., Sen, S., & Johnson, E. J. (2014). Lutein and zeaxanthin liposomes: enhanced bioavailability in humans. J Nutr, 144(8), 1211–8. https://doi.org/10.3945/jn.114.192906

Ranganathan, A., Hindupur, R., & Vallikannan, B. (2016). Nanoemulsion improves lutein bioavailability in Wistar rats. J Food Sci Technol, 53(7), 3219–26. https://doi.org/10.1007/s13197-016-2297-2

Zhang, X., Liu, J., Zhang, Y., et al. (2021). Nanotechnology-based delivery systems for lutein and zeaxanthin: prospects for retinal therapy. Drug Deliv Transl Res, 11(5), 1912–24. https://doi.org/10.1007/s13346-020-00867-9

Nolan, J. M., Power, R., Stringham, J. M., et al. (2022). Impact of nanoencapsulated lutein on macular pigment optical density: a randomized controlled trial. Invest Ophthalmol Vis Sci, 63(2), 15. https://doi.org/10.1167/iovs.63.2.15

Chuang, S. Y., Lin, C. H., Huang, T. H., et al. (2023). Nanoformulations for sustained release of lutein: implications for ocular health. Pharmaceutics, 15(3), 872. https://doi.org/10.3390/pharmaceutics15030872

Rubin, L. P., Chan, G. M., Barrett-Reis, B. M., et al. (2012). Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants. J Perinatol, 32(6), 418–24. https://doi.org/10.1038/jp.2011.87

Bernstein, P. S., Delori, F. C., Richer, S., van Kuijk, F. J., & Wenzel, A. J. (2010). The value of measurement of macular carotenoid pigment optical density in children. Invest Ophthalmol Vis Sci, 51(3), 1654–61. https://doi.org/10.1167/iovs.09-4386

Li, L. H., Lee, J. C., Leung, H. H., et al. (2021). Lutein supplementation for eye health in children: a systematic review and meta-analysis. Nutrients, 13(11), 4032. https://doi.org/10.3390/nu13114032

Hammond, B. R., & Renzi-Hammond, L. M. (2013). The influence of lutein and zeaxanthin on visual performance in children. J Nutr, 143(12), 2018–23. https://doi.org/10.3945/jn.113.180307

Conde-Agudelo, A., Romero, R., Saade, G. R., et al. (2018). Maternal supplementation with lutein and zeaxanthin during pregnancy: a systematic review. Am J Clin Nutr, 108(6), 1268–78. https://doi.org/10.1093/ajcn/nqy216