Zeaxanthin is one of the most common carotenoid alcohols found in nature. It is important in the xanthophyll cycle. Synthesized in plants and some micro-organisms, it is the pigment that gives paprika (made from bell peppers), corn, saffron, wolfberries, and many other plants and microbes their characteristic color.
3D model (JSmol)
|E number||E161h (colours)|
|Molar mass||568.88 g/mol|
|Melting point||215.5 °C (419.9 °F; 488.6 K)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
The name (pronounced zee-uh-zan'-thin) is derived from Zea mays (common yellow maize corn, in which zeaxanthin provides the primary yellow pigment), plus xanthos, the Greek word for "yellow" (see xanthophyll).
Xanthophylls such as zeaxanthin are found in highest quantity in the leaves of most green plants, where they act to modulate light energy and perhaps serve as a non-photochemical quenching agent to deal with triplet chlorophyll (an excited form of chlorophyll) which is overproduced at high light levels during photosynthesis.
Animals derive zeaxanthin from a plant diet. Zeaxanthin is one of the two primary xanthophyll carotenoids contained within the retina of the eye. Within the central macula, zeaxanthin is the dominant component, whereas in the peripheral retina, lutein predominates.
Zeaxanthin supplements are typically taken on the supposition of supporting eye health. Although there are no reported side effects from taking zeaxanthin supplements, this possible benefit remains scientifically unproven, despite extensive ongoing research to define dietary or supplemental effects of zeaxanthin and lutein.
Isomers and macular uptakeEdit
Lutein and zeaxanthin have identical chemical formulas and are isomers, but they are not stereoisomers. The only difference between them is in the location of the double bond in one of the end rings. This difference gives lutein three chiral centers whereas zeaxanthin has two. Because of symmetry, the (3R,3'S) and (3S,3'R) stereoisomers of zeaxanthin are identical. Therefore, zeaxanthin has only three stereoisomeric forms. The (3R,3'S) stereoisomer is called meso-zeaxanthin.
The principal natural form of zeaxanthin is (3R,3'R)-zeaxanthin. The macula mainly contains the (3R,3'R)- and meso-zeaxanthin forms, but it also contains much smaller amounts of the third (3S,3'S) form. Evidence exists that a specific zeaxanthin-binding protein recruits circulating zeaxanthin and lutein for uptake within the macula.
Due to the commercial value of carotenoids, their biosynthesis has been studied extensively in both natural products and non-natural (heterologous) systems such as the bacteria Escherichia coli and yeast Saccharomyces cerevisiae. Zeaxanthin biosynthesis proceeds from beta-carotene via the action of a single protein, known as a beta-carotene hydroxylase, that is able to add a hydroxyl group (-OH) to carbon 3 and 3' of the beta-carotene molecule. Zeaxanthin biosynthesis therefore proceeds from beta-carotene to zeaxanthin (a di-hydroxylated product) via beta-cryptoxanthin (the mono hydroxylated intermediate). Although functionally identical, several distinct beta-carotene hydroxylase proteins are known. Due to the nature of zeaxanthin, relative to astaxanthin (a carotenoid of significant commercial value) beta-carotene hydroxylase proteins have been studied extensively.
Relationship with diseases of the eyeEdit
Several observational studies have provided preliminary evidence for high dietary intake of foods including lutein and zeaxanthin with lower incidence of age-related macular degeneration (AMD), most notably the Age-Related Eye Disease Study (AREDS2). Because foods high in one of these carotenoids tend to be high in the other, research does not separate effects of one from the other. Three subsequent meta-analyses of dietary lutein and zeaxanthin all concluded that these carotenoids lower the risk of progression from early stage AMD to late stage AMD. In general, however, there remains insufficient evidence to assess the effectiveness of dietary or supplemental zeaxanthin or lutein in treatment or prevention of early AMD 
As for cataracts, two meta-analyses confirm a correlation between high serum concentrations of lutein and zeaxanthin and a decrease in the risk of nuclear cataract, but not cortical or subcapsular cataract. The reports did not separate zeaxanthin effect from lutein effect. There is only one published clinical intervention trial testing for an effect of lutein and zeaxanthin supplementation on cataracts. The AREDS2 trial enrolled subjects at risk for progression to advanced age-related macular degeneration. Overall, the group getting lutein (10 mg) and zeaxanthin (2 mg) were NOT less likely to progress to needed cataract surgery. The authors speculated that there may be a cataract prevention benefit for people with low dietary intake of lutein and zeaxanthin, but recommended more research. Any benefit is more likely to be apparent in subpopulations of individuals exposed to high oxidative stress, such as heavy smokers, alcoholics or those with low dietary intake of carotenoid-rich foods.
In 2005, the US Food and Drug Administration rejected a Qualified Health Claims application by Xangold, citing insufficient evidence supporting the use of a lutein- and zeaxanthin-containing supplement in prevention of AMD. Although more convincing evidence has accrued, no company had reapplied for a label health claim. Dietary supplement companies in the U.S. are allowed to sell lutein and lutein + zeaxanthin products using Structure:Function language such as "Helps maintain eye health" as long as the FDA disclaimer statement ("These statements have not been evaluated...") is on the label. In Europe, as recently as 2014, the European Food Safety Authority reviewed and rejected claims that lutein or lutein plus zeaxanthin improved vision.
Zeaxanthin is the pigment that gives paprika (made from bell peppers), corn, saffron, wolfberries, and many other plants their characteristic color. Spirulina is also a rich source and can serve as a dietary supplement. Zeaxanthin breaks down to form picrocrocin and safranal, which are responsible for the taste and aroma of saffron.
Foods containing the highest amounts of lutein and zeaxanthin are dark green leaf vegetables, such as kale, spinach, turnip greens, collard greens, romaine lettuce, watercress, Swiss chard and mustard greens.
An acceptable daily intake level for zeaxanthin was proposed as 0.75 mg/kg of body weight/day, or 53 mg/day for a 70 kg adult. In humans, an intake of 20 mg/day for up to six months had no adverse effects. As of 2016, neither the U.S. Food and Drug Administration nor the European Food Safety Authority have set a Tolerable Upper Intake Level (UL) for lutein or zeaxanthin.
- Encyclopedia.com. "Carotenoids". Retrieved 6 May 2012.
- "Lutein + Zeaxanthin Content of Selected Foods". Linus Pauling Institute, Oregon State University, Corvallis. 2014. Retrieved 20 May 2014.
- Age-Related Eye Disease Study 2 Research Group (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. PMID 23644932. doi:10.1001/jama.2013.4997.
- Pinazo-Durán, M. D.; Gómez-Ulla, F; Arias, L; Araiz, J; Casaroli-Marano, R; Gallego-Pinazo, R; García-Medina, J. J.; López-Gálvez, M. I.; Manzanas, L; Salas, A; Zapata, M; Diaz-Llopis, M; García-Layana, A (2014). "Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?". Journal of Ophthalmology. 2014: 901686. PMC . PMID 24672708. doi:10.1155/2014/901686.
- Koo, E; Neuringer, M; Sangiovanni, J. P. (2014). "Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration". American Journal of Clinical Nutrition. 100 (Supplement 1): 336S–346S. PMID 24829491. doi:10.3945/ajcn.113.071563.
- Nolan, J. M.; Meagher, K; Kashani, S; Beatty, S (2013). "What is meso-zeaxanthin, and where does it come from?". Eye. 27 (8): 899–905. PMC . PMID 23703634. doi:10.1038/eye.2013.98.
- Li, B; Vachali, P; Bernstein, P. S. (2010). "Human ocular carotenoid-binding proteins". Photochemical & Photobiological Sciences. 9 (11): 1418–25. PMC . PMID 20820671. doi:10.1039/c0pp00126k.
- Scaife, Mark A.; Ma, Cynthia A.; Ninlayarn, Thanyanun; Wright, Phillip C.; Armenta, Roberto E. (22 May 2012). "Comparative Analysis of β-Carotene Hydroxylase Genes for Astaxanthin Biosynthesis". Journal of Natural Products. 75 (6): 120522090507004. PMID 22616944. doi:10.1021/np300136t.
- "NIH study provides clarity on supplements for protection against blinding eye disease". US National Eye Institute, National Institutes of Health, Bethesda, MD. 5 May 2013. Retrieved 10 August 2017.
- Bernstein, P. S.; Li, B; Vachali, P. P.; Gorusupudi, A; Shyam, R; Henriksen, B. S.; Nolan, J. M. (2015). "Lutein, Zeaxanthin, and meso-Zeaxanthin: The Basic and Clinical Science Underlying Carotenoid-based Nutritional Interventions against Ocular Disease". Progress in Retinal and Eye Research. 50: 34–66. PMC . PMID 26541886. doi:10.1016/j.preteyeres.2015.10.003.
- Krishnadev N, Meleth AD, Chew EY (May 2010). "Nutritional supplements for age-related macular degeneration". Current Opinion in Ophthalmology. 21 (3): 184–9. PMC . PMID 20216418. doi:10.1097/ICU.0b013e32833866ee.
- SanGiovanni JP, Chew EY, Clemons TE, et al. (September 2007). "The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22". Archives of Ophthalmology. 125 (9): 1225–1232. PMID 17846363. doi:10.1001/archopht.125.9.1225.
- Liu R, Wang T, Zhang B, Qin L, Wu C, Li Q, Ma L (2014). "Lutein and zeaxanthin supplementation and association with visual function in age-related macular degeneration". Invest. Ophthalmol. Vis. Sci. 56 (1): 252–8. PMID 25515572. doi:10.1167/iovs.14-15553.
- Wang X, Jiang C, Zhang Y, Gong Y, Chen X, Zhang M (2014). "Role of lutein supplementation in the management of age-related macular degeneration: meta-analysis of randomized controlled trials". Ophthalmic Res. 52 (4): 198–205. PMID 25358528. doi:10.1159/000363327.
- Ma L, Dou HL, Wu YQ, Huang YM, Huang YB, Xu XR, Zou ZY, Lin XM (2012). "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis". Br. J. Nutr. 107 (3): 350–9. PMID 21899805. doi:10.1017/S0007114511004260.
- Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH (October 2007). "Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis". BMJ (Clinical Research Ed.). 335 (7623): 755. PMC . PMID 17923720. doi:10.1136/bmj.39350.500428.47.
- Liu XH, Yu RB, Liu R, Hao ZX, Han CC, Zhu ZH, Ma L (2014). "Association between lutein and zeaxanthin status and the risk of cataract: a meta-analysis". Nutrients. 6 (1): 452–65. PMC . PMID 24451312. doi:10.3390/nu6010452.
- Ma L, Hao ZX, Liu RR, Yu RB, Shi Q, Pan JP (2014). "A dose-response meta-analysis of dietary lutein and zeaxanthin intake in relation to risk of age-related cataract". Graefes Arch. Clin. Exp. Ophthalmol. 252 (1): 63–70. PMID 24150707. doi:10.1007/s00417-013-2492-3.
- Chew EY, SanGiovanni JP, Ferris FL, Wong WT, Agron E, Clemons TE, Sperduto R, Danis R, Chandra SR, Blodi BA, Domalpally A, Elman MJ, Antoszyk AN, Ruby AJ, Orth D, Bressler SB, Fish GE, Hubbard GB, Klein ML, Friberg TR, Rosenfeld PJ, Toth CA, Bernstein P (2013). "Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4". JAMA Ophthalmol. 131 (7): 843–50. PMID 23645227. doi:10.1001/jamaophthalmol.2013.4412.
- Fernandez MM, Afshari NA (January 2008). "Nutrition and the prevention of cataracts". Current Opinion in Ophthalmology. 19 (1): 66–70. PMID 18090901. doi:10.1097/ICU.0b013e3282f2d7b6.
- "Letter of Denial - Xangold Lutein Esters, Lutein, or Zeaxanthin and Reduced Risk of Age-related Macular Degeneration or Cataract Formation (Docket No. 2004Q-0180". US FDA, Qualified Health Claims. 19 December 2005.
- "Scientific Opinion on the substantiation of a health claim related to a combination of lutein and zeaxanthin and improved vision under bright light conditions pursuant to Article 13(5) of Regulation (EC) No 1924/2006". EFSA Journal. 12 (7): 3753. 2014. ISSN 1831-4732. doi:10.2903/j.efsa.2014.3753.
- Yu, B.; Wang, J.; Suter, P. M.; Russell, R. M.; Grusak, M. A.; Wang, Y.; Wang, Z.; Yin, S.; Tang, G. (2012). "Spirulina is an effective dietary source of zeaxanthin to humans". British Journal of Nutrition. 108 (4): 611–619. PMID 22313576. doi:10.1017/S0007114511005885.
- Frusciante, Sarah; Diretto, Gianfranco; Bruno, Mark; Ferrante, Paola; Pietrella, Marco; Prado-Cabrero, Alfonso; Rubio-Moraga, Angela; Beyer, Peter; Gomez-Gomez, Lourdes (2014-08-19). "Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis". Proceedings of the National Academy of Sciences. 111 (33): 12246–12251. ISSN 0027-8424. PMC . PMID 25097262. doi:10.1073/pnas.1404629111.
- "Foods highest in lutein-zeaxanthin per 100 grams". Conde Nast for the USDA National Nutrient Database, release SR-21. 2014. Retrieved 23 December 2015.
- Edwards JA (2016). "Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake". Journal of Ophthalmology. 2016: 3690140. PMC . PMID 26885380. doi:10.1155/2016/3690140. Retrieved 2016-07-23.
• In their evaluation of the safety of synthetic zeaxanthin as a Novel Food, the EFSA NDA Scientific Panel  applied a 200-fold safety factor to this NOAEL to define an ADI of 0.75 mg/kg bw/day, or 53 mg/day for a 70 kg adult.
• Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity.
• Information from human intervention studies also supports that an intake higher than 2 mg/day is safe, and an intake level of 20 mg/day for up to 6 months was without adverse effect.