Zeaxanthin is one of the most commoncarotenoids in nature, and is used in thexanthophyll cycle. Synthesized in plants and some micro-organisms, it is the pigment that givespaprika (made from bell peppers),corn,saffron, goji (wolfberries), and many other plants and microbes their characteristic color.[1][2]
The name (pronouncedzee-uh-zan'-thin) is derived fromZea mays (common yellow maize corn, in which zeaxanthin provides the primary yellow pigment), plusxanthos, the Greek word for "yellow" (seexanthophyll).
Xanthophylls such as zeaxanthin are found in highest quantity in theleaves of most greenplants, where they act to modulate light energy and perhaps serve as anon-photochemical quenching agent to deal with triplet chlorophyll (an excited form of chlorophyll) which is overproduced at high light levels during photosynthesis.[3] Zeaxanthin inguard cells acts as a blue lightphotoreceptor which mediates thestomatal opening.[4]
Animals derive zeaxanthin from a plant diet.[2] Zeaxanthin is one of the two primaryxanthophyllcarotenoids contained within theretina of theeye. Zeaxanthin supplements are typically taken on the supposition of supporting eye health. Although there are no reported side effects from taking zeaxanthin supplements, the actual health effects of zeaxanthin andlutein are not proven,[5][6][7] and, as of 2018, there is no regulatory approval in theEuropean Union or the United States forhealth claims about products that contain zeaxanthin.
Lutein and zeaxanthin have identical chemical formulas and areisomers, but they are notstereoisomers. The only difference between them is in the location of thedouble bond in one of the end rings. This difference gives lutein threechiral 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 calledmeso-zeaxanthin.
The principal natural form of zeaxanthin is (3R,3′R)-zeaxanthin. Themacula mainly contains the (3R,3′R)- and meso-zeaxanthin forms, but it also contains much smaller amounts of the third (3S,3′S) form.[8] Evidence exists that a specific zeaxanthin-binding protein recruits circulating zeaxanthin and lutein for uptake within the macula.[9]
Due to the commercial value of carotenoids, theirbiosynthesis has been studied extensively in bothnatural products and non-natural (heterologous) systems such as the bacteriaEscherichia coli and yeastSaccharomyces 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 toastaxanthin (a carotenoid of significant commercial value) beta-carotene hydroxylase proteins have been studied extensively.[10]
Severalobservational studies have provided preliminary evidence for high dietary intake of foods including lutein and zeaxanthin with lower incidence ofage-related macular degeneration (AMD), most notably theAge-Related Eye Disease Study (AREDS2).[11][12] 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.[13][14]
Three subsequent meta-analyses of dietary lutein and zeaxanthin concluded that these carotenoids lower the risk of progression from early stage AMD to late stage AMD.[15][16][17]
A 2023 (updated)Cochrane review of 26 studies from several countries, however, concluded thatdietary supplements containing zeaxanthin and lutein have little to no influence on the progression of AMD.[18] In general, there remains insufficient evidence to assess the effectiveness of dietary or supplemental zeaxanthin or lutein in treatment or prevention of early AMD.[2][13][18]
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 a zeaxanthin effect from a lutein effect.[19][20] 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) did not reduce the need for cataract surgery.[21] 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.[22]
In 2005, the USFood and Drug Administration rejected aQualified Health Claims application by Xangold, citing insufficient evidence supporting the use of a lutein- and zeaxanthin-containing supplement in prevention of AMD.[23] Dietary supplement companies in the U.S. are allowed to sell lutein and lutein plus zeaxanthin products usingdietary supplement, 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, theEuropean Food Safety Authority reviewed and rejected claims that lutein or lutein plus zeaxanthin improved vision.[24]
Zeaxanthin is the pigment that givespaprika,corn,saffron,wolfberries (goji), and many other plants their characteristic colors of red, orange or yellow.[2][18]Spirulina is also a rich source and can serve as a dietary supplement.[25] Zeaxanthin breaks down to formpicrocrocin andsafranal, which are responsible for the taste and aroma of saffron.[26]
Anacceptable 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.[29] In humans, an intake of 20 mg/day for up to six months had noadverse effects.[29] As of 2016, neither the U.S. Food and Drug Administration nor the European Food Safety Authority had set a Tolerable Upper Intake Level (UL) for lutein or zeaxanthin.
^Kochhar, S. L.; Gujral, Sukhbir Kaur (2020). "Transpiration".Plant Physiology: Theory and Applications (2 ed.). Cambridge University Press. pp. 75–99.doi:10.1017/9781108486392.006.ISBN978-1-108-48639-2.
^Scaife, Mark A.; Ma, Cynthia A.; Ninlayarn, Thanyanun; et al. (22 May 2012). "Comparative Analysis of β-Carotene Hydroxylase Genes for Astaxanthin Biosynthesis".Journal of Natural Products.75 (6):1117–24.doi:10.1021/np300136t.PMID22616944.
^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.doi:10.1001/archopht.125.9.1225.PMID17846363.
^Liu R, Wang T, Zhang B, et al. (2014). "Lutein and zeaxanthin supplementation and association with visual function in age-related macular degeneration".Invest. Ophthalmol. Vis. Sci.56 (1):252–8.doi:10.1167/iovs.14-15553.PMID25515572.
^Wang X, Jiang C, Zhang Y, et al. (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.doi:10.1159/000363327.PMID25358528.S2CID5055854.
^Ma L, Hao ZX, Liu RR, et al. (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.doi:10.1007/s00417-013-2492-3.PMID24150707.S2CID13634941.
^abEdwards JA (2016)."Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake".Journal of Ophthalmology.2016:1–15.doi:10.1155/2016/3690140.PMC4738691.PMID26885380. • In their evaluation of the safety of synthetic zeaxanthin as a Novel Food, the EFSA NDA Scientific Panel [37] 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.
