Zeaxanthin is one of the most common

carotenoids Carotenoids (), also called tetraterpenoids, are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, co ...

in nature, and is used in the

xanthophyll cycle Xanthophylls (originally phylloxanthins) are yellow pigments that occur widely in nature and form one of two major divisions of the carotenoid group; the other division is formed by the carotenes. The name is from Greek (, "yellow") and (, "l ...

. Synthesized in plants and some micro-organisms, it is the pigment that gives paprika (made from bell peppers), corn,

saffron Saffron () is a spice derived from the flower of ''Crocus sativus'', commonly known as the "saffron crocus". The vivid crimson stigma and styles, called threads, are collected and dried for use mainly as a seasoning and colouring agent in ...

, goji ( wolfberries), and many other plants and microbes their characteristic color. The name (pronounced ''zee-uh-zan'-thin'') is derived from ''

Zea mays Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maíz after tnq, mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. Th ...

'' (common yellow maize corn, in which zeaxanthin provides the primary yellow pigment), plus ''xanthos'', the Greek word for "yellow" (see

xanthophyll Xanthophylls (originally phylloxanthins) are yellow pigments that occur widely in nature and form one of two major divisions of the carotenoid group; the other division is formed by the carotenes. The name is from Greek (, "yellow") and (, "lea ...

). Xanthophylls such as zeaxanthin are found in highest quantity in the

leaves A leaf (plural, : leaves) is any of the principal appendages of a vascular plant plant stem, stem, usually borne laterally aboveground and specialized for photosynthesis. Leaves are collectively called foliage, as in "autumn foliage", wh ...

of most green

plants Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...

, where they act to modulate light energy and perhaps serve as a

non-photochemical quenching Non-photochemical quenching (NPQ) is a mechanism employed by plants and algae to protect themselves from the adverse effects of high light intensity. It involves the quenching of singlet excited state chlorophylls (Chl) via enhanced internal con ...

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

carotenoids contained within the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

of the eye. 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 and

lutein Lutein (;"Lutein"

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

or the United States for health claims about products that contain zeaxanthin. As a food additive, zeaxanthin is a

food dye Food coloring, or color additive, is any dye, pigment, or substance that imparts color when it is added to food or drink. They come in many forms consisting of liquids, powders, gels, and pastes. Food coloring is used in both commercial food ...

with

E number E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...

E161h.

Isomers and macular uptake

Lutein Lutein (;"Lutein"

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

s, but they are not

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

s. The only difference between them is in the location of the

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...

in one of the end rings. This difference gives lutein three

chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...

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 The macula (/ˈmakjʊlə/) or macula lutea is an oval-shaped pigmented area in the center of the retina of the human eye and in other animals. The macula in humans has a diameter of around and is subdivided into the umbo, foveola, foveal av ...

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 A binding protein is any protein that acts as an agent to bind two or more molecules together. Examples include: * DNA-binding protein ** Single-strand binding protein ** Telomere-binding protein *RNA-binding protein ** Poly(A)-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 Astaxanthin is a keto- carotenoid within a group of chemical compounds known as terpenes. Astaxanthin is a metabolite of zeaxanthin and canthaxanthin, containing both hydroxyl and ketone functional groups. It is a lipid-soluble pigment with r ...

(a carotenoid of significant commercial value) beta-carotene hydroxylase proteins have been studied extensively.

Relationship with diseases of the eye

Several

observational studies In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample to a population where the independent variable is not under the control of the researcher because of ethical concern ...

have provided preliminary evidence for high dietary intake of foods including lutein and zeaxanthin with lower incidence of

age-related macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...

(AMD), most notably the

Age-Related Eye Disease Study The Age-Related Eye Disease Study (AREDS) was a clinical trial sponsored by the National Eye Institute that ran from 1992-2001. The study was designed to: * investigate the natural history and risk factors of age-related macular degeneration (AMD) ...

(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 concluded that these carotenoids lower the risk of progression from early stage AMD to late stage AMD. * A 2017 Cochrane review of 19 studies from several countries, however, concluded that dietary supplements containing zeaxanthin and lutein have little to no influence on the progression of AMD. In general, 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 a zeaxanthin effect from a lutein effect. 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. 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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

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. Dietary supplement companies in the U.S. are allowed to sell lutein and lutein plus zeaxanthin products using '' dietary 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, the

European Food Safety Authority The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...

reviewed and rejected claims that lutein or lutein plus zeaxanthin improved vision.

Natural occurrence

Zeaxanthin is the pigment that gives paprika, corn,

, wolfberries (goji), and many other plants their characteristic colors of red, orange or yellow. Spirulina is also a rich source and can serve as a dietary supplement. Zeaxanthin breaks down to form

picrocrocin Picrocrocin is a monoterpene glycoside precursor of safranal. It is found in the spice saffron, which comes from the crocus flower. Picrocrocin has a bitter taste, and is the chemical most responsible for the taste of saffron. During the drying ...

and

safranal Safranal is an organic compound isolated from saffron, the spice consisting of the stigmas of crocus flowers (''Crocus sativus''). It is the constituent primarily responsible for the aroma of saffron. It is believed that safranal is a degradat ...

, which are responsible for the taste and aroma of saffron. Foods containing the highest amounts of lutein and zeaxanthin are dark green

leaf vegetable Leaf vegetables, also called leafy greens, pot herbs, vegetable greens, or simply greens, are plant leaves eaten as a vegetable, sometimes accompanied by tender petioles and shoots. Leaf vegetables eaten raw in a salad can be called salad gre ...

s, such as

kale Kale (), or leaf cabbage, belongs to a group of cabbage (''Brassica oleracea'') cultivars grown for their edible leaves, although some are used as ornamentals. Kale plants have green or purple leaves, and the central leaves do not form a head ...

spinach Spinach (''Spinacia oleracea'') is a leafy green flowering plant native to central and western Asia. It is of the order Caryophyllales, family Amaranthaceae, subfamily Chenopodioideae. Its leaves are a common edible vegetable consumed either f ...

turnip greens The turnip or white turnip (''Brassica rapa'' subsp. ''rapa'') is a root vegetable commonly grown in temperate climates worldwide for its white, fleshy taproot. The word ''turnip'' is a compound of ''turn'' as in turned/rounded on a lathe and ...

collard greens Collard is a group of certain loose-leafed cultivars of ''Brassica oleracea'', the same species as many common vegetables including cabbage ( Capitata group) and broccoli ( Italica group). Collard is a member of the Viridis group of ''Brassica ...

romaine lettuce Romaine or cos lettuce (''Lactuca sativa'' L. var. ''longifolia'') is a variety of lettuce that grows in a tall head of sturdy dark green leaves with firm ribs down their centers. Unlike most lettuces, it is tolerant of heat. In North America, ...

watercress Watercress or yellowcress (''Nasturtium officinale'') is a species of aquatic flowering plant in the cabbage family Brassicaceae. Watercress is a rapidly growing perennial plant native to Europe and Asia. It is one of the oldest known leaf v ...

Swiss chard Chard or Swiss chard (; ''Beta vulgaris'' subsp. ''vulgaris'', Cicla Group and Flavescens Group) is a green leafy vegetable. In the cultivars of the Flavescens Group, the leaf stalks are large and often prepared separately from the leaf blade; ...

and

mustard greens ''Brassica juncea'', commonly brown mustard, Chinese mustard, Indian mustard, leaf mustard, Oriental mustard and vegetable mustard, is a species of mustard plant. Cultivar ''Brassica juncea'' cultivars can be divided into four major subgroups ...

; in green plants, the zeaxanthin may still be present, but is secondary to the prominent green of chlorophyll.

Safety

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 An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...

. 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.

References

{{Carotenoids Carotenoids Cyclohexenes Food colorings Tetraterpenes