IngredientsCarotenoids are classified on their chemical composition as either carotenes or xanthophylls. Carotenoids are classified into two main groups: compounds that have a hydrocarbon long chain, known as carotenes, and compounds that have an oxygen atom in their structure, known as xanthophylls. The term "xanthophyll" is therefore not a single compound but rather a structural class of oxygenated carotenoids.
Xanthophylls are a subclass of carotenoids — naturally occurring yellow pigments essential for photosynthesis in plants, algae, and cyanobacteria — distinguished by their oxygenated chemical structure that includes hydroxyl or epoxy groups attached to a C40 isoprenoid backbone. These pigments absorb light in the blue-green spectrum (400–550 nm).
This difference in structure makes xanthophylls more polar than carotenes due to the presence of oxygen in the form of methoxy, hydroxy, keto, carboxy, and epoxy positions. However, except for lutein, they are still largely non-polar compounds.
The molecular formula of lutein, which is formally identified as the "xanthophyll" in many chemical reference databases (CAS 127-40-2), is C₄₀H₅₆O₂. The group of xanthophylls includes (among many other compounds) lutein, zeaxanthin, neoxanthin, violaxanthin, flavoxanthin, and α- and β-cryptoxanthin. The latter compound (β-cryptoxanthin) is the only known xanthophyll to contain a beta-ionone ring, and thus β-cryptoxanthin is the only xanthophyll that is known to possess pro-vitamin A activity for mammals.
The carotene group includes α-carotene, β-carotene, lycopene, and phytoene, among others. The most representative molecules of the xanthophyll group are fucoxanthin, astaxanthin, lutein, zeaxanthin, and β-cryptoxanthin.
Widely distributed across kingdoms, xanthophylls are found in green leaves, fruits, flowers, and even animal tissues like the human retina, where they contribute to coloration and biological functions beyond photosynthesis.
Xanthophyll is one of the most widespread carotenoid alcohols in nature. It was originally isolated from egg yolk, and also isolated by chromatography from nettles, algae, and petals of many yellow flowers.
Petals of marigold flowers (Tagetes erecta and Tagetes patula) currently represent the main source of commercial xanthophyll. Xanthophyll is rich in some green vegetables and fruits such as cabbage, spinach, lettuce, green beans, and rapes, but chlorophyll, β-carotene, and other carotenoid derivatives are also rich in such plants, making it difficult to extract pure xanthophyll. After long-term searching, researchers found very high levels of xanthophyll and zeaxanthin and fewer impurities of other carotenoids in flowers of marigold, which makes separation and purification easier, thus marigold can be a good source for industrial production of xanthophyll.
Lutein and zeaxanthin are relatively polar carotenoid pigments found at high levels in parsley, spinach, kale, egg yolk, and lutein-fortified foods. Other rich sources include papaya, peaches, prunes, and squash, which contain lutein diesters. For zeaxanthin specifically, sources include collard greens, Swiss chard, and parsley, among others.
The high bioavailability of a fat-soluble nutrient such as zeaxanthin from egg is due to the rich lipid matrix of the yolk. Egg yolk is a good dietary source of both zeaxanthin and lutein, particularly as part of a typical western diet, which is poor in vegetables and fruits.
Algae are considered pigment-producing organisms, and the function of these compounds in algae is to carry out photosynthesis. They have a great variety of pigments, which can be classified into three large groups: chlorophylls, carotenoids, and phycobilins. Within the carotenoids are xanthophylls.
In terms of esterification state: More than 95% of the xanthophyll in marigold is esterified, and about half of this fraction is esterified with fatty acid.
Xanthophylls are available commercially in several forms. Carotenoids such as lutein and zeaxanthin are generally recognized as safe (GRAS) for human consumption, which allows food manufacturers to use them as additives. In the EU, xanthophylls derived from natural sources are authorized as food colorants under the code E-161.
Supplement forms include free (non-esterified) lutein, lutein esters derived from marigold, and synthetic variants. Variable bioavailability of carotenoids has been reported due to the type of formulation matrix used, form of the bioactives (free versus esterified), and effects of other nutrients. Lutein and zeaxanthin in natural forms have low bioavailability after oral intake due to poor stability and inefficient absorption in the intestine, leading to varying plasma concentrations.
These pigments serve dual roles as accessory light-harvesting molecules that transfer excitation energy to chlorophylls in photosystems I and II, enhancing photosynthetic efficiency, and as photoprotective agents that mitigate damage from excess light by quenching reactive oxygen species and facilitating non-photochemical quenching.
For dietary supplementation, softgel capsules, beadlets, and tablets are the most common delivery formats. Xanthophylls are used as food additive E161 to feed farmed trout and salmon. It is also quite common to include xanthophyll in the diet of hens, chickens, and poultry to make the meat more orangish and therefore more appealing to the human eye.
The explicit concept of "xanthophyll" as a defined class of compounds is a product of modern chemistry (the term was coined in the 19th century), but the plants and foodstuffs rich in xanthophylls have been used across many cultures for millennia, primarily as colorants and foods rather than as targeted medicinal agents.
Annatto, saffron, and paprika are a few natural carotenoids that have traditionally been used for food coloring. Even in ancient Greece and Rome, colorants like crocus (saffron) — which contains zeaxanthin — were used in food offerings to the gods, symbolizing wealth and divine favor. This deep-rooted tradition of linking colors to spiritual significance persisted throughout history.
Marigold (Tagetes erecta), the primary modern commercial source of lutein, has a long history of use in Mesoamerican cultures. Native to Mexico and Central America, Tagetes species were cultivated by pre-Columbian peoples and incorporated into ceremonial, culinary, and medicinal contexts. The introduction of marigolds to Europe and Asia following the 16th-century Columbian Exchange subsequently made them a ubiquitous ornamental and functional plant worldwide.
Indigenous peoples of South America, Africa, and Asia extensively used natural colorants from plants. Indigenous knowledge globally preserved these pigments, often connecting them to spiritual and medicinal purposes.
Saffron (Crocus sativus), a rich source of zeaxanthin, has a well-documented history spanning approximately 3,500 years in Persian, Greek, Roman, Egyptian, and South Asian traditions. It was used as a flavoring, dye, perfume, and medicine. Similarly, dark leafy greens — kale, spinach, parsley — rich in lutein have constituted staple dietary components across Mediterranean, East Asian, and African culinary traditions for thousands of years, though their specific xanthophyll content was not identified until the modern era.
The scientific isolation and naming of xanthophylls began in the early 19th century. Lutein was first extracted from egg yolk in 1834 by Heinrich Wilhelm Ferdinand Wackenroder, and the term "xanthophyll" (from Greek xanthos, yellow, and phyllon, leaf) was introduced for yellow leaf pigments in the 1830s. Systematic chemical characterization proceeded through the 20th century, with the structures of lutein and zeaxanthin fully elucidated by the 1940s through the work of Richard Kuhn and colleagues.
Xanthophylls (fucoxanthin, astaxanthin, lutein, zeaxanthin, and β-cryptoxanthin) are a type of carotenoid with anti-tumor and anti-inflammatory activities, due to their chemical structure rich in double bonds that provides them with antioxidant properties. Xanthophylls can protect other molecules from oxidative stress by turning off singlet oxygen damage through various mechanisms.
Lutein and zeaxanthin absorb blue light to reduce oxidative stress in the retina and are believed to function as antioxidants that protect photoreceptor cells against free radicals produced by light and high oxygen tension.
The highest concentration of xanthophylls is found within the retina, and this selective presence has generated many theories regarding their role in supporting retinal function. Lutein and zeaxanthin are the dietary xanthophylls that constitute the macular pigment (MP) and act by filtering blue light, and as antioxidants, whereby they protect the retina from oxidative damage induced by light and a high rate of oxidative metabolism in this tissue.
Lutein absorbs blue light, thereby protecting the eye from blue light that can lead to vision disorders. These compounds are the only carotenoids found in high concentration in the macula of the eye, where they act as natural blue-light filters and antioxidants.
Humans require dietary carotenoid intake because the relevant carotenoid synthesis enzymes do not exist in the human body. Most dietary carotenoids are consumed and embedded within a food matrix. When they reach the gut, they will be released from the food matrix through the action of various enzymes including esterases which will cleave xanthophyll esters. The free carotenoids are then solubilized into micelles before being taken up by the intestinal mucosal cells, where they are packaged into chylomicrons.
Dietary lutein and zeaxanthin are delivered to the retina via plasma lipoproteins, chiefly LDL and HDL cholesterol. While LDL is the primary carrier for most carotenoids, LDL and HDL carry about equal amounts of lutein and zeaxanthin. Several studies suggest relatively low HDL levels could hinder transport and capture of these carotenoids.
A high intake of lutein can also increase the macular content of meso-zeaxanthin because lutein can convert to meso-zeaxanthin in the central retina.
Lutein significantly reduced several skin inflammatory responses, including increased expression of interleukin-(IL-) 6 from LPS-treated macrophages, upregulation of cyclooxygenase-(COX-) 2 from interferon-γ/TNF-α-treated cells, and the enhancement of matrix-metallopeptidase-(MMP-) 9 level in UV-irradiated keratinocytes.
Previous reports have suggested that lutein is able to ameliorate in vitro and in vivo inflammatory responses by suppressing NF-κB activation. These findings strongly suggest a role of lutein in modulating inflammatory processes by regulating cellular redox potential.
Lutein-mediated AP-1 suppression and anti-inflammatory effects are due to its antioxidative and p38/c-Jun-N-terminal kinase inhibitory activities.
In preventing eye diseases, an important gene regulated by lutein and zeaxanthin is the Nrf2 gene, whose increased activity leads to optimizing the cellular response to reactive oxygen species (ROS) and preventing related diseases.
The most extensively studied clinical application of xanthophyll supplementation is in the prevention of progression of age-related macular degeneration (AMD).
Observational studies have reported that increased dietary intake and higher serum levels of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD), especially late AMD.
AREDS (Age-Related Eye Disease Study): The AREDS study demonstrated that daily high-dose supplementation with antioxidant vitamins and zinc lowered the 5-year odds of progression to late AMD by 28%. The randomized AREDS 1 study published in 2001 showed that supplementing the diet with antioxidant vitamins and minerals (the AREDS formula) reduces the risk of developing advanced macular degeneration by 25%.
AREDS2: The NEI conducted the Age-Related Eye Disease Study (AREDS) and the follow-on AREDS2 to study cataract and age-related macular degeneration (AMD), testing whether taking nutritional supplements could prevent or slow these diseases. AREDS2 was a multicenter, phase III, randomized clinical trial evaluating lutein + zeaxanthin, ω-3, or both long-chain polyunsaturated fatty acid supplementation in intermediate AMD.
The AREDS2 was a multicenter, double-masked randomized trial of 4,203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in one eye.
In the AREDS2 trial, adding omega-3 fatty acids or lutein + zeaxanthin to the AREDS formula had no additional overall effect on the risk of advanced AMD. However, secondary analyses clarified the picture: the AREDS2 study group did find that individuals low in dietary lutein and zeaxanthin were about 25% less likely to develop advanced AMD compared to participants with similar dietary intake who did not take lutein and zeaxanthin.
The researchers found that formulations containing lutein and zeaxanthin and no beta-carotene had a reduction in developing advanced AMD by 18% compared to participants who took the AREDS2 formula with beta-carotene and no lutein or zeaxanthin.
The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta-carotene in the AREDS-type supplements.
Long-term AREDS2 follow-up (10 years): This study included 3,882 participants (mean baseline age, 72.0 years). At 10 years, the odds ratio of having lung cancer was 1.82 for those randomly assigned to beta-carotene and 1.15 (not statistically significant) for lutein/zeaxanthin.
Evidence characterization: The evidence base for lutein and zeaxanthin in AMD is among the strongest in nutritional ophthalmology. Randomized, placebo-controlled clinical trials have demonstrated that xanthophyll supplementation increases macular pigment levels, improves visual function, and decreases the risk of progression to late AMD, especially neovascular AMD. The AREDS and AREDS2 trials are the key references, but it should be noted that the primary outcomes of AREDS2 did not show a statistically significant overall benefit of adding lutein/zeaxanthin to the full AREDS formula; benefits were primarily seen in subgroup analyses of low dietary intake at baseline.
Current publications on the preventive and therapeutic effects of lutein and zeaxanthin on cataracts, diabetic retinopathy, and retinopathy of prematurity have reported encouraging results. However, the evidence in these conditions is predominantly observational or from small trials, and should be considered preliminary compared with the AMD evidence base.
The effect of xanthophylls in the prevention and treatment of various eye diseases has been examined through epidemiological studies, animal studies, and clinical trials.
Lutein and zeaxanthin are fat-soluble, dietary carotenoids with high concentrations in human brain tissue. There have been a number of studies confirming an association between lutein and zeaxanthin and cognitive function.
In an evaluation of the relation between lutein and zeaxanthin status and cognitive function, 118 healthy older subjects (aged 76–85 years) were assessed for serum lutein and zeaxanthin, macular pigment density, and various measures of cognitive function. Macular pigment density was significantly related to performance on a variety of indexes designed to assess processing speed, accuracy, and completion ability (P < 0.05). These relations remained significant after adjustment for age, sex, and ethnicity (P ≤ 0.05).
Randomized trial in older adults: High levels of xanthophyll carotenoids lutein and zeaxanthin in the central nervous system have been previously correlated with improved cognitive function. A double-masked, randomized, placebo-controlled trial tested the effects of supplementing L and Z in older men and women. A total of 62 older adults were randomized into groups receiving either 12 mg L+Z or a visually identical placebo. Data from 51 participants (mean age 73.7 years) were available for analysis. Retinal L+Z levels (macular pigment optical density, MPOD) were measured as a biomarker of cortical L+Z levels.
Randomized trial in younger adults: The purpose of this study was to determine whether supplementation with L + Z could improve cognitive function in young (age 18–30) healthy adults. A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited. Supplementation with L + Z was found to improve CNS xanthophyll levels and cognitive function in young, healthy adults.
In a human trial, 6 months of daily supplementation with macular xanthophylls (lutein, zeaxanthin and the zeaxanthin isomer meso-zeaxanthin) in healthy young adults reduced serum interleukin-1β, and increased serum antioxidant capacity.
Evidence characterization: Cross-sectional and intervention studies find that increased xanthophyll status is related to better cognitive performance in the elderly. The determination of a definitive role for lutein and zeaxanthin in cognitive health in the elderly requires longitudinal epidemiologic studies and clinical trials of xanthophyll supplementation. The cognitive evidence base is promising but preliminary; trials are generally small and the field lacks large-scale replications.
The antioxidative properties of xanthophylls are believed to play a role in protecting the skin against light-induced damage. Lutein and zeaxanthin are found in the skin as a result of dietary intake.
Carotenoids, especially lutein and zeaxanthin isomers, filter blue light and protect skin from environmental factors including high-energy sources. These carotenoids may block the formation of melanin pathways, decrease cytokines, and increase antioxidants. A randomized, double-blind, placebo-controlled clinical trial over a 12-week supplementation period included 50 healthy subjects (46 completed the study), males and females aged 18–45 years with mild-to-moderate dry skin.
Lutein provides also increasing of tolerance to UV radiation, reducing inflammatory processes in the skin and preventing oncogenesis.
EpiDerm tissue models of human keratinocytes were used; EpiDerm samples were cultured in medium supplemented with final concentrations of 5 μM lutein and 1 μM zeaxanthin. These conditions were chosen because xanthophylls have been detected at micromolar concentrations in human plasma, and the 5:1 ratio has been used as a dietary supplement in clinical studies.
Evidence characterization: Skin-related xanthophyll research is largely based on in vitro models, animal studies, and small human trials. The evidence is preliminary and does not yet support definitive clinical conclusions on human photoprotection.
Preliminary studies on lutein supplementation in various populations suggest it may reduce biomarkers for coronary vascular disease, increase serum and plasma lutein, and reduce inflammatory cytokines.
It has been extensively reported that consumption of lutein- and zeaxanthin-rich green leafy vegetables and orange and yellow fruits and vegetables is associated with lower incidence of cancer, cardiovascular disease, AMD, and cataract formation. However, this association is confounded by overall diet quality.
AREDS2 Cardiovascular Outcomes Study: The Cardiovascular Outcome Study (COS) was an ancillary study of AREDS2, a factorial-designed randomized clinical trial of 4,203 participants recruited from 82 US academic and community ophthalmology clinics, who were followed for a median of 4.8 years. Individuals were eligible if they were between the ages of 50 and 85 years. Interventions included daily supplementation with macular xanthophylls (10 mg lutein + 2 mg zeaxanthin). Dietary supplementation of macular xanthophylls in addition to daily intake of minerals and vitamins did not reduce the risk of CVD in elderly participants with age-related macular degeneration.
Evidence characterization: The prospective, randomized AREDS2 cardiovascular ancillary study found no significant benefit of lutein/zeaxanthin supplementation on cardiovascular outcomes. Observational associations between dietary xanthophyll intake and cardiovascular health cannot be separated from other dietary and lifestyle factors without further controlled evidence.
Lutein belongs to the carotenoid family of xanthophylls, which have antioxidant, anti-inflammatory, and anticancer properties.
Research confirms antiproliferative properties of lutein and zeaxanthin in certain human cancer cell lines, including HepG2 (hepatitis cancer) and MCF-7 (breast cancer), which treated in vitro with lutein solution showed reduction of cell growth.
In a hepatocellular carcinoma animal model, lutein reduced γ-glutamyl transpeptidase activity, a marker of cellular proliferation.
Evidence characterization: The human studies examined have shown that the effects of lutein on cancer are minimal, highlighting the need for further clinical research in this area. Anticancer evidence for xanthophylls is currently restricted to in vitro cell studies and animal models; no human clinical trial has established xanthophyll supplementation as a cancer treatment or primary preventive agent.
While supplementation with lutein and zeaxanthin from day one of life in preterm infants until discharge probably reduces the incidence of ROP stage 3 and above, it may have little or no effect on the incidence of ROP at any stage, IVH or NEC, or mortality assessed throughout the NICU stay. However, the pooled estimates for these outcomes may change with further rigorously conducted trials. There were no adverse effects reported.
Xanthophylls, primarily in the form of lutein and zeaxanthin, have been studied at the following doses:
No Tolerable Upper Intake Level (UL) for lutein or zeaxanthin has been formally set by US authorities: The Institute of Medicine (IOM) has not derived UL values for lutein, zeaxanthin, or meso-zeaxanthin. No UL value has been established by the EC SCF or EFSA for lutein, zeaxanthin, or meso-zeaxanthin. However, ADI values for specific forms as food additives have been derived.
The EFSA Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion re-evaluating the safety of lutein (E 161b). Lutein has been previously evaluated by the EU Scientific Committee.
The Panel concluded, based on the NOAEL of 200 mg/kg bw/day in a 90-day rat study, the absence of developmental toxicity at dose levels up to 1,000 mg/kg bw/day, the fact that lutein is not genotoxic, and that lutein is a normal constituent of the diet, that an ADI can be derived. Given the absence of a multigeneration reproductive toxicity study and of chronic toxicity/carcinogenicity studies, the Panel applied an uncertainty factor of 200 and established an ADI of 1 mg/kg bw/day. This ADI refers to lutein derived from Tagetes erecta containing at least 80% carotenoids.
EFSA concluded that an intake of 0.75 mg/kg bodyweight/day of synthetic zeaxanthin does not raise any safety concerns. These values correspond to a daily intake of 53 mg of zeaxanthin and 70 mg of lutein for a person weighing 70 kg.
Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, EFSA (NDA Panel), in association with a 200-fold safety factor, proposed an acceptable daily intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission.
A critical safety distinction emerged from the AREDS2 trial: At 10 years, the odds ratio of having lung cancer was 1.82 for those randomly assigned to beta-carotene and 1.15 (not statistically significant) for lutein/zeaxanthin. This finding, combined with earlier data, led to the replacement of beta-carotene with lutein/zeaxanthin in revised eye health supplement formulations. Importantly, the AREDS2 trial found that replacing beta-carotene with lutein/zeaxanthin eliminated the increased lung cancer risk associated with beta-carotene.
Beta-carotene from food and supplements may decrease the absorption of lutein, zeaxanthin, and astaxanthin. This interaction is reciprocal — lutein inhibits beta-carotene absorption in a dose-dependent manner. This competitive absorption is one reason the AREDS2 study replaced beta-carotene with lutein and zeaxanthin.
Beta-carotene was shown to compete with lutein and zeaxanthin, as individuals who took all three nutrients had lower levels of circulating lutein and zeaxanthin compared to participants who took lutein and zeaxanthin without beta-carotene.
When mixed carotenoids are delivered into the intestinal tract simultaneously, competition occurs for micelle formation and absorption, affecting carotenoid bioavailability.
Large amounts of divalent mineral ions such as calcium and magnesium can make carotenoids like lutein and zeaxanthin less bioavailable, likely due to a reaction between the carotenoid and the mineral ions. It is best to take lutein or any carotenoid supplement at a different time of day than a supplement or meal containing large amounts (hundreds of milligrams) of a mineral.
As fat-soluble compounds, xanthophylls require co-ingestion with dietary fat for meaningful intestinal absorption. The high bioavailability of a fat-soluble nutrient such as zeaxanthin from egg is due to the rich lipid matrix of the yolk. Supplementation without fat co-consumption may significantly reduce bioavailability.
The fat substitute olestra may reduce absorption of lutein and zeaxanthin.
High sustained intake of any carotenoids — including xanthophylls — can produce carotenodermia, a harmless yellowing of the skin. This is a well-recognized benign effect of high carotenoid consumption and is reversible upon dose reduction. It is not associated with toxicity.
Several studies suggest relatively low HDL levels could hinder transport and capture of lutein and zeaxanthin. This may contribute to individual variability in the macular pigment response to supplementation.
The IOM has not derived UL values for lutein, zeaxanthin, or meso-zeaxanthin. Clinical research generally shows lutein supplementation is well tolerated, and 20 mg/day is commonly used in supplements and several studies. No formal tolerable upper intake level has been set in the U.S., partly because serious adverse effects are uncommon at typical supplemental doses.
Health conditions that Xanthophyll may help support.
Body systems that Xanthophyll may help support.
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