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Lutein
Space-filling model of lutein
Names
IUPAC name
(3R,6R,3′R)-β,ε-Carotene-3,3′-diol
Systematic IUPAC name
(1R,4R)-4-{(1E,3E,5E,7E,9E,11E,13E,15E,17E)-18-[(4R)-4-Hydroxy-2,6,6-trimethylcyclohex-1-en-1-yl]-3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaen-1-yl}-3,5,5-trimethylcyclohex-2-en-1-ol
Other names
  • Luteine
  • trans-Lutein
  • Xanthophyll
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.004.401 Edit this at Wikidata
E number E161b (colours)
UNII
  • InChI=1S/C40H56O2/c1-29(17-13-19-31(3)21-23-37-33(5)25-35(41)27-39(37,7)8)15-11-12-16-30(2)18-14-20-32(4)22-24-38-34(6)26-36(42)28-40(38,9)10/h11-25,35-37,41-42H,26-28H2,1-10H3/b12-11+,17-13+,18-14+,23-21+,24-22+,29-15+,30-16+,31-19+,32-20+/t35-,36+,37-/m0/s1 checkY
    Key: KBPHJBAIARWVSC-RGZFRNHPSA-N checkY
  • InChI=1S/C40H56O2/c1-29(17-13-19-31(3)21-23-37-33(5)25-35(41)27-39(37,7)8)15-11-12-16-30(2)18-14-20-32(4)22-24-38-34(6)26-36(42)28-40(38,9)10/h11-25,35-37,41-42H,26-28H2,1-10H3/b12-11+,17-13+,18-14+,23-21+,24-22+,29-15+,30-16+,31-19+,32-20+/t35-,36+,37-/m0/s1
    Key: KBPHJBAIARWVSC-RGZFRNHPBY
  • Key: KBPHJBAIARWVSC-RGZFRNHPSA-N
  • CC1=C(C(C[C@@H](C1)O)(C)C)/C=C/C(=C/C=C/C(=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/[C@H]2C(=C[C@@H](CC2(C)C)O)C)/C)/C
Properties
C40H56O2
Molar mass 568.871 g/mol
Appearance Red-orange crystalline solid
Melting point 190 °C (374 °F; 463 K)[1]
Insoluble
Solubility in fats Soluble
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Lutein (/ˈljuːtiɪn, -tiːn/;[2] from Latin luteus meaning "yellow") is a xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants, and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach, kale and yellow carrots. In green plants, xanthophylls act to modulate light energy and serve as non-photochemical quenching agents to deal with triplet chlorophyll, an excited form of chlorophyll which is overproduced at very high light levels during photosynthesis. See xanthophyll cycle for this topic.

Animals obtain lutein by ingesting plants.[3] In the human retina, lutein is absorbed from blood specifically into the macula lutea,[4] although its precise role in the body is unknown.[3] Lutein is also found in egg yolks and animal fats.

Lutein is isomeric with zeaxanthin, differing only in the placement of one double bond. Lutein and zeaxanthin can be interconverted in the body through an intermediate called meso-zeaxanthin.[5] The principal natural stereoisomer of lutein is (3R,3′R,6′R)-beta,epsilon-carotene-3,3′-diol. Lutein is a lipophilic molecule and is generally insoluble in water. The presence of the long chromophore of conjugated double bonds (polyene chain) provides the distinctive light-absorbing properties. The polyene chain is susceptible to oxidative degradation by light or heat and is chemically unstable in acids.

Lutein is present in plants as fatty-acid esters, with one or two fatty acids bound to the two hydroxyl-groups[citation needed]. For this reason, saponification (de-esterification) of lutein esters to yield free lutein may yield lutein in any ratio from 1:1 to 1:2 molar ratio with the saponifying fatty acid.

As a pigment

[edit]

This xanthophyll, like its sister compound zeaxanthin, has primarily been used in food and supplement manufacturing as a colorant due to its yellow-red color.[3][6] Lutein absorbs blue light and therefore appears yellow at low concentrations and orange-red at high concentrations.

Many songbirds (like golden oriole, evening grosbeak, yellow warbler, common yellowthroat and Javan green magpies, but not American goldfinch or yellow canaries[7]) deposit lutein obtained from the diet into growing tissues to color their feathers.[8][9]

Role in human eyes

[edit]

Although lutein is concentrated in the macula – a small area of the retina responsible for three-color vision – the precise functional role of retinal lutein has not been determined.[3]

Macular degeneration

[edit]

In 2013, findings of the Age-Related Eye Disease Study (AREDS2) showed that a dietary supplement formulation containing lutein reduced progression of age-related macular degeneration (AMD) by 25 percent.[10][11] However, lutein and zeaxanthin had no overall effect on preventing AMD, but rather "the participants with low dietary intake of lutein and zeaxanthin at the start of the study, but who took an AREDS formulation with lutein and zeaxanthin during the study, were about 25 percent less likely to develop advanced AMD compared with participants with similar dietary intake who did not take lutein and zeaxanthin."[11]

In AREDS2, participants took one of four AREDS formulations: the original AREDS formulation, AREDS formulation with no beta-carotene, AREDS with low zinc, AREDS with no beta-carotene and low zinc. In addition, they took one of four additional supplement or combinations including lutein and zeaxanthin (10 mg and 2 mg), omega-3 fatty acids (1,000 mg), lutein/zeaxanthin and omega-3 fatty acids, or placebo. The study reported that there was no overall additional benefit from adding omega-3 fatty acids or lutein and zeaxanthin to the formulation. However, the study did find benefits in two subgroups of participants: those not given beta-carotene, and those who had little lutein and zeaxanthin in their diets. Removing beta-carotene did not curb the formulation's protective effect against developing advanced AMD, which was important given that high doses of beta-carotene had been linked to higher risk of lung cancers in smokers. It was recommended to replace beta-carotene with lutein and zeaxanthin in future formulations for these reasons.[10]

  • 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.[12][13][14]
  • An updated 2023 Cochrane review of 26 studies from several countries, however, concluded that dietary supplements containing zeaxanthin and lutein alone have little effect when compared to placebo on the progression of AMD.[15] In general, there remains insufficient evidence to assess the effectiveness of dietary or supplemental zeaxanthin or lutein in treatment or prevention of early AMD.[16][15]

Cataract research

[edit]

There is preliminary epidemiological evidence that increasing lutein and zeaxanthin intake lowers the risk of cataract development.[3][17][18] Consumption of more than 2.4 mg of lutein/zeaxanthin daily from foods and supplements was significantly correlated with reduced incidence of nuclear lens opacities, as revealed from data collected during a 13- to 15-year period in one study.[19]

Two meta-analyses confirm a correlation between high diet content or high serum concentrations of lutein and zeaxanthin and a decrease in the risk of cataract.[20][21] 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 needing 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.[22]

In diet

[edit]

Lutein is a natural part of a human diet found in orange-yellow fruits and flowers, and in leafy vegetables. According to the NHANES 2013-2014 survey, adults in the United States consume on average 1.7 mg/day of lutein and zeaxanthin combined.[23] No recommended dietary allowance currently exists for lutein. Some positive health effects have been seen at dietary intake levels of 6–10 mg/day.[24] The only definitive side effect of excess lutein consumption is bronzing of the skin (carotenodermia).[citation needed]

As a food additive, lutein has the E number E161b (INS number 161b) and is extracted from the petals of Mexican marigold (Tagetes erecta).[25] It is approved for use in the EU[26] and Australia and New Zealand.[27] In the United States lutein may not be used as a food coloring for foods intended for human consumption, but can be added to animal feed and is allowed as a human dietary supplement often in combination with zeaxanthin. Example: lutein fed to chickens will show up in skin color and egg yolk color.[28][29]

Some foods contain relatively high amounts of lutein:[3][17][30][31][32][33]

Product Lutein + zeaxanthin[3]
(micrograms per 100 grams)
nasturtium (yellow flowers, lutein levels only) 45,000[31]
pot marigold (yellow and orange flowers, lutein levels only) 29,800
kale (raw) 39,550
kale (cooked) 18,246
dandelion leaves (raw) 13,610
nasturtium (leaves, lutein levels only) 13,600[31]
turnip greens (raw) 12,825
spinach (raw) 12,198
spinach (cooked) 11,308
swiss chard (raw or cooked) 11,000
turnip greens (cooked) 8,440
collard greens (cooked) 7,694
watercress (raw) 5,767
garden peas (raw) 2,593
romaine lettuce 2,312
zucchini (courgettes) 2,125
brussels sprouts 1,590
broccoli, raw 1,403
pistachio nuts 1,205
broccoli, cooked 1,121
carrot (cooked) 687
maize/corn 642
egg (hard boiled) 353
avocado (raw) 271
carrot (raw) 256
kiwifruit 122

Safety

[edit]

In humans, the Observed Safe Level (OSL) for lutein, based on a non-government organization evaluation, is 20 mg/day.[34] Although much higher levels have been tested without adverse effects and may also be safe, the data for intakes above the OSL are not sufficient for a confident conclusion of long-term safety.[3][34] Neither the U.S. Food and Drug Administration nor the European Food Safety Authority considers lutein an essential nutrient or has acted to set a tolerable upper intake level.[3]

Commercial value

[edit]

The lutein market is segmented into pharmaceutical, dietary supplement, food, pet food, and animal and fish feed. The pharmaceutical market for lutein is estimated to be about US$190 million, and the nutraceutical and food categories are estimated to be about US$110 million.[citation needed] Pet food and other animal applications for lutein are estimated at US$175 million annually. This includes chickens (usually in combination with other carotenoids), to get color in egg yolks, and fish farms to color the flesh closer to wild-caught color.[35] In the dietary supplement industry, the major market for lutein is for products with claims of helping maintain eye health.[36] Newer applications are emerging in oral and topical products for skin health. Skin health via orally consumed supplements is one of the fastest growing areas of the US$2 billion carotenoid market.[37]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Lutein

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from Grokipedia
Lutein is a with the molecular formula C₄₀H₅₆O₂, classified as a fat-soluble derived from the of a (6'R)-β,ε-carotene. It serves as a and agent, accumulating primarily in the of the human where it functions as part of the macular to filter harmful blue light and provide protection against . Naturally occurring in a free or esterified form, lutein is obtained exclusively through dietary sources, with the richest concentrations found in green leafy vegetables such as and , as well as in yolks, corn, and certain fruits like and kiwis. Average daily intake in Western diets is typically low, ranging from 1 to 2 mg, though supplementation up to 20 mg per day is considered safe and may enhance its bioavailability when consumed with fats. Lutein plays a critical role in eye health by reducing the risk of age-related macular degeneration (AMD) and cataracts through its ability to improve visual performance, such as contrast sensitivity, and mitigate photo-oxidative damage in the retina. Emerging research also highlights its broader antioxidant and anti-inflammatory properties, which may support cognitive function and skin health, though further studies are needed to confirm these benefits. Recommendations suggest aiming for at least 6 mg daily from diet or supplements to support optimal ocular protection, particularly for individuals at risk of vision loss.

Chemical Properties

Molecular Structure and Classification

Lutein is a tetraterpenoid belonging to the subclass of , characterized by its oxygenated structure that distinguishes it from hydrocarbon-only carotenes. Its molecular formula is C40H56O2, with a molecular weight of 568.87 g/mol. As a xanthophyll, lutein features a linear polyene chain of 11 conjugated double bonds flanked by two β-ionone rings, one of which is modified into an ε-ionone ring, and bears hydroxyl groups (-OH) attached at the 3 and 3' positions on these rings. The predominant natural form is the all-trans (all-E) isomer, where all double bonds in the polyene chain are in the trans configuration, contributing to its stability and yellow pigmentation. A notable is , which differs from lutein in the structure of the second ionone ring, having two β-ionone rings instead of one β-ionone and one ε-ionone ring. Lutein is classified as a non-provitamin A , meaning it lacks the β-ionone ring structure necessary for cleavage into (), in contrast to provitamin A carotenes such as β-carotene. The class of xanthophyll pigments was first isolated in 1837 by the Swedish chemist from autumn leaves, marking an early recognition of such pigments in plant material. Lutein itself was first isolated in 1907.

Physical and Chemical Characteristics

Lutein is typically isolated and observed as a yellow-to-orange crystalline powder, reflecting its nature and conjugated polyene structure. In solution, it displays characteristic UV-Vis absorption maxima at 445 nm and 474 nm in , with a shoulder around 424 nm, enabling straightforward spectroscopic identification. As a lipophilic , lutein is insoluble in but readily soluble in fats, oils, , and , a profile attributed to its nonpolar polyene chain and polar hydroxyl termini. Its is approximately 195–196 °C, indicating thermal stability suitable for extraction and processes. Lutein exhibits low optical rotation in organic solvents, often showing negligible in the due to its symmetric chiral centers. Lutein demonstrates notable activity, particularly in quenching through physical and chemical mechanisms, with a rate constant of 1.1×108 M−1s−11.1 \times 10^{8} \, \mathrm{M^{-1} s^{-1}} in model membrane systems. This property underscores its role in scavenging , though it is less efficient than some other carotenoids like . For quantification and purity assessment, lutein is routinely detected and measured using (HPLC) with UV-Vis detection at 445–450 nm, often in reversed-phase columns with acetonitrile-based mobile phases. This method provides high , with limits of detection typically in the low per milliliter range for extracts from sources.

Biosynthesis and Stability

Lutein is biosynthesized in through the methylerythritol (MEP) pathway, which occurs in plastids and begins with the formation of isopentenyl (IPP) from glyceraldehyde-3- and pyruvate, catalyzed by enzymes such as 1-deoxy-D-xylulose-5- synthase (DXS) and 1-deoxy-D-xylulose-5- reductoisomerase (DXR). IPP is then converted to dimethylallyl () and geranylgeranyl (), the C40 precursor for , via prenyltransferases. The committed step involves phytoene (), which condenses two GGPP molecules to form phytoene, followed by desaturation steps yielding . From , the α-branch leading to lutein requires cyclization by lycopene ε-cyclase (LCYE), producing δ-carotene, and lycopene β-cyclase (LCYB), forming through sequential β-ring closure. is then hydroxylated at the β-ring by enzyme CYP97A3 and at the ε-ring by CYP97C1, yielding lutein as the primary product, while the parallel β-branch from produces via β-carotene hydroxylase (BCH). These hydroxylations introduce the characteristic groups, distinguishing lutein as a . Lutein's chemical stability is limited by its conjugated double bonds and allylic hydroxyl groups, making it susceptible to degradation from environmental factors such as , , oxygen, and extreme values, which promote to cis forms or oxidation. Exposure to induces geometric , reducing the all-trans configuration essential for its bioactivity, while above 40°C accelerates breakdown, particularly in aqueous environments. Oxidative degradation, often catalyzed by pro-oxidants like metals or peroxides, leads to products such as 3'-oxolutein (3-hydroxy-β,ε-caroten-3'-one), formed via allylic oxidation at the ε-ring hydroxyl group. To mitigate degradation for commercial applications, techniques embed lutein in matrices like or proteins, shielding it from oxygen and light while improving shelf-life during storage; for instance, spray-dried microcapsules with isolates retain over 80% lutein after months at ambient conditions. These methods enhance and prevent oxidation by creating a physical barrier, extending stability in formulations. Evolutionarily, lutein's production pathway emerged in early photosynthetic organisms, such as and , to facilitate light harvesting and in , with the ε-cyclase gene arising from duplication and divergence of ancestral β-cyclase sequences in higher , enabling the α-branch diversification. This adaptation underscores lutein's conserved role in photoprotection across photosynthetic lineages, from prokaryotes to angiosperms.

Natural Occurrence

In Plants and Algae

Lutein is widely distributed in photosynthetic organisms, serving as a key xanthophyll carotenoid in plants and algae. It is particularly abundant in leafy vegetables, where contains up to 11.4 mg of lutein per 100 g fresh weight and up to 7.9 mg per 100 g. In , species such as exhibit notably high levels, often exceeding 150 mg per 100 g dry weight, making them significant natural sources. These concentrations highlight lutien's prevalence in autotrophic organisms adapted to diverse light environments. In plant and algal photosynthesis, lutein plays an essential role in light harvesting by integrating into chlorophyll-protein complexes within photosystems I and II. It binds specifically to (LHC) proteins, such as those in the major LHCII trimer, facilitating efficient energy transfer from absorbed photons to reaction centers. This structural integration ensures optimal capture of light across the , supporting the of these organisms. Beyond light harvesting, lutein provides critical photoprotection during periods of high light exposure. By quenching excited triplets and dissipating excess energy as , it prevents the formation of that could cause oxidative damage to cellular components. This mechanism is vital for maintaining photosynthetic apparatus integrity under fluctuating light conditions, contributing to the of and algae in varied habitats. Lutein also accumulates in chromoplasts of fruits and flowers, where it imparts yellow pigmentation and attracts pollinators or seed dispersers. In marigold (Tagetes erecta) flowers, for instance, lutein accounts for up to 90% of total , stored primarily in esterified forms within these specialized plastids. Such accumulation underscores lutien's role in reproductive strategies and visual signaling in flowering . Lutein concentrations vary significantly across species and environmental conditions, reflecting adaptations to local light and stress regimes. For example, tropical forages like pangola grass (Digitaria decumbens) and bermudagrass () in humid tropics show two- to three-fold higher lutein levels compared to the same species in drier or temperate regions, enhancing photoprotection in intense . These variations influence the overall profiles and ecological fitness of photosynthetic organisms.

In Animal Tissues

Animals acquire lutein solely through dietary sources, as they cannot synthesize de novo and must rely on intake from plant-based foods or other dietary components. This dependence underscores lutein's role as an essential dietary in animal physiology, with uptake occurring via intestinal absorption and subsequent systemic distribution. Lutein exhibits distinct tissue distribution in animals, with elevated concentrations observed in , , and ocular structures such as the lutea, where levels can reach up to 1-2 mg total in humans and . In adipose depots, lutein accumulates preferentially due to its lipophilic properties, serving as a storage reservoir that varies with dietary intake and individual adiposity. tissues also harbor significant amounts, as evidenced in mammals like bats and birds, where it contributes to pigmentation and photoprotection. The liver often shows high initial uptake, acting as a processing hub before redistribution to peripheral sites. Circulating lutein is transported primarily through lipoproteins, with over 50% associating with (HDL) particles and the remainder with (LDL), facilitating its delivery to target tissues. This lipoprotein-mediated transport leverages lutein's fat-soluble nature, enabling incorporation into lipid membranes where it embeds within cell and organelle bilayers, particularly in neural and epithelial tissues. Once deposited, lutein integrates into these hydrophobic environments, influencing and stability without undergoing extensive modification in most species. Interspecies variations highlight adaptive accumulation patterns; for instance, birds selectively deposit lutein in feathers to produce vibrant yellow and red hues for signaling and . Similarly, incorporate lutein into and scales, enhancing coloration and UV protection in aquatic environments. These differences reflect evolutionary pressures on utilization beyond mere storage. Primates exhibit unique metabolic processing, where lutein is converted to meso-zeaxanthin within the via the , yielding minor but functionally significant amounts of this isomer. This conversion represents a specialized in higher mammals, distinguishing their lutein handling from other vertebrates.

Physiological Roles

In

Lutein plays a critical role in (NPQ), a photoprotective mechanism that dissipates excess as in chloroplasts to prevent photodamage during high-light stress. In the absence of , lutein accumulation can restore NPQ capacity, enabling thermal dissipation of and maintaining under fluctuating conditions. This lutein-dependent NPQ is particularly evident in mutants lacking , where lutein binding to light-harvesting complexes facilitates rapid . Additionally, structural changes in lutein binding sites within antenna proteins enhance NPQ under excess , underscoring lutin's direct involvement in . As a key , lutein protects from (ROS) generated during abiotic stresses such as drought and UV exposure. Lutein quenches and other ROS in membranes, preventing and maintaining integrity under oxidative pressure. In drought-stressed , elevated lutein levels correlate with reduced ROS accumulation and preserved photosynthetic function, as seen in species like where lutein supports antioxidant networks in chloroplasts. Under UV stress, lutin's lipophilic properties enable it to scavenge ROS at sites of production, complementing enzymatic defenses to mitigate photooxidative damage. Lutein contributes to signaling processes in , particularly through its accumulation patterns that influence and flower pigmentation. During , such as in and , lutein levels modulate color transitions and serve as precursors for apocarotenoid signaling molecules that regulate responses and progression. In flowers, lutein imparts pigmentation and supports developmental cues, with higher expression in yellow-orange varieties linked to visual signaling for pollinators. These roles highlight lutin's integration into hormonal and light-mediated pathways that coordinate maturation. Genetic regulation of lutein levels primarily involves key enzymes like β-cyclase (LCYB) and hydroxylase CYP97C, which direct flux through the pathway. LCYB catalyzes the formation of β-rings in precursors, rate-limiting lutein synthesis, while CYP97C hydroxylates α-carotene to produce lutein stereospecifically in the ε-branch. Mutations or overexpression of these genes, as observed in and horticultural crops, alter lutein accumulation and affect photosynthetic performance. Environmental factors, particularly light intensity, modulate these physiological responses by upregulating LCYB and CYP97C expression under high , enhancing lutein-mediated photoprotection.

In Human Vision and Eye Health

Lutein, along with , selectively accumulates in the macula lutea of the human , forming the macular that provides optical and biochemical protection. This accumulation occurs primarily through (LDL)-mediated uptake in the (RPE), where LDL particles deliver lutein to RPE cells via LDL receptors, enabling its transport to the photoreceptor layer. Unlike , which is more dependent on (HDL) pathways, lutein's LDL-dependent mechanism ensures its preferential deposition in the central , reaching concentrations that contribute significantly to the macular optical (MPOD). In healthy adults, MPOD typically peaks at 0.5-1.0 optical (OD) units in the foveal region, reflecting lutein's high in this area. One of lutein's primary roles in vision is blue light filtration, where it absorbs harmful wavelengths in the 400-500 nm range, reducing phototoxic damage to the . By acting as an in the macular pigment, lutein attenuates blue light before it reaches the underlying photoreceptors, thereby minimizing photochemical reactions that could lead to cellular injury. Complementing this, lutein's activity neutralizes (ROS) and free radicals generated during photooxidation in photoreceptors, preventing and in retinal tissues. This dual protective function—optical and chemical—helps maintain photoreceptor integrity under normal light exposure conditions. The density of macular pigment, largely attributable to lutein, is commonly assessed using heterochromatic flicker photometry (HFP), a psychophysical technique that quantifies MPOD non-invasively. In HFP, subjects view a flickering disk alternating between a test light (around 460 nm, absorbed by macular pigment) and a green reference light (around 540 nm, minimally absorbed), adjusting the blue light intensity until flicker is minimized at central and peripheral retinal locations; MPOD is then calculated as the logarithmic of these intensities. This method provides a reliable measure of lutein's contribution to retinal protection, with validated reproducibility in clinical settings.

Health Effects in Humans

Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, and epidemiological studies have linked higher dietary intake of lutein to reduced risk of its development and progression. In a prospective cohort study of over 113,000 participants followed for up to 18 years, higher lutein/zeaxanthin intake was associated with a 28% lower risk of neovascular AMD (pooled multivariate relative risk [RR] 0.72, 95% CI 0.53-0.99 for highest vs. lowest quintile, median intake ~4.9 mg/day), with a stronger effect among never smokers (RR 0.41, 95% CI 0.18-0.97). Similarly, a meta-analysis of cohort studies reported that higher lutein/zeaxanthin intake was associated with a 41% reduced risk of AMD (hazard ratio [HR] 0.59, 95% CI 0.48-0.73). The Age-Related Eye Disease Study 2 (AREDS2) further supported these links through supplementation data, showing that adding 10 mg lutein and 2 mg zeaxanthin to the original AREDS formula reduced progression to late AMD by 9% overall (HR 0.91, 95% CI 0.84-0.99) and by 20% in participants previously on beta-carotene (HR 0.80, 95% CI 0.68-0.92) over 10 years. The Carotenoids in Age-Related Maculopathy (CARMA) study, involving 433 adults with early or advanced AMD, found that 12 mg lutein plus 2 mg zeaxanthin with co-antioxidants improved best-corrected visual acuity by a statistically significant margin at 24 and 36 months compared to placebo, though it did not significantly alter AMD progression rates. Lutein's protective effects in are primarily mediated through augmentation of macular pigment optical density (MPOD), which filters harmful blue light and neutralizes to safeguard photoreceptors. Supplementation with 10 mg lutein daily for 12 months increased MPOD by 39.5% (p < 0.001), enhancing contrast sensitivity (p < 0.05) and preserving retinal structure. This MPOD elevation helps prevent drusen formation, with higher dietary lutein/zeaxanthin intake linked to a 27% lower odds of large or extensive intermediate drusen (odds ratio [OR] 0.73, 95% CI 0.56-0.96). Additionally, lutein mitigates choroidal neovascularization (CNV) by reducing oxidative injury, inflammation, and vascular endothelial growth factor (VEGF) secretion in retinal pigment epithelium cells, resulting in a 22% lower risk of neovascular AMD progression (HR 0.78, 95% CI 0.64-0.94). Clinical trials have demonstrated that 10 mg/day lutein supplementation slows AMD progression in intermediate stages. In the Lutein Antioxidant Supplementation Trial (LAST), 90 patients with atrophic AMD receiving 10 mg lutein alone or with antioxidants showed improved visual acuity (5.4 letters gain on Snellen equivalent) and contrast sensitivity after 12 months, alongside a 0.09 log unit increase in MPOD, compared to no changes in the placebo group. AREDS2 updates confirmed that lutein/zeaxanthin supplementation slowed geographic atrophy (GA) progression toward the fovea by 20% (84.5 μm/year vs. 105.3 μm/year, p = 0.017) in eyes with noncentral GA, particularly in those not previously exposed to beta-carotene (80.1 μm/year vs. 114.4 μm/year, p = 0.011). Genetic factors, such as variants in the SCARB1 gene encoding the scavenger receptor class B type 1 involved in carotenoid transport, influence individual responses to lutein. The rs11057841 T allele was associated with 24% higher serum lutein levels per allele (p = 2 × 10⁻⁴), replicated in independent cohorts, and positively correlated with family history of (p = 0.028), suggesting enhanced lutein uptake may modulate AMD susceptibility. Recent 2020s meta-analyses reinforce lutein's long-term efficacy. A 2022 meta-analysis found higher plasma lutein/zeaxanthin concentrations linked to an 79% lower risk (OR 0.21, 95% CI 0.05-0.84), while a 2021 umbrella review of 24 systematic reviews confirmed inverse correlations between dietary lutein intake and AMD incidence. These analyses, incorporating data from trials like AREDS2, highlight sustained benefits of 6-10 mg/day intake or supplementation for preventing AMD advancement.

Cataract Formation

Prospective cohort studies have demonstrated an association between higher dietary intake of lutein and a reduced risk of nuclear cataracts, a common age-related opacity in the lens nucleus. In the Nurses' Health Study, involving over 36,000 women, higher consumption of lutein and zeaxanthin was linked to a lower incidence of cataract extraction, with multivariable-adjusted relative risks indicating significant protection for those in the highest quintile of intake compared to the lowest. Similarly, a meta-analysis of observational data reported that each 0.3 mg/day increment in dietary lutein and zeaxanthin intake was associated with a 3% reduction in nuclear cataract risk, equating to approximately 10% risk reduction per 1 mg/day increase, highlighting the potential dose-dependent protective effect. The protective mechanism of lutein against cataract formation primarily involves its antioxidant properties, which mitigate UV-induced oxidative damage in the lens. Ultraviolet radiation generates reactive oxygen species that trigger lipid peroxidation of lens cell membranes and proteins, particularly crystallins, leading to protein aggregation and opacification. Lutein, accumulating in the lens, neutralizes these free radicals and reduces peroxidation, thereby preserving lens transparency and delaying cataract progression. This action is complemented by lutien's ability to filter blue light, further limiting photooxidative stress on lens tissues. Intervention trials examining lutein supplementation for cataract prevention have yielded mixed results, with doses ranging from 6 to 20 mg/day over periods of 6 months to 5 years. The Age-Related Eye Disease Study 2 (AREDS2), a large randomized trial, found no overall significant reduction in cataract surgery rates with 10 mg lutein plus 2 mg zeaxanthin daily, but subgroup analysis revealed a 32% lower risk of surgery among participants with the lowest baseline dietary intake, suggesting modest benefits in delaying progression for high-risk groups. A 2015 systematic review corroborated these findings, noting inconsistent effects across trials but potential efficacy in vulnerable populations. Lutein exhibits synergy with zeaxanthin in lens protection, as both carotenoids co-accumulate in the lens and enhance each other's antioxidant capacity against oxidative insults. Their combined presence strengthens the lens's defense against ROS and UV damage, with studies showing greater risk reductions for nuclear cataracts when intake of both is elevated compared to lutein alone. Recent cohort data from the Carotenoids in Age-Related Eye Disease Study (CAREDS), involving postmenopausal women aged 50-79, reinforce this, reporting a 23% lower prevalence of nuclear cataracts in those with high dietary lutein and zeaxanthin levels, consistent with ongoing analyses through 2022.

Other Potential Benefits

Lutein exhibits potential benefits for skin health, particularly in mitigating UV-induced damage and photoaging. Randomized controlled trials have demonstrated that oral supplementation with 10 mg/day of lutein for 12 weeks significantly reduces skin erythema and enhances photoprotection by increasing the minimal erythema dose by approximately 20-40%. Doses ranging from 10-30 mg/day, administered orally or topically, have also been linked to decreased oxidative stress and improved skin elasticity in human studies. Emerging research suggests associations between lutein and enhanced cognitive function in older adults, including improvements in memory domains. A 2021 meta-analysis of randomized controlled trials reported non-significant overall effects of lutein supplementation at doses around 10 mg/day on memory (SMD 0.03, 95% CI -0.26 to 0.32) and executive function (SMD 0.13, 95% CI -0.26 to 0.51), though some individual studies noted better verbal fluency outcomes and potential to prevent decline. A 2024 systematic review of 17 studies confirmed improvements in cognitive function in 4 studies and reduced progression of in 8, supporting lutein's neuroprotective potential. These effects are attributed to lutein's accumulation in brain tissues and its antioxidant properties. In cardiovascular health, lutein may inhibit low-density lipoprotein (LDL) oxidation, a key factor in atherosclerosis development. A 2023 systematic review of intervention studies found that carotenoid supplementation, including lutein, was associated with minor elevations in high-density lipoprotein (HDL) cholesterol levels, alongside reductions in inflammatory markers. These findings highlight lutein's role in modulating lipid profiles, though effects remain modest.31047-1/fulltext) Preclinical studies indicate lutein's anti-inflammatory potential in metabolic conditions such as diabetes, where it attenuates oxidative stress and cytokine production in animal models of hyperglycemia. For instance, lutein supplementation has reduced inflammatory responses and protected against diabetic complications in rodent studies by downregulating pro-inflammatory pathways. While these areas show promise, substantial gaps in the evidence persist, with 2024 reviews emphasizing the need for larger, long-term randomized controlled trials to validate efficacy and optimal dosing beyond preliminary observations. Current data, primarily from small-scale human trials and preclinical models, underscore ongoing research requirements for broader clinical translation.

Dietary Aspects

Sources in Foods

Lutein, a xanthophyll carotenoid, is abundant in various plant-based foods, particularly green leafy vegetables, where it accumulates as a key photosynthetic pigment. Top dietary sources include kale, which provides approximately 23 mg of lutein per 100 g of cooked product, spinach with about 12 mg per 100 g cooked, and collard greens offering around 11 mg per 100 g cooked. Egg yolks represent a notable animal-derived source, containing roughly 0.25 mg of lutein per yolk, primarily esterified forms accumulated from the hen's diet. These values are derived from comprehensive USDA nutrient databases, highlighting the potential for substantial intake from a serving of leafy greens alone. Cooking methods can influence lutein retention in vegetables, with heat and water exposure potentially leading to some degradation or leaching. Steaming typically preserves a high percentage of the lutein content (often >80%) by minimizing water contact and oxidative loss, making it preferable for nutrient conservation. In contrast, may result in minor losses due to into cooking liquid, though studies show variable retention generally above 80%. These effects have been quantified in studies on stability, emphasizing the importance of preparation techniques for maximizing dietary availability. Efforts to enhance lutein levels in staple crops through have yielded promising results. Genetically enhanced corn varieties, developed via transgenic approaches targeting biosynthesis pathways, exhibit 5-10 times higher lutein concentrations compared to conventional types, reaching up to 2-5 mg per 100 g in kernels. Similarly, rice lines overexpressing genes like OsGLK1 show elevated content, including lutein increases of several fold, aimed at addressing deficiencies in -dependent populations. These biofortified crops maintain agronomic performance while boosting nutritional profiles. Global dietary patterns influence lutein consumption, with vegetable-rich regimens providing higher averages. The , emphasizing leafy greens and colorful produce, typically delivers 2-3 mg of lutein per day, surpassing the 1-2 mg average in Western diets. This elevated intake stems from cultural staples like and in regional cuisines. Accurate quantification of lutein in foods relies on analytical methods such as saponification extraction, where alkaline (e.g., with KOH) liberates esterified lutein from matrices, followed by solvent partitioning and (HPLC) for precise measurement. This technique ensures reliable detection even in complex food samples.

Absorption and Bioavailability

Lutein, a fat-soluble , undergoes absorption primarily in the through a process initiated by . In the , dietary lutein is released from food matrices and incorporated into mixed micelles composed of salts, phospholipids, and products of such as fatty acids and monoglycerides. This solubilization is essential for enhancing the bioaccessibility of lutein, as it allows the non-polar molecule to be presented to the enterocyte membrane. salts play a critical role in micelle formation, while co-consumption of dietary fats further promotes this process by stimulating secretion and increasing micelle stability, resulting in up to 3-fold higher uptake compared to fat-free conditions. Once solubilized, esterified forms of lutein—common in plant sources—are hydrolyzed in the intestinal lumen by enzymes such as carboxyl ester lipase (CEL), releasing free lutein for absorption. Unesterified lutein formulations, such as the patented FloraGLO® lutein derived from marigold flowers, provide the free form directly without requiring hydrolysis, which is associated with high bioavailability and makes them a common choice in dietary supplements for eye health support, including protection against blue light and antioxidant benefits to the retina. The free lutein then enters enterocytes mainly via passive across the apical membrane, facilitated by transporters including scavenger receptor class B type I (SR-BI) and CD36. Inside the enterocytes, lutein is packaged into chylomicrons and secreted into the for systemic distribution. is notably influenced by dietary ; for instance, consuming lutein with oils or high-fat meals can substantially increase plasma response relative to low-fat conditions. Following absorption, lutein appears in plasma within hours, with peak concentrations typically occurring 4-6 hours post-ingestion for supplemental forms, though this can extend to 9-14 hours depending on the matrix. The plasma of lutein is approximately 5-7 days, reflecting its accumulation in tissues over repeated dosing. Individual variations in arise from genetic factors, such as polymorphisms in the BCMO1 gene (also known as BCO1), which modulates metabolism, and variants in uptake-related genes like and , leading to differences in plasma levels among individuals. Additionally, composition may indirectly affect absorption by influencing lipid digestion and short-chain fatty acid production that supports stability. There is no official Recommended Dietary Allowance (RDA) established for lutein by major health authorities such as the (NIH) or the (EFSA). However, guidelines suggest a daily intake of 6-10 mg for supporting eye health, based on evidence from intervention studies and population data; for instance, studies suggest at least 6 mg/day to maintain macular pigment density, while the Age-Related Eye Disease Study 2 (AREDS2) protocol, endorsed by the National Eye Institute, utilizes 10 mg/day of lutein combined with 2 mg/day of for reducing progression of age-related . Typical dietary intake in the United States averages 1-2 mg/day, which is below these suggested levels for optimal benefits. Bioavailability considerations, such as enhanced absorption with dietary fats, may influence individual requirements. Lutein holds (GRAS) status from the U.S. (FDA) for use in foods and supplements, with no established upper intake limit due to its low toxicity profile. Doses exceeding 20 mg/day may lead to benign yellowing known as carotenodermia, a reversible condition resulting from accumulation in the , though this is rare at typical supplemental levels. Comprehensive safety assessments confirm no serious adverse effects at intakes up to 20 mg/day across multiple clinical trials. Toxicity studies demonstrate high safety margins for lutein. In animal models, the (LD50) exceeds 2,000 mg/kg body weight, with no observed adverse effects in subchronic studies at doses up to 250 mg/kg/day. clinical trials, including long-term interventions up to 30 mg/day for five years, report no significant adverse effects beyond minor, transient gastrointestinal discomfort in isolated cases. Potential interactions exist between lutein and certain cholesterol-lowering medications, such as sequestrants (e.g., cholestyramine), which may reduce lutein's intestinal absorption by binding dietary fats and . Consultation with a healthcare provider is advised for individuals on such therapies to monitor efficacy. For vulnerable populations, lutein at dietary levels is considered safe during , with 2024 reviews and studies indicating no evidence of adverse maternal or fetal outcomes and potential benefits for neurodevelopment from maternal intake, including increased systemic and ocular levels. Supplementation during should align with recommended doses and medical guidance to avoid exceeding typical dietary amounts.

Commercial Uses

As a Dietary Supplement

Lutein used in dietary supplements is primarily sourced from the extraction of oleoresin from dried petals of marigold flowers (Tagetes erecta L.), where the carotenoid is isolated through solvent extraction and purification processes to yield lutein esters or free lutein at concentrations often reaching 80% purity or higher. Synthetic production of lutein is also feasible via chemical synthesis methods, such as the Wittig reaction involving phosphonium salts and aldehydes to construct the carotenoid backbone, though natural extraction from marigolds accounts for the majority of commercial supply. Dietary supplements containing lutein are formulated in various types, including free (unesterified) lutein, lutein diesters, and blends with ; a common combination mirrors the 10:2 lutein-to- ratio found in the human , as exemplified by FloraGLO®, a patented, naturally sourced, unesterified lutein ingredient (often combined with zeaxanthin) derived from marigold flowers. FloraGLO is widely used in eye health supplements for its high bioavailability and efficacy in supporting vision, filtering harmful blue light, and providing antioxidant protection to the retina. Popular products featuring FloraGLO include Doctor's Best Lutein 20 mg (with FloraGLO), The Vitamin Shoppe Opti-Vue with FloraGLO Lutein (a multi-ingredient formula for vision support), and Nature's Plus Ultra Lutein with Zeaxanthin. These forms are typically encapsulated in softgels or tablets to enhance stability and , with free lutein often preferred for its similarity to dietary intake from . The global lutein market surpassed $380 million in 2024, fueled by rising demand from aging populations seeking preventive measures against age-related eye conditions like . As of 2025, the market is projected to reach approximately $414 million. Evidence from pharmacokinetic studies demonstrates that daily oral supplementation with 10-20 mg of lutein significantly elevates serum levels, with increases ranging from 3- to 10-fold observed after 4-6 weeks of consistent intake, depending on the formulation and individual baseline concentrations. Quality control remains a critical aspect of lutein supplements due to potential risks of microbial contamination from natural plant sources and inconsistencies in potency; the (USP) provides standardization monographs that verify identity, purity, strength, and absence of harmful contaminants through rigorous testing protocols.

In Food and Cosmetics

Lutein serves as a colorant designated E161b in the , where it imparts yellow to orange hues in products such as items like and beverages including non-alcoholic flavored drinks. Maximum permitted levels are category-specific, reaching up to 100 mg/kg in flavored and in certain fat-based spreads and drinks under Regulation (EC) No 1333/2008. In the United States, lutein from marigold is affirmed as (GRAS) for use in foods, including as a color additive in various applications without specific numerical limits beyond good manufacturing practices. Beyond coloration, lutein is incorporated into formulas as a fortificant to enhance nutritional profiles, often at levels approximating those in (around 25-200 μg/L), supporting eye and without affecting growth or tolerance. In June 2025, the FDA granted GRAS clearance for OmniActive's Lutemax Free Lutein for use in . It is also added to margarines and similar spreads for nutritional , leveraging its properties to improve product functionality in line with global standards for carotenoid-enriched fats. In cosmetics, lutein is formulated into sunscreens and anti-aging creams at concentrations typically ranging from 0.1% to 1%, where it contributes to photoprotection by absorbing harmful UV and blue light wavelengths, reducing oxidative stress and inflammation in skin cells. Topical applications demonstrate improved skin hydration and decreased lipid peroxidation, enhancing overall skin resilience against environmental damage. Commercially, lutein is predominantly extracted from marigold () flowers via solvent-based processes, such as or extraction followed by , producing oleoresins with 5-15% lutein content on a dry weight basis. These methods optimize yield while maintaining purity, often achieving up to 97% lutein in refined forms suitable for industrial dispersion. Regulatory frameworks support these applications, with the FDA affirming lutein from as a color additive for s in 2001 under GRAS notifications, enabling its use in a broad range of products.

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