Lutein zeaxanthin side effects


Medically reviewed by Last updated on Nov 20, 2019.

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Clinical Overview


There is a lack of consensus and limited evidence from clinical and epidemiological studies as to whether an association exists between a higher intake of xanthophylls (lutein with or without zeaxanthin) and protection against age-related macular degeneration (AMD) and cataracts. The use of lutein in the management of cardiovascular conditions and cancer has been proposed.

A dose of lutein 5 mg/day is widely used. AMD trials have used lutein 10 to 20 mg/day for 3 to 6 months or longer.


Contraindications have not been identified.


Generally recognized as safe (GRAS) when consumed as food. Lutein and zeaxanthin are found in the milk of lactating women, as well as in the umbilical cord.

None well documented.

No clinically important adverse reactions were reported at doses up to lutein 20 mg/day.

Purified crystalline lutein derived from marigold has US Food and Drug Administration (FDA) GRAS status and can be added to certain foods and beverages. There is strong safety evidence at doses up to 20 mg/day.


Humans (and other primates) are unable to synthesize lutein and must obtain it from dietary vegetable and fruit sources. High amounts of lutein are found in green, leafy vegetables, particularly in spinach and kale. Flowers and the leaves of the nasturtium plant are also rich sources of lutein; carrots and kiwi fruits contain lesser amounts. Wide variation in the lutein content exists in these foods, and processing and storage also influence lutein levels. Animal sources are consequent to animal consumption of vegetable-based lutein and include egg yolks and animal fats. Lutein-fortified milk and eggs are commercially available. Lutein as a commercial food additive is obtained from the petals of the marigold flower (food additive number E161b), and can also be sourced from microalgae.1, 2, 3, 4


Lutein has traditionally been used since the 1950s for the treatment of eye diseases and for its purported protective effect on visual function. In 1996, the incorporation of lutein into dietary substances was accepted (at 6 to 7 mg/day), with marigold-sourced lutein used as a food additive and colorant. Most studies conducted up to the 1990s have investigated the efficacy of total carotenoid content, whereas more recent studies focus specifically on lutein.1, 5, 6


Lutein is a xanthophyll carotenoid, one of about 600 natural carotenoids; however, lutein is not a precursor of vitamin A. It is a red/orange crystalloid substance that is insoluble in water and has a melting point of 190°C (374°F). Lutein is biosynthesized in plants and some microalgae. It is generally accepted that lutein in vegetables exists in the trans form; however cis-lutein has been described. In food substances, lutein may exist in the free or esterified form, or bound to protein. Zeaxanthin is isomeric with lutein. Methods for extraction, identification, and quantification have been described. Crystalline lutein is difficult to handle and is often suspended in corn or safflower oils or in microcapsule form.1, 2, 5, 6, 7

Uses and Pharmacology

In vitro and animal studies show activity of lutein in inhibition of monocyte-mediated inflammatory response, immune enhancement, antioxidant activity, inhibition of peroxidation of membrane lipids, and protection against macular degeneration.5, 8, 9


Lutein and zeaxanthin are found concentrated in the eye, especially in the macula in the retina, and in the lens, where they screen high-energy blue light, which can cause retinal injury.10, 11, 12

Animal data

In vitro studies show antioxidant activity of lutein and suggest macula protection.5 Carotenoid absorption is poor in most animal species, and few relevant animal studies exist. Limited studies in monkeys show diets supplemented with xanthophyll resulted in increased serum lutein concentrations and incorporation into the retina.13 An inverse correlation was demonstrated between orally administered lutein and the incidence of cataracts in mice models of diabetic retinopathy. Clinical trials are lacking for this indication.11

Clinical data

Healthy populations

Most,14, 15, 16, 17 but not all,18 studies in healthy populations demonstrated an increase in serum lutein and macular pigment optical density; wide variations in the response of populations have been noted.15 One study in healthy adults failed to demonstrate any difference in distance and near visual acuity, contrast sensitivity, or photo-stress recovery time with supplemental lutein 6 mg/day taken over 18 months.19 However, a 1-year randomized clinical trial conducted in healthy Chinese professional drivers (n = 121) found that supplementation with lutein 20 mg/day significantly improved central macular pigment optical density as well as contrast and glare sensitivity, especially in low light conditions.51

Age-related macular degeneration and cataract

Most clinical studies have shown a correlation between lutein supplementation and increased serum lutein concentrations and macular pigment optical density.12, 20, 21, 22 A relationship between these outcomes and AMD has not been established, however, and the FDA does not recognize them as surrogate end points for the measurement of AMD or age-related cataracts.12, 23 In addition, it has been noted that a poor correlation exists between serum and tissue lutein concentrations and dietary intake.12 In 2004, based on the evidence of 12 interventions and 23 observational studies, the FDA rejected a health claim that supplementation with lutein and zeaxanthin changes the risk of AMD or cataract.23 A meta-analysis of 6 trials (through April 2010) found an overall relative risk of 1.07 (95% confidence interval , 0.8 to 1.45) for the effect of dietary lutein on reducing the risk of early AMD.25 Dietary supplementation with only lutein (10 to 20 mg/day for 4 to 12 months) significantly improved macular pigment optical density, but not visual acuity, in patients with or at risk of AMD according to a 2014 meta-analysis of 5 randomized clinical trials (N = 445 participants).57 Visual performance was found to be improved with lutein and zeaxanthin supplementation in AMD patients according to a meta-analysis of 8 placebo-controlled trials through April 2014.56 Most epidemiological studies support the conclusion that a higher intake of xanthophylls is protective of AMD12, 23; however, an 18-year follow-up in the Nurses’ Health Study did not support a protective role of lutein regarding the risk of early AMD.27

An age-adjusted odds ratio26 of 0.77 (95% CI, 0.62 to 0.96) supported correlation with a lower prevalence of age-related cataracts.7, 27 Other observational studies report equivocal or, at best, modest associations.11, 12, 28, 29 A 2013, multicenter, double-masked, randomized clinical trial evaluated 6,027 study eyes (N = 3,159) for effects of daily lutein 10 mg/zeaxanthin 2mg on subsequent need for cataract surgery in elderly patients at risk of progression to advanced AMD. No difference was found among the treatment groups and placebo in the 5-year probability to progression to cataract surgery. A statistically significant improvement was observed; however, for participants in the lowest quintile of dietary intake of lutein/zeaxanthin.50 Data from a secondary analysis of this multicenter study suggest that supplements with lutein/zeaxanthin may be more beneficial than those with beta-carotene in patients at risk of progressing to late AMD.53 A meta-analysis of 13 observational studies (n =18,999), however, evaluated the association between blood levels of antioxidants and vitamins to the risk of age-related cataract. Based on the results of 6 relevant studies with no substantial heterogeneity, lutein was associated with significantly reduced risk of cataract.52 Another meta-analysis of 8 studies found blood levels of lutein plus zeaxanthin to be associated with a significant reduction in risk of nuclear, but not cortical or subcapsular, cataracts.55 Whereas, dietary intake of lutein/zeaxanthin was not found to be statistically significantly associated with baseline or development of nuclear or cortical lens opacity outcomes in report 37 of the Age-Related Eye Disease Study (N = 3,115).58

Retinitis pigmentosa

Limited clinical studies exist to support a role in therapy. In an efficacy and safety study, an increase in visual field was demonstrated in participants with retinitis pigmentosa,30 while no effect of lutein was found on edema, foveal thickness, or visual acuity. Lutein 10 mg/day was administered for 12 weeks, followed by 12 weeks at 30 mg/day.31 Another study found no difference in the rate of decline of central visual field sensitivity over 4 years with supplemental lutein 12 mg/day. Participants in this study were already taking a vitamin A supplement. Secondary outcome measures were suggestive of improvements.32

Prevention of retinopathy of prematurity

Despite a plausible role for lutein supplementation,33 clinical trials have failed to demonstrate a protective effect of lutein supplementation for any grade of retinopathy of prematurity or other relevant outcome measures. Published data include a multicenter trial of 114 infants up to 32 weeks gestational age evaluating a daily oral dose of lutein 0.14 mg and zeaxanthin 0.006 mg until discharge (mean, 49 days)35 and a similar trial of 63 participants using 0.5 mg/kg/day until discharge (mean, 45 days).36


In vitro and rodent studies have shown inhibition of angiogenesis, modulation of apoptosis and immune function, and the prevention of oxidative damage.7

An epidemiological association has been shown for xanthophylls and cancer.5, 7 Clinical trials are lacking.

Other uses

Cardiovascular disease

An epidemiological association has been shown for xanthophylls and cardiovascular health.5, 7 An ancillary Cardiovascular Outcomes Study of the Age-Related Eye Disease Study (AREDS) 2 evaluated the effect of omega-3 fatty acids (DHA 350 mg/day + EPA 650 mg/day) versus macular xanthophylls (lutein 10 mg/day + zeaxanthin 2 mg/day) versus a combination of the 2 versus placebo on cardiovascular outcomes in 4,203 AREDS patients (median age, 74 years) over a median of 4.8 years. Only patients with a negative baseline history for hypertension, cardiovascular disease, or hypercholesterolemia showed significant protective effects from either group of supplements. Serious hyponatremia requiring hospitalization that was considered possibly related to the supplements occurred in one 76-year-old patient who was randomized to the combination supplement group.54

Cognitive health

In a subgroup analysis of a study of eye health, some positive effects on verbal fluency (memory test), but not on other memory tests or mental processing tests, were shown with supplemental lutein 12 mg/day in elderly women. An additive effect with docosahexaenoic acid was demonstrated.37

Oxidative stress

A small clinical study found reduced total hydroperoxides and increased antioxidant potential in healthy neonates at 48 hours who were given lutein 0.28 mg at 12 and 36 hours after birth. Clinical applications have yet to be determined.8 Lutein supplementation in adequately nourished elderly people does not appear to improve markers of oxidative stress.38


Animal studies suggest lutein may be protective against ultraviolet (UV) damage.39 A small clinical trial found improvements in all evaluated skin parameters, including skin lipid content, lipid peroxidation, elasticity, hydration, and protective effects, with oral lutein (10 mg/day) or topical lutein application (100 ppm/day) when skin was exposed to UV light irradiation.39


Data from the United States Department of Agriculture (USDA) suggest the average daily intake of lutein by Americans is 1.7 mg/day, possibly reflecting an inadequate intake of green, leafy vegetables.10 Raw spinach yields approximately 12 mg lutein and zeaxanthin per 100 g, kale contains up to 40 mg lutein per 100 g, and eggs contain approximately 140 mcg lutein per yolk.10, 40, 41

Consumption of or supplementation with lutein 5 mg/day is widely accepted.4

Bioavailability of lutein depends on the source.6 A study comparing free lutein with lutein esters found greater increases in serum lutein with the free form42; another found no difference between free lutein and the supplement lutein diacetate taken over 24 weeks.43

Fat consumption promotes lutein solubility and uptake.7 Body fat may act as a reservoir for carotenoids, including lutein. Weight loss has been associated with a positive and important correlation with increased macular pigment optical density and serum xanthophylls.44 Gains in increased lutein plasma concentrations are mitigated by any increase in body mass index.45

AMD trials have used lutein 10 to 20 mg/day for 3 to 6 months or longer,16, 20, 46, 47, 57 and a linear dose-response (macular pigment optical density) has been described.17 Higher doses and longer durations have been used in limited clinical studies; however, safety at those dosages has not been established.48

Pregnancy / Lactation

GRAS status when consumed as food. Lutein and zeaxanthin are found in the milk of lactating women, as well as in the umbilical cord. The concentration of lutein in breast milk in healthy women has been measured between 3 and 200 mcg/L.6, 8, 49 A randomized clinical study demonstrated that lutein serum concentrations in infants who were fed unfortified milk formula (no added lutein) were approximately one-sixth the amount of those in breast-fed infants.49


Case reports are lacking.

Beta-carotene: Lutein and beta-carotene may compete with each other for absorption. Beta-carotene may decrease the serum concentration of lutein.6, 10, 59, 60, 61

Adverse Reactions

No clinically important adverse reactions were reported at doses up to lutein 20 mg/day.24, 46, 47


Purified crystalline lutein derived from Tagetes erecta (marigold) has FDA GRAS status and can be added to foods and beverages.6, 7 Animal and in vitro toxicological studies report no terato-, embryo- or genotoxicity or mutagenicity; however, data are limited.6, 48 There is strong evidence of safety at doses up to 20 mg/day. Higher doses (40 mg/day for 9 weeks) have been used in clinical trials; however, methodological issues exist, and safety is not clearly established.48 Serum concentrations of lutein up to 1.05 mcmol/L (less than 600 mcg/L) seem to be safe based on clinical studies and show no evidence of an unacceptable serum lutein profile at this concentration, including an absence of biochemical and hematological changes or carotenodermia.5

1. Calvo MM. Lutein: a valuable ingredient of fruit and vegetables. Crit Rev Food Sci Nutr. 2005;45(7-8):671-696.163713342. Granado-Lorencio F, Herrero-Barbudo C, Olmedilla-Alonso B, Blanco-Navarro I, Pérez-Sacristán B. Lutein bioavailability from lutein ester-fortified fermented milk: in vivo and in vitro study. J Nutr Biochem. 2010;21(2):133-139.192011833. Chung HY, Rasmussen HM, Johnson EJ. Lutein bioavailability is higher from lutein-enriched eggs than from supplements and spinach in men. J Nutr. 2004;134(8):1887-1893.152843714. Fernández-Sevilla JM, Acién Fernández FG, Molina Grima E. Biotechnological production of lutein and its applications. Appl Microbiol Biotechnol. 2010;86(1):27-40.200913055. Granado F, Olmedilla B, Blanco I. Nutritional and clinical relevance of lutein in human health. Br J Nutr. 2003;90(3):487-502.145138286. Shegokar R, Mitri K. Carotenoid lutein: A promising candidate for pharmaceutical and nutraceutical applications. J Diet Suppl. 2012;9(3):183-210. Germany.228891437. Ribaya-Mercado JD, Blumberg JB. Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr. 2004;23(6 suppl):567S-587S.156405108. Perrone S, Longini M, Marzocchi B, et al. Effects of lutein on oxidative stress in the term newborn: a pilot study. Neonatology. 2010;97(1):36-40.195902449. Shanmugasundaram R, Selvaraj RK. Lutein supplementation alters inflammatory cytokine production and antioxidant status in F-line turkeys. Poult Sci. 2011;90(5):971-976.2148994110. Alves-Rodrigues A, Shao A. The science behind lutein. Toxicol Lett. 2004;150(1):57-83.1506882511. Kijlstra A, Tian Y, Kelly ER, Berendschot TT. Lutein: More than just a filter for blue light. Prog Retin Eye Res. 2012;31(4):303-315.2246579112. Trumbo PR, Ellwood KC. Lutein and zeaxanthin intakes and risk of age-related macular degeneration and cataracts: an evaluation using the food and drug administration’s evidence-based review system for health claims. Am J Clin Nutr. 2006;84(5):971-974.1709314513. Carpentier S, Knaus M, Suh M. Associations between lutein, zeaxanthin, and age-related macular degeneration: An overview. Crit Rev Food Sci Nutr. 2009;49(4):313-326.1923494314. Johnson EJ, Chung HY, Caldarella SM, Snodderly DM. The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation. Am J Clin Nutr. 2008;87(5):1521-1529.1846927915. Rodriguez-Carmona M, Kvansakul J, Harlow JA, Köpcke W, Schalch W, Barbur JL. The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision. Ophthalmic Physiol Opt. 2006;26(2):137-147.1646031416. Schalch W, Cohn W, Barker FM, et al. Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin − the LUXEA (LUtein xanthophyll eye accumulation) study. Arch Biochem Biophys. 2007;458(2):128-135.1708480317. Bone RA, Landrum JT. Dose-dependent response of serum lutein and macular pigment optical density to supplementation with lutein esters. Arch Biochem Biophys. 2010;504(1):50-55.2059966018. Graydon R, Hogg RE, Chakravarthy U, Young IS, Woodside JV. The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation, inflammation and oxidation: Pilot studies in healthy volunteers. Br J Nutr. 2012;108(2):334-342.2231352219. Bartlett HE, Eperjesi F. A randomised controlled trial investigating the effect of lutein and antioxidant dietary supplementation on visual function in healthy eyes. Clin Nutr. 2008;27(2):218-227.1829473920. Bartlett HE, Eperjesi F. Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease: a randomized controlled trial. Eur J Clin Nutr. 2007;61(9):1121-1127.1726841721. Ma L, Dou HL, Huang YM, et al. Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: A randomized, double-masked, placebo-controlled trial. Am J Ophthalmol. 2012;154(4):625-634.e1.2283551022. Zeimer M, Dietzel M, Hense HW, Heimes B, Austermann U, Pauleikhoff D. Profiles of macular pigment optical density and their changes following supplemental lutein and zeaxanthin: New results from the LUNA study. Invest Ophthalmol Vis Sci. 2012;53(8):4852-4859.2274332123. Weigert G, Kaya S, Pemp B, et al. Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52(11):8174-8178.2187366824. Ma, L, Dou HL, Wu YQ, et al. Lutein and zeaxanthin intake and the risk of age-related macular degernation: a systematic review and meta-analysis. Br J Nutr. 2012;107(3):350-359.2189980525. Ma L, Lin XM. Effects of lutein and zeaxanthin on aspects of eye health. J Sci Food Agric. 2010;90(1):2-12.2035500626. Cho E, Hankinson SE, Rosner B, Willett WC, Colditz GA. Prospective study of lutein/zeaxanthin intake and risk of age-related macular degeneration. Am J Clin Nutr. 2008;87(6):1837-1843.1854157527. Moeller SM, Voland R, Tinker L, et al. Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the carotenoids in the age-related eye disease study, an ancillary study of the women’s health initiative. Arch Ophthalmol. 2008;126(3):354-364.1833231628. Renzi LM, Johnson EJ. Lutein and age-related ocular disorders in the older adult: A review. J Nutr Elder. 2007;26(3-4):139-157.1828529629. Krinsky NI, Landrum JT, Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr. 2003;23:171-201.1262669130. Bahrami H, Melia M, Dagnelie G. Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial . BMC Ophthalmol. 2006;6:23.1675939031. Adackapara CA, Sunness JS, Dibernardo CW, Melia BM, Dagnelie G. Prevalence of cystoid macular edema and stability in oct retinal thickness in eyes with retinitis pigmentosa during a 48-week lutein trial. Retina. 2008;28(1):103-110.1818514632. Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010;128(4):403-411.2038593533. Hammond BR Jr. Possible role for dietary lutein and zeaxanthin in visual development. Nutr Rev. 2008;66(12):695-702.1901903834. Dani C, Lori I, Favelli F, et al. Lutein and zeaxanthin supplementation in preterm infants to prevent retinopathy of prematurity: A randomized controlled study. J Matern Fetal Neonatal Med. 2012;25(5):523-527.2200396035. Romagnoli C, Giannantonio C, Cota F, et al. A prospective, randomized, double blind study comparing lutein to placebo for reducing occurrence and severity of retinopathy of prematurity. J Matern Fetal Neonatal Med. 2011;24(Suppl 1):147-150.2194261436. Johnson EJ, McDonald K, Caldarella SM, Chung HY, Troen AM, Snodderly DM. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr Neurosci. 2008;11(2):75-83.1851080737. Li L, Chen CY, Aldini G, et al. Supplementation with lutein or lutein plus green tea extracts does not change oxidative stress in adequately nourished older adults. J Nutr Biochem. 2010;21(6):544-549.1944702038. Roberts RL, Green J, Lewis B. Lutein and zeaxanthin in eye and skin health. Clin Dermatol. 2009;27(2):195-201.1916800039. Palombo P, Fabrizi G, Ruocco V, et al. Beneficial long-term effects of combined oral/topical antioxidant treatment with the carotenoids lutein and zeaxanthin on human skin: A double-blind, placebo-controlled study. Skin Pharmacol Physiol. 2007;20(4):199-210.1744671640. Goodrow EF, Wilson TA, Houde SC, et al. Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations. J Nutr. 2006;136(10):2519-2524.1698812041. Burns-Whitmore BL, Haddad EH, Sabaté J, Jaceldo-Siegl K, Tanzman J, Rajaram S. Effect of n-3 fatty acid enriched eggs and organic eggs on serum lutein in free-living lacto-ovo vegetarians. Eur J Clin Nutr. 2010;64(11):1332-1337.2066461642. Norkus EP, Norkus KL, Dharmarajan TS, Schierle J, Schalch W. Serum lutein response is greater from free lutein than from esterified lutein during 4 weeks of supplementation in healthy adults. J Am Coll Nutr. 2010;29(6):575-585.2167712143. Landrum J, Bone R, Mendez V, Valenciaga A, Babino D. Comparison of dietary supplementation with lutein diacetate and lutein: Aapilot study of the effects on serum and macular pigment. Acta Biochim Pol. 2012;59(1):167-169.2242814444. Kirby ML, Beatty S, Stack J, et al. Changes in macular pigment optical density and serum concentrations of lutein and zeaxanthin in response to weight loss. Br J Nutr. 2011;105(7):1036-1046.2114409345. Waters D, Clark RM, Greene CM, Contois JH, Fernandez ML. Change in plasma lutein after egg consumption is positively associated with plasma cholesterol and lipoprotein size but negatively correlated with body size in postmenopausal women. J Nutr. 2007;137(4):959-963.1737466146. Richer S, Stiles W, Statkute L, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the veterans LAST study (lutein antioxidant supplementation trial). Optometry. 2004;75(4):216-230.1511705547. Rosenthal JM, Kim J, de Monasterio F, et al. Dose-ranging study of lutein supplementation in persons aged 60 years or older. Invest Ophthalmol Vis Sci. 2006;47(12):5227-5233.1712210748. Shao A, Hathcock JN. Risk assessment for the carotenoids lutein and lycopene. Regul Toxicol Pharmacol. 2006;45(3):289-298.1681443949. Bettler J, Zimmer JP, Neuringer M, DeRusso PA. Serum lutein concentrations in healthy term infants fed human milk or infant formula with lutein. Eur J Nutr. 2010;49(1):45-51.1967255050. Age-Related Eye Disease Study 2 (AREDS2) Research Group; Chew EY, SanGiovanni JP, Ferris FL, et al. Lutein/zeaxanthin for the treatment of age-related cataract-AREDS2 randomized trial report No.4. JAMA Ophthamol. 2013;13(7):843-850.2364522751. Yao Y, Qiu QH, Wu XW, Cai ZY, Xu S, Liang XQ. Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study. Nutrition. 2013;29(7-8):958-964.2336069252. Cui YH, Jing CX, Pan HW. Association of blood antioxidants and vitamins with risk of age-related cataract: a meta-analysis of observationsl studies. Am J Clin Nutr. 2013;98(3):778-786.2384245853. Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, Clemons TE, Sangiovanni JP, Danis RP, et al. Secondary analyses of the effects of lutein/zeaxanthin on age-rlated macular degeneration progression–AREDS2 Report No.3. JAMA Ophthalmol. 2014;132(2):142-149.2431034354. Writing Group for the AREDS2 Research Group; Bonds DE, Harrington M, Worrall BB, et al. Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med. 2014;174(5):763-771.2463890855. Liu XH, Yu RB, Liu R, et al. Association between lutein and zeaxanthin status and the risk of cataract: a meta-analysis. Nutrients. 2014;6:452-465.2445131256. Liu R, Wang T, Zhang B, et al. Lutein and zeaxanthin supplementation and association with visual function in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2015;56(1):252-258.2551557257. Wang X, Jiang C, Zhang Y, Gong Y, Chen X, Zhang M. Role of lutein supplementation in the management of age-related macular degeneration: meta-analysis of randomized controlled trials. Ophthalmic Res. 2014;52:198-205.253582858. Glaser TS, Doss LE, Shih G, et al; Age-Related Eye Disease Study Research Group. The association of dietary lutein plus zeaxanthin and B vitamins with cataracts in the age-related eye disease study. Ophthalmol. 2015;122(7):1471-1479.2597225759. Kostic D, White WS, Olson JA. Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses. Am J Clin Nutr. 1995;62(3):604-610.766112360. van den Berg H, van Vliet T. Effect of simultaneous, single oral doses of beta-carotene with lutein or lycopene on the beta-carotene and retinyl ester responses in the triacylglycerol-rich lipoprotein fraction of men. Am J Clin Nutr. 1998;68(1):82-89.966510061. van den Berg H. Effect of lutein on beta-carotene absorption and cleavage. Int J Vitam Nutr Res. 1998;68(6):360-365.9857262


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Are you a new drug developer? Contact us to learn more about our customized products and solutions. Stay in the know! As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages. #DrugBankUpdates Name Lutein Accession Number DB00137 (NUTR00036, DB11138) Type Small Molecule Groups Approved, Investigational, Nutraceutical Description

Lutein is an 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.

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Structure for Lutein (DB00137)

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  • Xanthophyll
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External IDs E 161 / E-161B / E-161B(I) / INS NO.161B(I) / INS-161B(I) Over the Counter Products

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Doctor Super Lutein Capsule 20 g/100g Oral Health-Love Co. 2016-01-30 2018-02-12 US

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Unapproved/Other Products Categories UNII X72A60C9MT CAS number 127-40-2 Weight Average: 568.886
Monoisotopic: 568.428031043 Chemical Formula C40H56O2 InChI Key KBPHJBAIARWVSC-RGZFRNHPSA-N InChI 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 IUPAC Name (1R,4R)-4–3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaen-1-yl]-3,5,5-trimethylcyclohex-2-en-1-ol SMILES C\C(\C=C\C=C(/C)\C=C\1C(C)=C(O)CC1(C)C)=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/C1=C(C)C(O)CC1(C)C



Xanthophylls are taken for nutritional supplementation, and also for treating dietary shortage or imbalance.

Associated Therapies

  • Dietary and Nutritional Therapies
  • Folate supplementation therapy
  • Mineral supplementation
  • Vitamin supplementation


Lutein was found to be present in a concentrated area of the macula, a small area of the retina responsible for central vision. The hypothesis for the natural concentration is that lutein helps protect from oxidative stress and high-energy light. Several studies show that an increase in macula pigmentation decreases the risk for eye diseases such as Age-related Macular Degeneration (AMD).

Mechanism of action

Xanthophylls have antioxidant activity and react with active oxygen species, producing biologically active degradation products. They also can inhibit peroxidation of membrane phospholipids and reduce lipofuscin formation, both of which contribute to their antioxidant properties. Lutein is naturally present in the macula of the human retina. It filters out potentially phototoxic blue light and near-ultraviolet radiation from the macula. The protective effect is due in part, to the reactive oxygen species quenching ability of these carotenoids. Lutein is more stable to decomposition by pro-oxidants than are other carotenoids such as beta-carotene and lycopene. Lutein is abundant in the region surrounding the fovea, and lutein is the predominant pigment at the outermost periphery of the macula. Zeaxanthin, which is fully conjugated (lutein is not), may offer somewhat better protection than lutein against phototoxic damage caused by blue and near-ultraviolet light radiation. Lutein is one of only two carotenoids that have been identified in the human lens, may be protective against age-related increases in lens density and cataract formation. Again, the possible protection afforded by lutein may be accounted for, in part, by its reactive oxygen species scavenging abilities. Carotenoids also provide protection from cancer. One of the mechanisms of this is by increasing the expression of the protein connexin-43, thereby stimulating gap junctional communication and preventing unrestrained cell proliferation.

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Learn more Absorption Not Available Volume of distribution Not Available Protein binding Not Available Metabolism Not Available Route of elimination Not Available Half life Not Available Clearance Not Available Toxicity Not Available Affected organisms

  • Humans and other mammals

Pathways Not Available Pharmacogenomic Effects/ADRs Not Available Drug Interactions This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist. Not Available Food Interactions Not Available Synthesis Reference

Helmut Auweter, Heribert Bohn, Erik Luddecke, “Stable, aqueous dispersions and stable, water-dispersible dry xanthophyll powder, their production and use.” U.S. Patent US6296877, issued September, 1994.

US6296877 General References External Links KEGG Compound C08601 PubChem Compound 5281243 PubChem Substance 46508835 ChemSpider 4444655 ChEBI 28838 ChEMBL CHEMBL173929 PharmGKB PA164748318 HET LUT PDRhealth PDRhealth Drug Page Wikipedia Xanthophyll MSDS (73.1 KB)

Clinical Trials

Clinical Trials

Phase Status Purpose Conditions Count
1 Completed Treatment Macular Degeneration 1
1, 2 Completed Treatment Retinitis Pigmentosa (RP) 1
1, 2 Recruiting Other Glaucoma 1
1, 2 Unknown Status Treatment Age-Related Macular Degeneration (ARMD) 1
1, 2 Unknown Status Treatment Oxidative Stress in Healthy Subjects 1
2 Completed Treatment Macular Degeneration 1
2 Completed Treatment NPDR – Non Proliferative Diabetic Retinopathy / Type 2 Diabetes Mellitus 1
2 Recruiting Supportive Care Nutrient Deficiency / Pregnancy Related 1
3 Completed Treatment Age-Related Macular Degeneration (ARMD) / Cataracts 1
3 Completed Treatment Retinitis Pigmentosa (RP) 1
4 Completed Prevention Macular Pigment Optical Density 1


Manufacturers Not Available Packagers Not Available Dosage forms

Form Route Strength
Tablet, coated Oral
Capsule Oral 20 g/100g
Capsule Oral
Tablet Oral
Capsule, gelatin coated Oral

Prices Not Available Patents Not Available


State Liquid Experimental Properties

Property Value Source
melting point (°C) 196 °C PhysProp
water solubility Insoluble Not Available
logP 7.9 Not Available

Predicted Properties

Property Value Source
Water Solubility 0.000732 mg/mL ALOGPS
logP 8.29 ALOGPS
logP 8.55 ChemAxon
logS -5.9 ALOGPS
pKa (Strongest Acidic) 18.22 ChemAxon
pKa (Strongest Basic) -0.91 ChemAxon
Physiological Charge 0 ChemAxon
Hydrogen Acceptor Count 2 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 40.46 Å2 ChemAxon
Rotatable Bond Count 10 ChemAxon
Refractivity 195.06 m3·mol-1 ChemAxon
Polarizability 73.81 Å3 ChemAxon
Number of Rings 2 ChemAxon
Bioavailability 0 ChemAxon
Rule of Five No ChemAxon
Ghose Filter No ChemAxon
Veber’s Rule No ChemAxon
MDDR-like Rule No ChemAxon

Predicted ADMET features

Property Value Probability
Human Intestinal Absorption + 0.9972
Blood Brain Barrier + 0.6588
Caco-2 permeable + 0.7904
P-glycoprotein substrate Substrate 0.5199
P-glycoprotein inhibitor I Inhibitor 0.5819
P-glycoprotein inhibitor II Non-inhibitor 0.8202
Renal organic cation transporter Non-inhibitor 0.876
CYP450 2C9 substrate Non-substrate 0.8299
CYP450 2D6 substrate Non-substrate 0.8408
CYP450 3A4 substrate Substrate 0.6607
CYP450 1A2 substrate Non-inhibitor 0.9079
CYP450 2C9 inhibitor Non-inhibitor 0.7723
CYP450 2D6 inhibitor Non-inhibitor 0.9368
CYP450 2C19 inhibitor Inhibitor 0.5225
CYP450 3A4 inhibitor Non-inhibitor 0.8808
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6267
Ames test Non AMES toxic 0.8391
Carcinogenicity Non-carcinogens 0.7489
Biodegradation Not ready biodegradable 0.9655
Rat acute toxicity 2.5006 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9273
hERG inhibition (predictor II) Non-inhibitor 0.8259

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)


Mass Spec (NIST) Not Available Spectra

Spectrum Spectrum Type Splash Key
Predicted MS/MS Spectrum – 10V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum – 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum – 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum – 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum – 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum – 40V, Negative (Annotated) Predicted LC-MS/MS Not Available


Description This compound belongs to the class of organic compounds known as xanthophylls. These are carotenoids containing an oxygenated carotene backbone. Carotenes are characterized by the presence of two end-groups (mostly cyclohexene rings, but also cyclopentene rings or acyclic groups) linked by a long branched alkyl chain. Carotenes belonging form a subgroup of the carotenoids family. Xanthophylls arise by oxygenation of the carotene backbone. Kingdom Organic compounds Super Class Lipids and lipid-like molecules Class Prenol lipids Sub Class Tetraterpenoids Direct Parent Xanthophylls Alternative Parents Secondary alcohols / Hydrocarbon derivatives Substituents Xanthophyll / Secondary alcohol / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Alcohol / Aliphatic homomonocyclic compound Molecular Framework Aliphatic homomonocyclic compounds External Descriptors carotenol (CHEBI:28838) / C40 isoprenoids (tetraterpenes), Carotenoids (C08601) / C40 isoprenoids (tetraterpenes) (LMPR01070274)


Details1. Serum albumin Kind Protein Organism Humans Pharmacological action Unknown General Function Toxic substance binding Specific Function Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid… Gene Name ALB Uniprot ID P02768 Uniprot Name Serum albumin Molecular Weight 69365.94 Da

  1. Zsila F, Nadolski G, Lockwood SF: Association studies of aggregated aqueous lutein diphosphate with human serum albumin and alpha1-acid glycoprotein in vitro: evidence from circular dichroism and electronic absorption spectroscopy. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3797-801. Epub 2006 May 5.
  2. Yemelyanov AY, Katz NB, Bernstein PS: Ligand-binding characterization of xanthophyll carotenoids to solubilized membrane proteins derived from human retina. Exp Eye Res. 2001 Apr;72(4):381-92.

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Drug created on June 13, 2005 07:24 / Updated on February 02, 2020 00:09

Lutein & Zeaxanthin

Cataracts and age-related macular degeneration (AMD) are the leading causes of visual impairment and acquired blindness in the U.S, affecting millions of aging Americans. Nutrition is one promising way to prevent or delay the progression of these diseases.
Two carotenoids, lutein (pronounced loo-teen) and zeaxanthin (pronounced zee-uh-zan-thin), are antioxidants that are located in the eye. (Insert – Several dark) green leafy vegetables, as well as other foods such as eggs, contain these important nutrients. Many studies have shown that lutein and zeaxanthin reduce the risk of chronic eye diseases, including AMD and cataracts.

Benefits to Eye Health

Lutein and zeaxanthin filter harmful high-energy blue wavelengths of light and help protect and maintain healthy cells in the eyes. Of the 600 carotenoids found in nature, only these two are deposited in high quantities in the retina (macula) of the eye.
The amount of lutein and zeaxanthin in the macular region of the retina is measured as macular pigment optical density (MPOD). Recently, MPOD has become a useful biomarker for predicting disease and visual function.

Unfortunately, the human body does not naturally make the lutein and zeaxanthin it needs. This is why eating green vegetables is important. Getting daily amounts of lutein and zeaxanthin through your diet or nutritional supplements can help maintain good eye health. (Insert – Like many other naturally occuring nutrients, the way the vegetables are prepared/consumed and the items that they are consumed with can affect how well the body can absorb them. As such sometimes additional supplements may be needed for optimal therapy.)

Lutein, Zeaxanthin and Cataracts

The crystalline lens (the natural lens in the eye) primarily collects and focuses light on the retina. To do this throughout your life, the lens must remain clear. Oxidation of the lens is a major cause of cataracts, which cloud the lens.
Antioxidant nutrients neutralize free radicals (unstable molecules) that are associated with oxidative stress and retinal damage. This is why the antioxidants lutein and zeaxanthin likely play a role in preventing cataracts. In fact, a recent study demonstrated that higher dietary intake of lutein and zeaxanthin and vitamin E was associated with a significantly decreased risk of cataract formation.

Lutein, Zeaxanthin and AMD

There is a lot of evidence that lutein and zeaxanthin reduce the risk of AMD. In fact, in the Age-Related Eye Disease Studies (AREDS and AREDS2), the National Eye Institute found that taking certain nutritional supplements every day reduces the risk of developing late AMD. Beyond reducing the risk of eye disease, separate studies have shown that lutein and zeaxanthin improve visual performance in AMD patients, cataract patients and people in good health.

Daily Intake*

Discover great recipes rich in Lutein
The USDA Nutrient Database offers comprehensive
information on raw and prepared foods.

If you are not getting enough lutein and zeaxanthin through your diet alone, consider taking daily supplements. Although there is no recommended daily intake for lutein and zeaxanthin, most recent studies show health benefits in taking 10 mg/day of a lutein supplement and 2 mg/day of a zeaxanthin supplement. .

Daily Intake

Most Western diets are low in lutein and zeaxanthin, which can be found in spinach, corn, broccoli and eggs. The USDA Nutrient Database offers comprehensive information on raw and prepared foods.

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