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Associations between Lutein, Zeaxanthin, and Age-Related Macular Degeneration: An OverviewShannon Carpentier a , Maria Knaus a b & Miyoung Suh aa Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba,R3T 2N2b Misericordia Health Centre, Winnipeg, Manitoba, Canada, R3C 1A2Published online: 18 Feb 2009.

To cite this article: Shannon Carpentier , Maria Knaus & Miyoung Suh (2009) Associations between Lutein, Zeaxanthin,and Age-Related Macular Degeneration: An Overview, Critical Reviews in Food Science and Nutrition, 49:4, 313-326, DOI:10.1080/10408390802066979

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Critical Reviews in Food Science and Nutrition, 49:313–326 (2009)Copyright C©© Taylor and Francis Group, LLCISSN: 1040-8398DOI: 10.1080/10408390802066979

Associations between Lutein,Zeaxanthin, and Age-Related MacularDegeneration: An Overview

SHANNON CARPENTIER,1 MARIA KNAUS1,2 and MIYOUNG SUH1

1Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, R3T 2N22Misericordia Health Centre, Winnipeg, Manitoba, Canada R3C 1A2

Age-related macular degeneration, the leading cause of blindness in the elderly, is a degenerative condition of the maculacharacterized by death or dysfunction of the photoreceptors. With the aging population growing, the incidence of age-relatedmacular degeneration is expected to increase. This raises concern about the future of visual dysfunction related falls and theresulting injuries in the elderly population. Lutein and zeaxanthin are macular pigments that may play a role in reducing thedevelopment and progression of age-related macular degeneration. Evidence is accumulating on the consumption of luteinand zeaxanthin (in whole food or supplemental form), the resulting concentrations in the serum, and tissue distributionthroughout the body, particularly in the retina. Lutein and zeaxanthin intake increases serum concentrations which in turnincreases macular pigment density. Existing literature focuses on factors affecting macular pigment density, functions of luteinand zeaxanthin as blue-light filters and antioxidants, and risk factors associated with age-related macular degeneration.Few studies have focused on the impact of dietary lutein and zeaxanthin on retinal function and the potential to preservevision and prevent further degeneration. This presents an opportunity for further research to determine an effective dose thatdelays the progression of age-related macular degeneration.

Keywords lutein, zeaxanthin, carotenoids, age-related macular degeneration, eye health, elderly

INTRODUCTION

Age-related macular degeneration (AMD) is the leadingcause of blindness in the elderly in Western countries (Chopdaret al., 2003). Many researchers have found significant associa-tions between lutein and zeaxanthin concentrations in ocular tis-sues, serum, and plasma, with a possible reduced risk of AMD.Lutein and zeaxanthin are the only carotenoids present in boththe macula and lens of the human eye (Yeum et al., 1995) and arealso referred to as macular pigment (MP). Functions of MP in-clude improving visual function (Richer, 1999, 2004; Dagnalieet al., 2000; Falsini et al., 2003), quenching free radicals andthereby acting as an antioxidant to protect the macula from ox-idative damage (Davies and Morland, 2004; Sujak et al., 1999;Bone et al., 2003) and filtering blue light (Bone et al., 2003;Junghans et al., 2001). It is of interest that we explore exist-ing evidence that lutein and zeaxanthin protect the retina fromdamage and possibly prevent or slow the progression of AMD.

Address correspondence to Miyoung Suh, H514 Duff Roblin Bldg., De-partment of Human Nutritional Sciences, University of Manitoba, Canada R3T2N2. Tel: 204-474-8651; Fax: 204-474-7593. E-mail: suh@ms.umanitoba.ca

Understanding the absorption and transport of lutein and zeax-anthin to tissues, accumulation in the macula, and their role inhuman eye health is of paramount importance.

LUTEIN AND ZEAXANTHIN

Structure

Lutein and zeaxanthin belong to the xanthophyll family ofdietary carotenoids containing 40-carbon atoms with hydrox-ylated cyclic structures at both ends. The difference betweenthe two molecules is the location of one double bond in oneof the hydroxyl groups (Fig. 1), which may contribute to thebiological function of these xanthophylls (Johnson, 2002). Di-etary lutein may be metabolized to meso-zeaxanthin by theretina, although the exact metabolism is unknown (Bone et al.,1993). Unlike other carotenoids, lutein, zeaxanthin, and meso-zeaxanthin are enriched in the macular region of the retina, thusthey are referred to as MP. These carotenoids cannot be synthe-sized in the body and must be supplied in the diet and therefore

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Figure 1 Molecular structure of lutein, zeaxanthin, and beta-carotene

should be considered essential in the protection of retinaldamage.

Dietary Sources

There are currently no dietary reference intakes forcarotenoids. In the United States, the average daily intakefor lutein and zeaxanthin is 2.0–2.3 mg/d for men and 1.7–2.0 mg/day for women (Food and Nutrition Board, 2001). Notoxicities or adverse reactions have been reported for lutein andzeaxanthin at doses of up to 40 mg/day for two months (Dagnelieet al., 2000). Lutein and zeaxanthin are present in a wide varietyof plant sources, such as leafy green vegetables (kale, turnip,and spinach etc.) as well as a few animal sources, such as eggyolk (Monograph, 2005).

Absorption and Metabolism

It is of interest how lutein and zeaxanthin are supplied tothe macular region. Lutein and zeaxanthin are absorbed by theenterocytes of the intestinal mucosa and are then transported inchylomicrons to hepatocytes. Low and high-density lipoproteins(LDL, HDL) transport lutein and zeaxanthin to various tissues(Yeum and Russell, 2002). HDL carries primarily lutein andzeaxanthin whereas LDL transports other carotenoids (Clevi-dence and Bieri, 1993). It is not known whether conformationalchanges of these molecules take place in the liver or in extrahep-atic tissues. It is not clearly understood how the retina takes upspecific carotenoids. Bernstein (1997) indicates that lutein andzeaxanthin selectively bind to tubulin, a structural protein thathelps form the cytoskeleton in cone axons, possibly maintainingthe structural integrity and improving visual function. Tubulin isabundant in the retina, which may explain the selective accumu-

lation of lutein and zeaxanthin in the macula in comparison toother carotenoids (Crabtree et al., 2001). Xanthophyll-bindingproteins may be involved in taking up the specific carotenoidsin the retina.

Xanthophylls are fat-soluble therefore bioavailability to tis-sues depends on many factors including dietary source (wholefood or supplement form), state of the food (raw, cooked, or pro-cessed), the presence of digestive enzymes, and the absorptionby enterocytes. Cooking foods containing lutein and zeaxan-thin may increase bioavailability by disrupting the cellular ma-trix and the carotenoid-protein complexes (Castenmiller et al.,1999). It is not clear if the absorption is different based on theindividual form of xanthophyll or food and crystalline forms.There are only a few studies to support that lutein is betterabsorbed than zeaxanthin (Bone et al., 2003) and that puri-fied lutein crystalline supplement is more effectively absorbedthan dietary sources (Castenmiller et al., 1999). Some studieshave found that carotenoids compete for absorption, particular-ily beta-carotene and lutein (Kostic et al., 1995; Albanes et al.,1997; Van den Berg, 1998). It is yet to be determined if there is amaximum amount of lutein and zeaxanthin that can be absorbedby the human body. This information would be valuable as sup-plementation studies use varying doses. It would also be helpfulto know if supplementation with large doses compared to smalldoses throughout the day has a beneficial effect on absorptionand transport to tissues.

Transport to Tissues and Tissue Distribution

The mechanisms of incorporation of lutein and zeaxanthininto retinal tissues are poorly understood. As Bone et al. (2003)pointed out, the transport mechanism of lutein and zeaxanthininto the serum may be different from the serum into retinal tis-sues. Dietary intake of carotenoids is shown to have a directly

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Table 1 Lutein and zeaxanthin levels in human ocular tissues.

Ocular region Eyes examined Area (mm2) Lutein (ng/tissue) Zeaxanthin (ng/tissue) L:Z ratio

Macular retina 14 20 13.98 19.06 0.7Peripheral retina 19 1000 64.18 34.11 1.9Superior retina 78 20 1.68 0.80 2.1Inferior retina 78 20 1.46 0.63 2.3Nasal retina 7 20 1.76 0.81 2.2Temporal retina 7 20 1.42 0.65 2.2RPE/choroid 17 whole 11.58 5.89 2.0Superior RPE/choroid 78 20 0.63 0.19 3.3Inferior RPE/choroid 78 20 0.53 0.16 3.3Submacular RPE/choroid 25 20 0.77 0.32 2.4Ciliary body 20 whole 12.72 5.98 2.1Iris 21 whole 4.03 1.54 2.7Lens 18 whole 1.66 1.43 1.2Cornea 3 whole trace trace —Sclera 5 20 trace trace —Vitreous 3 0.5 ml nd nd —

Adapted from Bernstein et al. (2001). With permission from Elsevier Ltd.nd, not detected.

proportional relationship to serum concentrations, which re-flects the bioavailability of lutein and zeaxanthin. Accordingto the Third National Health and Nutrition Examination Sur-vey (NHANES III), median serum concentrations in Americanadults ranged from 0.19 umol/L in the lowest quintile to 0.79umol/L in the highest quintile (Mares-Perlman et al., 2001).

Lutein and zeaxanthin are concentrated not only in the mac-ular retina, but also in many ocular tissues as shown in Table 1(Bernstein et al., 2001). These molecules are also high in liver,adrenal, adipose, pancreas, kidney, and breast tissue, whereaslower levels have been reported in the lung, spleen, heart, testes,thyroid, ovary (Kaplan et al., 1990; Schmitz et al., 1991; Zhanget al., 1997), and skin (Wingerath et al., 1998). Meso-zeaxanthinhas been found in the human macula, retina, and RPE-choroid,but is lacking in the human plasma and liver (Khachik et al.,2002).

Adipose tissue and retina may compete for uptake of luteinand zeaxanthin. When compared with the retina, adipose tissuepreferentially takes up lutein (Thomson et al., 2002). It is esti-mated that more than 80% of the total number of carotenoidsin the body are found in adipose tissue, which may serve asa reservoir (Olson, 1984). Higher body percentages are likelyassociated with lower retinal lutein and zeaxanthin (Hammondet al., 2002; Nolan et al., 2004; Burke et al., 2005), thereforeit is possible that any dietary intake of lutein and zeaxanthin isstored in the excess adipose tissue and is therefore not trans-ported to the retina. In this regard, it is of interest to know ifobesity contributes to lower MP.

Further research is needed on the consumption of lutein andzeaxanthin and reflected amounts present in the retina. It isknown that lutein and zeaxanthin are not synthesized by the bodyand the only sources are from the diet. It is also known that luteinmay be converted to meso-zeaxanthin but just how much luteinis converted into meso-zeaxanthin remains unknown. Most ofthe absorption and transport information is based on healthysubjects but further study is needed to determine if the mecha-

nisms are the same for those with clinical signs of AMD. Forexample, are the ratios of lutein to zeaxanthin in tissues sim-ilar in AMD subjects? It is possible that certain mechanismsare impaired resulting in lower retinal lutein and zeaxanthin butconclusions cannot be made without sufficient evidence.

LUTEIN AND ZEAXANTHIN IN THE RETINA

Macular Pigments

The macular pigments lutein, zeaxanthin, and meso-zeaxanthin comprise approximately 36%, 18%, and 18%, re-spectively, of the total carotenoid content of the retina (Landrumand Bone, 2001). These carotenoids are most dense at the centerof the fovea, a depression in the center of the retina also referredto as the macula lutea (Snodderly, 1995), and decline rapidlyin the peripheral regions. With extensive studies completed byBone et al. (1997), it is now known that the concentration oflutein is greater than that of zeaxanthin in the peripheral regionof the macula and zeaxanthin is more abundant in the centralregion (Bone et al., 1988, 1992, and 1997). The ratio of zeax-anthin to lutein is much higher in the central retina (1:1 in themacula, 2:1 in the fovea, 1:1 in the lens) (Bernstein et al., 2001)and 1:2 and 1:3 in the peripheral retina (Bone et al., 1988:Handelman et al., 1988). These distributions in the retina maysuggest the role of lutein in protecting the rods concentrated inthe peripheral retina (Sommerburg et al., 1999) and zeaxanthinin protecting the cones concentrated in the central retina (Boneet al., 1988).

Variables Affecting Macular Pigment

Macular pigment optical density (MPOD) is a measure oflutein and zeaxanthin in the retina (Handelman et al., 1991).

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Table 2 Variables associated with macular pigment optical density in the retina

Variable # of Subjects Results References

Age n = 28–98 No difference in MPOD Burke et al. (2005)Chen et al. (2001)Ciulla et al. (2001)Chang et al. (2002)

n = 46–217 Significant age-related decline Beatty et al. (2001)Nolan et al. (2004)Bernstein et al. (2002)Liew et al. (2005)Hammond and Caruso-Avery (2000)

Gender n = 63–438 No difference in MPOD Burke et al. (2005)Ciulla et al. (2001)Berendschot et al. (2002)Bernstein et al. (2002)

n = 88–217 Higher MPOD in males Hammond et al. (1996a), Hammondand Caruso-Avery (2000)

Eye Comparison n = 10–46 No difference in MPOD Hammond and Fuld (1992), Beattyet al. (2001)

n = 2 Higher MPOD in left eye Landrum et al. (1997)Iris Color n = 63 No difference in MPOD Bernstein et al. (2002)

n = 217–280 Light irises had lower MPOD thandark irises

Ciulla et al. (2001), Hammond andCaruso-Avery (2000)

Smoking n = 280 No difference in MPOD Ciulla et al. (2001)n = 6174–21,157 Smokers have increased risk of

developing AMDChristen et al. (1996), Vingerling

et al. (1996)n = 15–217 Smokers had lower MPOD and lower

serum and plasma antioxidantconcentrations

Hammond et al. (1996b), Dietrichet al. (2003), Polidori et al.(2003),Hammond and Caruso-Avery(2000)

Obesity n = 98–690 High BMI and body fat % associatedwith low MPOD associated withlow MPOD

Burke et al. (2005), Nolan et al.(2004), Hammond et al. (2002)

n = 261 High BMI and waist circumferenceassociated with increasedprogression of AMD

Seddon et al. (2003)

Heritability n = 150 MOPD correlated highly inmonozygotic twins

Liew et al. (2005)

n = 20 50% of monozygotic twin pairs haddifferences in MPOD

Hammond et al. (1995)

Dietary intake n = 19–280 Significant positive associationbetween lutein and zeaxanthinintake and MPOD

Ciulla et al. (2001), Burke et al.(2005), Bone et al. (2001)

Serum Lutein and Zeaxanthin Concentrations n = 4 No association between serumconcentrations and MPOD

Nolan et al. (2006)

n = 28–88 Significant positive associationbetween serum concentrations andMPOD

Ciulla et al. (2001) Hammond et al.(1996a) Bone et al. (2001)

There are many different factors that may influence MP lev-els in individuals. It is possible that these factors also affectlutein and zeaxanthin metabolism, and therefore are importantconsiderations, which are summarized in Table 2.

Since increasing age has been proven as a risk factor forthe development and progression of AMD, it is of interest toknow if MP declines with age. More solid findings are requiredon age-related MP. Studies need to measure MPOD in subjectswith AMD who are generally older and compare with healthysubjects of the same age to examine differences in MPOD. Fewstudies have measured the MPOD of subjects with AMD.

Few studies attempted to investigate if MP differs betweenright and left eyes. There is likely no significant difference be-tween the right and the left eyes of healthy subjects thereforebiochemical and electrophysiological measurements in one eyeaccurately represent both eyes. With regard to subjects withAMD, it may be important to measure both eyes, as there maybe significant differences between one eye compared to the pre-dominantly affected eye.

Light-colored irises transmit 100 times as much light thanthat of dark brown irises (Snodderly, 1995). It may be expectedthat light-colored irises have lower MPOD and therefore are

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more susceptible to light damage. MP density was 18% lowerin subjects with light-colored irises compared to dark-coloredirises, blue-grey < green-hazel < brown-black (Ciulla et al.,2001; Hammond and Caruso-Avery, 2000). The relationshipbetween the iris color and the risk of developing AMD shouldalso be examined.

Accumulated oxidative stress to tissues due to cigarettesmoking may increase the risk of developing neovascular AMD(Hammond et al., 1996c; Vingerling et al., 1996). It is difficultto generalize findings because the amount of cigarettes and fre-quency of smoking vary dramatically in studies. In general, moststudies are finding negative correlations between smoking andMPOD as well as serum concentrations. It has been proventhat smoking is a risk factor for the development of AMD(Vingerling et al., 1996; Guymer and Chong, 2006; Christenet al., 1996). Studies have found that concentrations of antioxi-dants are lower in smoking subjects compared to non-smokingsubjects and that smoking cessation raises plasma antioxidantconcentrations.

Metabolic changes associated with being overweight orobese may contribute to lower carotenoid concentrations andMPOD (Facchini et al., 2000). The largest fractions of luteinand zeaxanthin are stored in adipose tissue therefore higherbody fat percentage and BMI may be expected to influence reti-nal lutein and zeaxanthin (Hammond et al., 2002). Obesity mayalso be associated with reduced antioxidant defense mechanisms(Trevisan et al., 2001). Johnson (2005) noted that increased adi-posity may be due to one of the following mechanisms: adiposetissue acting as a “sink” for lutein and zeaxanthin; increasedoxidative capacity; increased inflammation; or increased LDL-to-HDL ratio. Overall, obese subjects tend to have lower retinallutein and zeaxanthin. This may be related to lower dietary in-take of carotenoids or competition between adipose and retinaltissues for the uptake of lutein and zeaxanthin, resulting in lessincorporation into the retina. Although adipose tissue containslarge amounts of lutein and zeaxanthin, studies are showing thatthese high quantities are not reflected in retinal tissues, whichis interesting. Further research should focus on the transport oflutein and zeaxanthin from adipose tissue to serum and retinaltissues. Future studies should also focus on the percentage ofobese subjects that have AMD. Our population has a high rateof obesity, a high intake of saturated and trans fats, and a low in-take of fruits, vegetables, and whole grains (all primary sourcesof lutein and zeaxanthin).

Serum carotenoid concentrations are inversely associatedwith type 2 diabetes and impaired glucose metabolism (Coyneet al., 2005). Cataracts, retinitis pigmentosa, diabetic retinopa-thy, hyperlipidemia, hypercholesterolemia, atherosclerosis, andother conditions that may contribute to oxidative stress or theproduction of reactive oxygen species in the body may be as-sociated with AMD (Paolisso and Giugliano, 1996). Also, type2 diabetes is often associated with higher BMI and body fatpercentage. Researchers should investigate if those with type 2diabetes have lower MPOD which is related to having a higherBMI.

Dietary intake in the form of whole foods or supplementa-tion indicates that serum lutein and zeaxanthin concentrationsare affected as well as MPOD. Dietary intake of carotenoid-containing foods may reflect fluctuations in serum concentra-tions but not MPOD (Nolan et al., 2006). This may provide anexplanation for why some short-term supplementation studiesmay only see changes in serum concentrations and little effecton MPOD.

Lutein and Zeaxanthin Functions

The structural and functional characteristics of the retinarespond to the light environment. There are two different the-oretical mechanisms of light induced retinal damage. One isrhodopsin-mediated, since elevated rhodopsin levels correlateto increased damage susceptibility (Noell, 1980). Rhodopsinis responsible for the production of photoreceptor cells and isextremely sensitive to light. The reason is that the action spec-trum of light damage coincides with the absorbance spectrumof rhodopsin. The other is lipid-mediated, since lipid is pho-tooxidized and produces peroxides causing the lesions of theretina (Wiegand et al., 1986). The involvement of lutein andzeaxanthin is protection against photo-induced damage by act-ing as antioxidants and shielding potentially harmful short-waveradiation by acting as blue light filters.

Antioxidant Function

The retina is susceptible to oxidative stress because of itshigh demand for oxygen, the high proportion of polyunsatu-rated fatty acids (PUFA), and aerobic metabolism. Docosahex-anoic acid (DHA, C22:6n-3) makes up approximately 50% ofthe vertebrate rod photoreceptor phospholipids (Stone et al.,1979). The rod outer segments have a high concentration oflong-chain PUFA (Fliesler and Anderson, 1983) accounting forapproximately 50% of the lipid bilayer. They are susceptible tofree radical damage because their conjugated double bonds aresources of hydrogen atoms. The retina is also rich in antioxidantenzymes and has a high capacity for scavenging free radicals(Dasch et al., 2005). Reactive oxygen intermediates, such asfree radicals, hydrogen peroxide, and singlet oxygen, are by-products of oxygen metabolism (Beatty et al., 2000). There aremany different conditions associated with oxidative injury, in-cluding aging, diabetes, atherosclerosis, and retinopathy (Beattyet al., 2000). Lutein and zeaxanthin have polar end groups thatprotrude from the lipid cell membrane and interact with radicalsoutside the membrane (Britton, 1995) making them effective an-tioxidants by reducing the amount of short-wave light reachingthe photoreceptor outer segments (Snodderly et al., 1984). Lightdamage to the retina may stimulate peroxidation of PUFA in themembrane (Anderson et al., 1984), which may result in lossof membrane function and structural integrity (Anderson andKrinsky, 1973; Arstila et al., 1972). Evidence shows protective

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effects of lutein and zeaxanthin against uv-induced oxidativedamage (Sujak et al., 1999), lipid peroxidation, quenching sin-glet oxygen (Bone et al., 2003, Sujak et al., 1999), reducinginflammatory response (Stahl and Sies, 1993), and filtering bluelight (Bone et al., 2003).

Oxidative processes may also increase the concentration oflipofuscin (LF) in the retinal pigment epithelium, which phago-cytes continuously shedding photoreceptor outer segment. Ex-cessive accumulation of LF may interfere with RPE cell func-tions through free radical generation (Boulton et al., 1993) pos-sibly causing cell death. Antioxidants lutein, zeaxanthin, ly-copene, and α-tocopherol may significantly reduce LF forma-tion. Antioxidant deficiency has been shown to accelerate LFbuildup in the RPE (Handelman and Dratz, 1986) but it is un-clear if its composition is similar to the LF that accumulatesduring aging or if it contributes to AMD.

Filtering of Blue Light

There is a growing body of evidence that lutein and zeaxan-thin in the retina may inhibit blue light damage by reducing theintensity of light reaching the macula lutea. The wavelengths oflight that damage the retina are between 400–500 nm, where MPabsorbs most strongly. The absorbance maximum of lutein andzeaxanthin is between 445 and 472 nm, therefore they absorbthe radiation and lower the intensity of blue light passing themembrane (Junghans et al., 2001). This may retard photooxi-dation, therby reducing the formation of harmful LF (Junghanset al., 2001). The molecular structure of lutein and zeaxanthinabsorbs light by having nine conjugated double bonds (Krinskyet al., 2003). Thus, PUFA-enriched photoreceptors may be pro-tected from light by these molecules. Junghans et al. (2001)found that the filter effects in order of efficiency were lutein >

zeaxanthin > β-carotene > lycopene. Lutein was found to havea greater filtering efficacy than zeaxanthin and it is suggestedthat different filter effects may be due to their orientation withinthe lipid membranes.

AGE-RELATED MACULAR DEGENERATION

Classification and Clinical Signs

With advancing age RPE cells become less efficient. RPEcells play a central role in the retina by forming the outer blood-retinal barrier and supporting the function of the photoreceptors.The retina and RPE are the areas where the greatest percent-age of rod photoreceptors are lost during the aging process,and therefore are vulnerable to degeneration. RPE and photore-ceptors (rods and blue light-sensitive cones) are most affected.With declining RPE function, the retina can no longer receiveits proper nourishment and accumulateswaste material, whichleads to amorphous deposits termed drusen.As RPE cells slowlydegenerate and over time, central vision is lost (Hyman, 1992).

Nowak (2006) describes molecular and cellular events thathelp to further understand the pathogenesis of AMD. AMDis associated with abnormalities seen in photoreceptors, RPE,Bruch’s membrane, and choriocapillaries. The impairment ofRPE cell functions is an early event that leads to clinicallyrelevant changes in AMD. As RPE progressively degenerates,progressive irreversible degeneration of photoreceptors results.The two forms of AMD, the dry form (non-exudative, atrophic)and the wet form (exudative, neovascular), are associated withlipofuscinogenesis, drusogenesis, inflammation, and neovascu-larization, in addition to genetic predispositions. The dry formis characterized by degeneration of RPE and photoreceptors.The wet form is linked to choroidal neovascularization withbleeding or fluid leakage, eventually resulting in loss of centralvision. Clinical features for both types include the presence ofdrusen, and hypo and/or hyperpigmentation of RPE (Algvereand Seregard, 2003: Bressler et al., 1994). Degeneration of theretina and RPE in the macula may lead to AMD (Landrum andBone, 2001). Geographic atrophy progresses slowly over manyyears until legal blindness occurs (Chopdar et al., 2003). Whenthe loss of short-wave sensitivity is more pronounced, higherconcentrations of MP may retard the loss (Hammond et al.,1998).

Prevalence

Several population-based studies have estimated the preva-lence of AMD in the general population. The Rotterdampopulation-based study (1990–1993) in the Netherlands deter-mined the prevalence of age-related maculopathy (ARM), a dis-order of the macular area, in 6251 participants ages 55–98, usingthe International Classification System for AMD. The preva-lence of at least one drusen of 63 microns or larger increasedfrom 40.8% in those between the ages of 55–64 to 52.6% inthose 85 years or older. The prevalence of atrophic or neovas-cular AMD in this population was 1.7% and increased stronglywith age. The 14–year incidence of ARM lesions and visionloss was determined in the population-based cohort study in theCopenhagen City Eye Study. Those between the ages of 75–80years had higher incidences of medium or large drusen (≥125microm), soft drusen, pigment abnormalities, pure geographicatrophy, and exudative ARM than those ages 60–64 (Bush et al.,2005). The Beaver Dam Eye Study found associations betweenthe 5 year incidence and progression of ARM age, and sex.Women 75 years or older had a 2.2 times higher incidence ofARM compared to men of the same age. Eyes with soft drusenor retinal pigment abnormalities at baseline were at greater riskof developing AMD (Klein et al., 1997). The 10 year incidenceof early ARM was 12.1% and late ARM was 2.1%. Those 75years and older were 14 times as likely to develop early ARMthan those 43–54 years of age and the incidence of early ARMwas 2 times as likely in women than in men in the same agegroup (Klein et al., 2002).

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Risk Factors

Many factors may increase one’s risk of developing AMD.Proven risk factors include age, family history, and smoking,but cigarette smoking is the only proven modifiable risk factorfor AMD (Guymer and Chong, 2006). Studies have identifiedthat the progression of AMD is strongly dependent on age (vanLeeuwen et al., 2003; Bush et al., 2005; Klein et al., 1997; Kleinet al., 2002) and sex (Klein et al., 1997; Klein et al., 2002). In-dividuals 75 years and older had a higher incidence of medium-large drusen and women had a higher incidence of ARM thanmen. Additional population-based cohort studies are needed toverify that incidence and progression rates may be greater inNorth American populations in comparison to European pop-ulations (Vingerling et al., 1995). More research is needed onmodifiable risk factors and if low serum or retinal concentrationsof lutein and zeaxanthin contribute to an increased risk.

LUTEIN AND ZEAXANTHIN INTAKE

There have been many studies examining the effect of luteinand zeaxanthin supplementation (both in whole food and sup-plementation form) on serum concentrations, MPOD, and rela-tionship to AMD.

Food Form of Lutein and Zeaxanthin

Healthy Subjects

Hammond et al. (1997a) measured MP in 13 healthy subjectsbetween the ages of 30 and 65 over the course of 15 weeks. Tensubjects added spinach and corn to their diet (11.2 mg lutein,0.7 mg zeaxanthin, 5 mg β-carotene). One subject added spinachonly (10.8 mg lutein, 0.3 mg zeaxanthin, 5 mg β-carotene), andtwo added corn only (0.4 mg lutein, 0.3 mg zeaxanthin). Eightsubjects experienced at least a 13% increase in MP densityand increased serum concentrations of lutein, but not zeaxan-thin and β-carotene. The main finding was a significant in-crease in MP density from dietary modification with corn andspinach. Johnson et al. (2000) supplemented 7 patients withcorn and spinach over 15 weeks, measured MPOD, and deter-mined carotenoid concentrations in the serum, buccal mucosacells, and adipose tissue. Serum and buccal cell concentrationsof lutein increased significantly from the baseline during dietarymodification. There was no change in buccal cell and adiposetissue concentrations of zeaxanthin. Lutein concentrations inadipose tissue peaked at week 8. Changes in adipose tissuelutein concentrations were inversely related to the changes inMP density, which may indicate an association between adi-pose tissue and retina in lutein metabolism. After examiningthe cross-sectional relationship among serum, tissue, and di-etary lutein concentrations, anthropometric measures, and MPdensity in healthy adults, significant negative correlations were

found between lutein concentrations in adipose tissue and MPfor women, but a significant positive relationship was found formen. This finding suggests the possibility of gender differencesin lutein metabolism. Overall, the dietary intake of >10 mg oflutein over 15 weeks in healthy subjects is shown to increasemacular pigment density and serum concentrations of lutein.

Subjects with AMD

Richer (1999) found that 92% of male patients with atrophicAMD supplemented with 5 oz of spinach four to seven timesper week over the course of one year had significant short-termimprovements in visual function in one or both eyes (AmslerGrid (87%), Snellen Acuity (71%), Contrast Sensitivity (92%),SKILL (65%), Glare Recovery (69%), Activities of Daily VisionSubscale (60%)).

The Eye Disease Case Control Study Group (1993) evaluatedthe relationship between the dietary intake of carotenoids, vita-min A, C, and E, and the risk of neovascular AMD. Participantsincluded 356 case subjects diagnosed with advanced AMD ages55 to 80, and 520 control subjects from the same geographicareas. Adjusting for risk factors for AMD, those in the highestquintile (6 mg daily) of dietary carotenoid intake had a 43%lower risk for AMD than those in the lowest quintile (0.5 mgdaily). The carotenoids found in dark green leafy vegetableswere most strongly associated with a decreased risk. Vitamin Cand E consumption was not associated with a statistically signif-icant reduced risk for AMD, although higher intakes of vitaminC possibly lower the risk. Overall, a significant association wasfound between high levels of lutein and zeaxanthin (>0.67 uM)in the serum and a reduced risk of advanced neovascular AMD.Lutein and zeaxanthin had the strongest protective effect againstneovascular AMD but lutein and zeaxanthin intake were not an-alyzed separately which does not indicate if one has more of aprotective effect over the other.

In the Third National Health and Nutrition Examination Sur-vey (NHANES III), Mares-Perlman et al. (2001) found that inthe youngest age group (40–59 years), those in high quintilesfor dietary lutein and zeaxanthin had a 90% lower risk for pig-ment abnormalities compared with those in the lowest quintile.The relationship with serum lutein and zeaxanthin did not reachstatistical significance. No relationship of lutein and zeaxanthinin the diet or serum to ARM were found in the overall NHANESIII sample (n = 8222). Mares-Perlman et al. (1995) investigatedrelationships between serum levels of tocopherols, carotenoids,and AMD. The study included subjects with retinal pigmentabnormalities with the presence of soft drusen (n = 127), lateAMD (geographic atrophy (n = 9)), or neovascular or exuda-tive macular degeneration (n = 13). The results showed thataverage levels of individual carotenoids were similar in casesand controls. Lutein and zeaxanthin in the serum were unrelatedto AMD. Mares-Perlman et al. (1996) examined relationshipsbetween dietary intake of zinc, antioxidant nutrients, and earlyand late ARM in 1968 participants aged 43–86 years from theBeaver Dam Eye Study. Although a weak protective effect of

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zinc on the development of some forms of early ARM wasfound, the levels of carotenoids were unrelated to early or lateARM.

In a case-controlled study, Bone et al. (2001) found a sig-nificant relationship between a reduction in risk for AMD withincreased amounts of lutein and zeaxanthin in the retinas when56 donors with and 56 donors without AMD were comparedduring autopsies. Those in the highest quartile of lutein andzeaxanthin had an 82% lower risk for AMD compared to thosein the lowest quartile. Similarily, Landrum et al. (1996) foundthat autopsy eyes had 30% lower concentrations of lutein andzeaxanthin in AMD retinas compared to controls as well asreduced carotenoid levels throughout the retina.

There is little epidemiological data on associations betweenlutein, zeaxanthin, and AMD. In most studies, lutein and zeax-anthin plasma concentrations have been combined but recentlyDelcourt et al. (2006) assessed the associations of plasma luteinand zeaxanthin separately, as well as other carotenoids withthe risk of ARM and cataract in the population-based Patholo-gies Oculaires Liees a l’Age (POLA) Study. Plasma carotenoidswere measured in 899 subjects. Because of the small numberof subjects with late ARM, early and late ARM were pooled inall statistical analyses. The highest quintile of plasma zeaxan-thin was significantly associated with a reduced risk of ARM,nuclear cataract, and any cataract. Compared with subjects withlow levels of zeaxanthin (<0.4 uM), subjects with high levels ofplasma zeaxanthin (>0.9 uM) had a 93% reduced risk of ARM.ARM was significantly associated with combined plasma luteinand zeaxanthin, and was associated with plasma lutein, whereasthe cataract showed no such association. Subjects with high totalplasma lutein and zeaxanthin (>0.56 uM) had a 79% reducedrisk of ARM compared with subjects with low plasma luteinand zeaxanthin (<0.25uM) (Delcourt et al., 2006). These resultsstrongly suggest a protective role of xanthophylls, particularlyzeaxanthin, for protection against ARM and cataract.

Gale et al. (2003) performed a cross-sectional study in theUnited Kingdom and reported a 50% reduced risk of early orlate ARM in subjects with high plasma zeaxanthin (>0.5 uM),compared with subjects having low levels (<0.3 uM). Plasmaconcentrations of zeaxanthin were significantly lower (30 nM)in those with AMD than those without AMD (36 nM). Concen-trations of lutein and lutein plus zeaxanthin were also lower, butnot statistically significant. Of the 380 participants ages 66 to75 years, 20.5% had signs of early or late AMD, 16.8% had earlyAMD, and 3.7% had late AMD, therefore early and late num-bers were combined for analysis. Past studies have analyzed thecombined concentrations of these two carotenoids on plasmalevels, thereby making it difficult to determine if it was lowplasma concentrations of lutein or zeaxanthin that contributedto an increased risk of AMD. This study may carry great im-portance because poor zeaxanthin status may play an even moreimportant role in the pathogenesis of AMD than previously re-ported.

Cardinault et al. (2005) investigated the concentration ofcarotenoids in different lipoproteins in AMD patients (n = 37)

and controls (n = 24). Carotenoid status was not significantlydifferent between early and late stage maculopathy groups.AMD patients had decreased concentrations of lutein, zeaxan-thin, lycopene, α-carotene, β-carotene, and β– cryptoxanthin,yet the decrease was only significant for lycopene. Even if ly-copene is not directly involved in the prevention of AMD, thisstudy suggests it may help preserve available levels of luteinand zeaxanthin.

Overall, dietary supplementation of lutein and zeaxanthin insubjects with AMD is found to influence plasma concentrations.These studies show that >0.5 uM plasma lutein and zeaxanthinconcentrations were associated with at least a 50% reduced riskof early or late ARM and percentage of risk decreases as plasmaconcentrations increased. The influence of visual function wasonly measured in one study, which found significant short-termimprovements.

Supplemental Form of Lutein and Zeaxanthin

Healthy Subjects

Bone et al. (2003) compared the effects of a range of luteindoses (2.4–30 mg/d) and a high zeaxanthin dose (30 mg/d). Therate of increase in MPOD was positively correlated with theplateau concentration of carotenoids in the serum and showedstatistical significance, but not with the pre-supplementation op-tical density. The general trend in all 38 subjects was an increasein serum lutein and zeaxanthin concentrations to a plateau, thenan exponential decline once supplementation ceased. The higherlutein doses resulted in higher plateau concentrations than thelow lutein doses. Most subjects were females under 30 yearsand for this group, there was no significant correlation betweenthe rate of increase in MPOD and serum plateau concentrationsof lutein and zeaxanthin (Bone et al., 2003).

In a study by Landrum et al. (1997), two healthy male sub-jects consumed 30 mg of free lutein/day for 140 days. MPODincreased 39% and 21% in the 2 subjects 20 to 40 days af-ter supplementation and serum lutein concentrations increasedten-fold within about 10–20 days. Week-to-week fluctuations inlutein concentrations were observed, which may be attributedto dietary intake. MPOD remained elevated 40 to 50 days af-ter discontinuing supplementation but serum concentrations de-clined. It is estimated that the 140 day supplementation resultedin a 30–40% reduction in the amount of blue light reachingthe macular photoreceptors, Bruch’s membrane, and RPE, thevulnerable tissues in AMD. Prior to this study, Landrum et al.(1996) found a significant increase in MPOD after 70–80 daysof supplementation.

Five-week lutein supplementation (9 mg/d) was compared in12 young male subjects (26.9 ± 0.8 years) and 17 older malesubjects (67.3 ± 1.1 years) after following a carotenoid-poordiet for three weeks. Elderly subjects had significantly higherfat mass and plasma cholesterol than the young subjects, as wellas lower fat intake. Initial lutein status and basal mucosal cell

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lutein were not significantly different between groups. Follow-ing lutein supplementation, mean plasma lutein concentrations(0.65 umol/L) and BMC lutein concentrations (2.12 nmol/g)significantly increased for both groups, with little difference be-tween the two groups. There was no significant effect on MPODor adipose tissue lutein for either group after supplementation(Cardinault et al., 2003).

The above studies show that supplemental lutein in healthysubjects (9–30 mg/day) for a minimum of 4 weeks demon-strated an overall increase in serum lutein concentrations. Therewere inconsistent findings to support if short-term supplemen-tation increases MPOD, which may indicate that long-term sup-plementation is necessary to elevate MP concentrations in theretina.

Subjects with AMD

The Lutein Antioxidant Supplementation Trial (LAST)double-blind, randomized, placebo-controlled study supple-mented 90 males with atrophic AMD with either 10 mg lutein, 10mg lutein plus formula containing antioxidants, or a placebo, forthe course of one year. Those receiving 10 mg of lutein experi-enced a 36% increase in MP density, and a 43% increase resultedin the group receiving 10 mg lutein plus antioxidants. Visual acu-ity, function, photo-stress recovery, and contrast sensitivity weresignificantly improved (Richer et al., 2004). Though results arebased entirely on a male population, the LAST is an impor-tant follow-up study to Richer (1999) demonstrating that luteinsupplementation with 5 oz spinach 4–7 times/week had short-term improvements in visual function and therefore may have animpact on slowing the progression of atrophic AMD. Dagnelieet al. (2000) supplemented 16 patients with 40 mg lutein/day for2 months followed by 20 mg/day for 4 months and found thatvisual function was significantly improved in all patients withcongenital retinal degenerations. In a non-randomized, compar-ative clinical trial, 30 patients ages 54–84 with early ARM and 8controls were divided into antioxidant groups and no treatmentgroups (Falsini et al., 2003). Antioxidant groups were given15 mg lutein, 20 mg vitamin E, and 18 mg nicotinamide dailyfor 180 days, while others received no supplementation. Retinalfunction was measured using a focal electroretinogram (fERG).At 180 days, the antioxidant group amplitudes significantly in-creased, suggesting improvement in retinal function, whereas nosignificant changes occurred in the no treatment groups. Withcontinued supplementation, amplitudes increased from baselineafter 180 days but stabilized at 360 days. With discontinuedsupplementation, amplitudes eventually returned to baseline.Overall, retinal antioxidants may influence short-term signifi-cant improvements in macular function in early ARM patients.

Koh et al. (2004) evaluated the effect of marigold flowers(10 mg/day free lutein) in patients with early ARM. MPOD andplasma concentrations of lutein were measured over 18 to 20weeks in 7 ARM patients and 6 controls ages 58 to 81. Plasmalutein concentrations increased six-fold in ARM patients, andseven-fold in controls. Plasma lutein concentrations declined to

baseline levels 8–9 weeks after supplementation ceased. MPODincreased from 0.24 to 0.31 in ARM patients with no statisticallysignificant difference from eyes without ARM. These results in-dicate that ARM patients may not malabsorb lutein, and diseasedmacula may accumulate and stabilize lutein and/or zeaxanthin.

Bernstein et al. (2002) compared MP levels in 64 subjectswith AMD to 138 normal subjects. AMD subjects who did notregularly consume lutein or zeaxanthin supplements had 32%lower macular carotenoid concentrations than age-matched con-trols and significantly higher MP densities among AMD sub-jects compared to the control subjects not receiving supplemen-tation. AMD subjects who had consumed lutein supplements(≥4 mg/day) for at least three months after diagnosis of AMDhad macular carotenoid levels considered normal for their age,and levels were significantly higher than AMD subjects notconsuming lutein supplements. Usual dietary intake was not as-sessed and therefore is unknown if lower MP levels in AMDsubjects were a result of diet or other factors. The results ofthis study do indicate that low MP may present a risk factor forAMD.

Potentially only ongoing supplementation may prove to havebeneficial effects in AMD subjects as supplementation studiesfind that serum concentrations reached a plateau and returned tobaseline after supplementation ceased. Short-term supplemen-tation may result in short-term improvements in AMD patientsbut further long-term studies are needed to support the thera-peutic effects of lutein and zeaxanthin. Additional studies areneeded to support the recommended amount of lutein and/orzeaxanthin and length of supplementation that would have apreventative and protective effect on AMD. Table 3 illustrates asummary of various levels of lutein and/or zeaxanthin and theresulting effects that have been reported.

Together these studies show that low levels of lutein (2–4 mg/d) may have no affect on decreasing the progression orrisk of AMD. Potential benefits from supplementation wereshown with intermediate levels of lutein (10–15 mg/d) as wellas high levels (>30 mg/d). Plasma concentrations increased withsupplementation of at least 5 mg lutein and 0.3 mg zeaxanthin.As the doses of lutein and zeaxanthin increased, so did plasmaconcentrations, suggesting a directly proportional relationship.

Supplementation in Animals

There are few animal studies, primarily because carotenoidabsorption is relatively poor in rats, mice, hampsters, as well aschicks, rabbits, pigs, and sheep (Wang, 1994).

Toyoda et al. (2002) studied the carotenoid composition ofretina, serum, liver, and fat in cone dominant quail to see ifdietary zeaxanthin alters zeaxanthin or lutein concentrationsin these tissues. Over a six-month period, quails were fedeither a commercial turkey diet, a carotenoid-deficient diet,or a carotenoid-deficient diet supplemented with zeaxeanthin(35 mg/kg food). The retina accumulated zeaxanthin, lutein, andcryptoxanthin, and preferentially absorbed zeaxanthin. Lutein

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Table 3 Effect of dietary intervention with lutein and/or zeaxanthin on progression of age-related macular degeneration.

Lutein and Zeaxanthin Intake Effect on AMD, MPOD,Stage of Disease or Concentrations or Serum Concentrations

Early ARM 5 oz spinach (∼35 mg/d) ↑visual acuity,-Soft distinct drusen, (≥63 um <125 um) ↑contrast sensitivity- Hyperpigmentation 15 mg/d ↑retinal function- Hypopigmentation

20 mg/d Plasma L ↑ (6-fold), MPOD ↑ to 3.1Plasma Z > 0.5 uM 50% reduced riskPlasma Z > 0.9 uM 93% reduced riskPlasma L and Z > 0.56 uM 79% reduced riskL (5.22 mg/d) and Z (0.32 mg/day) 2 X higher median serum concentrations

Dry/Atrophic 10 mg/d 36% ↑ in MPOD,-Soft distinct or indistinct drusen (125 um–249 um) ↑visual acuity,- Geographic atrophy ↑contrast sensitivity- Retinal pigment abnormalities 9 mg/d Plasma L ↑ (0.65 umol)

30 mg/d MPOD ↑ by 1.13 mAU/day,serum L ↑ (10-fold),30–40% blue-light ↓

Late/Exudative/Neovascular Plasma Z > 0.5 uM 50% reduced risk- Soft indistinct drusen (≥250 um) Serum L and Z > 0.67 uM Reduced risk of advanced- Central geographic atrophy- Choroidal neovascularization neovascular AMD- RPE detachment- Subretinal hemorrhage >6 mg carotenoids 43% reduced risk- depigmentation/hyperpigmentation

was preferentially absorbed by the liver and fat. Different con-centrations and preferential uptake of xanthophylls in tissuesmay indicate the presence of different xanthophyll-binding pro-teins, shared uptake mechanisms, or specific roles in differenttissues, which is not yet known. Dorey et al. (2005) found thatfemale quail had 5–10 times higher serum lutein and zeaxanthinthan males, as well as higher lens zeaxanthin after zeaxanthinsupplementation. This study suggests that responses to zeaxan-thin were sex-related.

Rhesus monkeys on xanthophyll-free diets were supple-mented with lutein or zeaxanthin to see the accumulation ofserum carotenoids and MP over time. Monkeys were fed ei-ther lutein, zeaxanthin (2.2 mg/kg/d), or a stock diet for 24–56weeks. No serum lutein or zeaxanthin and no MP were de-tectable in monkeys on xanthophyll-free diets. Lutein or zeax-anthin concentrations increased rapidly over the first 4 weeksand stabilized around 16 weeks. MPOD increased to a steadylevel by 24–32 weeks (Neuringer et al., 2004) showing a sig-nificant dietary xanthophyll impact on MP. In the same sample,Leung et al. (2004) determined the effect of age, n-3 fatty acids,lutein, and zeaxanthin on RPE. They found that supplementalxanthophylls interact with n-3 fatty acids to produce asymme-tries in the RPE and concluded that xanthophylls and n-3 fattyacids are both essential components for the development andmaintenance of normal distribution of RPE cells. Johnson et al.(2005) found that lutein and meso-zeaxanthin were incorpo-rated into retinas of monkeys after being supplemented withlutein. All zeaxanthin, but not meso-zeaxanthin accumulated inthe retinas of monkeys supplemented with zeaxanthin, suggest-ing that lutein is the precursor to meso-zeaxanthin. However,the accumulation of these compounds in the retina did not pro-

duce consistent effects on S-cone or rod cell densities (Leunget al., 2005). Further studies are necessary to determine thedefinite effect of supplementation on retinal function by usingelectroretinograph (ERG).

FUTURE PROSPECTS

Potential as Functional Nutrients

Many studies have examined the potential health benefitsof lutein and zeaxanthin beyond basic nutrition, including areduced risk of AMD. Semba and Dagnelie (2003) suggestthat although lutein and zeaxanthin are not essential nutrients,they may be conditionally essential for eye health. The cri-teria for conditional essentiality are a decline of the plasmalevel of the nutrient into the subnormal range, the appearanceof chemical, structural, or functional abnormalities, and correc-tion of both of these by dietary supplementation of the nutrient(Harper, 1999). Any health claims should be based on repli-cated, randomized, placebo-controlled, intervention trials usinghuman subjects (Hasler, 2002). The consumption of lutein andzeaxanthin-containing foods such as spinach, kale, and collardgreens, or dietary supplements may reduce the risk of AMDbut the strength of evidence based on an intake of 6 mg/d isreported to be weak to moderate in epidemiological studies.More evidence is needed at higher levels of supplementation.An FDA-approved health claim is generally supported by ≥24well-designed clinical trials (Hasler, 2002) and there are cur-rently few clinical studies to support a claim that lutein and

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zeaxanthin can decrease the risk of developing AMD (Hasler,2002).

Future Research

Lutein and zeaxanthin have been studied extensively in sup-plemental form. Increases in MPOD and serum concentrationshave resulted from supplementation (Bone et al., 2003; Landrumet al., 1997; Hammond et al., 1997). Epidemiological studiessuggest subjects with high dietary intakes or high serum con-centrations of lutein and zeaxanthin have a reduced risk of AMD(Gale et al., 2003; Snellen et al., 2002, Eye Disease Case-ControlStudy Group, 1993, 1994), therefore serum concentrations oflutein and zeaxanthin are important outcomes to measure.

Few studies have measured the potential benefits of supple-mentation on retinal function. Furthermore, retinal function hasbeen assessed using traditional methods, such as the AmslerGrid. Future studies could utilize electroretinography to deter-mine the integrity of rod and cone specific function for theeffectiveness of supplementation. Preserving or improving reti-nal function may delay the onset of AMD and is therefore anessential outcome to measure.

There is increasing evidence for a beneficial role of luteinin eye health but there is concern that lutein supplementationmay not provide the same benefit as lutein found naturally infoods (Mares-Perlman and Klein, 1999). Few studies have sup-plemented using egg yolk, which is a highly bioavailable sourceof lutein and zeaxanthin (Handelman et al., 1999). The highestconcentration of lutein and zeaxanthin, expressed as mole%,is egg yolk, with 89 mole% lutein and zeaxanthin combined(O’Connell et al., 2006). Egg yolk contains 0.3 mg lutein and0.5 mg zexanthin (Monograph, 2005). It is well documentedthat increasing dietary consumption of foods high in lutein andzeaxanthin increases serum concentrations.

The impairment of RPE cell functions is an early eventthat leads to clinically relevant changes in AMD. It is there-fore important to study the effects of supplementation on sub-jects with clinical signs of early stage AMD. The effect ofegg yolk supplementation on the progression of early AMDis not known, therefore presenting an area of opportunity forresearch.

Recommendations

Dietary intake of foods containing lutein and zeaxanthinshould be emphasized for all individuals, as foods high in thesexanthophylls are also high in antioxidants and other nutrients.Those diagnosed with AMD may benefit from dietary interven-tion with lutein and/or zeaxanthin, as disease progression maybe affected. Dietary and lifestyle practices that enhance MP den-sity and may prevent vision loss could potentially improve thequality of life of those living with AMD. Dietary interventionis a cost-effective strategy in the prevention of AMD. Future

research needs to focus where there are deficiencies in research,and where incompatible findings have occurred.

CONCLUSIONS

There is accumulating evidence on the importance of luteinand zeaxanthin in eye health. Stronger evidence is needed tosupport that lutein and zeaxanthin may reduce the risk of devel-oping AMD or slow the progression to late-stage AMD. Associ-ations have been made between MP density, AMD, and relationto gender, age, iris color, smoking, dietary intake, BMI, andthe presence of existing diseases. Lutein and zeaxanthin playimportant roles in absorbing blue light and exhibit antioxidantproperties, which supports their role in preventing degenera-tion of photoreceptors. More research is needed on the presenceof lutein and zeaxanthin in the diet, serum, and tissues in sub-jects with and without AMD. Many studies have drawn parallelsbetween risk for AMD, low dietary intake, and low serum con-centrations of lutein and zeaxanthin. There is a need to betterunderstand lutein and zeaxanthin uptake and tissue distributionmechanisms to show how they accumulate in the retina.

Determining effective dietary or supplemental doses of luteinand zeaxanthin is challenging as there is a lack of long-term sup-plementation studies. Short-term increases in serum concentra-tions and MPOD have been documented but few studies haveexamined the effects on visual function. If lutein and zeaxan-thin have the potential to preserve retinal function, the onset andprogression of AMD may be delayed.

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