Lutein

Pennington Biomedical Research Center

Division of Education
Heli J. Roy PhD Shanna Lundy, BS Phillip Brantley, Director
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Lutein and Zeaxanthin:

Sources
Lutein and zeaxanthin are xanthophyll carotenoids found in
a wide variety of plant foods, especially in dark-green leafy vegetables, such as kale, spinach, turnip greens, and collards

Their concentrations in these plant foods, as well as in

others such as mustard greens, green peas, summer squash, and broccoli are higher than those of beta-carotene concentrations

Also highly concentrated in egg yolks from which they are

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highly bioavailable due most probably to the lipid matrix in which they reside

Content of Lutein + Zeaxanthin in Selected Vegetables

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Lutein + Zeaxanthin Lutein + Zeaxanthin

Food Kale Spinach Turnip greens Collards Mustard greens Parsley, raw Dandelion greens Peas, green, frozen Lettuce, romaine, raw Squash, summer Micrograms/cup 23720 20354 12154 14619 8347 556 4944 3840 1295 4048 Micrograms/100 grams 18246 11308 8440 7694 5962 5560 4709 2400 2313 2249

Lutein + Zeaxanthin Lutein + Zeaxanthin Food Beet Greens Lettuce, green leaf, raw Micrograms/cup 2619 969 Micrograms/100 g 1819 1730

Broccoli
Squash, winter Brussels sprouts Onions, spring or scallions, raw Corn, sweet, yellow, canned Pumpkin

2367
2901 2012 1137 2195 2484

1517
1415 1290 1137 1045 1014

Content of Lutein and Zeaxanthin in Chicken Egg Yolk Lutein Micrograms/ yolk Micrograms/mg cholesterol Micrograms/ 100 g yolk 292 +/- 117 1.19 +/- 0.32 1732 +/- 690 Zeaxanthin 213+/-85 .87+/-.23 1257+/-502 Total 505 2.06 2980

Mean +/- SD values for amounts

Structure
Structures of lutein and zeaxanthin are characterized by the
presence of a hydroxyl group attached to each of the 2 terminal beta-ionone rings in the molecule

These xanthophylls are more hydrophilic than other carotenoids

found in blood and tissues such as the hydrocarbon carotenoids alpha and beta carotene and lycopene

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Roles of Lutein and Zeaxanthin

Research involving cell cultures, animal models, and human
studies has been directed to the potential role of lutein and zeaxanthin in protecting against several chronic diseases, particularly age-related macular degeneration (AMD) and cataract, cancer at various sites, and heart disease and stroke

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Diseases of the Eye

The xanthophylls are uniquely concentrated in the macular
region of the eye (central portion of the retina) with zeaxanthin being the dominant component in the central macula and lutein distributed throughout the retina

Lutein and zeaxanthin are the only carotenoids reported to be

present in the eye lens

There is an inverse relationship between macular pigment

density and lens density, suggesting that the macular pigment may serve as a marker for xanthophylls in the lens
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Age-Related Macular Degeneration (AMD)

AMD is the most common cause of visual
impairment and irreversible blindness among elderly Americans

A number of investigations are looking at the

relationship between lutein and zeaxanthin and AMD.

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AMD
In one case-controlled study examining human
autopsy retinas from 56 donors with AMD and from 56 controls without the disease, Bone et al. found that lutein and zeaxanthin concentrations in 3 concentric regions centered on the fovea were lower, on average, in AMD donors than controls

macula

Also, those in the highest quartile of lutein and

zeaxanthin content in peripheral retina had an 82% lower odds ratio for AMD than those in the lowest quartile.
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Age-Related Macular Degeneration (AMD)

In a study in the Netherlands involving 72 cases and
66 controls, Snellen et al. found that the prevalence rate of AMD in subjects with low lutein was more than twice that in subjects with high intakes

In a cross-sectional study of 380 elderly men and

women in Sheffield, UK, Gale et al. found that plasma zeaxanthin was significantly associated with risk of AMD

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CATARACT
Oxidative damage to lens cell membranes is considered an
important factor in the initiation and progression of age-related cataract and increased lipid peroxidation products have been detected in lens and aqueous humor of patients with cataracts

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CATARACT
The Nurses Health Study found that women with the highest
intakes of lutein plus zeaxanthin (top 10%) had a 22% reduction in relative risk of cataract severe enough to require extraction as compared to those with poorest intakes (bottom 20%)

Other carotenoids were not associated with cataract extraction

Increased frequency of intakes of lutein-rich spinach and kale

was associated with a moderate decreased risk of cataract extraction
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CATARACT
In a prospective 5 year follow-up, Lyle et al. reported those in the
highest quintile of lutein intake 10 years prior to study enrollment were 50% less likely to have an incident nuclear cataract as those in the lowest quintile of intake

Intakes of spinach in the highest compared to the lowest quintile

during the year preceding baseline was related to lower risk for nuclear cataract

In persons <65, intake of eggs in the highest compared to the

lowest quintile was markedly related to lower risk for nuclear cataract
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CANCER
Xanthophylls may possess antimutagenic and anticarcinogenic
properties and play a role in the health of body tissues other than the eye as suggested by research studies related to carcinogenesis and the risk for cancer

In humans, plasma lutein has been inversely associated with

cytochrome CYP1A2 activity, a hepatic enzyme responsible for the metabolic activation of a number of putative human carcinogens
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CANCER
In animal models of colon and breast cancers, lutein has been
demonstrated to exhibit chemopreventative activity

The immuno-modulatory action of dietary lutein has been

demonstrated in domestic cats and dogs.

In mice fed lutein-containing diets, lutein uptake by the spleen

suggests a role for lutein in modulating immunity

It has been shown to enhance antibody production in response to Tdependant antigens in spleen cells in vitro, as well as in mice in vitro.
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Breast Cancer Breast Cancer

The associations of xanthophyll intake or serum levels with
breast cancer risk in humans have been investigated in many epidemiological studies and the results have been inconsistent

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Breast Cancer
Zhang et al reported that during a 14 year follow-up of a large
prospective study of 82,234 female nurses who were 34-59 years of age at baseline, 2,697 developed invasive breast cancer

Researchers found that prediagnostic intake of lutein plus

zeaxanthin was inversely associated with breast cancer risk in premenopausal but not in postmenopausal women.

The inverse association for increasing quintiles of intake and

breast cancer risk was stronger among premenopausal women with a positive family history of breast cancer
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Breast Cancer
In contrast to the first study, Cho et al. found no association of
lutein plus zeaxanthin intakes and breast cancer risk in a prospective cohort of 90,655 female nurses who were 25-42 years of age at baseline

During this 8 year follow-up, 714 incident cases of invasive

breast cancer were documented

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Breast Cancer
Although human studies regarding the relationship of lutein and
zeaxanthin with breast cancer have been inconclusive, studies in human mammary cells and in animal models support a protective role of xanthophylls

Also, low levels of dietary lutein from marigold extract was found to
have: enhanced lymphocyte proliferation, lowered lipid peroxidation, lowered mammary tumor incidence, increased tumor latency, and suppressed tumor growth in susceptible mice

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Lung Cancer
The Alpha-Tocopherol, Beta-Carotene Prevention (ATBC) Study:

Holick et al. reported that of 27,084 male smokers who

completed a dietary questionnaire at baseline, 1,644 developed lung cancer during the 14 year follow-up

Men in the highest quintile of lutein plus zeaxanthin intake at

baseline had a 17% lower risk of lung caner compared to men in the lowest quintile of lutein plus zeaxanthin intake
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Lung Cancer
De Stefani et al. reported that in a case-controlled study in
Uruguay involving 541 cases of lung cancer and 540 hospitalized controls, retrospective dietary information obtained for the year before onset of symptoms (for cases) or the year before study enrollment (for controls) showed that those in the highest quartile of lutein intake had a 43% lower risk of lung cancer

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Colorectal Cancer
In a large case-controlled study, Slattery et al. investigated associations of
dietary lutein and the risk of colon cancer in 1,993 subjects with first primary incident adenocarcinoma of the colon and 2,410 population-based control subjects

An inverse association between dietary lutein intake during the 2 year prior
to diagnosis or study admission versus colon cancer was detected

A stronger inverse association was observed in persons in whom cancer

was diagnosed before they were 67 years of age and among those with tumors located in the proximal segment of the colon
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Colorectal Cancer
Animal studies lend support for a chemopreventative
role of lutein against colon carcinogenesis

The formation of colonic aberrant crypt foci in rats

that received intrarectal doss of N-methylnitrosourea was inhibited by a daily gavage of lutein

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Prostate Cancer
Although lycopene and all trans beta-carotene are the
predominant carotenoids in human prostate, lutein and zeaxanthin are consistently detectable at about half their level, .30 and .24 nmol,g, respectively, in this tissue

Several large prospective studies have reported that dietary

intake or circulating levels of the xanthophylls are unrelated to risk of prostate caner; however, other studies have reported a reduction in risk associated with xanthophylls
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Prostate Cancer
Generally, studies indicating inverse relationships between
prostate cancer and lutein intake were small and less frequently occurring that those finding no associations between the two

It is also worth noting that Hall et al. found that lutein and
zeaxanthin were less effective than beta-carotene, canthaxanthin, or lycopene in inhibiting the growth of human DU145 prostate cancer cells
Prostate Gland Cancerous nodule

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Urethra

Upper Aerodigestive Tract Cancers

A 5 year case-controlled study in northern Italy conducted by
Franceshi et al. showed that lutein + zeaxanthin intake was significantly inversely associated with risk of esophageal cancer

Zhang et al. examined 95 incident cases of adenocarcinoma of

the esophagus and gastric cardia (ACEGC) and 132 controls and found high dietary lutein associated with a decreased risk of ACEGC
Esophagus

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Ovarian Cancer
Results seem to be more consistent with inverse associations
between lutein and ovarian cancer

A case controlled study conducted by Bidoli et al. showed that

those in the highest quintile of lutein plus zeaxanthin intake had a 40% lower risk of developing ovarian cancer than those in the lowest quintile of intake

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Kidney Cancer
Yuan et al. found strong inverse associations between the intake
of cruciferous and dark green leafy vegetables and cancer risk

A significant inverse association of lutein intake with cancer

risk was also observed

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Bladder Cancer
Very mixed results have been observed
Several studies have failed to find a significant association
between lutein intake with the risk of bladder cancer

And although the Health Professionals Follow-up study did find a

significant inverse association with the risk of bladder cancer in lutein-rich cruciferous vegetables, this only held true for broccoli consumption, not for kale or Brussels sprouts
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Gastric Caner
Several studies indicate no association between lutein and the
development of gastric carcinoma

Interestingly, one study suggests a potential adverse association

between xanthophylls and gastric cancer, finding that high baseline serum concentrations of lutein plus zeaxanthin were directly associated with incident gastric non-cardia adenocarcinoma

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Skin Cancer
Animal studies have shown that lutein may have a
protective role against light-induced skin damage

In rat studies, evidence has been reported that

xanthophylls play a protective role against incident squamous cell carcinoma of the skin, however this has not held true in human studies

Possibly due to the fact that in humans it has been found that

only very low amounts of xanthophyll esters are present in the skin compared to the concentrations of beta-carotene and lycopene in this tissue
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Coronary Heart Disease

That lutein may have a protective effect against the progression
of early atherosclerosis is supported by epidemiologic data from 2 studies which related circulating xanthophylls with carotid artery intimamedia thickness (IMT)

In a prospective study of a random sample of 480 participants

from the Los Angeles Atherosclerosis Study cohort with no history of heart attack, angina, revascularization or stroke, it was found that on average, for every 1 umol/L increase of plasma lutein or zeaxanthin, IMT progression was reduced by 3.2 or 4.7 um/18 mo, respectively
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Coronary Heart Disease

Another approach to determining the relationship between
xanthophylls and risk for heart disease employs measures of oxidative stress as intermediary biomarkers

In the plasma of 30 patients with congestive heart failure, it was

found that lutein was significantly lower and malondialdehyde, a product of lipid peroxidation, was significantly higher as compared to 55 controls

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Stroke
Among the ATBC cohort (n=26,593) of male smokers without a
history of stroke, Hirvonen et al. observed a significant inverse relationship between intake of lutein plus zeaxanthin and risk for subarachnoid hemorrhage after a 6.1 year follow-up

In plasma, an inverse correlation between lutein and

malondialdehyde in 28 ischemic stroke patients in comparison to matched controls was found by Polidori et al

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Stroke
Lower lutein and higher malondialdehyde concentrations in
plasma were observed in patients with poor early phase recoveries relative to those who were functionally stable

Suggesting that lutein may modulate clinical outcomes following

ischemic stroke

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References
http://www.jacn.org/cgi/content/full/23/suppl_6/567S

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