Plasma Lutein Concentrations Research Articles

Effect of antioxidants on the oxidative stress in cataract patients

To determine the relationship between oxidative stress and eye disease, and the impact of antioxidant supplementation, forty subjects (50–70 y, F25, M15) were enrolled in a double blinded randomized study. Subjects were randomized to receive either 1) lutein (12 mg) or 2) lutein (12 mg) + green tea extract (200 mg) for 16 wks, and underwent eye examinations before (wk 0) and after supplementation (wk 16). Lutein is present in human lens and macula. Blood samples were collected at 0, 4, 8, 12 & 16 wks and analyzed for antioxidants by HPLC systems, total antioxidant performance by fluorometry, malondialdehyde by an HPLC with a fluorescent detector, 8‐iso‐prostaglandin‐F2α & total hydroxyoctadecadienoic acid (tHODE) by a GC‐MS. Twenty seven subjects (F17, M10) were determined to have cataract at wk 0. In these subjects, tHODE level was significantly higher than the healthy subjects (P<0.05) at wk 0. Lutein supplementation resulted in a significant increase in plasma lutein in cataract patients as early as wk 4 & throughout the study period without any significant change in other antioxidants or oxidative stress biomarkers. Our data suggest that cataract patients were under high oxidative stress and their plasma lutein concentration can be significantly increased by a daily dose of 12 mg lutein, which did not affect overall antioxidant capacity/oxidative status in plasma. (Supported by NEI R03EY015674 & USDA #581950‐7‐707)

Development and validation of a brief food frequency questionnaire for dietary lutein and zeaxanthin intake assessment in Italian women

There is increasing evidence that higher intakes of carotenoids could protect against oxidative and light damage in premature infants and may promote other health benefits in both mothers during pregnancy and lactation and in newborn infants. To develop and validate a brief quantitative food frequency questionnaire (FFQ) aimed at assessing lutein and zeaxanthin intake in women. In this cross-sectional study, estimates of lutein and zeaxanthin intake from the FFQ were compared with a 7-day dietary record and with plasma concentrations of these carotenoids. This primary care study was conducted in Pavia, Italy. Subjects were all female volunteers, aged 20-25 years (mean age 22.7 +/- 2.1 years), university students. Of the 110 women initially recruited, 87 completed diet questionnaires and donated a blood sample. Dietary intake was assessed by the FFQ by interview and 7-day dietary records chosen as a reference standard, using photographic estimations of portion sizes. Plasma concentrations of lutein and zeaxanthin were measured by HPLC. Pearson's correlation coefficient and Bland Altman Regression analysis were used. Mean dietary lutein and zeaxanthin intakes were 1,107 +/- 113 microg/day from the FFQ questionnaire and 1,083 +/- 116 microg/day from the 7 day dietary records. The mean difference in intake assessed by the two methods (-24.5 +/- 38.3 microg/day) did not differ significantly from zero. Dietary intake of lutein and zeaxanthin measured with the FFQ and plasma nutrient concentration among this sample were significantly correlated (r = 0.76, P < 0.0001). Mean plasma lutein and zeaxanthin concentrations were 0.33 +/- 0.09 micromol/l. This FFQ could be used to assess lutein and zeaxanthin intake in adult women.

Human Plasma Levels of Vitamin E and Carotenoids Are Associated with Genetic Polymorphisms in Genes Involved in Lipid Metabolism , ,3

Vitamin E and carotenoids are fat-soluble micronutrients carried by plasma lipoproteins. Their plasma concentrations are governed by several factors, some of which are genetic, but data on these genetic factors remain scarce. We hypothesized that genes involved in lipid metabolism, i.e. the genes implicated in intestinal uptake, intracellular trafficking, and the lipoprotein distribution of lipids, play a role in the plasma concentrations of these micronutrients. To verify this hypothesis, we assessed whether the plasma status of vitamin E and carotenoids is related to genes involved in lipid metabolism. Fasting plasma vitamin E (α- and γ-tocopherol) and carotenoid (α- and β-carotene, lutein, lycopene, β-cryptoxanthin, and zeaxanthin) concentrations were measured in 48 males and 80 females. The following genes were genotyped [single nucleotide polymorphisms (SNP)]: apolipoprotein (apo) A-IV, apo B, apo E, lipoprotein lipase, and scavenger-receptor class B type I (SR-BI). Plasma α-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV, apo E, and SR-BI. Plasma γ-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and SR-BI. α-Carotene concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. β-Carotene concentrations were different (P < 0.05) in subjects bearing different SNP in apo B and SR-BI. Lycopene concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and apo B. β-Cryptoxanthin concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Plasma lutein and zeaxanthin concentrations did not differ in subjects bearing different SNP. Most of the differences remained significant after the plasma micronutrients were adjusted for plasma triglycerides and cholesterol. These results suggest that genes involved in lipid metabolism influence the plasma concentrations of these fat-soluble micronutrients.

Eggs increase plasma HDL cholesterol and lutein concentrations in overweight/obese men following a carbohydrate restricted diet

Eggs increase plasma HDL cholesterol and lutein concentrations in overweight/obese men following a carbohydrate restricted diet

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

We investigated associations between plasma concentrations of cholesterol and lutein after consumption of eggs. Using a crossover design, 22 postmenopausal women (50–77 y) consumed an egg treatment (640 mg/d additional cholesterol and 600 μg/d additional lutein + zeaxanthin) or a baseline treatment (no additional cholesterol or lutein + zeaxanthin) for 30 d, followed by a 3-wk washout period and the alternate diet. The increases in plasma total cholesterol and lutein due to egg consumption were related (r = 0.48, P < 0.05). There was a positive correlation between LDL size (r = 0.45, P < 0.05), HDL size (r = 0.64, P < 0.01), and plasma lutein, but no relation with the number of LDL or HDL particles. The activities of cholesterol ester transfer protein and lecithin cholesterol acyltransferase, although important in the exchange of cholesterol among lipoproteins, were not associated with changes in plasma lutein. Plasma lutein concentrations observed during the baseline period were a strong predictor of the increase in plasma lutein after egg treatment (r = 0.50 P < 0.05). There was a negative association between the change in lutein due to egg consumption and BMI (r = −0.40, P < 0.06) and waist circumference (r = −0.49, P < 0.05). This was particularly evident in individuals with BMI >29. We conclude that the increase in plasma lutein after egg consumption is associated with the change in plasma total cholesterol, but that the effect is diminished by obesity. Lipoprotein size, but not number, also affects plasma response to dietary lutein.

Xanthophyll and Hydrocarbon Carotenoid Patterns Differ in Plasma and Breast Milk of Women Supplemented with Red Palm Oil during Pregnancy and Lactation

Currently limited information exists on how maternal supplementation with provitamin A carotenoids might influence the carotenoid pattern in breast milk during lactation. This study was designed to investigate the effect of maternal red palm oil supplementation ( approximately 12 g/d) throughout the 3rd trimester of pregnancy and the first 3 mo postpartum on carotenoid pattern in both plasma and breast milk. Plasma and breast milk alpha- and beta-carotene concentrations increased in response to red palm oil supplementation and were different (P < 0.001) from the control group at both 1 and 3 mo postpartum. Plasma lutein and zeaxanthin concentrations were reduced (P < 0.001) from pregnancy to 1 mo postpartum and remained stable until 3 mo postpartum. However, breast milk lutein concentrations, expressed per gram of milk fat, increased (P < 0.05) in both groups from 1 to 3 mo postpartum. The results of this study show that there are proportionally more hydrocarbon carotenoids such as alpha- and beta-carotene in plasma than in breast milk, whereas xanthophylls, such as lutein and zeaxanthin, are proportionally more prevalent in breast milk. More importantly, red palm oil supplementation increases the milk concentrations of provitamin A carotenes without decreasing the milk concentrations of xanthophylls. In summary, this study demonstrates that a regulated uptake of polar carotenoids into breast milk exists and that supplementation with alpha- and beta-carotene does not negatively affect this transfer. The mechanisms behind this transport are not fully understood and merit further study.

Hypo- and Hyperresponse to Egg Cholesterol Predicts Plasma Lutein and β-Carotene Concentrations in Men and Women

The purpose of this study was to determine whether the plasma response to dietary cholesterol from eggs is associated with the plasma carotenoid response and whether gender influences the carotenoid response. Using a crossover design, 40 subjects classified as either hyper- (10 men and 10 women) or hyporesponders (10 men and 10 women) to dietary cholesterol consumed an egg (EGG, 640 mg/d additional dietary cholesterol and 600 microg lutein + zeaxanthin) or placebo (SUB, 0 mg/d cholesterol, 0 microg lutein + zeaxanthin and 568 microg beta-carotene) diet for 30 d, followed by a 3-wk washout period and the alternate diet. Plasma concentrations of lutein and beta-carotene after each dietary period were then examined to determine whether the response to carotenoid intake was similar to that seen for dietary cholesterol. After the EGG period, the increase in plasma lutein in female hyperresponders (mean increase +/- SD; 0.32 +/- 0.19 micromol/L) and male hyperresponders (0.26 +/- 0.11 micromol/L) was significantly greater than that of their hyporesponsive counterparts (0.16 +/- 0.18 micromol/L for women and 0.14 +/- 0.11 micromol/L men). Gender was not a significant factor influencing lutein response. Both men and women classified as hyperresponders significantly increased plasma beta-carotene after the SUB period, whereas their hyporesponsive counterparts were not affected. The increase in plasma beta-carotene in female hyperresponders (0.29 +/- 0.48 micromol/L) was significantly greater than that in male hyperresponders (0.07 +/- 0.07 micromol/L). We conclude that plasma responses to cholesterol and carotenoids are related and that gender influences the beta-carotene response to a greater degree than the lutein response.

Plasma kinetics of lutein, zeaxanthin, and 3-dehydro-lutein after multiple oral doses of a lutein supplement

Adequate intake of lutein is postulated to reduce the risk of age-related macular degeneration, but kinetic information for developing a dosing regimen is sparse. The objective was to characterize lutein plasma kinetics in a multiple dosing design and to assess the effects of lutein intake on concentrations of other plasma carotenoids. After a run-in period of 7 d, 19 healthy volunteers were assigned to receive daily oral doses of 4.1 mg lutein (n = 8; group 1) or 20.5 mg lutein (n = 8; group 2) for 42 d or no lutein (n = 3; control group). The supplement contained 8.3% zeaxanthin relative to lutein (100%). The time profiles of plasma xanthophyll concentrations were monitored over the dosing phase, and samples were collected frequently on day 42 and for 24 d after dosing. Average plasma all-E-lutein concentrations increased from 0.14 to 0.52 +/- 0.13 and 1.45 +/- 0.69 micromol/L in groups 1 and 2, respectively. Dose-normalized lutein bioavailability in group 2 was approximately 60% of that in group 1. Kinetic disposition half-life did not differ significantly between groups. On average, dosing for 18 d was required to reach a >90% fraction of the steady state concentration, which is consistent with an effective half-life for accumulation of approximately 5.6 d. Plasma kinetics of all-E-lutein were paralleled by those of all-E-3-dehydro-lutein. Kinetic analysis indicated formation of all-E-3-dehydro-lutein from lutein. Lutein was well tolerated and did not affect the concentrations of other carotenoids. Long-term supplementation with 4.1 and 20.5 mg lutein as beadlets increased plasma lutein concentrations approximately 3.5- and 10-fold, respectively.

Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study

There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18–20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127) ng ml −1 to a peak of 1077 (165) ng ml −1 in ARM patients, and from 152 (57) to 1110 (605) ng ml −1 in control subjects. Mean MPOD had increased significantly from baseline of 0·24 to a peak of 0·31 in ARM sufferers. This mean increment of 0·07 was the same for the age-matched controls (baseline: 0·20; peak: 0·27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM.

Are lutein and zeaxanthin conditionally essential nutrients for eye health?

The carotenoids lutein and zeaxanthin are found in the macula in high concentrations and may play a role in the pathogenesis of age-related macular degeneration (ARMD). Lutein and zeaxanthin may protect the macula and photoreceptor outer segments throughout the retina from oxidative stress and play a role in an antioxidant cascade that safely disarms the energy of reactive oxygen species. Although lutein and zeaxanthin are not essential nutrients, studies are beginning to suggest that they fit the criteria for conditionally essential nutrients. Low plasma lutein and zeaxanthin concentrations or dietary intake are associated with low macular pigment density and increased risk of ARMD. Dietary deprivation of lutein and zeaxanthin in primates causes pathological changes in the macula. Should controlled clinical trials show lutein and/or zeaxanthin supplementation protects against the development or progression of ARMD and other eye diseases, then lutein and zeaxanthin could be considered as conditionally essential nutrients for humans.

Breeding time and sex-specific health status in the barn swallow (Hirundo rustica)

Health status has been hypothesized to be an important factor associated with individual reproductive performance in birds. Sex-specific health status of early- and late-breeding barn swallows (Hirundo rustica) was studied during the prelaying and brood-rearing periods to test the prediction that early-arriving birds are in better health status than late-arriving individuals. During prelaying, early breeders (of both sexes) had lower leukocyte counts than late breeders, and males had fewer lymphocytes, heterophils, and total white blood cells than females. Sex differences in health status at arrival disappeared during brood rearing, owing to an increase in leukocytes of early-breeding males and a decrease in leukocytes of late-breeding females. Late-breeding males had a higher plasma lutein concentration than early breeders during brood rearing, and the lutein concentration increased significantly for both sexes between prelaying and brood rearing. T-cell immune response of late-breeding females was stronger than for early breeders. These results are consistent with the prediction that health status of breeding barn swallows affects individual performance in terms of breeding time. Individuals differing in quality experience different costs and benefits of early breeding, and these costs and benefits are sex specific.

Carotenoid composition of human milk during the first month postpartum and the response to β-carotene supplementation , ,

Information is lacking regarding normal changes in milk carotenoid concentrations in healthy, well-nourished women during the first month of lactation. This study investigated milk carotenoid concentrations during days 4-32 postpartum and assessed the effects of maternal beta-carotene supplementation. Subjects (n = 21; aged 19-39 y) were randomly assigned to receive beta-carotene (30 mg/d) or placebo from days 4 to 32 postpartum. Each subject provided 8 diet records and 8 milk samples during the study. Diet records were analyzed for energy, macronutrients, vitamins A and E, and carotenoids. Milk samples were analyzed with HPLC for concentrations of carotenoids, retinol, and alpha-tocopherol. Data were analyzed by using repeated-measures analysis and orthogonal contrasts. No significant differences in average dietary intakes, body mass index, age, or parity were found between groups at baseline or after supplementation. Milk carotenoid concentrations decreased over time (P < 0.01), as did retinol and alpha-tocopherol concentrations (P < 0.003). Concentrations of most carotenoids decreased to those reported for mature milk by day 32 postpartum. Milk lutein concentrations remained elevated throughout the study compared with values reported for mature milk, whereas plasma lutein concentrations decreased significantly over time. beta-carotene supplementation did not significantly change the milk concentrations of beta-carotene, the other carotenoids, retinol, or alpha-tocopherol. The lack of increase in milk beta-carotene despite supplementation suggests that transitional milk may be already nearly saturated with beta-carotene. The elevated milk lutein concentration and simultaneous decrease in plasma lutein suggest that lutein metabolism may be altered during early lactation.

Recovery of human lymphocytes from oxidative DNA damage; the apparent enhancement of DNA repair by carotenoids is probably simply an antioxidant effect

Many epidemiological studies have identified a protection against cancer associated with consumption of fruit and vegetables. One factor in this protection may be the enhancement of cellular DNA repair activity by micronutrients, such as carotenoids, found in these foods. To measure the capacity of lymphocytes isolated from volunteers supplemented with beta-carotene, lutein or lycopene to recover from DNA damage induced in vitro by treatment with H2O2. Healthy volunteers were given supplements of lutein (15 mg/day), lycopene (15 mg/day) and beta-carotene (15 mg/day), each for 1 week, the supplementation periods being separated by 3-week wash-out periods. Blood samples were taken at the beginning and end of each supplementation, and at 1 week and 3 weeks during the wash-out period. Carotenoid levels were measured in plasma. Lymphocytes were isolated and frozen. Subsequently, they were treated with 100 microM H2O2 and incubated for up to 24 h; DNA damage was measured with the comet assay (single cell gel electrophoresis) after 0, 2, 4, 8 and 24 h. Increases of 2- to 3-fold in mean plasma lutein and beta-carotene concentrations were seen at the end of the respective supplementation periods; they returned virtually to basal levels after wash-out. Lycopene concentrations were less affected by supplementation, and were more variable. H2O2-induced DNA strand breaks were apparently only slowly rejoined by the lymphocytes. The rejoining of breaks in the first few hours appeared substantially faster in lymphocytes following supplementation with beta-carotene, but no such effect was seen with lutein. In those individuals who showed increases in lycopene concentrations, the recovery was significantly faster. Lymphocytes that were not treated with H2O2 showed a transient increase in DNA breakage to about double the background level in 2 h, presumably as a result of exposure to atmospheric oxygen; this effect, too, was relieved by supplementation with lycopene or beta-carotene. While certain carotenoids appear to enhance recovery from oxidative damage, this is probably in fact an antioxidant protective effect against additional damage induced by atmospheric oxygen, rather than a stimulation of DNA repair.

Modulation of humoral and cell-mediated immune responses by dietary lutein in cats

The immuno-modulatory role of dietary lutein in domestic cats is unknown. Female Tabby cats (10-month old; n=56) were supplemented daily for 12 weeks with 0, 1, 5 or 10 mg lutein. Blood was collected on Weeks 0, 2, 4, 8 and 12 to assess the following: (1) mitogen-induced peripheral blood mononuclear cells (PBMCs) proliferation, (2) changes in PBMC subpopulations, (3) interleukin-2 (IL-2) production and (4) plasma immunoglobulin (Ig)G production. In addition, delayed-type hypersensitivity (DTH) response to concanavalin A (Con A) or a polyvalent vaccine was performed on Weeks 0, 6 and 12. Dietary lutein increased plasma lutein concentrations in a dose-dependent manner ( p<0.001) and concentrations had not reached steady state after 12 weeks of feeding in cats given 5 or 10 mg lutein. Concentrations of plasma retinol and α-tocopherol were not influenced by diet. The DTH response to vaccine but not to Con A increased ( p<0.05) in a dose-dependent manner on Week 6. Compared to control, cats fed lutein also showed enhanced Con A- and pokeweed mitogen-stimulated PBMCs proliferation. Dietary lutein also increased the percentages of CD4+ and CD21+ lymphocytes on Week 12 but had no significant effect on pan T, CD8 and MHC class II markers. Plasma IgG was higher ( p<0.05) in cats fed 10 mg lutein on Weeks 8 and 12. These results support the immuno-modulatory action of lutein in domestic cats.

Lutein and zeaxanthin concentrations in plasma after dietary supplementation with egg yolk

The food matrix in which carotenoids are found affects their bioavailability. Lutein and zeaxanthin are abundant in egg yolks and accumulate in the macular region of the retina, where they may affect visual function. We sought to determine whether plasma lutein and zeaxanthin concentrations are elevated after dietary supplementation with egg yolk. Eleven moderately hypercholesterolemic men and women consumed 2 separate baseline diets, which contained 29-33% of energy as total fat, with 20% of energy as either beef tallow or corn oil. These diets were supplemented with cooked chicken egg yolks (1.3 egg yolks/d for an intake of 10.4 MJ). Each subject consumed all 4 diets. Each diet was consumed for 4.5 wk, with a washout period of >/=2 wk between diet phases. At the end of each diet phase, fasting morning plasma samples were collected and stored for carotenoid analysis by HPLC. Commercial chicken egg yolks were analyzed for carotenoids and cholesterol. Egg yolk supplementation of the beef tallow diet increased plasma lutein by 28% (P < 0.05) and zeaxanthin by 142% (P < 0.001); supplementation of the corn oil diet increased plasma lutein by 50% (P < 0.05) and zeaxanthin by 114% (P < 0.001). Changes in plasma lycopene and beta-carotene were variable, with no consistent trend. Egg yolk supplementation increased plasma LDL-cholesterol concentrations by 8-11% (P < 0.05). Egg yolk is a highly bioavailable source of lutein and zeaxanthin. The benefit of introducing these carotenoids into the diet with egg yolk is counterbalanced by potential LDL-cholesterol elevation from the added dietary cholesterol.

Effects of 4 y of oral supplementation with beta-carotene on serum concentrations of retinol, tocopherol, and five carotenoids

beta-Carotene has been studied widely as a potential cancer-preventing agent. Recent studies found that subjects who took beta-carotene supplements orally had increases in their serum concentrations of alpha-carotene and lycopene that were large (> 150% increase) and significantly greater than such increases in subjects who received placebo and that similar supplementation was associated with a decrease of approximately 37% in plasma lutein concentrations. A biologic interaction between beta-carotene and other carotenoids was suggested. We measured concentrations of retinol, alpha-tocopherol, and five carotenoids in serum specimens from a random sample of subjects enrolled in a clinical trial of the use of antioxidant vitamins in preventing colonic adenomas. We used serum specimens obtained at enrollment and after the subjects took placebo (n = 54) or 25 mg beta-carotene/d (n = 54) orally for 4 y. In a multivariate analysis, baseline serum concentrations of the analytes, sex, body mass index, diet, smoking status, and age were associated with variable changes in some analytes over the 4-y period but supplementation with beta-carotene was related only to a mean increase in serum beta-carotene itself of 151%. We excluded with 95% confidence an increase in lycopene > 4.9%, an increase in alpha-carotene > 17.6%, and a decrease in lutein > 14.7% in subjects given beta-carotene. These results confirm previous findings that supplementation with beta-carotene given orally does not alter serum concentrations of retinol or alpha-tocopherol. The findings also indicate that beta-carotene supplementation, which results in a moderate increase in serum beta-carotene concentration, does not significantly change serum concentrations of other carotenoids.

Dietary Manipulation of Plasma Carotenoid Concentrations of Squirrel Monkeys (Saimiri sciureus) ,

Primate retinas accumulate the dihydroxy xanthophylls, lutein and zeaxanthin, from the diet via the plasma. Control of plasma concentrations of these carotenoids may be useful for prevention of retinal disease by manipulating carotenoid content of the retina. We have measured the plasma response of male squirrel monkeys to changes in the carotenoid content of a nonpurified diet. We have also supplemented the diet with zeaxanthin and β-carotene. Plasma responses to dietary changes were rapid. Within one week, most of the change in plasma concentrations had already occurred. Within two weeks of increasing zeaxanthin intake, plasma zeaxanthin concentrations were at a new, relatively stable level. β-carotene concentrations in the plasma were low while the monkeys were consuming a standard laboratory diet, and were only slightly increased by supplementation. Plasma lutein concentrations were unaffected by zeaxanthin supplementation. Our results suggest that it should be possible to manipulate plasma concentrations of each of the retinal carotenoids with little impact on the plasma concentrations of the other. This will facilitate exploration of the rates of accumulation of lutein and zeaxanthin in the retina, as well as exploration of the possibility of bioconversion from one xanthophyll to another.

Iris Color and Macular Pigment Optical Density

The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density ( P<0.02) were found for different colored irises (group I, n=38, MP=0.25; group II, n=26, MP=0.32; group III, n=31, MP=0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.

Carotenoids, vitamin A, and estrogen receptor status in breast cancer.

Among patients with breast cancer, tumors that contain estrogen receptors (ER) are associated with improved survival and better response to hormone therapy than those not expressing these receptors. The purpose of these case comparison studies was to examine the relationship between carotenoids, vitamin A, and the tumor ER status in women at diagnosis of primary breast cancer. The focus of the first study was the relationship between dietary intake and ER status, and the focus of the second study was the relationship between ER status and the plasma carotenoid, retinol, and tocopherol concentrations. We evaluated tumor ER status and self-reported dietary intake in 142 women and plasma concentrations of carotenoids, retinol, and tocopherols in 149 women, at diagnosis of breast cancer, before any medical or surgical treatment. In the first study the overall odds of ER-positive status were increased in relation to number of mammograms in the past five years, number of breast-fed babies, dietary carotenoid intake, and more frequent intake of yellow and green vegetables. Overall odds of ER-positive status were decreased in relation to years of oral contraceptive use and preformed vitamin A intake. In the second study older women, women with higher plasma lutein concentration, and women not using beta-carotene supplements were more likely to be ER positive, when data were adjusted for body mass index and factors that may influence breast cancer risk or hormonal status. Significant independent relationships between plasma retinol or tocopherol concentrations and ER status were not observed. The strong and independent relationships between carotenoid intake, plasma lutein concentration, and ER status may relate to observations linking a carotenoid-rich diet with improved prognosis after diagnosis of breast cancer.