beta-carotene and meso-zeaxanthin

The macular region of the primate retina is yellow in color due to the presence of the macular pigment, composed of two dietary xanthophylls, lutein and zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably formed from either lutein or zeaxanthin in the retina. By absorbing blue-light, the macular pigment protects the underlying photoreceptor cell layer from light damage, possibly initiated by the formation of reactive oxygen species during a photosensitized reaction. There is ample epidemiological evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration, an irreversible process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to be protective against the development of age-related macular degeneration, a causative relationship has yet to be experimentally demonstrated.

Topics: Age Factors; Aging; Antioxidants; beta Carotene; Cataract; Humans; Lutein; Macula Lutea; Macular Degeneration; Retina; Retinal Pigments; Risk Factors; Xanthophylls; Zeaxanthins

The predominant carotenoids of the macular pigment are lutein, zeaxanthin, and meso-zeaxanthin. The regular distribution pattern of these carotenoids within the human macula indicates that their deposition is actively controlled in this tissue. The chemical, structural, and optical characteristics of these carotenoids are described. Evidence for the presence of minor carotenoids in the retina is cited. Studies of the dietary intake and serum levels of the xanthophylls are discussed. Increased macular carotenoid levels result from supplementation of humans with lutein and zeaxanthin. A functional role for the macular pigment in protection against light-induced retinal damage and age-related macular degeneration is discussed. Prospects for future research in the study of macular pigment require new initiatives that will probe more accurately into the localization of these carotenoids in the retina, identify possible transport proteins and mechanisms, and prove the veracity of the photoprotection hypothesis for the macular pigments.

Topics: Animals; beta Carotene; Canthaxanthin; Carotenoids; Chromatography; Dietary Supplements; Humans; Lutein; Macaca; Models, Chemical; Pigment Epithelium of Eye; Protein Conformation; Retina; Retinal Pigments; Xanthophylls; Zeaxanthins

Age-related macular degeneration (AMD) is one of the most common eye diseases of elderly individuals. It has been suggested that lutein and zeaxanthin may reduce the risk for AMD. Information concerning the absorption of non-esterified or esterified zeaxanthin is rather scarce. Furthermore, the formation pathway of meso (3R,3'S)-zeaxanthin, which does not occur in plants but is found in the macula, has not yet been identified. Thus, the present study was designed to assess the concentration of 3R,3R'-zeaxanthin reached in plasma after the consumption of a single dose of native 3R,3'R-zeaxanthin palmitate from wolfberry (Lycium barbarum) or non-esterified 3R,3'R-zeaxanthin in equal amounts. In a randomised, single-blind cross-over study, twelve volunteers were administered non-esterified or esterified 3R,3'R-zeaxanthin (5 mg) suspended in yoghurt together with a balanced breakfast. Between the two intervention days, a 3-week depletion period was inserted. After fasting overnight, blood was collected before the dose (0 h), and at 3, 6, 9, 12, and 24 h after the dose. The concentration of non-esterified 3R,3'R-zeaxanthin was determined by chiral HPLC. For the first time, chiral liquid chromatography-atmospheric pressure chemical ionisation-MS was used to confirm the appearance of 3R,3'R-zeaxanthin in pooled plasma samples. Independent of the consumed diet, plasma 3R,3'R-zeaxanthin concentrations increased significantly (P=0.05) and peaked after 9-24 h. Although the concentration curves were not distinguishable, the respective areas under the curve were distinguishable according to a two-sided F and t test (P=0.05). Thus, the study indicates an enhanced bioavailability of 3R,3'R-zeaxanthin dipalmitate compared with the non-esterified form. The formation of meso-zeaxanthin was not observed during the time period studied.

Topics: Adult; beta Carotene; Chromatography, High Pressure Liquid; Cross-Over Studies; Dietary Supplements; Female; Humans; Lycium; Male; Mass Spectrometry; Palmitates; Plant Extracts; Single-Blind Method; Stereoisomerism; Xanthophylls; Zeaxanthins

We measured the blood uptake of meso-zeaxanthin (MZ) from a mixture of macular pigments since its bioavailability in man has not been studied. Volunteers (ten men and nine women) were recruited and received one capsule of Lutein Plus/d. Blood was taken at baseline, day 10 and day 22. One capsule contained 10.8 mg lutein, 1.2 mg (3R,3'R)-zeaxanthin and 8.0 mg MZ. Plasma lutein and total zeaxanthin concentrations were quantified using isocratic liquid chromatography and the eluting xanthophyll fractions were collected and re-chromatographed on a chiral column to assess the proportion of MZ. Plasma concentrations per mg dose at day 22 suggested that (3R,3'R)-zeaxanthin (0.088 micromol/l per mg) was about 50 % more actively retained by the body than lutein (0.056 micromol/l per mg) (although the difference was not significant in women) and 2.5-3.0 times more than MZ (0.026 micromol/l per mg). Concentrations of MZ at day 22 were 2.5 times higher in women than men. The plasma responses from lutein and (3R,3'R)-zeaxanthin in the Lutein Plus were lower than literature values for the pure substances. That is, their uptake into plasma appeared to be slightly depressed by the presence of MZ. Plasma concentrations of beta-carotene were depressed by about 50 % at day 10 and about 35 % at day 22. In conclusion, the lower plasma response to MZ compared with (3R,3'R)-zeaxanthin probably indicates that MZ is less well absorbed than (3R,3'R)-zeaxanthin but work with pure MZ will be needed to confirm that the lower plasma response was not due to the large amount of lutein in the Lutein Plus.

Topics: Adult; beta Carotene; Cholesterol; Chromatography, Liquid; Dietary Supplements; Drug Combinations; Female; Humans; Isomerism; Lutein; Male; Middle Aged; Xanthophylls; Young Adult; Zeaxanthins

There is growing evidence that high levels of the macular xanthophyll carotenoids lutein and zeaxanthin may be protective against visual loss due to age-related macular degeneration, but the actual mechanisms of their protective effects are still poorly understood. We have recently purified, identified and characterized a pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye which specifically and saturably binds to the two forms of zeaxanthin endogenously found in the foveal region. In this report, we studied the synergistic antioxidant role of zeaxanthin and GSTP1 in egg yolk phosphatidylcholine (EYPC) liposomes using hydrophilic 2,2'-azobis(2-methyl-propionamidine) dihydrochloride (AAPH) and lipophilic 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) as lipid peroxyl radical generators. The two zeaxanthin diastereomers displayed synergistic antioxidant effects against both azo lipid peroxyl radical generators when bound to GSTP1. In the presence of GSTP1, nondietary (3R,3'S-meso)-zeaxanthin was observed to be a better antioxidant than dietary (3R,3'R)-zeaxanthin. This effect was found to be independent of the presence of glutathione. Carotenoid degradation profiles indicated that the zeaxanthin diastereomers in association with GSTP1 were more resistant to degradation which may account for the synergistic antioxidant effects.

Topics: Amidines; Antioxidants; Azo Compounds; beta Carotene; Drug Stability; Glutathione; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Isoenzymes; Lipid Peroxidation; Liposomes; Nitriles; Oxidants; Phosphatidylcholines; Retina; Stereoisomerism; Xanthophylls; Zeaxanthins

Uptake, metabolism, and stabilization of xanthophyll carotenoids in the retina are thought to be mediated by specific xanthophyll-binding proteins (XBPs). A membrane-associated XBP was purified from human macula using ion-exchange chromatography followed by gel-exclusion chromatography. Two-dimensional gel electrophoresis showed a prominent spot of 23 kDa and an isoelectric point of 5.7. Using mass spectral sequencing methods and the public NCBI database, it was identified as a Pi isoform of human glutathione S-transferase (GSTP1). Dietary (3R,3'R)-zeaxanthin displayed the highest affinity with an apparent Kd of 0.33 microm, followed by (3R,3'S-meso)-zeaxanthin with an apparent Kd of 0.52 microm. (3R,3'R,6'R)-Lutein did not display any high-affinity binding to GSTP1. Other human recombinant glutathione S-transferase (GST) proteins, GSTA1 and GSTM1, exhibited only low affinity binding of xanthophylls. (3R,3'S-meso)-Zeaxanthin, an optically inactive nondietary xanthophyll carotenoid present in the human macula, exhibited a strong induced CD spectrum in association with human macular XBP that was nearly identical to the CD spectrum induced by GSTP1. Like-wise, dietary (3R,3'R)-zeaxanthin displayed alterations in its CD spectrum in association with GSTP1 and XBP. Other mammalian xanthophyll carrier proteins such as tubulin, high-density lipoprotein, low-density lipoprotein, albumin, and beta-lactoglobulin did not bind zeaxanthins with high affinity, and they failed to induce or alter xanthophyll CD spectra to any significant extent. Immunocytochemistry with an antibody to GSTP1 on human macula sections showed highest labeling in the outer and inner plexiform layers. These results indicate that GSTP1 is a specific XBP in human macula that interacts with (3R,3'S-meso)-zeaxanthin and dietary (3R,3'R)-zeaxanthin in contrast to apparently weaker interactions with (3R,3'R,6'R)-lutein.

Topics: Adult; beta Carotene; Carotenoids; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Circular Dichroism; Databases as Topic; Electrophoresis, Gel, Two-Dimensional; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Immunohistochemistry; Isoelectric Focusing; Isoenzymes; Kinetics; Lutein; Macula Lutea; Mass Spectrometry; Models, Chemical; Protein Binding; Protein Isoforms; Recombinant Proteins; Temperature; Ultracentrifugation; Xanthophylls; Zeaxanthins

To determine the stereochemistry of carotenoids in human ocular tissues in comparison with plasma and liver and to elucidate the possible transformations of dietary (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin in the eye. Similarly, to characterize the carotenoid profiles in the eye tissues, plasma, and liver of quails and frogs to determine whether these can serve as appropriate nonprimate animal models for metabolic studies.. Configurational isomers of carotenoids and their nondietary by-products from pooled human plasma, liver, retinal pigment epithelium (RPE-choroid), ciliary body, iris, and lens were characterized and quantified by high-performance liquid chromatography (HPLC) on a chiral column. Carotenoids and their nondietary by-products in pooled extracts from quail and frog plasma, liver, retina, RPE-choroid, iris, and lens were similarly characterized and quantified.. (3R,3'R,6'R)-lutein, (3R,3'R)-zeaxanthin, (3R,3'S; meso)-zeaxanthin, (3R,3'S,6'R)-lutein (3'-epilutein), 3-hydroxy-beta, epsilon -carotene-3'-one, and 5Z- and all-E-lycopene were detected in nearly all human ocular tissues examined. (3R,3'S; meso)-zeaxanthin was not detected in the human plasma and liver but was present in human macula, retina, and RPE-choroid. (3S,3'S)-zeaxanthin was detected in human macula in minute quantities. The carotenoid profiles in quail and frog ocular tissues were somewhat similar to those in humans, with the exception that lycopene was absent. Frog retina, plasma, and liver revealed the presence of (3S,3'S)-zeaxanthin.. The most likely transformations of carotenoids in the human eye involve a series of oxidation-reduction and double-bond isomerization reactions. Quail and frog appear to possess the appropriate enzymes for conversion of dietary (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin to the same nondietary by-products observed in humans and thus may serve as excellent nonprimate animal models for metabolic studies.

Topics: Animals; beta Carotene; Biotransformation; Chromatography, High Pressure Liquid; Coturnix; Diet; Eye; Humans; Liver; Lutein; Models, Animal; Rana pipiens; Stereoisomerism; Xanthophylls; Zeaxanthins

The question raised in the title was answered. (3R, 3'S)-meso-Zeaxanthin was submitted to iodine catalyzed photochemical stereoisomerisation. The enantiomeric (9Z) and (9'Z) geometrical isomers were isolated by semipreparative HPLC and separated as diastereomeric dicarbamates on a chiral column only. Cleavage of the carbamate could not be effected. CD-Spectra of (1"S, 1"S)- and (1"R, 1"R)-dicarbamates of geometrical isomers of (3R, 3'R)- and (3R, 3'S)-meso-zeaxanthin were systematically studied and the contribution from the carbamate moieties revealed. It was concluded that (9Z, 3R, 3'S)-"meso"-zeaxanthin, in spite of having no symmetry elements, is optically inactive. The result has been rationalised in line with the current hypothesis on the origin of carotenoid CD spectra.

Topics: beta Carotene; Chromatography, High Pressure Liquid; Circular Dichroism; Stereoisomerism; Xanthophylls; Zeaxanthins

The distribution of macular pigment stereoisomers in the human retina has been mapped and a pathway to account for the presence of the non-dietary carotenoid, meso-zeaxanthin, is proposed. Adult neural retinas were cut into three concentric areas centered on the fovea, and the extracted carotenoids were analysed and purified by high-performance liquid chromatography. The dicarbamate or dibenzoate derivatives of the collected zeaxanthin fractions for each tissue sample were further analysed by HPLC to determine their stereoisomer composition. Whole retinas from infant eyes were similarly analysed. The results show that, relative to zeaxanthin, the concentration of lutein in the adult neural retina increases with radial distance from the fovea while that of meso-zeaxanthin decreases. Infant retinas were found to have more lutein and less meso-zeaxanthin, relative to zeaxanthin, than adult retinas. Small quantities of (3S, 3'S)-zeaxanthin were also found in the adult retina, particularly in the macula. It is proposed that lutein and zeaxanthin are transported into an individual's retina in the same proportions found in his or her blood serum. Some of the lutein is then converted into meso-zeaxanthin, primarily in the macula, by a mechanism which is less developed in infants than adults.

Topics: Age Factors; Analysis of Variance; beta Carotene; Chromatography, High Pressure Liquid; Humans; Infant; Infant, Newborn; Lutein; Middle Aged; Retina; Stereoisomerism; Xanthophylls; Zeaxanthins

To complete identification of the major components of the human macular pigment.. Chemical ionization mass spectra of the macular pigment components were obtained and compared with those of zeaxanthin and lutein standards. A comparison was also made using chiral column high-performance liquid chromatography, which is capable of resolving individual stereoisomers of these carotenoids. Zeaxanthin and lutein from human blood plasma were similarly analyzed.. The mass spectrometry data supported earlier work in which high-performance liquid chromatography, UV-visible spectrometry and chemical modification showed that the macular pigment comprises two carotenoids with identical properties to those of zeaxanthin and lutein. Chiral column chromatography showed that the "zeaxanthin" fraction is a mixture of two stereoisomers, zeaxanthin itself [(3R,3'R)-beta,beta-Carotene-3,3'-diol] and meso-zeaxanthin [(3R,3'S)-beta,beta-Carotene-3,3'-diol]. The other fraction is the single stereoisomer, lutein [(3R,3'R,6'R)-beta,epsilon-Carotene-3,3'-diol]. In human blood plasma, only zeaxanthin and lutein were found.. The results strongly suggest that meso-zeaxanthin results from chemical processes within the retina. Noting that lutein exceeds zeaxanthin in plasma but that the combined zeaxanthin stereoisomers exceed lutein in the retina, the possibility was considered that meso-zeaxanthin is a conversion product derived from retinal lutein. Under nonphysiologic conditions, the authors demonstrate that a base-catalyzed conversion of lutein to zeaxanthin yields only the meso-(3R,3'S) stereoisomer.

Topics: beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Humans; Lutein; Macula Lutea; Retinal Pigments; Spectrophotometry, Ultraviolet; Stereoisomerism; Xanthophylls; Zeaxanthins

Racemic mixtures of (3RS, 3'RS)-zeaxanthin were separated into the three optical isomers, (3R, 3'R)-zeaxanthin (1), (3R,3'S;meso)-zeaxanthin (2) and (3S,3'S)-zeaxanthin (3), by converting to their corresponding dibenzoates and by using HPLC on an optical resolution column Sumipax OA-2000. According to this procedure, it has been shown that only (1) is isolated from higher plants, shellfish, starfish, sea squirt, sea cucumber and then examined; on the other hand (1), (2) and (3) are isolated from zeaxanthin fraction of shrimp, fish and turtle examined. This is the first isolation of enantiomeric and meso-zeaxanthin in nature.

Topics: Animals; Arthropods; beta Carotene; Carotenoids; Chickens; Chordata, Nonvertebrate; Echinodermata; Egg Yolk; Female; Fishes; Mollusca; Plants; Species Specificity; Stereoisomerism; Turtles; Xanthophylls; Zeaxanthins