Current Insights on the Photoprotective Mechanism of the Macular Carotenoids, Lutein and Zeaxanthin: Safety, Efficacy and Bio-Delivery.

Ocular health has emerged as one of the major issues of global health concern with a decline in quality of life in an aging population, in particular and rise in the number of associated morbidities and mortalities. One of the chief reasons for vision impairment is oxidative damage inflicted to photoreceptors in rods and cone cells by blue light as well as UV radiation. The scenario has been aggravated by unprecedented rise in screen-time during the COVID and post-COVID era. Lutein and Zeaxanthin are oxygenated carotenoids with proven roles in augmentation of ocular health largely by virtue of their antioxidant properties and protective effects against photobleaching of retinal pigments, age-linked macular degeneration, cataract, and retinitis pigmentosa. These molecules are characterized by their characteristic yellow-orange colored pigmentation and are found in significant amounts in vegetables such as corn, spinach, broccoli, carrots as well as fish and eggs. Unique structural signatures including tetraterpenoid skeleton with extensive conjugation and the presence of hydroxyl groups at the end rings have made these molecules evolutionarily adapted to localize in the membrane of the photoreceptor cells and prevent their free radical induced peroxidation. Apart from the benefits imparted to ocular health, lutein and zeaxanthin are also known to improve cognitive function, cardiovascular physiology, and arrest the development of malignancy. Although abundant in many natural sources, bioavailability of these compounds is low owing to their long aliphatic backbones. Under the circumstances, there has been a concerted effort to develop vegetable oil-based carriers such as lipid nano-emulsions for therapeutic administration of carotenoids. This review presents a comprehensive update of the therapeutic potential of the carotenoids along with the challenges in achieving an optimized delivery tool for maximizing their effectiveness inside the body.

Lutein and zeaxanthin are the two most abundant natural xanthophylls (oxygenated carotenoids) with a linear C40 tetraterpene/isoprenoid lycopene-based backbone.Presence of extensive conjugation (more than 10 double bonds) enable these molecules to act as accessory light harvesting pigments apart from chlorophyll.More importantly, the xanthophylls prevent photobleaching of the pigments and proteins in the Light Harvesting Complex (LHC) by sequestering the excess unutilized blue light and preventing triplet chlorophyll associated formation of Reactive Oxygen Species.In human eye, lutein, zeaxanthin along with mesozeaxanthin constitute the three macular pigments forming the so called "yellow spot" of the macula and are implicated in maintaining the redox balance, homeostasis and normal physiology of the eyes.However, unlike plants, xanthophylls must be acquired from dietary sources such as colored leafy vegetables and egg yolk.Increase in the number of eye diseases in the aging population coupled with insufficient bioavailability of xanthophylls has mandated the industrial production of supplements enriched in xanthophylls.The bioavailability and delivery of xanthophylls can be significantly enhanced by suspension in a blend of extra-virgin olive oil and other vegetable oils.

Carotenoids in familial hypobetalipoproteinemia disorders: Malabsorption in Caco2 cell models and severe deficiency in patients.

BACKGROUND: Familial hypobetalipoproteinemias (FHBL) are rare genetic diseases characterized by lipid malabsorption. We focused on abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3), caused by mutations in microsomal triglyceride transfer protein (MTTP) and SAR1B genes, respectively. Treatments include a low-fat diet and high-dose fat-soluble vitamin supplementations. However, patients are not supplemented in carotenoids, a group of lipid-soluble pigments essential for eye health. OBJECTIVE: Our aim was to evaluate carotenoid absorption and status in the context of hypobetalipoproteinemia. METHODS: We first used knock-out Caco-2/TC7 cell models of FHBL-SD1 and FHBL-SD3 to evaluate carotenoid absorption. We then characterized FHBL-SD1 and FHBL-SD3 patient status in the main dietary carotenoids and compared it to that of control subjects. RESULTS: In vitro results showed a significant decrease in basolateral secretion of α- and ß-carotene, lutein, and zeaxanthin (-88.8 ± 2.2 % to -95.3 ± 5.8 %, -79.2 ± 4.4 % to -96.1 ± 2.6 %, -91.0 ± 4.5 % to -96.7 ± 0.3 % and -65.4 ± 3.6 % to -96.6 ± 1.9 %, respectively). Carotenoids plasma levels in patients confirmed significant deficiencies, with decreases ranging from -89 % for zeaxanthin to -98 % for α-carotene, compared to control subjects. CONCLUSION: Given the continuous loss in visual function despite fat-soluble vitamin treatment in some patients, carotenoid supplementation may be of clinical utility. Future studies should assess the correlation between carotenoid status and visual function in aging patients and investigate whether carotenoid supplementation could prevent their visual impairment.

Enrichment efficiency of lutein in eggs and its function in improving fatty liver hemorrhagic syndrome in aged laying hens.

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.

Genetic deletion of Bco2 and Isx establishes a golden mouse model for carotenoid research.

OBJECTIVE: Low plasma levels of carotenoids are associated with mortality and chronic disease states. Genetic studies in animals revealed that the tissue accumulation of these dietary pigments is associated with the genes encoding ß-carotene oxygenase 2 (BCO2) and the scavenger receptor class B type 1 (SR-B1). Here we examined in mice how BCO2 and SR-B1 affect the metabolism of the model carotenoid zeaxanthin that serves as a macular pigment in the human retina. METHODS: We used mice with a lacZ reporter gene knock-in to determine Bco2 expression patterns in the small intestine. By genetic dissection, we studied the contribution of BCO2 and SR-B1 to zeaxanthin uptake homeostasis and tissue accumulation under different supply conditions (50 mg/kg and 250 mg/kg). We determined the metabolic profiles of zeaxanthin and its metabolites in different tissues by LC-MS using standard and chiral columns. An albino Isx-/-/Bco2-/- mouse homozygous for Tyrc-2J was generated to study the effect of light on ocular zeaxanthin metabolites. RESULTS: We demonstrate that BCO2 is highly expressed in enterocytes of the small intestine. Genetic deletion of Bco2 led to enhanced accumulation of zeaxanthin, indicating that the enzyme serves as a gatekeeper of zeaxanthin bioavailability. Relaxing the regulation of SR-B1 expression in enterocytes by genetic deletion of the transcription factor ISX further enhanced zeaxanthin accumulation in tissues. We observed that the absorption of zeaxanthin was dose-dependent and identified the jejunum as the major zeaxanthin-absorbing intestinal region. We further showed that zeaxanthin underwent oxidation to ε,ε-3,3'-carotene-dione in mouse tissues. We detected all three enantiomers of the zeaxanthin oxidation product whereas the parent zeaxanthin only existed as (3R, 3'R)-enantiomer in the diet. The ratio of oxidized to parent zeaxanthin varied between tissues and was dependent on the supplementation dose. We further showed in an albino Isx-/-/Bco2-/- mouse that supra-physiological supplementation doses (250 mg/kg) with zeaxanthin rapidly induced hypercarotenemia with a golden skin phenotype and that light stress increased the concentration of oxidized zeaxanthin in the eyes. CONCLUSIONS: We established the biochemical basis of zeaxanthin metabolism in mice and showed that tissue factors and abiotic stress affect the metabolism and homeostasis of this dietary lipid.

Dynamic change of the carotenoid metabolic pathway profile during oolong tea processing with supplementary LED light.

Carotenoid-derived volatiles are important contributors to tea aroma quality. However, the profile of the carotenoid pathway and carotenoid-derived volatiles (CDVs) artificial regulation in oolong tea processing has yet to be investigated. In the present work, the content and varieties of carotenoid-derived volatiles, the genome-wide identification of carotenoid cleavage dioxygenase (CsCCD) gene family, the expression level of CsCCD and other key genes in the carotenoid pathway, and the profile of carotenoid substances were analyzed by multi-omics and bioinformatics methods with innovative postharvest supplementary LED light during oolong tea processing. The results showed that during oolong tea processing, a total of 17 CDVs were identified. The content of ß-ionone increased up to 26.07 times that of fresh leaves and its formation was significantly promoted with supplementary LED light from 0.54 µg/g to 0.83 µg/g in the third turning over treatment. A total of 11 CsCCD gene family members were identified and 119 light response cis-acting regulatory elements of CsCCD were found. However, the expression level of most genes in the carotenoid pathway including CsCCD were reduced due to mechanical stress. 'Huangdan' fresh tea leaves had a total of 1 430.46 µg/g 22 varieties of carotenoids, which mainly composed of lutein(78.10%), ß-carotene(8.24%) and zeaxanthin(8.18%). With supplementary LED light, the content of antherxanthin and zeaxanthin in xanthophyll cycle was regulated and CDVs such as α-ionone, ß-ionone, pseudoionone, damascenone, 6,10-dimethyl-5,9-undecadien-2-one, citral, geranyl acetate and α-farnesene were promoted significantly in different phases during oolong tea processing. Our results revealed the profile of the carotenoid metabolism pathway in oolong tea processing from the perspective of precursors, gene expression and products, and put forward an innovative way to improve CDVs by postharvest supplementary LED light.

Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.

The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.

Association of dietary and plasma carotenoids with urinary F2-isoprostanes.

PURPOSE: Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally evaluated associations between carotenoids and biomarkers of oxidative stress or inflammation. METHODS: From 2003 to 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35-74. Post-menopausal participants (n = 512) were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Dietary carotenoid consumption was assessed using a validated 110-item Block 1998 food frequency questionnaire; use of ß-carotene-containing supplements was also assessed. Plasma carotenoids were quantified, adjusting for batch. Urinary markers of lipid peroxidation, 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were also measured. Since the biomarker 8-iso-PGF2α can reflect both oxidative stress and inflammation, we used a modeled 8-iso-PGF2α to prostaglandin F2α ratio approach to distinguish effects reflecting oxidative stress versus inflammation. Multivariable linear regression was used to assess the associations of dietary and plasma carotenoids with the estimated biomarker concentrations. RESULTS: Total plasma carotenoids were inversely associated with 8-iso-PGF2α-M concentrations (P for trend across quartiles = 0.009). Inverse trends associations were also seen for α-carotene and ß-carotene. In contrast, lutein/zeaxanthin showed associations with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations. The inverse association for total carotenoids appeared to be specific for oxidative stress (chemical 8-iso-PGF2α; Phighest vs. lowest quartile = 0.04 and P for trend across quartiles = 0.02). The pattern was similar for α-carotene. However, lutein/zeaxanthin tended to have a stronger association with enzymatic 8-iso-PGF2α, suggesting an additional anti-inflammatory effect. Supplemental ß-carotene was inversely associated with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations, as well as with both chemical and enzymatic 8-iso-PGF2α. Dietary carotenoids were not associated with either biomarker. CONCLUSION: Plasma carotenoids and supplemental ß-carotene were associated with lower concentrations of 8-iso-PGF2α metabolite. Plasma carotenoids associations may reflect antioxidant effects.

HDL is the primary transporter for carotenoids from liver to retinal pigment epithelium in transgenic ApoA-I-/-/Bco2-/- mice.

Supplementation with antioxidant carotenoids is a therapeutic strategy to protect against age-related macular degeneration (AMD); however, the transport mechanism of carotenoids from the liver to the retina is still not fully understood. Here, we investigate if HDL serves as the primary transporter for the macular carotenoids. ApoA-I, the key apolipoprotein of HDL, was genetically deleted from BCO2 knockout (Bco2-/-) mice, a macular pigment mouse model capable of accumulating carotenoids in the retina. We then conducted a feeding experiment with a mixed carotenoid chow (lutein:zeaxanthin:ß-carotene = 1:1:1) for one month. HPLC data demonstrated that the total carotenoids were increased in the livers but decreased in the serum, retinal pigment epithelium (RPE)/choroids, and retinas of ApoA-I-/-/Bco2-/- mice compared to Bco2-/- mice. In detail, ApoA-I deficiency caused a significant increase of ß-carotene but not lutein and zeaxanthin in the liver, decreased all three carotenoids in the serum, blocked the majority of zeaxanthin and ß-carotene transport to the RPE/choroid, and dramatically reduced ß-carotene and zeaxanthin but not lutein in the retina. Furthermore, surface plasmon resonance spectroscopy (SPR) data showed that the binding affinity between ApoA-I and ß-carotene â‰« zeaxanthin > lutein. Our results show that carotenoids are transported from the liver to the eye mainly by HDL, and ApoA-I may be involved in the selective delivery of macular carotenoids to the RPE.

Goji Berry Intake Increases Macular Pigment Optical Density in Healthy Adults: A Randomized Pilot Trial.

Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide. Macular pigment optical density (MPOD), a biomarker for AMD, is a non-invasive measure to assess risk. The macula xanthophyll pigments lutein (L) and zeaxanthin (Z) protect against blue light and provide oxidant defense, which can be indexed by MPOD. This study examined the effects of Z-rich goji berry intake on MPOD and skin carotenoids in healthy individuals. A randomized, unmasked, parallel-arm study was conducted with 27 participants, aged 45-65, who consumed either 28 g of goji berries or a supplement containing 6 mg L and 4 mg Z (LZ), five times weekly for 90 days. After 90 days, MPOD was significantly increased in the goji berry group at 0.25 and 1.75 retinal eccentricities (p = 0.029 and p = 0.044, respectively), while no changes were noted in the LZ group. Skin carotenoids were significantly increased in the goji berry group at day 45 (p = 0.025) and day 90 (p = 0.006), but not in the LZ group. Regular intake of goji berries in a healthy middle-aged population increases MPOD may help prevent or delay the development of AMD.

Carotenoids and fatty liver disease: Current knowledge and research gaps.

Carotenoids form an important part of the human diet, consumption of which has been associated with many health benefits. With the growing global burden of liver disease, increasing attention has been paid on the possible beneficial role that carotenoids may play in the liver. This review focuses on carotenoid actions in non-alcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD). Indeed, many human studies have suggested an association between decreased circulating levels of carotenoids and increased incidence of NAFLD and ALD. The literature describing supplementation of individual carotenoids in rodent models of NAFLD and ALD is reviewed, with particular attention paid to ß-carotene and lycopene, but also including ß-cryptoxanthin, lutein, zeaxanthin, and astaxanthin. The effect of beta-carotene oxygenase 1 and 2 knock-out mice on hepatic lipid metabolism is also discussed. In general, there is evidence to suggest that carotenoids have beneficial effects in animal models of both NAFLD and ALD. Mechanistically, these benefits may occur via three possible modes of action: 1) improved hepatic antioxidative status broadly attributed to carotenoids in general, 2) the generation of vitamin A from ß-carotene and ß-cryptoxanthin, leading to improved hepatic retinoid signaling, and 3) the generation of apocarotenoid metabolites from ß-carotene and lycopene, that may regulate hepatic signaling pathways. Gaps in our knowledge regarding carotenoid mechanisms of action in the liver are highlighted throughout, and the review ends by emphasizing the importance of dose effects, mode of delivery, and mechanism of action as important areas for further study. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

Metabolomic Profiling of Carotenoid Constituents in Physalis peruviana During Different Growth Stages by LC-MS/MS Technology.

With the current ongoing changes in global food demands, natural carotenoids are preferred by consumers and are gaining attention among food scientists and producers alike. Metabolomic profiling of carotenoid constituents in Physalis peruviana during distinct on-tree growth stages was performed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology. The results show that the ß rings of ß-carotene are hydroxylated with great efficiency, and there is a continual synthesis of zeaxanthin at half-ripe and full-ripe stages, which is confirmed by relating the zeaxanthin content to that of its precursor (ß-carotene). Lutein was, in terms of mass intensity, the most abundant carotenoid constituent (64.61 µg/g at the half-ripe stage) observed in this study. In addition, γ-carotene, which is rare in dietary fruits and vegetables, was detected in the mature and breaker stages, albeit at a relatively low level. The results suggest that when we consider the variation in carotenoid content during different growth stages, Physalis peruviana can be considered a good source of natural carotenoids.

Abscisic acid deficiency caused by phytoene desaturase silencing is associated with dwarfing syndrome in citrus.

KEY MESSAGE: In citrus, abscisic acid-deficiency was associated with a dwarfing phenotype, slow growth, small leaves, decreased fresh weight, and faster water loss. ABA supplementation reversed the dwarfing phenotype and enhanced growth. Abscisic acid (ABA) is a ubiquitously distributed phytohormone, which is almost produced by all living kingdoms. In plants, ABA plays pleiotropic physiological roles in growth, development, and stress responses. We explored the hidden relationship between ABA deficiency, and citrus dwarfing. We used targeted-HPLC, targeted-GC-MS, molecular genetics, immunoassays, and gene expression techniques to investigate the effects of the silencing of phytoene desaturase (PDS) gene on the ABA-biosynthetic pathway, endogenous ABA content, and other phytohormones. Silencing of PDS directly suppressed the carotenoids compounds involved in ABA biosynthesis, altered phytohormonal profile, and caused phytoene accumulation and ABA deficiency. The reduction of ABA presumably due to the limited availability of its precursor, zeaxanthin. The ABA-deficient citrus cuttings displayed photobleaching, a dwarf phenotype with impaired growth characteristics that included slow growth, small leaves, decreased fresh weight, and faster water loss. ABA supplementation enhanced the growth and reversed the dwarfing phenotype of the ABA-deficient cuttings. Our data demonstrate that ABA-deficiency may lead to dwarfing phenotype and impaired growth in citrus cuttings. The negative influence of ABA-deficiency on growth rate is the result of altered water relations. Addition of ABA to the CTV-tPDS roots restored shoot growth and reversed the dwarfing phenotype.

Effects of dietary fat source on lutein, zeaxanthin and total carotenoids content of the egg yolk in laying hens during the early laying period.

1. The study was conducted to investigate the effects of different dietary levels of an unsaturated or saturated fat source and the effects of different dietary energy levels in laying hen diets on the carotenoid content of the egg yolk. 2. Seventy-two ISA Brown laying hens aged 22 weeks old were allocated, for a 10 week period, to three treatments: control diet (HE group) with a 3.4% supplemented fat containing 2.1% soybean and 1.3% palm oil as fat sources and a ratio of unsaturated to saturated fatty acid (u/s) of 3.33; a lowered energy diet with 2.4% supplemented fat containing 1.4% soybean and 1.0% palm oil and u/s of 3.41 (LE+high u/s); a lowered energy diet with 2.4% supplemented fat containing 0.5% soybean and 1.9% palm oil and a u/s of 2.39 (LE+low u/s). A marigold plant extract supplement was used as a source of lutein. 3. Performance parameters (feed consumption, feed conversion, body weight), egg production rate and egg quality parameters were similar between treatments. Dietary fat digestibility at the middle of the study period was not different. Egg yolk total fat content was similar in all treatments at the middle and at the end of the study period. 4. Lutein, zeaxanthin, cis-lutein and total carotenoids content were significantly lower in eggs produced from the LE+low u/s group compared to those from the HE and the LE+high u/s groups (P < 0.01 for all parameters). 5. It was concluded that feeding laying hens with a diet containing 1% less supplemented fat and a lower u/s ratio compared to a control diet and to a diet with 1% less supplemented fat with a higher u/s ratio resulted in a significant reduction of carotenoid expression in the egg yolk at the end of experimental period. Performance and egg quality parameters were not affected by treatments.

Effects of astaxanthin-rich dried cell powder from Paracoccus carotinifaciens on carotenoid composition and lipid peroxidation in skeletal muscle of broiler chickens under thermo-neutral or realistic high temperature conditions.

Thirty-two 15-day old broiler chicks (Chunky strain ROSS 308) were randomly divided into four treatments in a 2 × 2 factorial design. The main factors were diet (basal diet or basal diet supplemented with 0.15% astaxanthin-rich dried cell powder (Panaferd-P [astaxanthin 30 ppm]) and ambient temperature (thermo-neutral [25 ± 1°C] or high [35 ± 1°C for 6 hr]). Dietary supplementation with Panaferd-P did not affect growth performance, though high ambient temperature decreased feed intake and the weight of breast tender muscle, liver, and heart. High ambient temperature also decreased redness in both breast and leg muscles of chickens, while Panaferd-P increased redness and yellowness of breast and leg muscles of chickens. Panaferd-P increased Paracoccus carotinifaciens-derived pigments (i.e., adonixanthin, astaxanthin, adonirubin, and cantaxanthin) as well as corn-derived pigments such as zeaxanthin and lutein in breast and leg muscles. High ambient temperature increased the malondialdehyde (MDA) concentration in breast muscle, while Panaferd-P decreased the MDA concentration in breast muscle under both temperature conditions. Our results suggest that dietary supplementation with Panaferd-P increases muscle carotenoid content, the redness and yellowness of meat and decreases the muscle MDA concentration in broiler chickens kept under thermo-neutral or high ambient temperature conditions.

Lutein, zeaxanthin and mammalian development: Metabolism, functions and implications for health.

It is now widely accepted that nutrition during critical periods in early development, both pre- and postnatal, may have lifetime consequences in determining health or onset of major diseases in the adult life. Dietary carotenoids have shown beneficial health effects throughout the life cycle due to their potential antioxidant properties, their ability to serves as precursors of vitamin A and to the emerging signaling functions of their metabolites. The non-provitamin A carotenoids lutein and zeaxanthin are emerging as important modulators of infant and child visual and cognitive development, as well as critical effectors in the prevention and treatment of morbidity associated with premature births. This review provides a general overview of lutein and zeaxanthin metabolism in mammalian tissues and highlights the major advancements and remaining gaps in knowledge in regards to their metabolism and health effects during pre- and early post-natal development. Furthering our knowledge in this area of research will impact dietary recommendation and supplementation strategies aimed at sustaining proper fetal and infant growth.

ß-Carotene bioaccessibility from biofortified maize (Zea mays) is related to its density and is negatively influenced by lutein and zeaxanthin.

Biofortification of maize with provitamin A (pro-VA) carotenoids has been successful, but the bioavailability of carotenoids needs to be explored. In the present study, we investigated the carotenoid content, micellarization and intestinal cell uptake of carotenoids from 10 maize hybrids [normal maize, quality protein maize (QPM), pro-VA carotenoid and double biofortified QPM + pro-VA maize hybrids] using a simulated in vitro digestion/Caco-2 cell model. The pro-VA carotenoid content of biofortified maize hybrids is 2-10 fold higher compared to that of normal maize. Furthermore, the ratio of non-pro-VA carotenoids lutein (LUT) plus zeaxanthin (ZEA) to the sum of pro-VA carotenoids ß-cryptoxanthin (BCX), α-carotene (AC) and ß-carotene (BC) in biofortified maize was much lower compared to that of normal maize. The consumption of 200 g day-1 of biofortified Pusa-PV-16-3 (BC = 808.4 µg per 100 g; AC = 839.3 µg per 100 g; BCX = 59 µg per 100 g) and Pusa-APQH8 (BC = 345.9 µg per 100 g; AC = 1739 µg per 100 g; BCX = 644.2 µg per 100 g) maize would contribute to 52 and 64% of RDAs for adult Indian men, respectively, after adjusting for cooking losses and conversion factors. The mean efficiency of micellarization of LUT (62.2% ± 5.3), ZEA (65% ± 4.7), and BCX (54% ± 9.5) exceeded that of AC (43% ± 8.9) and BC (49.8% ± 7.8) from all the maize hybrids. Furthermore, the micellarization and uptake in Caco-2 cells during a 4 h incubation period showed high correlation (P < 0.05) with the concentration of carotenoids in the maize digesta and micellar fraction, respectively. However, the LUT + ZEA content in the maize digesta and micellar fraction was inversely (p < 0.05) related to the BC micellarization and intestinal cell uptake, respectively. These results together suggest that the enrichment of pro-VA carotenoids together with decreasing the oxygenated carotenoid metabolites such as LUT and ZEA will further improve the bioavailability of BC from maize hybrids.

Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration.

BACKGROUND: Lutein and zeaxanthin are suggested micronutrient supplements to prevent the progression of age-related macular degeneration (AMD), a leading cause of blindness worldwide. To monitor the levels of lutein/zeaxanthin in the macula, macular pigment optical density (MPOD) is measured. A commercially available device (MPSII®, Elektron Technology, Switzerland), using technology based on heterochromatic flicker photometry, can measure both absolute and estimated values of MPOD. However, whether the estimated value is applicable to Asian individuals and/or AMD patients remains to be determined. METHODS: The absolute and estimated values of MPOD were measured using the MPSII® device in 77 participants with a best-corrected visual acuity (BCVA) > 0.099 (logMAR score). RESULTS: The studied eyes included 17 young (20-29 years) healthy, 26 aged (>50 years) healthy, 18 aged and AMD-fellow, and 16 aged AMD eyes. The mean BCVA among the groups were not significantly different. Both absolute and estimated values were measurable in all eyes of young healthy group. However, absolute values were measurable in only 57.7%, 66.7%, and 43.8%, of the aged healthy, AMD-fellow, and AMD groups, respectively, and 56.7% of the eyes included in the 3 aged groups. In contrast, the estimated value was measurable in 84.6%, 88.9% and 93.8% of the groups, respectively, and 88.3% of eyes in the pooled aged group. The estimated value was correlated with absolute value in individuals from all groups by Spearman's correlation coefficient analyses (young healthy: R2 = 0.885, P = 0.0001; aged healthy: R2 = 0.765, P = 0.001; AMD-fellow: R2 = 0.851, P = 0.0001; and AMD: R2 = 0.860, P = 0.013). Using the estimated value, significantly lower MPOD values were found in aged AMD-related eyes, which included both AMD-fellow and AMD eyes, compared with aged healthy eyes by Student's t-test (P = 0.02). CONCLUSIONS: Absolute, in contrast to estimated, value was measurable in a limited number of aged participants; however, it was correlated with estimated value both in young and aged Asian populations with or without AMD. These results may inform future clinical studies investigating the measurement of MPOD in understanding the role of macular pigments in the pathogenesis of AMD.

Retinal accumulation of zeaxanthin, lutein, and ß-carotene in mice deficient in carotenoid cleavage enzymes.

Carotenoid supplementation can prevent and reduce the risk of age-related macular degeneration (AMD) and other ocular disease, but until now, there has been no validated and well-characterized mouse model which can be employed to investigate the protective mechanism and relevant metabolism of retinal carotenoids. ß-Carotene oxygenases 1 and 2 (BCO1 and BCO2) are the only two carotenoid cleavage enzymes found in animals. Mutations of the bco2 gene may cause accumulation of xanthophyll carotenoids in animal tissues, and BCO1 is involved in regulation of the intestinal absorption of carotenoids. To determine whether or not mice deficient in BCO1 and/or BCO2 can serve as a macular pigment mouse model, we investigated the retinal accumulation of carotenoids in these mice when fed with zeaxanthin, lutein, or ß-carotene using an optimized carotenoid feeding method. HPLC analysis revealed that all three carotenoids were detected in sera, livers, retinal pigment epithelium (RPE)/choroids, and retinas of all of the mice, except that no carotenoid was detectable in the retinas of wild type (WT) mice. Significantly higher amounts of zeaxanthin and lutein accumulated in the retinas of BCO2 knockout (bco2-/-) mice and BCO1/BCO2 double knockout (bco1-/-/bco2-/-) mice relative to BCO1 knockout (bco1-/-) mice, while bco1-/- mice preferred to take up ß-carotene. The levels of zeaxanthin and lutein were higher than ß-carotene levels in the bco1-/-/bco2-/- retina, consistent with preferential uptake of xanthophyll carotenoids by retina. Oxidative metabolites were detected in mice fed with lutein or zeaxanthin but not in mice fed with ß-carotene. These results indicate that bco2-/- and bco1-/-/bco2-/- mice could serve as reasonable non-primate models for macular pigment function in the vertebrate eye, while bco1-/- mice may be more useful for studies related to ß-carotene.

Lutein and Zeaxanthin Isomers in Eye Health and Disease.

Current evidence suggests lutein and its isomers play important roles in ocular development in utero and throughout the life span, in vision performance in young and later adulthood, and in lowering risk for the development of common age-related eye diseases in older age. These xanthophyll (oxygen-containing) carotenoids are found in a wide variety of vegetables and fruits, and they are present in especially high concentrations in leafy green vegetables. Additionally, egg yolks and human milk appear to be bioavailable sources. The prevalence of lutein, zeaxanthin, and meso-zeaxanthin in supplements is increasing. Setting optimal and safe ranges of intake requires additional research, particularly in pregnant and lactating women. Accumulating evidence about variable interindividual response to dietary intake of these carotenoids, based on genetic or metabolic influences, suggests that there may be subgroups that benefit from higher levels of intake and/or alternate strategies to improve lutein and zeaxanthin status.

Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease.

The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Lutein and zeaxanthin must be obtained from dietary sources such as green leafy vegetables and orange and yellow fruits and vegetables, while meso-zeaxanthin is rarely found in diet and is believed to be formed at the macula by metabolic transformations of ingested carotenoids. Epidemiological studies and large-scale clinical trials such as AREDS2 have brought attention to the potential ocular health and functional benefits of these three xanthophyll carotenoids consumed through the diet or supplements, but the basic science and clinical research underlying recommendations for nutritional interventions against age-related macular degeneration and other eye diseases are underappreciated by clinicians and vision researchers alike. In this review article, we first examine the chemistry, biochemistry, biophysics, and physiology of these yellow pigments that are specifically concentrated in the macula lutea through the means of high-affinity binding proteins and specialized transport and metabolic proteins where they play important roles as short-wavelength (blue) light-absorbers and localized, efficient antioxidants in a region at high risk for light-induced oxidative stress. Next, we turn to clinical evidence supporting functional benefits of these carotenoids in normal eyes and for their potential protective actions against ocular disease from infancy to old age.