Early Pediatric Benefit of Lutein for Maturing Eyes and Brain-An Overview.

Lutein is a dietary carotenoid preferentially accumulated in the eye and the brain in early life and throughout the life span. Lutein accumulation in areas of high metabolism and oxidative stress such as the eye and the brain suggest a unique role of this ingredient during the development and maturation of these organs of common embryological origin. Lutein is naturally provided to the developing baby via the cord blood, breast milk and then infant diet. The presence of this carotenoid depends on fruit and vegetable intakes and its bioavailability is higher in breastmilk. This paper aims to review the anatomical development of the eye and the brain, explore the presence and selective deposition of lutein in these organs during pregnancy and infancy and, based on its functional characteristics, present the latest available research on the beneficial role of lutein in the pediatric population. The potential effects of lutein in ameliorating conditions associated with increase oxidative stress such as in prematurity will be also addressed. Since consumption of lutein rich foods falls short of government guidelines and in most region of the world infant formulas lack this bioactive, dietary recommendations for pregnant and breastfeeding women and their child can help to bridge the gap.

Carotenoids in the Management of Glaucoma: A Systematic Review of the Evidence.

Primary open-angle glaucoma (POAG) remains a leading cause of irreversible blindness globally. Recent evidence further substantiates sustained oxidative stress, and compromised antioxidant defenses are key drivers in the onset of glaucomatous neurodegeneration. Overwhelming oxidative injury is likely attributed to compounding mitochondrial dysfunction that worsens with age-related processes, causing aberrant formation of free radical species. Thus, a compromised systemic antioxidant capacity exacerbates further oxidative insult in glaucoma, leading to apoptosis, neuroinflammation, and subsequent tissue injury. The purpose of this systematic review is to investigate the neuroprotective benefits of the macular carotenoids lutein, zeaxanthin, and meso-zeaxanthin on glaucomatous neurodegeneration for the purpose of adjunctive nutraceutical treatment in glaucoma. A comprehensive literature search was conducted in three databases (PubMed, Cochrane Library, and Web of Science) and 20 records were identified for screening. Lutein demonstrated enhanced neuroprotection on retinal ganglion cell survival and preserved synaptic activity. In clinical studies, a protective trend was seen with greater dietary consumption of carotenoids and risk of glaucoma, while greater carotenoid levels in macular pigment were largely associated with improved visual performance in glaucomatous eyes. The data suggest that carotenoid vitamin therapy exerts synergic neuroprotective benefits and has the capacity to serve adjunctive therapy in the management of glaucoma.

[Involvement of egg antioxidant components in macular protection and vision improvement]. / Implicación de los componentes antioxidantes del huevo en la protección macular y la mejora de la visión.

INTRODUCTION: Age-related macular degeneration (AMD) is an ocular pathology that occurs with excess free radicals, which damages the photoreceptors of the retina producing a disability in the pigment epithelium, which leads, in the most advanced cases, to severe and irreversible vision loss. Lutein and zeaxanthin (L & Z) intake, which are abundant pigments in the macula and have antioxidant and anti-inflammatory action, as well as a role as blue light filter, seem to have a positive effect on the prevention of AMD. These carotenoids cannot be synthesized in the body and must be ingested with the diet. Green leafy vegetables and eggs are the main sources. The former have a higher L & Z content than the latter, but their bioavailability is lower, due to the lipid matrix of the egg yolk, which improves absorption. In relation to the consumption of eggs and AMD prevention, short-term consumption has been associated with an increase in serum concentrations of L & Z, long-term consumption with an increase in the density of macular pigment, and very long- term consumption with a decrease in the risk of developing advanced and neovascular AMD. These facts highlight the advantages of consuming eggs, which should be incorporated into the usual diet in order to minimize the progression of this ocular disease.

INTRODUCCIÓN: La degeneración macular asociada a la edad (DMAE) es una patología ocular que cursa con exceso de radicales libres y que daña los fotorreceptores de la retina, produciendo incapacidad en el epitelio pigmentario, lo que lleva, en los casos más avanzados, a una pérdida de visión severa e irreversible. La ingesta de luteína y zeaxantina (L y Z), que son pigmentos muy abundantes en la mácula y presentan acción antioxidante y antiinflamatoria, así como de filtro de luz azul, parece presentar un efecto positivo en la prevención de la DMAE. Estos carotenoides no pueden ser sintetizados por el organismo y hay que ingerirlos con la dieta, siendo los vegetales de hoja verde y los huevos sus principales fuentes. Los primeros presentan un mayor contenido de L y Z que los segundos, pero su biodisponibilidad es menor debido a la matriz lipídica de la yema del huevo, que hace mejorar su absorción. Con respecto al consumo de huevo y el padecimiento de DMAE, a corto plazo se ha relacionado con un aumento de las concentraciones séricas de L y Z, a largo plazo con un aumento de la densidad del pigmento macular y a muy largo plazo con una disminución del riesgo de desarrollar DMAE avanzada y neovascular, lo que pone de manifiesto las ventajas de consumir este alimento y su recomendación para incorporarlo a la dieta habitual con el fin de minimizar la progresión de esta enfermedad ocular.

Protective Effect of Lutein/Zeaxanthin Isomers in Traumatic Brain Injury in Mice.

Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood-brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1ß), interleukin 6 (IL-6), and NF-κB levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway.

Impact of different dietary lutein levels on growth performance, biochemical and immuno-physiological parameters of oriental river prawn (Macrobrachium nipponense).

A 56-day trial was conducted to evaluate the effects of dietary lutein pigment on growth, biochemical, and immuno-physiological parameters of the oriental river prawn. Prawns were fed five formulated diets containing different lutein levels, 0 (control), 50, 100, 150, and 200 mg/kg. Growth performance, except hepatosomatic index, was affected by different lutein levels, and biochemical parameters (urea, uric acid, glucose, creatinine, and triglycerides) decreased. However, high-density and low-density lipoprotein elevated significantly compared to the control treatment. Furthermore, calcium, phosphorus, and cholesterol did not show a significant difference. Hemato-immunological parameters (albumin, total protein, cortisol, lysozyme, phenoloxidase, total hemocyte count, granular cells, semi-granular cells, hyaline cells, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase), and hepatopancreatic antioxidant statuses (total antioxidant capacity, superoxide dismutase, catalase, and malondialdehyde), were significantly affected; however, alkaline phosphatase and glutathione peroxidase were not affected by lutein treatments. By increasing dietary lutein levels, digestive enzyme activities, total bacteria count, total carotenoid content, significantly increased. Conversely, lactic acid bacteria were not affected. Overall, the research results demonstrated that adding 200 mg/kg of lutein to the diet improved growth performance, biochemical and immuno-physiological parameters of the oriental river prawn.

Potential health benefits of carotenoid lutein: An updated review.

Carotenoids in food substances are believed to have health benefits by lowering the risk of diseases. Lutein, a carotenoid compound, is one of the essential nutrients available in green leafy vegetables (kale, broccoli, spinach, lettuce, and peas), along with other foods, such as eggs. As nutrition plays a pivotal role in maintaining human health, lutein, as a nutritional substance, confers promising benefits against numerous health issues, including neurological disorders, eye diseases, skin irritation, etc. This review describes the in-depth health beneficial effects of lutein. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The step-by-step biosynthesis of lutein has also been taken into account in this review. Besides, this review demonstrates the drug interactions of lutein with ß-carotene, as well as safety concerns and dosage. The potential benefits of lutein have been assessed against neurological disorders, eye diseases, cardiac complications, microbial infections, skin irritation, bone decay, etc. Additionally, recent studies ascertained the significance of lutein nanoformulations in the amelioration of eye disorders, which are also considered in this review. Moreover, a possible approach for the use of lutein in bioactive functional foods will be discussed.

Predictors of macular pigment and contrast threshold in Spanish healthy normolipemic subjects (45-65 years) with habitual food intake.

INTRODUCTION: The dietary carotenoids lutein (L) and zeaxanthin (Z) are transported in the bloodstream by lipoproteins, sequestered by adipose tissue, and eventually captured in the retina where they constitute macular pigment. There are no L&Z dietary intake recommendations nor desired blood/tissue concentrations for the Spanish general population. Our aim was to assess the correlation of L&Z habitual dietary intake (excluding food supplements), resulting serum concentrations and lipid profile with macular pigment optical density (MPOD) as well as the contrast sensitivity (CT), as visual outcome in normolipemic subjects (n = 101) aged 45-65. METHODS: MPOD was measured by heterochromatic flicker photometry, serum L&Z by HPLC, the dietary intake by a 3-day food records and CT using the CGT-1000-Contrast-Glaretester at six stimulus sizes, with and without glare. RESULTS: Lutein and zeaxanthin concentrations (median) in serum: 0.361 and 0.078 µmol/L, in dietary intake: 1.1 mg L+Z/day. MPOD: 0.34du. L+Z intake correlates with their serum concentrations (rho = 0.333, p = 0.001), which in turn correlates with MPOD (rho = 0.229, p = 0.000) and with fruit and vegetable consumption (rho = 0.202, p = 0.001), but not with lutein+zeaxanthin dietary intake. MPOD correlated with CT, with and without glare (rho ranges: -0.135, 0.160 and -0.121, -0.205, respectively). MPOD predictors: serum L+Z, L+Z/HDL-cholesterol (ß-coeficient: -0.91±0.2, 95%CI: -1.3,-0.5) and HDL-cholesterol (R2 = 15.9%). CT predictors: MPOD, mainly at medium and smaller visual angles (corresponding to spatial frequencies for which sensitivity declines with age) and gender (ß-coefficients ranges: -0.95,-0.39 and -0.13,-0.39, respectively). CONCLUSION: A higher MPOD is associated with a lower ratio of L+Z/HDL-cholesterol and with a lower CT (higher contrast sensitivity). The HDL-cholesterol would also act indirectly on the CT improving the visual function.

Nanoencapsulation of lutein within lipid-based delivery systems: Characterization and comparison of zein peptide stabilized nano-emulsion, solid lipid nanoparticle, and nano-structured lipid carrier.

Three lipid-based carriers encapsulating lutein, nano-emulsion (NE), solid lipid nanoparticle (SLN), and nano-structured lipid carrier (NLC), were developed from zein peptides hydrolyzed by trypsin (TZP) and flavourzyme (FZP) as stabilizers. The physiochemical properties of FZP and TZP were evaluated. The particle size, potential, microstructure, environmental stability, rheological properties, in vitro digestion stability, and bioavailability of the lutein-loaded NE, SLN, and NLC were compared. The results showed that the surface hydrophobicity of TZP was higher than that of FZP. Except for the SLN, most samples were stable against droplet aggregation during storage, and carriers stabilized by TZP exhibited more favorable storage stabilities than those prepared from FZP. All the samples presented characteristics of fluid with good fluidity. The bioavailability of lutein was between 42.61% and 62.81%. In summary, these results provide valuable insights into the design of lipid-based delivery systems for fat-soluble biologically active compounds using zein peptides as stabilizers.

A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration.

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.

Fatty Acids and Lipid Derivatives Protecting Photooxidative Attack in Age-related Macular Degeneration.

The objective is the systematic review of studies published in Scielo, Redalyc, Dialnet, Web of Science, Scopus and Pubmed, related to the inclusion of fatty acids and lipid derivatives in the daily diet to prevent or delay the appearance or progression of Age-Related Macular Degeneration (AMD). The analysis of the research results consulted shows that AMD is one of the most frequent causes of blindness in subjects over 55 years of age. AMD is characterized by decreased vision, metamorphopsia, macropsies, micropsies, and central scotoma. Disease that must be diagnosed early as it can lead to irreversible blindness. Among the components of the diet that in numerous epidemiological studies have shown an association in the treatment of AMD and that are reviewed in this work are fatty acids, vitamins and carotenoids. There is ample evidence that fatty acids and lipid derivatives can be included in the diet plans of subjects with AMD.

Maternal Intake of Lutein and Zeaxanthin during Pregnancy Is Positively Associated with Offspring Verbal Intelligence and Behavior Regulation in Mid-Childhood in the Project Viva Cohort.

BACKGROUND: Lutein and zeaxanthin are carotenoids associated with better cognition at older age. To our knowledge, no previous study has evaluated their cognitive implications in the prenatal period, when the brain undergoes its most rapid development. OBJECTIVE: The objective of this study was to examine associations of maternal lutein and zeaxanthin (L/Z) intake during pregnancy with child cognition. DESIGN: Among 1580 mother-child pairs in Project Viva, a prospective cohort, we assessed maternal intake of L/Z during pregnancy using food frequency questionnaires and offspring cognition by the Visual Recognition Memory paradigm in infancy, the Peabody Picture Vocabulary Test and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) in early childhood, and the Kaufman Brief Intelligence Test (KBIT-II), the WRAVMA drawing subtest, and the Wide Range Assessment of Memory and Learning in mid-childhood. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Strengths and Difficulties Questionnaire. RESULTS: Mothers consumed a daily mean (SD) of 2.6 (2.0) mg L/Z in the first and second trimesters of pregnancy. Mean mid-childhood KBIT-II verbal scores were higher with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: 2.67 (95% CI: 0.13, 5.20) and for second trimester: 3.55 (95% CI: 0.81, 6.28)], indicating better verbal intelligence. Secondary analyses on cognitive subtests showed that mean mid-childhood BRIEF Behavioral Regulation Index scores were lower with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: -1.63 (95% CI: -3.22, -0.04) and for second trimester: -1.89 (95% CI: -3.58, -0.21)], indicating better behavior regulation ability. CONCLUSIONS: Higher maternal L/Z intake during pregnancy was associated with better offspring verbal intelligence and behavior regulation ability in mid-childhood, suggesting a potential benefit during prenatal development. We did not find a benefit of higher maternal L/Z intake on other child cognitive or behavioral outcomes. Project Viva is registered at clinicaltrials.gov as NCT02820402.

Lutein supplementation combined with a low-calorie diet in middle-aged obese individuals: effects on anthropometric indices, body composition and metabolic parameters.

Lutein is considered as a major biologically active carotenoid, with potential benefits for obesity and cardiometabolic health. This double-blind, randomised controlled trial aimed to assess whether the consumption of lutein along with a low-calorie diet (LCD) can influence anthropometric indices, body composition and metabolic parameters in obese middle-aged individuals. After a 2-week run-in period with an LCD, forty-eight participants aged 45-65 years were randomly assigned to consume 20 mg/d lutein or placebo along with the LCD for 10 weeks. Dietary intake, anthropometric indices, body composition, lipid profile, glucose homoeostasis parameters, NEFA and appetite sensations were assessed at the beginning and end of the study. After 10 weeks, body weight and waist circumference significantly decreased in both groups, although between-group differences were not significant. There was more of a decrease in the percentage of body fat in the lutein group v. the placebo group. Moreover, the placebo group experienced a significant reduction in fat-free mass (FFM), whereas the lutein group preserved FFM during calorie restriction, although the between-group difference did not reach statistical significance. Visceral fat and serum levels of total cholesterol (TC) and LDL-cholesterol were significantly decreased only in the lutein group, with a statistically significant difference between the two arms only for TC. No significant changes were observed in the TAG, HDL-cholesterol, glucose homoeostasis parameters, NEFA and appetite sensations. Lutein supplementation in combination with an LCD could improve body composition and lipid profile in obese middle-aged individuals.

Chitosan-sodium alginate-fatty acid nanocarrier system: Lutein bioavailability, absorption pharmacokinetics in diabetic rat and protection of retinal cells against H2O2 induced oxidative stress in vitro.

Aiming to enhance therapeutic efficiency of lutein, lutein loaded chitosan-sodium alginate (CS-SA) based nanocarrier system (LNCs) were prepared and evaluated for lutein bioavailability and pharmacokinetics in diabetic rats in comparison to micellar lutein (control). Further, cytotoxicity, cellular uptake and protective activity against H2O2 induced oxidative stress in ARPE-19 cells were studied. Results revealed that LNCs displayed maximal lutein AUC in plasma, liver and eye respectively in normal (3.1, 2.7 and 5.2 folds) and diabetic (7.3, 3.4 and 2.8 folds) rats. Lutein from LNCs exhibited a higher half-life time, mean residence time and slow clearance from the plasma, indicating prolonged circulation compared to control. In ARPE-19 cells, pre-treatment with LNCs (10 µM) have significantly attenuated H2O2 induced cell death, intracellular ROS and mitochondrial membrane potential compared to control. In conclusion, LNCs improve the lutein bioavailability in conditions like diabetes, diabetic retinopathy and cataract to curtail oxidative stress in retinal cells.

Maternal Docosahexaenoic Acid Status during Pregnancy and Its Impact on Infant Neurodevelopment.

Dietary components are essential for the structural and functional development of the brain. Among these, docosahexaenoic acid, 22:6n-3 (DHA), is critically necessary for the structure and development of the growing fetal brain in utero. DHA is the major n-3 long-chain polyunsaturated fatty acid in brain gray matter representing about 15% of all fatty acids in the human frontal cortex. DHA affects neurogenesis, neurotransmitter, synaptic plasticity and transmission, and signal transduction in the brain. Data from human and animal studies suggest that adequate levels of DHA in neural membranes are required for maturation of cortical astrocyte, neurovascular coupling, and glucose uptake and metabolism. Besides, some metabolites of DHA protect from oxidative tissue injury and stress in the brain. A low DHA level in the brain results in behavioral changes and is associated with learning difficulties and dementia. In humans, the third trimester-placental supply of maternal DHA to the growing fetus is critically important as the growing brain obligatory requires DHA during this window period. Besides, DHA is also involved in the early placentation process, essential for placental development. This underscores the importance of maternal intake of DHA for the structural and functional development of the brain. This review describes DHA's multiple roles during gestation, lactation, and the consequences of its lower intake during pregnancy and postnatally on the 2019 brain development and function.

Multiple Micronutrients, Lutein, and Docosahexaenoic Acid Supplementation during Lactation: A Randomized Controlled Trial.

Breastfed infants require an adequate supply of critical nutrients for growth, tissue functions, and health. Recommended intakes for several nutrients are considerably higher in lactating than non-lactating women but are not always met with habitual diets. We report a randomized, double-blind clinical trial in 70 healthy lactating women in Germany evaluating the effects of supplementation with multiple micronutrients, lutein, and docosahexaenoic acid (DHA) compared to placebo on maternal nutrient status and milk composition. The primary endpoint was the effect on the change of human milk DHA content (as a proportion of total milk fatty acids) during 12 weeks of supplementation. Maternal blood and milk biomarkers were measured as secondary endpoints. Supplementation increased maternal milk DHA by 30% compared to a decline in the placebo group. Supplementation also increased maternal blood DHA (17%), eicosapentaenoic acid (4%), 25-OH-vitamin D (24%), vitamin B12 (12%), lutein (4%), and beta carotene (49%), while homocysteine decreased. No significant difference in the number of adverse events was observed between supplementation and placebo groups. In conclusion, multi-micronutrient supplementation was safe and increased maternal blood and milk concentrations of selected nutrients in healthy women.

Visual Function and Macular Carotenoid Changes in Eyes with Retinal Drusen-An Open Label Randomized Controlled Trial to Compare a Micronized Lipid-Based Carotenoid Liquid Supplementation and AREDS-2 Formula.

PURPOSE: To compare the changes in visual and ocular parameters in individuals with retinal drusen who were treated with two commercially available nutritional supplements. METHODS: An open-label, single-center, randomized, parallel-treatment with an observational control group design was utilized. The treatment groups included individuals with fine retinal drusen sub-clinical age-related macular degeneration (AMD), while the control group consisted of ocular normal individuals. The treatment groups were randomly assigned to the micronized lipid-based carotenoid supplement, Lumega-Z (LM), or the PreserVision Age-Related Eye Disease Study 2 (AREDS-2) soft gel (PV). Visual performance was evaluated using the techniques of visual acuity, dark adaptation recovery and contrast sensitivity, at baseline, three months, and six months. Additionally, the macular pigment optical density (MPOD) was measured. The control group was not assigned any carotenoid supplement. The right eye and left eye results were analyzed separately. RESULTS: Seventy-nine participants were recruited for this study, of which 68 qualified and 56 participants had useable reliable data. Of the individuals who completed this study, 25 participants belonged to the LM group, 16 belonged to the PV group, and 15 to the control group. The LM group demonstrated statistically significant improvements in contrast sensitivity function (CSF) in both eyes at six months (p < 0.001). The LM group displayed a positive linear trend with treatment time in CSF (p < 0.001), with benefits visible after just three months of supplementation. Although there was a trend showing improvement in CSF in the PV group, the change was not significant after a Bonferroni-corrected p-value of p < 0.00625. Visual acuity, dark adaptation recovery and MPOD did not significantly improve in either treatment groups. CONCLUSION: The LM group demonstrated greater and faster benefits in visual performance as measured by CSF when compared to the PV group. This trial has been registered at clinicaltrials.gov (NCT03946085).

Comparative Encapsulation Efficiency of Lutein in Micelles Synthesized via Batch and High Throughput Methods.

PURPOSE: Black raspberries (BRBs) and their anthocyanin-rich hydrophilic fractions (BRB-H) have exhibited significant chemopreventative activity across aerodigestive cancers. Lutein, the primary component of the BRB lipophilic fraction (BRB-L), also demonstrates bioactivity potential, but is less well characterized, in part because of its poor, innate bioavailability. For these lipophilic compounds to be accurately evaluated for anticancer efficacy, it is necessary to increase their functional bioavailability using delivery vehicles. Lutein has been delivered in commercial settings in emulsion form. However, emulsions are unstable, particularly in the gastrointestinal tract, which limit their use as an oral nutraceutical. Here, we evaluated lutein encapsulation and cellular uptake for nanoparticle (NP) delivery vehicles composed of three different materials synthesized via two different approaches. METHODS: Specifically, NPs were synthesized via smaller scale batch interfacial instability (II) sonication and semi-continuous high throughput electrohydrodynamic-mediated mixing nanoprecipitation (EM-NP) methods using polystyrene-polyethylene oxide (PSPEO) or polycaprolactone-polyethylene glycol (PCLPEG) block copolymers and PHOSPHOLIPON 90G® (P90G, Lipoid GmbH) lipids. Size distribution, lutein encapsulation efficiency (EE), and cellular uptake and delivery were evaluated for each NP formulation. RESULTS: NPs produced via high throughput EM-NP had higher EEs than NPs produced via batch II sonication, and P90G had the greatest EE (55%) and elicited faster cellular uptake in premalignant oral epithelial cells (SCC83) compared to other delivery systems. CONCLUSION: These qualities suggest P90G could be a beneficial candidate for future lutein in vitro delivery research and clinical translation for oral cancer prevention.

Dietary Intake of Carotenoid-Rich Vegetables Reduces Visceral Adiposity in Obese Japanese men-A Randomized, Double-Blind Trial.

Metabolic syndrome, whose main diagnostic component is obesity, is a risk factor for lifestyle-related diseases, type 2 diabetes, and cardiovascular disease. Diet is known to affect the prevalence of metabolic syndrome. However, the effect of diet on metabolic syndrome in Japanese subjects has not been thoroughly explored. In the present study, we investigated the effect of carotenoid-rich vegetables, particularly lycopene- and lutein-rich vegetables, on the metabolic syndrome in obese Japanese men. We conducted an 8-week long randomized, double-blinded, controlled clinical trial in which, 28 middle-aged (40 ≤ age < 65) Japanese men with high body mass index (BMI ≥ 25) were randomized into four dietary groups: high lycopene + high lutein (HLyHLu), high lycopene + low lutein (HLyLLu), low lycopene + high lutein (LLyHLu), and low lycopene + low lutein (LLyLLu). Our results showed that daily beverage-intake increased the plasma levels of carotenoids without adverse effects, and the visceral fat level was significantly decreased in all the groups. The waist circumference was significantly decreased only in the HLyLLu group, whereas the CoQ10 oxidation rate was decreased in all the groups. The gene expression profiles of whole blood samples before and after ingestion differed only in the LLyLLu group, indicating the effect of carotenoids on gene expression profile. In conclusion, our results suggest that dietary uptake of carotenoid-rich vegetables increases their concentration in blood and reduces the intra-abdominal visceral fat.

Preparation and characterization of lutein loaded folate conjugated polymeric nanoparticles.

AIM: To prepare and characterise lutein-loaded polylactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOLATE) nanoparticles and evaluate enhanced uptake in SK-N-BE(2) cells. METHODS: Nanoparticles were prepared using O/W emulsion solvent evaporation and characterised using DLS, SEM, DSC, FTIR and in-vitro release. Lutein-uptake in SK-N-BE(2) cells was determined using flow-cytometry, confocal-microscopy and HPLC. Control was lutein PLGA nanoparticles. RESULTS: The size of lutein-loaded PLGA and PLGA-PEG-FOLATE nanoparticles were 189.6 ± 18.79 nm and 188.0 ± 4.06 nm, respectively. Lutein entrapment was ∼61%(w/w) and ∼73%(w/w) for PLGA and PLGA-PEG-FOLATE nanoparticles, respectively. DSC and FTIR confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies showed ∼1.6 and ∼2-fold enhanced uptake of lutein from PLGA-PEG-FOLATE nanoparticles compared to PLGA nanoparticles and lutein, respectively. Cumulative release of lutein was higher in PLGA nanoparticles (100% (w/w) within 24 h) compared to PLGA-PEG-FOLATE nanoparticles (∼80% (w/w) in 48 h). CONCLUSION: Lutein-loaded PLGA-PEG-FOLATE nanoparticles could be a potential treatment for hypoxic ischaemic encephalopathy.

Fatty acids influence the efficacy of lutein in the modulation of α-crystallin chaperone function: Evidence from selenite induced cataract rat model.

BACKGROUND: Loss of α-crystallin chaperone function results in the lens protein aggregation leading to cataract. In this study, we evaluated the efficacy of micellar lutein with different fatty acids in modulating α-crystallin chaperone function under selenite cataract conditions. METHODS: Cataract was induced in rat pups by giving sodium selenite (25 µM/kg body weight) by IP. Lutein [(L), 1.3 µmol/kg body weight)] was given day before and five days after selenite injection as a micelle with 7.5 mM linoleic acid (LA), or 7.5 mM eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) or 7.5 mM oleic acid (OA). Lens α-crystallins was purified, and its chaperone function and integrity was assessed. Cholesterol, calcium, calpain-2, procaspase-3, and expression of α-A and ß-B1 crystallin in the lens of cataract and micellar lutein administered rats were evaluated. RESULTS: Cataract induction significantly (p < 0.05) decreased lens α-crystallin chaperone function. Cataract rats had increased cholesterol and calcium level, increased the expression of calpain-2, and α-A and ß-B1 crystallin, and reduced the pro-caspase-3 level in the lens. However, micellar lutein administration significantly (p < 0.05) protected client proteins from aggregation via the modulation of calcium-dependent calpain-2 protease activity. The chaperone function of lens α-crystallins in rats administered micellar lutein with EPA + DHA was found to be highest when compared to OA and LA. CONCLUSIONS: Micellar lutein with unsaturated fatty acids beneficially modulates α-crystallin chaperone function. Among the fatty acids tested, micellar lutein with EPA + DHA exhibited superior effects, thereby offering a promising strategy for cataract management.