Bioavailability of Lutein from Marigold Flowers (Free vs. Ester Forms): A Randomised Cross-Over Study to Assess Serum Response and Visual Contrast Threshold in Adults.

Lutein (Lut) and zeaxanthin (Zeax) are found in the blood and are deposited in the retina (macular pigment). Both are found in the diet in free form and esterified with fatty acids. A high intake and/or status is associated with a lower risk of chronic diseases, especially eye diseases. There is a large global demand for Lut in the dietary supplement market, with marigold flowers being the main source, mainly as lutein esters. As the bioavailability of Lut from free or ester forms is controversial, our aim was to assess the bioavailability of Lut (free vs. ester) and visual contrast threshold (CT). Twenty-four healthy subjects (twelve women, twelve men), aged 20-35 and 50-65 years, were enrolled in a cross-sectional study to consume 6 mg lutein/day from marigold extract (free vs. ester) for two months. Blood samples were taken at baseline and after 15, 40, and 60 days in each period. Serum Lut and Zeax were analysed using HPLC, and dietary intake was determined with a 7-day food record at the beginning of each period. CT, with and without glare, was at 0 and 60 days at three levels of visual angle. Lut + Zeax intake at baseline was 1.9 mg/day, and serum lutein was 0.36 µmol/L. Serum lutein increased 2.4-fold on day 15 (up to 0.81 and 0.90 µmol/L with free and ester lutein, respectively) and was maintained until the end of the study. Serum Zeax increased 1.7-fold. There were no differences in serum Lut responses to free or ester lutein at any time point. CT responses to lutein supplementation (free vs. ester) were not different at any time point. CT correlated with Lut under glare conditions, and better correlations were obtained at low frequencies in the whole group due to the older group. The highest correlations occurred between CT at high frequency and with glare with serum Lut and Lut + Zeax. Only in the older group were inverse correlations found at baseline at a high frequency with L + Z and with Lut/cholesterol and at a low frequency with Lut/cholesterol. In conclusion, daily supplementation with Lut for 15 days significantly increases serum Lut in normolipemic adults to levels associated with a reduced risk of age-related eye disease regardless of the chemical form of lutein supplied. Longer supplementation, up to two months, does not significantly alter the concentration achieved but may contribute to an increase in macular pigment (a long-term marker of lutein status) and thus improve the effect on visual outcomes.

Changes in Lutein Status Markers (Serum and Faecal Concentrations, Macular Pigment) in Response to a Lutein-Rich Fruit or Vegetable (Three Pieces/Day) Dietary Intervention in Normolipemic Subjects.

Lutein is mainly supplied by dietary fruit and vegetables, and they are commonly jointly assessed in observational and interventional studies. Lutein bioavailability and health benefits depend on the food matrix. This study aimed to assess the effect of dietary intervention with lutein-rich fruit or vegetables on lutein status markers, including serum and faecal concentrations (by high pressure liquid chromatography), dietary intake (24 h recalls ×3), and macular pigment optical density (MPOD) and contrast threshold (CT) as visual outcomes. Twenty-nine healthy normolipemic subjects, aged 45-65 y, consumed 1.8 mg lutein/day supplied from fruits (14 subjects, 500 g/day of oranges, kiwi and avocados) or vegetables (15 subjects, 180 g/day of green beans, pumpkin, and sweet corn) for four weeks. Serum lutein concentration increased by 37%. The effect of the food group intervention was statistically significant for serum lutein+zeaxanthin concentration (p = 0.049). Serum α- and ß-carotene were influenced by food type (p = 0.008 and p = 0.005, respectively), but not by time. Serum lutein/HDL-cholesterol level increased by 29% (total sample, p = 0.008). Lutein+zeaxanthin/HDL-cholesterol increased, and the intervention time and food group eaten had an effect (p = 0.024 and p = 0.010, respectively) which was higher in the vegetable group. The MPOD did not show variations, nor did it correlate with CT. According to correlation matrixes, serum lutein was mainly related to lutein+zeaxanthin expressed in relation to lipids, and MPOD with the vegetable group. In faecal samples, only lutein levels increased (p = 0.012). This study shows that a relatively low amount of lutein, supplied by fruit or vegetables, can have different responses in correlated status markers, and that a longer intervention period is needed to increase the MPOD. Therefore, further study with larger sample sizes is needed on the different responses in the lutein status markers and on food types and consumption patterns in the diet, and when lutein in a "pharmacological dose" is not taken to reduce a specific risk.

The ALGOVUE Clinical Trial: Effects of the Daily Consumption of Eggs Enriched with Lutein and Docosahexaenoic Acid on Plasma Composition and Macular Pigment Optical Density.

BACKGROUND: Carotenoids and docosahexaenoic acid (DHA) were identified as essential components for eye health and are both naturally present in eggs. OBJECTIVE: We aimed to evaluate the effect of the daily consumption of two eggs enriched with lutein/zeaxanthin and DHA on macular pigment optical density (MPOD) and on circulating xanthophyll and fatty acid concentrations in healthy participants. METHODS: Ninety-nine healthy volunteers consumed either two standard eggs or two enriched eggs per day for 4 months. MPOD was measured at baseline (V0) and at follow-up (V4) using a modified confocal scanning laser ophthalmoscope (primary outcome). Blood samples were collected to determine total plasma and lipoprotein fatty acids and lutein/zeaxanthin compositions at V0 and V4 (secondary outcomes). RESULTS: A slight but significant increase in MPOD was observed for all study participants consuming two eggs per day for 4 months at all eccentricities (0.5°, 1°, 2°, and 4°). Plasma and lipoprotein lutein, zeaxanthin, and DHA concentrations significantly increased in both groups but were greater in the enriched group (for the enriched group (V0 vs. V4): lutein, 167 vs. 369 ng/mL; zeaxanthin, 17.7 vs. 29.2 ng/mL; DHA, 1.89 vs. 2.56% of total fatty acids). Interestingly, lutein from high-density lipoprotein (HDL) was strongly correlated with MPOD at 0.5 and 1° eccentricities (rho = 0.385, p = 0.008, and rho = 0.461, p = 0.001, respectively). CONCLUSIONS: MPOD was slightly increased in both groups. Lutein, zeaxanthin, and DHA plasma concentrations were strongly enhanced in the enriched group compared with the standard group. A significant correlation was found between MPOD level and lutein concentration in HDL.

Higher circulating α-carotene was associated with better cognitive function: an evaluation among the MIND trial participants.

There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.

Plasma Lutein, a Nutritional Biomarker for Development of Advanced Age-Related Macular Degeneration: The Alienor Study.

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006-2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41-0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39-0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD.

The Associations of Plasma/Serum Carotenoids with Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer's disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD. OBJECTIVE: Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis. METHODS: Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger's test. RESULTS: Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMD = -0.86, 95% CI: -1.67 to -0.05, p = 0.04) and zeaxanthin (SMD = -0.59; 95% CI: -1.12 to -0.06, p = 0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMD = 0.21, 95% CI: -0.68 to 0.26, p = 0.39), ß-carotene (SMD = 0.04, 95% CI: -0.57 to 0.65, p = 0.9), lycopene (SMD = -0.12, 95% CI: -0.96 to 0.72, p = 0.78), and ß-cryptoxanthin (SMD = -0.09, 95% CI: -0.83 to 0.65, p = 0.81) did not achieve significant differences. CONCLUSION: Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.

Physiological significance of link between polycyclic aromatic hydrocarbons and serum nutritional biomarkers.

It is well-known that exposure to polycyclic aromatic hydrocarbons (PAH) may cause adverse health impacts. However, there are few investigations assessing the association between PAH exposure and the nutritional status of the general population. Thus, the purpose of this investigation was to assess the correlation between PAH metabolites and nutritional biomarkers in the U.S. general population. From the 2003-2006 National Health and Nutrition Examination Survey, 4,545 eligible participants were included in this cross-sectional study. To assess PAH exposure, ten urinary PAH metabolites were measured. Eleven serum nutritional biomarkers including carotenoids and vitamins were measured. The association between PAH metabolites and serum nutritional biomarkers was investigated using multivariate linear regression models. Increased 2-hydroxyfluorene was inversely correlated with elven serum nutritional biomarkers: α-carotene (ß = -0.529, p < 0.001), ß-cryptoxanthin (ß = -0.968, p < 0.001), cis-ß carotene (ß = -0.149, p < 0.001), lutein and zeaxanthin (ß = -1.188, p < 0.001), retinyl palmitate (ß = -0.145, p < 0.001), retinyl stearate (ß = -0.025, p = 0.006), total lycopene (ß = -1.074, p < 0.001), trans-ß carotene (ß = -2.268, p < 0.001), trans-lycopene (ß = -0.466, p < 0.003), retinol (ß = -0.694, p = 0.004) and 25-hydroxyvitamin D (ß = -1.247, p = 0.007). Increased 3-hydroxyfluorene was inversely correlated with eleven serum nutritional biomarkers: α-carotene (ß = -0.740, p < 0.001), ß-cryptoxanthin (ß = -1.377, p < 0.001), cis-ß carotene (ß = -0.205, p < 0.001), lutein and zeaxanthin (ß = -1.521, p < 0.001), retinyl palmitate (ß = -0.209, p < 0.001), retinyl stearate (ß = -0.034, p = 0.014), total lycopene (ß = -1.20, p = 0.007), trans-ß carotene (ß = -3.185, p < 0.001), trans-lycopene (ß = -0.490, p = 0.039), retinol (ß = -1.366, p < 0.001) and 25-hydroxyvitamin D (ß = -2.483, p < 0.001). Increased 1-hydroxypyrene was inversely correlated with eight serum nutritional biomarkers: α-carotene (ß = -0.601, p = 0.001), ß-cryptoxanthin (ß = -1.071, p = 0.001), cis-ß carotene (ß = -0.170, p = 0.001), lutein and zeaxanthin (ß = -1.074, p < 0.001), retinyl palmitate (ß = -0.214, p = 0.005), retinyl stearate (ß = -0.041, p = 0.043), total lycopene (ß = -1.664, p = 0.011) and retinol (ß = -1.381, p = 0.011). These results demonstrate that PAH exposure is significantly correlated with decreased levels of serum nutritional biomarkers.

Validity and Reproducibility of a Culture-Specific Food Frequency Questionnaire in Lebanon.

This study aims to assess the validity and reproducibility of a culture-specific semi-quantitative food frequency questionnaire (FFQ) for Lebanese adults. The 94-item FFQ captures intake of traditional Mediterranean dishes and Western food, reflective of current Lebanese nutrition transition. Among 107 participants (18-65 years), the FFQ was administered at baseline (FFQ-1) and one year thereafter (FFQ-2); 2-3 24-h recalls (24-HRs)/season were collected for a total of 8-12 over four seasons. A subset (n = 67) provided a fasting blood sample in the fall. Spearman-correlation coefficients, Bland-Altman plots, joint-classification and (ICC) were calculated. Mean intakes from FFQ-2 were higher than from the total 24-HRs. Correlations for diet from FFQ-2 and 24-HRs ranged from 0.17 for α-carotene to 0.65 for energy. Joint classification in the same/adjacent quartile ranged from 74.8% to 95%. FFQ-2-plasma carotenoid correlations ranged from 0.18 for lutein/zeaxanthin to 0.59 for ß-carotene. Intra-class correlations for FFQ-1 and FFQ-2 ranged from 0.36 for ß-cryptoxanthin to 0.85 for energy. 24-HRs carotenoid intake varied by season; combining season-specific 24-HRs proximal to biospecimen collection to the FFQ-2 improved diet-biochemical correlations. By applying dietary data from two tools with biomarkers taking into consideration seasonal variation, we report a valid, reproducible Lebanese FFQ for use in diet-disease research.

Efficacy of Commercially Available Nutritional Supplements: Analysis of Serum Uptake, Macular Pigment Optical Density and Visual Functional Response.

Purpose: To compare the change in serum carotenoids, macular pigment optical density (MPOD) and visual function with the intake of two commercially available nutritional supplements. Methods: Participants were given a 24-week supply of a lipid-based micronized liquid medical food, Lumega-Z™ (LM), containing 28 mg of the macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), or given PreserVision™ AREDS 2 Formula (gel-caps; PV) containing 12 mg of the macular carotenoids L and Z, but no reported MZ. Serum levels of L, Z and MZ were obtained at baseline and after 12 weeks. Macular pigment optical densities (MPOD) and visual function were assessed at baseline and after 24 weeks. Results: Average blood serum concentrations of L, Z and MZ in the two groups at baseline were similar. The increases in L, Z and MZ were 0.434, 0.063 and 0.086 mol/L vs. 0.100, 0.043 and 0.001 mol/L, respectively, in the LM vs. PV group. From baseline to week 24, average MPOD in the LM-group increased by 0.064 from 0.418 to 0.482, whereas in the PV-group, it was essentially unchanged (0.461 to 0.459;). Although log-contrast sensitivity was improved in all groups under three conditions (photopic, mesopic and mesopic with glare), the change in log-contrast sensitivity was not statistically significant. Conclusion: Despite only a 2.3-fold higher carotenoid concentration than PV, LM supplementation provides approximately 3-4-fold higher absorption, which leads to a significant elevation of MPOD levels.

Maternal Lutein and Zeaxanthin Concentrations in Relation to Offspring Visual Acuity at 3 Years of Age: The GUSTO Study.

Lutein and zeaxanthin play important roles in visual functions, but their influence on early visual development is unclear. We related maternal lutein and zeaxanthin concentrations during pregnancy to offspring visual acuity (VA) in 471 mother-child pairs from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Maternal concentrations of plasma lutein and zeaxanthin were determined at delivery. We measured uncorrected distance of VA in 3-year old children using a LEA Symbols chart; readings were converted to the logarithm of Minimum Angle of Resolution (logMAR), with >0.3 logMAR indicating poor VA. Associations were examined using linear or Poisson regression adjusted for confounders. The median (inter-quartile range) of maternal lutein and zeaxanthin concentrations were 0.13 (0.09, 0.18) and 0.09 (0.07, 0.12) µmol/L, respectively. A total of 126 children had poor VA. The highest tertile of maternal zeaxanthin concentration was associated with 38% lower likelihood of poor VA in children (95% CI: 0.42, 0.93, p-Trends = 0.02). Higher maternal lutein concentrations were associated with a lower likelihood of poor VA in children (RR 0.60 (95% CI: 0.40, 0.88) for middle tertile; RR 0.78 (95% CI: 0.51, 1.19) for highest tertile (p-Quadratic = 0.02)). In conclusion, lutein and zeaxanthin status during pregnancy may influence offspring early visual development; but the results require confirmation with further studies, including more comprehensive measurements of macular functions.

Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study (the Montrachet Study).

Purpose: The aim of this study was to investigate the prevalence of subretinal drusenoid deposits (SDD) and to identify associated factors in an elderly population. Methods: The participants of the population-based Montrachet study underwent an exhaustive ophthalmologic examination, including color fundus photography and macular spectral domain-optical coherence tomography (SD-OCT), coupled with infrared reflectance imaging. The presence of SDD and other age-related macular degeneration lesions, according to the European Eye Epidemiology SD-OCT classification of macular diseases, and subfoveal choroidal thickness were recorded. Moreover, the association of SDD and both clinical and demographic factors as well as plasma levels of vitamin E and lutein/zeaxanthin (L/Z) were analyzed. Results: The mean age of patients was 82.3 ± 3.8 years and 62.7% were female. The prevalence of SDD was 18.1% (n = 205) in the subjects with at least one eye interpretable (n = 1135). In multivariate analysis, SDD was positively associated with increasing age (OR, 4.6; 95% CI, 2.8-7.7; P < 0.001 for subjects aged >85 years), female sex (OR, 1.7; 95% CI, 1.2-2.4; P = 0.005), and plasma L/Z level (OR, 1.2; 95% CI, 1.0-1.5; P = 0.039), and negatively associated with lipid-lowering drugs use (OR, 0.5; 95% CI, 0.3-0.9; P = 0.014 for statin medications) and subfoveal choroidal thickness (OR, 0.8; 95% CI, 0.7-0.9; P = 0.002). Conclusions: The prevalence of SDD was high in subjects older than 75 years, more frequent in women, and was associated with a thinner choroid. The association with lipid-lowering drugs deserves further investigation.

Application of blood concentration biomarkers in nutritional epidemiology: example of carotenoid and tocopherol intake in relation to chronic disease risk.

BACKGROUND: Biomarkers provide potential to objectively measure the intake of nutrients and foods, and thereby to strengthen nutritional epidemiology association studies. However, there are only a few established intake biomarkers, mostly based on recovery of nutrients or their metabolites in urine. Blood concentration measures provide a potential biomarker source for many additional nutritional variables, but their use in disease-association studies requires further development. OBJECTIVE: The aim of this study was to apply recently proposed serum-based carotenoid and tocopherol intake biomarkers and to examine their association with the incidence of major cardiovascular diseases, cancers, and diabetes in a subset of Women's Health Initiative (WHI) cohorts. METHODS: Serum concentrations of α- and ß-carotene, lutein plus zeaxanthin (L + Z), and α-tocopherol were routinely measured at baseline in a subset of 5488 enrollees in WHI cohorts. Intake biomarkers for these 4 micronutrients, obtained by combining serum concentrations with participant characteristics, were recently proposed using a 153-woman feeding study within WHI. These biomarker equations are augmented here to include pertinent disease risk factors and are associated with subsequent chronic disease incidence in this WHI subset. RESULTS: HRs for a doubling of micronutrient intake differed only moderately from the null for the outcomes considered. However, somewhat lower risks of specific cardiovascular outcomes, breast cancer, and diabetes were associated with a higher intake of α- and ß-carotene, lower risk of diabetes was associated with higher L + Z intake, and elevated risks of certain cardiovascular outcomes were associated with a higher intake of α-tocopherol. These patterns remained following the exclusion of baseline users of dietary supplements. CONCLUSIONS: Concentration biomarkers can be calculated from blood specimens obtained in large epidemiologic cohorts and applied directly in disease-association analyses, without relying on self-reported dietary data. Observed associations between carotenoid and tocopherol biomarkers and chronic disease risk could be usefully evaluated further using stored serum specimens on the entire WHI cohort. This study was registered at www.clinicaltrials.gov as NCT00000611.

Quantification of Lutein + Zeaxanthin Presence in Human Placenta and Correlations with Blood Levels and Maternal Dietary Intake.

Lutein + zeaxanthin (L + Z) are carotenoids recognized in eye health, but less is known about their status during pregnancy. While quantified in maternal and umbilical cord blood, they have never been analyzed in placenta. The purpose of this study is to quantify combined L + Z concentrations in human placenta and correlate with levels in maternal dietary intake, maternal serum, and umbilical cord blood. The proportions of combined L + Z were compared within diet, placenta, maternal serum, and umbilical cord blood among additional carotenoids (lycopene, ß-cryptoxanthin, α-carotene, and ß-carotene). This Institutional Review Boardapproved cross-sectional study enrolled 82 mother-infant pairs. Placenta, maternal serum, and umbilical cord blood samples were analyzed for carotenoids concentrations. Mothers completed a food frequency questionnaire and demographic/birth outcome data were collected. L + Z were present in placenta, median 0.105 micrograms/gram (mcg/g) and were significantly correlated with maternal serum (r = 0.57; p < 0.001), umbilical cord blood levels (r = 0.49; p = 0.001), but not dietary intake (p = 0.110). L + Z were the most prevalent in placenta (49.1%) umbilical cord blood (37.0%), but not maternal serum (18.6%) or dietary intake (19.4%). Rate of transfer was 16.0%, the highest of all carotenoids. Conclusively, L + Z were identified as the two most prevalent in placenta. Results highlight unique roles L + Z may play during pregnancy.

Antioxidants linked with physical, cognitive and psychological frailty: Analysis of candidate biomarkers and markers derived from the MARK-AGE study.

Frailty among elderly people leads to an increased risk for negative health outcomes. To prevent frailty, we need a better understanding of the underlying mechanisms and early detection of individuals at risk. Both may be served by identifying candidate (bio)markers, i.e. biomarkers and markers, for the physical, cognitive, and psychological frailty domains. We used univariate (Rank-ANOVA) and multivariate (elastic net) approaches on the RASIG study population (age range: 35-74 years, n = 2220) of the MARK-AGE study to study up to 331 (bio)markers between individuals with and without frailty for each domain. Biomarkers and markers identified by both approaches were studied further regarding their association with frailty using logistic regression. Univariately, we found lower levels of antioxidants, including ß-cryptoxanthin and zeaxanthin, in those who were physically, cognitively or psychologically frail. Additionally, self-reported health was worse in these three frail groups. Multivariately, we observed lower levels of ß-cryptoxanthin and zeaxanthin in the cognitively frail. Levels of these carotenoids were inversely associated with the risk of being cognitively frail after adjusting for confounders. Antioxidants and self-reported health are potential (bio)markers to detect persons at risk of becoming frail. The biomarkers identified may indicate the involvement of inflammation in frailty, especially for physical and cognitive frailty.

(3R, 3'R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers.

PURPOSE: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan®; OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. METHODS: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration. Retinal morphology was analyzed by histopathology, and target gene expressions were detected with real-time polymerase chain reaction methods. RESULTS: OMX treatment significantly increased the serum zeaxanthin concentration (p < 0.001) and ameliorated oxidative damage by increasing the antioxidant enzyme activities in the retina induced by light (p < 0.001). OMX administration significantly upregulated the expression of genes, including Rhodopsin (Rho), Rod arrestin (SAG), Gα Transducin 1 (GNAT-1), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP43), nuclear factor-(erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase (HO-1) and decreased the expression of nuclear factor-κB (NF- κB) and GFAP by OMX treatment rats. The histologic findings confirmed the antioxidant and gene expression data. CONCLUSIONS: This study suggests that OMX is a potent substance that can be used to protect photoreceptor cell degeneration in the retina exposed to intense light.

ß-Cryptoxanthin and zeaxanthin are highly bioavailable from whole-grain and refined biofortified orange maize in humans with optimal vitamin A status: a randomized, crossover, placebo-controlled trial.

Background: Biofortification of staple crops with ß-carotene is a strategy to reduce vitamin A deficiency, and several varieties are available in some African countries. ß-Cryptoxanthin (BCX)-enhanced maize is currently in field trials. To our knowledge, maize BCX bioavailability has not been assessed in humans. Serum retinol 13C content and xanthophyll concentrations are proposed effectiveness biomarkers for biofortified maize adoption. Objective: We determined the relative difference in BCX and zeaxanthin bioavailability from whole-grain and refined BCX-biofortified maize during chronic feeding compared with white maize and evaluated short-term changes in 13C-abundance in serum retinol. Design: After a 7-d washout, 9 adults (mean ± SD age: 23.4 ± 2.3 y; 5 men) were provided with muffins made from BCX-enhanced whole-grain orange maize (WGOM), refined orange maize (ROM), or refined white maize (RWM) for 12 d in a randomized, blinded, crossover study followed by a 7-d washout. Blood was drawn on days 0, 3, 6, 9, 12, 15, and 19. Carotenoid areas under the curve (AUCs) were compared by using a fixed-effects model. 13C-Abundance in serum retinol was determined by using gas chromatography/combustion/isotope-ratio mass spectrometry on days 0, 12, and 19. Vitamin A status was determined by 13C-retinol isotope dilution postintervention. Results: The serum BCX AUC was significantly higher for WGOM (1.70 ± 0.63 µmol ⋅ L-1 ⋅ d) and ROM (1.66 ± 1.08 µmol ⋅ L-1 ⋅ d) than for RWM (-0.06 ± 0.13 µmol ⋅ L-1 ⋅ d; P < 0.003). A greater increase occurred in serum BCX from WGOM muffins (131%) than from ROM muffins (108%) (P ≤ 0.003). Zeaxanthin AUCs were higher for WGOM (0.94 ± 0.33) and ROM (0.96 ± 0.47) than for RWM (0.05 ± 0.12 µmol ⋅ L-1 ⋅ d; P < 0.003). The intervention did not affect predose serum retinol 13C-abundance. Vitamin A status was within an optimal range (defined as 0.1-0.7 µmol/g liver). Conclusions: BCX and zeaxanthin were highly bioavailable from BCX-biofortified maize. The adoption of BCX maize could positively affect consumers' BCX and zeaxanthin intakes and associated health benefits. This trial is registered at www.clinicaltrials.gov as NCT02800408.

Reduced Carotenoid and Retinoid Concentrations and Altered Lycopene Isomer Ratio in Plasma of Atopic Dermatitis Patients.

Carotenoids and retinoids are known to alter the allergic response with important physiological roles in the skin and the immune system. In the human organism various carotenoids are present, some of which are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors such as the retinoic acid receptor and the retinoid X receptor. In this study, we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n = 20) compared to healthy volunteers (HV, n = 20). The study indicated that plasma levels of the carotenoids lutein (HV 198 ± 14 ng/mL, AD 158 ± 12 ng/mL, p = 0.02; all values in mean ± SEM), zeaxanthin (HV 349 ± 30 ng/mL, AD 236 ± 18 ng/mL, p ≤ 0.01), as well as the retinoids retinol (HV 216 ± 20 ng/mL, AD 167 ± 17 ng/mL, p = 0.04) and all-trans-retinoic acid (HV 1.1 ± 0.1 ng/mL, AD 0.7 ± 0.1 ng/mL, p = 0.04) were significantly lower in the AD-patients, while lycopene isomers, α-carotene, and ß-carotene levels were comparable to that determined in the healthy volunteers. In addition, the ratios of 13-cis- vs. all-trans-lycopene (HV 0.31 ± 0.01, AD 0.45 ± 0.07, p = 0.03) as well as 13-cis- vs. all-trans-retinoic acid (HV 1.4 ± 0.2, AD 2.6 ± 0.6, p = 0.03) were increased in the plasma of AD-patients indicating an AD-specific 13-cis-isomerisation. A positive correlation with SCORAD was calculated with 13-cis- vs. all-trans-lycopene ratio (r = 0.40, p = 0.01), while a negative correlation was observed with zeaxanthin plasma levels (r = -0.42, p = 0.01). Based on our results, we conclude that in the plasma of AD-patients various carotenoids and retinoids are present at lower concentrations, while the ratio of selected lycopene isomers also differed in the AD-patient group. An increase in plasma isomers of both lycopene and retinoic acid may cause an altered activation of nuclear hormone receptor signaling pathways and thus may be partly responsible for the AD-phenotype.

Association of serum lutein and zeaxanthin with quantitative measures of retinal vascular parameters.

To evaluate the association between serum carotenoids and quantitative measures of retinal vasculature in elderly Singapore Chinese subjects. The following details were collected in 128 healthy subjects: sociodemographics, lifestyle information, medical and drug history, and anthropometric measurements. Serum concentrations of carotenoids were estimated in fasting venous blood using high performance liquid chromatography. Retinal vascular parameters were quantitatively measured from retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). The mean age of the population was 54.1 years (range 40 to 81 years). In multiple linear regression analysis, per SD decrease in retinal arteriolar caliber [ß = 0.045 (0.003 to 0.086), p = 0.036], per SD increase in retinal venular caliber [ß = -0.045 (-0.086 to -0.003), p = 0.036] and per SD increase in arteriolar branching angle [ß = -0.039 (-0.072 to -0.006), p = 0.021] were associated with decreased serum lutein. Per SD increase in retinal venular tortuosity [ß = -0.0075 (-0.0145 to -0.0004), p = 0.039] and per SD increase in arteriolar branching angle (ß = -0.0073 [-0.0142 to -0.0059], p = 0.041) were associated with decreased serum zeaxanthin. None of the other carotenoids demonstrated meaningful relationship with quantitative measures of retinal vasculature. Lower levels of lutein and zeaxanthin demonstrated significant relationship with adverse quantitative measures of retinal vasculature in elderly healthy subjects.

Serum lipophilic antioxidants levels are associated with leucocyte telomere length among US adults.

BACKGROUND: To examine the association between serum concentrations of antioxidant and telomere length (TL) in U.S adults. METHODS: Participants of the National Health and Nutrition Examination Survey (NHANES) with data available on TL measures from 2001 to 2002 were included. Serum lipophilic antioxidants level was measured using high performance liquid chromatography with photodiode array detection. We used analysis of co-variance and multivariable-adjusted linear regression models, accounting for the survey design and sample weights. RESULTS: Of the 5992 eligible participants, 47.5% (n = 2844) were men. The mean age was 46.9 years overall, 47.2 years in men and 46.6 in women (p = 0.071). In age, sex, race, education, marital status, adiposity, smoking, C-reactive protein adjusted linear regressions, antioxidant, serum α-carotene, trans-ß-carotene, cis- ß-carotene, ß-cryptoxanthin and combined Lutein/zeaxanthin were positively and significantly associated with TL (all p < 0.001). CONCLUSIONS: Our findings support a possible positive association between serum concentrations of lipophylic antioxidant and TL. The implications of this association deserve further investigation.

Effect of Long-Term Xanthophyll and Anthocyanin Supplementation on Lutein and Zeaxanthin Serum Concentrations and Macular Pigment Optical Density in Postmenopausal Women.

Xanthophylls (lutein, L; zeaxanthin, Z) and anthocyanins are often included in food supplements to improve ocular health. There are no dietary reference intakes for them. The aim was to assess the effects of L, Z and anthocyanin supplementation on short and long-term lutein status markers (serum concentration and macular pigment optical density (MPOD)). Seventy-two postmenopausal women were randomized into a parallel study of 8 months: Group A-anthocyanines (60 mg/day); Group X-xanthophylls (6 mg L + 2 mg Z/day); Group X+A-anthocyanines (60 mg/day) + xanthophylls (6 mg L + 2 mg Z/day). At the beginning of the study, 4 and 8 month serum L and Z concentrations were determined (HPLC), as well as L, Z and anthocyanine dietary intake and MPOD (heterochromic flicker photometry). Baseline concentrations of L (0.35 ± 0.19 µmol/L), Z (0.11 ± 0.05 µmol/L), L+Z/cholesterol/triglycerides (0.07 ± 0.04 µmol/mmol) increased in Group X (2.8- and 1.6-fold in L and Z concentrations) and in group XA (2- and 1.4-fold in L and Z concentrations). MPOD (baseline: 0.32 ± 0.13 du) was not modified in any of the groups at the end of the study. There were no differences in the dietary intake of L+Z and anthocyanin at any point in time in any group. Supplementation of L and Z at a dietary level provoked an increase in their serum concentration that was not modified by simultaneous supplementation with anthocyanins.