Lutein, zeaxanthin, and meso-zeaxanthin supplementation attenuates inflammatory cytokines and markers of oxidative cardiovascular processes in humans.

BACKGROUND AND AIMS: Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the vascular endothelium has been hypothesized to be an initial step in the formation of atherosclerotic plaques, with inflammatory cytokines serving as the signaling mechanism for concomitant macrophage activation. Supplementation with the antioxidative macular xanthophylls (lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]) has been shown to aid in the reduction of inflammatory physiologic responses; therefore, we hypothesized that in our study population, supplementation with these xanthophylls would facilitate a systemic reduction in markers of inflammation and cardiovascular lipid oxidation. METHODS AND RESULTS: In this double-blind placebo-controlled supplementation study, participants were randomly allocated to receive the active intervention containing L (10 mg) + MZ (10 mg) + Z (2 mg) or placebo (containing sunflower oil). Serum concentrations of carotenoids (assessed by HPLC), inflammatory cytokines (IL-6, IL-1ß, TNF-α) and oxidized LDL (OxLDL; by solid-phase sandwich ELISA) were measured at baseline and at 6-months. Results showed that over the supplementation period, compared to placebo, the active group demonstrated statistically significant increases in serum concentrations of L, Z, & MZ (p < 0.05), reductions in inflammatory cytokines IL-1ß (p < 0.001) and TNF-α (p = 0.003), as well as a corresponding reduction in serum OxLDL (p = 0.009). CONCLUSIONS: Our data show that L, Z, & MZ supplementation results in decreased serum IL-1ß, TNF-α, and OxLDL. This suggests that these carotenoids are acting systemically to attenuate oxidative lipid products and inflammation, thus reducing their contribution to atherosclerotic plaque formation.

Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers.

BACKGROUND AND OBJECTIVE: Astaxanthin is a naturally occurring carotenoid with high anti-oxidant properties, but it is a very lipophilic compound with low oral bioavailability. This study was conducted to compare the pharmacokinetic parameters of a novel astaxanthin preparation based on micellar solubilization technology, NovaSOL® 400-mg capsules (Test product), and those of astaxanthin 400-mg capsules (reference product), after single oral dose administration to healthy male adults. METHODS: A single oral dose (400 mg equivalent to 8 mg astaxanthin) of test and reference astaxanthin were administered with 240 mL of water to 12 volunteers according to crossover design, in two phases, with a washout period of 1 week in between. Blood samples were collected at hourly intervals for the first 12 h, then at 24.0, 48.0, and 72.0 h after administration. Aliquots of plasma were centrifuged and the clear supernatant was injected into the high performance liquid chromatography-diode array detection (HPLC-DAD) system. Plasma concentration of astaxanthin versus time profiles were constructed, and the primary pharmacokinetic parameters, maximum concentration (Cmax), area under concentration time curve from time of administration (0) to time (t) [AUC0-t] or to infinity ∞, [AUC0-∞],  half-life (T½) and time to reach Cmax (Tmax) were calculated. RESULTS: The test micellar astaxanthin reached a Cmax of 7.21 µg/ml after 3.67 h compared to only 3.86 µg/ml after 8.5 h for the reference native astaxanthin. CONCLUSION: Micellar formulation of astaxanthin is capable of producing a high concentration of astaxanthin in plasma in a shorter time, thereby expected to provide faster potential therapeutic efficacy.

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.

Astaxanthin Z-isomer-rich diets enhance egg yolk pigmentation in laying hens compared to that in all-E-isomer-rich diets.

The effects of feeding diets containing astaxanthin with different Z-isomer ratios to laying hens on egg qualities, such as astaxanthin concentration in egg yolk and yolk color, were investigated. As the astaxanthin source, a natural microorganism Paracoccus carotinifaciens was used. Astaxanthin with different Z-isomer ratios was prepared by thermal treatment with different conditions and then added to the basal diet at a final astaxanthin concentration of 8 mg/kg. We found that, as the Z-isomer ratios of astaxanthin in the diet increased, the astaxanthin concentration in egg yolk and the yolk color fan score also increased significantly. Importantly, feeding a 50.6% Z-isomer ratio diet increased astaxanthin concentration in egg yolk by approximately fivefold and the color fan score by approximately 2 compared to that in hens fed an all-E-isomer-rich diet. Moreover, we showed that feeding Z-isomer-rich astaxanthin to laying hens increased plasma astaxanthin concentration by more than five times in comparison to that in hens fed an all-E-isomer-rich diet. These results indicate that Z-isomers of astaxanthin have higher bioavailability than that of the all-E-isomer and thus they exhibit greater egg yolk-accumulation efficiency.

Evaluation of Intestinal Absorption of Dietary Halocynthiaxanthin, a Carotenoid from the Sea Squirt Halocynthia roretzi.

Halocynthiaxanthin is an acetylenic carotenoid mainly found in Halocynthia roretzi. To date, several bioactivities of halocynthiaxanthin have been reported, but its mechanism of digestion and absorption in mammals has not been studied yet. In this study, we evaluated the intestinal absorption of halocynthiaxanthin in mice. The halocynthiaxanthin-rich fraction was prepared from the tunicate Halocynthia roretzi. Mice were orally administered the fraction at a dose of 5 mg/kg body weight. The halocynthiaxanthin levels in the plasma, liver, and small intestine, were quantified using HPLC-PDA, 1, 3, 6, and 9 h after ingestion. The halocynthiaxanthin-rich fraction mainly consisted of the all-trans form and a small amount of cis forms. These three isomers were detected in the plasma of mice 3 h after ingestion. Time-course changes after the ingestion of this fraction were found, with cis isomers being more abundant than the all-trans isomer in the mouse plasma and liver. In the small intestine, however, the all-trans isomer was primarily detected. The possibility that cis isomers might be absorbed rapidly from the small intestine cannot be denied, but our results suggest that dietary all-trans-halocynthiaxanthin might be isomerized to the cis isomer after intestinal absorption.

Absorbability of Astaxanthin Was Much Lower in Obese Mice Than in Normal Mice.

Astaxanthin has been favored as a health food supplement by obese consumers. However, no detailed descriptions are available concerning the absorption of astaxanthin in obese individuals. In this study, we conducted acute and chronic feeding experiments in C57BL/6J mice to study the differences in astaxanthin absorption in normal and obese bodies. The obesity condition greatly decreased astaxanthin concentration in the blood and liver, its accumulation in tissues and organs, and the bioaccessibility. This may be related to the excessive intake of sucrose, fatty acids, and cholesterol, the increased gastrointestinal motility, and the disorder of gut microbiota in the obese body. Overall, our study showed that the obese body had a far less oral absorbability of astaxanthin than a normal body, and we suggest that the recommended or approved doses of astaxanthin can be properly increased for the obese body in the hope that astaxanthin will play a more active role in obese individuals.

Safety assessment of astaxanthin from Haematococcus pluvialis: Acute toxicity, genotoxicity, distribution and repeat-dose toxicity studies in gestation mice.

Natural astaxanthin is the strongest antioxidant ever discovered, with many biological functions, and it is widely used in the fields of health food and biomedical research. In the present study, we aimed to investigate the plasma concentration, distribution and safety of astaxanthin from Haematococcus pluvialis in pregnant mice. In the acute studies, the oral LD50 of astaxanthin was greater than 20 g/kg·bw. In mouse bone marrow micronucleus test, 10 g/kg·bw astaxanthin did not cause damage to chromosomes and mitotic apparatus of pregnant mice. After treatment with a single dose of 500 mg/kg·bw astaxanthin, the concentration of astaxanthin in plasma reached the maximum at 8 h (55.7 µg/L), which was completely metabolized after 48 h. In the repeat-dose toxicity test, 100, 250 and 500 mg/kg·bw astaxanthin showed no abnormalities in terms of body and organ weight as well as hematological and biochemical parameters in clinical observation throughout the pregnancy. During pregnancy, the liver accumulated the highest content of astaxanthin, while the eye exhibited the least. The results indicated that administration of astaxanthin from H. pluvialis throughout pregnancy had no adverse effect on mice.

Capsanthin extract prevents obesity, reduces serum TMAO levels and modulates the gut microbiota composition in high-fat-diet induced obese C57BL/6J mice.

The present study investigated the anti-obesity effects and its mechanism of capsanthin (CAP) in high-fat diet-induced obese C57BL/6J mice. Compared with untreated mice on a high-fat diet for 12 weeks, CAP at 200 mg kg-1 reduced the body weight by 27.5%, significantly reversed glucose tolerance, effectively decreased the serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and trimethylamine N-oxide levels, markedly increased microbial diversity. Furthermore, 16S rRNA gene sequencing of the cecal microbiota suggested that CAP increased the abundance of Bacteroidetes, Bifidobacterium and Akkermansia, decreased the abundance of Ruminococcus and the ratio of Firmicutes/Bacteroidetes. Moreover, predicted functional domain analysis indicated that CAP increased the gene abundance of replication and repair, and decreased the gene abundance of membrane transports and carbohydrate metabolisms. Therefore, it seems CAP exhibit anti-obesity effect and might be used as a potential agent against obesity.

Serum xanthophyll carotenoids are associated with estimated glomerular filtration rate in an aged cohort.

Progressive renal decline is associated with increasing oxidative stress. However, the majority of studies have investigated endogenous antioxidants in predominantly advanced stages of kidney disease. Many traditional risk factors associated with renal dysfunction have been linked with cognitive decline as the kidneys and brain share comparable anatomic and haemodynamic characteristics that leave them susceptible to common pathogenic mechanisms. The objective of this study was to examine serum dietary antioxidants and their association with renal function characterised by estimated glomerular filtration rate (eGFR) in a cross-sectional analysis of 570 participants. High performance liquid chromatography quantified serum levels of retinol, α-tocopherol, γ-tocopherol and six carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, lycopene and zeaxanthin) in participants. Multiple regression analyses were used to evaluate associations while adjusting for potential confounders. A sensitivity analysis was performed in cognitively-intact participants only. Serum levels of the xanthophyll carotenoid lutein were positively associated with eGFR in analyses adjusted for age (years), gender, smoking, APOE4 status and Alzheimer's disease. Retinol was inversely associated with eGFR, although was no longer significant in the smaller sensitivity analysis. Our findings identify significant associations between the xanthophyll carotenoids and eGFR. Further investigations are required to confirm these findings.

Niemann-Pick C1-like 1 Promotes Intestinal Absorption of Siphonaxanthin.

Siphonaxanthin is a carotenoid found in certain green algae, and its promising beneficial properties, such as its anti-obesity effect, have recently been demonstrated. However, there is little information about the molecular mechanisms underlying intestinal absorption of siphonaxanthin. In this study, we aimed to elucidate how siphonaxanthin is transported across the intestinal epithelium using differentiated Caco-2 cells (dCaco-2 cells), recombinant proteins, and an animal model. Siphonaxanthin was taken up by dCaco-2 cells, a model of intestinal epithelial cells, and its uptake linearly increased up to at least 6 h. Pharmacological inhibition of Nieman-Pick C1-like 1 (NPC1L1), but not that of scavenger receptor class B type 1 (SR-B1), significantly suppressed siphonaxanthin uptake by dCaco-2 cells. Results from an in vitro binding assay suggested that the N-terminal domain of NPC1L1, which is an extracellular domain of NPC1L1, binds with siphonaxanthin. Moreover, pretreatment with ezetimibe, an inhibitor of NPC1L1, significantly decreased the plasma level of siphonaxanthin following oral administration in mice. Considered together, we concluded that NPC1L1 promotes siphonaxanthin transport across the intestinal epithelium.

Oleic acid as a protein ligand improving intestinal absorption and ocular benefit of fucoxanthin in water through protein-based encapsulation.

In this work, fucoxanthin-oleic acid-protein complexes were constructed to improve the dispersibility and intestinal absorption of fucoxanthin in water. The in vivo absorption/antioxidant capacity was evaluated using a mouse model, and the binding processes were investigated using multi-spectroscopic methods and molecular docking. Results showed that the oleic acid-protein delivery system dramatically improved the absorption of fucoxanthin mainly in its original form. When the molar ratio of oleic acid to bovine serum albumin (BSA) was 4 : 1, the plasma response level of fucoxanthin at 4 h could reach 91.25% that of the pure soybean oil delivery system (336.9 pg mL-1vs. 369.2 pmol mL-1). Furthermore, the loading capacity of BSA to fucoxanthin was increased 5 times when oleic acid acted as a protein ligand. Fucoxanthin, oleic acid and BSA can form complexes with good water dispersibility (transmittance nearly 90% and particle size 265 nm) at the molar ratio of 5 : 4 : 1. Spectral analysis and molecular docking indicated that oleic acid and fucoxanthin have different binding domains in BSA and that fucoxanthin can bind to the hydrophobic cavity of BSA in a static manner. After administration of fucoxanthin-oleic acid-BSA complexes for 15 days in mice, only fucoxanthinol accumulation was discovered in eyes and the ocular antioxidant capability increased by 71.02%. These results suggest that the oleic acid-protein delivery system may be useful in facilitating the application of fat-soluble active substances to hydrophilic food systems.

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.

Serum Carotenoids Reveal Poor Fruit and Vegetable Intake among Schoolchildren in Burkina Faso.

The health benefits of fruits and vegetables are well-documented. Those rich in provitamin A carotenoids are good sources of vitamin A. This cross-sectional study indirectly assessed fruit and vegetable intakes using serum carotenoids in 193 schoolchildren aged 7 to 12 years in the Western part of Burkina Faso. The mean total serum carotenoid concentration was 0.23 ± 0.29 µmol/L, which included α- and ß-carotene, lutein, and ß-cryptoxanthin, and determined with serum retinol concentrations in a single analysis with high performance liquid chromatography. Serum retinol concentration was 0.80 ± 0.35 µmol/L with 46% of children (n = 88) having low values <0.7 µmol/L. Total serum carotene (the sum of α- and ß-carotene) concentration was 0.13 ± 0.24 µmol/L, well below the reference range of 0.9⁻3.7 µmol carotene/L used to assess habitual intake of fruits and vegetables. Individual carotenoid concentrations were determined for α-carotene (0.01 ± 0.05 µmol/L), ß-carotene (0.17 ± 0.24 µmol/L), ß-cryptoxanthin (0.07 ± 0.06 µmol/L), and lutein (0.06 ± 0.05 µmol/L). These results confirm the previously measured high prevalence of low serum vitamin A concentrations and adds information about low serum carotenoids among schoolchildren suggesting that they have low intakes of provitamin A-rich fruits and vegetables.

Nutritional Intervention to Prevent Alzheimer's Disease: Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined.

BACKGROUND: A growing body of scientific evidence suggests that enrichment of certain nutritional compounds in the brain may reduce the risk of Alzheimer's disease (AD). OBJECTIVE: To investigate the impact of supplemental xanthophyll carotenoids plus omega-3 fatty acids on disease progression in patients with AD. METHODS: Three trial experiments were performed. In Trials 1 and 2 (performed on patients with AD over an 18-month period), 12 patients (AD status at baseline: 4 mild and 8 moderate) were supplemented with a xanthophyll carotenoid only formulation (Formulation 1; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day) and 13 patients (AD status at baseline: 2 mild, 10 moderate, and 1 severe) were supplemented with a xanthophyll carotenoid and fish oil combination (Formulation 2; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day plus 1 g/day of fish oil containing 430 mg docohexaenoic acid [DHA] and 90 mg eicopentaenoic acid [EPA]), respectively. In Trial 3, 15 subjects free of AD (the control group) were supplemented for 6 months with Formulation 1. Blood xanthophyll carotenoid response was measured in all trials by HPLC. Omega-3 fatty acids were profiled by direct infusion mass spectrometry. RESULTS: Xanthophyll carotenoid concentration increases were significantly greater for Formulation 2 compared to Formulation 1 (p < 0.05), and progression of AD was less for this group (p = 0.003), with carers reporting functional benefits in memory, sight, and mood. CONCLUSION: This preliminary report suggests positive outcomes for patients with AD who consumed a combination of xanthophyll carotenoids plus fish oil, but further study is required to confirm this important observation.

Dietary astaxanthin can accumulate in the brain of rats.

We evaluated the distribution of astaxanthin in rat brains after a single dose administration and after feeding 0.1% astaxanthin diet for 5 days. Astaxanthin was detected in the hippocampus and cerebral cortex 4 and 8 h after a single dose. Astaxanthin concentration in rat brains was higher after consumption of astaxanthin diet for 5 days than after a single dose.

Provitamin A-biofortified maize consumption increases serum xanthophylls and 13C-natural abundance of retinol in Zambian children.

Plants that undergo C4 photosynthesis, such as maize, are enriched in the stable isotope of carbon (13C) compared with other dietary plants and foods. Consumption of maize that has been biofortified to contain elevated levels of provitamin A carotenoids (orange maize) increased the abundance of 13C in serum retinol of Mongolian gerbils. We evaluated this method in humans to determine if it has potential for further use in intervention effectiveness studies. A random subset of samples from a two-month randomized controlled feeding trial of rural three- to five-year old Zambian children were used to determine the impact of orange maize intake on serum carotenoid concentrations ( n = 88) and 13C-natural abundance in serum retinol ( n = 77). Concentrations of ß-cryptoxanthin (a xanthophyll provitamin A carotenoid) and the dihydroxy xanthophylls lutein and zeaxanthin, which do not have vitamin A activity, were elevated in children consuming orange maize compared with those consuming a white maize control ( P < 0.001), while ß-carotene was not different ( P > 0.3). Furthermore, 13C natural abundance was higher after two months' intervention in the orange maize group compared with the white maize group ( P = 0.049). Predictions made from equations developed in the aforementioned gerbil study estimated that maize provided 11% (2-21%, 95% confidence interval) of the recent dietary vitamin A to these children. These results demonstrate that orange maize is efficacious at providing retinol to the vitamin A pool in children through provitamin A carotenoids, as monitored by the change in 13C enrichment, which was not reflected in serum ß-carotene concentrations. Further effectiveness studies in countries who have adopted orange maize should consider determining differences in retinol 13C-enrichment among target groups in addition to profiling serum xanthophyll carotenoids with specific emphasis on zeaxanthin. Impact statement Maize biofortified with provitamin A carotenoids (orange) has been released in some African markets. Responsive and sensitive methods to evaluate dissemination effectiveness are needed. This study investigated methods to evaluate effectiveness of orange maize consumption using serum from Zambian children fed orange maize for two months. Many varieties of orange maize contain higher amounts of the xanthophyll carotenoids in addition to ß-carotene compared with typical varieties. This study uniquely showed higher concentrations of the maize xanthophylls lutein, zeaxanthin, and ß-cryptoxanthin in children who consumed orange maize compared with white. Furthermore, maize is a C4 plant and is therefore naturally enriched with 13C. Higher 13C was detected in the serum retinol of the orange maize consumers with no change in serum ß-carotene concentration suggesting preferential bioconversion to retinol. The combined analyses of serum zeaxanthin specifically and 13C-natural abundance of retinol could prove useful in effectiveness studies between orange maize adopters and non-adopters.

Plasma Carotenoids Are Inversely Associated With Dementia Risk in an Elderly French Cohort.

BACKGROUND: Although intake of fruits and vegetables has been associated with a decreased risk of dementia, studies focusing on nutrients underlying this association are lacking. Our objective was to analyze the relation between plasma carotenoids and the risk of dementia and Alzheimer's disease (AD) in French elderly community dwellers. METHODS: The study population consisted of 1,092 nondemented older participants, from the Three-City-Bordeaux cohort followed for up to 10 years (range: 1.8-10.8 years, median: 9.5 years). Dementia and AD were diagnosed by a committee of neurologists. The concentration of plasma carotenoids (beta-carotene, alpha-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin) was determined at baseline. Longitudinal analyses of the association between each plasma carotenoid, either crude or expressed as a ratio to plasma lipids (total cholesterol + triglycerides), and the risk of dementia or AD were performed by multivariate Cox models. RESULTS: During follow-up, 199 dementia cases, including 132 AD, occurred. After adjustment for sociodemographic data, diet quality, and clinical variables, including baseline cognitive performances, only higher lutein concentration, considered as a function of plasma lipids, was consistently significantly associated with a decreased risk of all-cause dementia and AD (hazard ratio = 0.808, 95% confidence interval = 0.671-0.973, p = .024 and hazard ratio = 0.759, 95% confidence interval = 0.600-0.960, p = .021, respectively for +1 SD). CONCLUSION: This large cohort of older participants suggests that maintaining higher concentrations of lutein in respect to plasma lipids may moderately decrease the risk of dementia and AD.

Pretreatment serum xanthophyll concentrations as predictors of head and neck cancer recurrence and survival.

BACKGROUND: The purpose of this study was to examine associations of pretreatment serum carotenoids, tocopherols, and quercetin with prognosis in 154 patients newly diagnosed with head and neck cancer. METHODS: Pretreatment blood and health surveys were collected. Serum micronutrients were measured by high performance liquid chromatography. Data on recurrence and death were collected annually. Cox proportional hazards models measured associations of serum nutrient concentrations with recurrence and overall survival. RESULTS: During a median follow-up time of 37 months, there were 32 recurrences and 27 deaths. After controlling for covariates, subjects with high versus low serum xanthophyll and total carotenoid concentrations had significantly longer recurrence-free time (p = .002 and p = .02, respectively). Overall survival time was significantly longer in patients with high versus low serum xanthophyll concentrations (p = .02). CONCLUSION: Future research should evaluate the possible benefits of interventions to increase intakes of rich food sources of xanthophylls in this patient population. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1591-E1597, 2016.

A New Method to Simultaneously Quantify the Antioxidants: Carotenes, Xanthophylls, and Vitamin A in Human Plasma.

A simple and accurate reversed phase high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) method for simultaneously determining and quantifying the antioxidants carotenes, xanthophylls, and retinol in human plasma is presented in this paper. Compounds were extracted with hexane, a C30 column, and a mobile phase of methanol, methyl tert-butyl ether, and water were used for the separation of the compounds. A total of 8 carotenoids, 3 Z-ß-carotene isomers, and 1 fat-soluble vitamin (retinol) were resolved within 72 min at a flow rate of 0.6 mL/min. Detection was achieved at 450 nm for carotenoids and 330 nm for retinol. To evaluate the effectiveness of themethod, it has been applied to an intervention study conducted on eight volunteers. Results. Limits of detection were between 0.1 µg/mL for lycopene and astaxanthin and 1.3 µg/mL for 15-Z-ß-carotene. Recoveries were ranged between 89% and 113% for α-carotene and astaxanthin, respectively. Accuracy was between 90.7% and 112.2% and precision was between 1% and 15% RSD. In human plasma samples compounds studied were identified besides three lycopene isomers, demonstrated to be suitable for application in dietary intervention studies. Conclusions. Due to its accuracy, precision, selectivity, and reproducibility, this method is suitable to dietary habits and/or antioxidants status studies.

Accumulation of Paprika Carotenoids in Human Plasma and Erythrocytes.

The accumulation (incorporation) of paprika carotenoid in human plasma and erythrocytes was investigated. A paprika carotenoid supplement (14 mg/day) was ingested for 4 weeks by 5 young healthy volunteers (3 men and 2 women). After 2 weeks of carotenoid ingestion, the carotenoid levels in plasma and erythrocytes increased by 1.2-fold and 2.2-fold, respectively. Characteristic carotenoids found in paprika (capsanthin, cucurbitaxanthin A, and cryptocapsin) were detected in both plasma and erythrocytes. An oxidative metabolite of capsanthin (capsanthone) was also found in both plasma and erythrocytes.