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.

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.

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.

Increases in plasma lutein through supplementation are correlated with increases in physical activity and reductions in sedentary time in older adults.

Cross-sectional studies have reported positive relationships between serum lutein concentrations and higher physical activity levels. The purpose of the study was to determine whether increasing plasma lutein levels increases physical activity. Forty-four older adults (BMI, 25.3 ± 2.6 kg/m²; age, 68.8 ± 6.4 year) not meeting Australian physical activity guidelines (150 min/week of moderate to vigorous activity) were randomized to consume capsules containing 21 mg of lutein or placebo with 250 mL of full-cream milk per day for 4 weeks and encouraged to increase physical activity. Physical activity was assessed by self-report, pedometry and accelerometry (daily activity counts and sedentary time). Exercise self-efficacy was assessed by questionnaire. Thirty-nine participants competed the study (Lutein = 19, Placebo = 20). Lutein increased plasma lutein concentrations compared with placebo (p < 0.001). Absolute and percentage changes in plasma lutein were inversely associated with absolute (r = -0.36, p = 0.03) and percentage changes (r = -0.39, p = 0.02) in sedentary time. Percentage change in plasma lutein was positively associated with the percentage change in average daily activity counts (r = 0.36, p = 0.03). Exercise self-efficacy did not change (p = 0.16). Lutein increased plasma lutein, which was associated with increased physical activity and reduced sedentary time in older adults. Larger trials should evaluate whether Lutein can provide health benefits over the longer term.

Serum carotenoid levels and risk of lung cancer death in US adults.

Lung cancer is one of the most common cancers worldwide and is the leading cause of cancer-induced death in the USA. Although much attention has been focused on the anti-carcinogenic effect of consuming carotenoid-containing food or supplements, the results have been inconsistent. We investigated whether serum carotenoid levels were associated with the mortality risk of lung cancer in US adults using data from a nationally representative sample. The data were obtained from the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. A total of 10,382 participants aged over 20,years with available serum carotenoid levels and no other missing information on questionnaires and biomarkers at baseline (NHANES III) were included in the present study. Of the 10,382 participants, 161 subjects died due to lung cancer. We found that high serum levels of alpha-carotene and beta-cryptoxanthin at baseline were significantly associated with a lower risk of lung cancer death. When we stratified the risk by current smoking status, the risk of death of current smokers was significantly decreased to 46% (95% confidence interval, 31-94%) for alpha-carotene and 61% (95% confidence interval, 19-80%) for beta-cryptoxanthin. By contrast, no association was observed among never/former smokers at baseline. High serum levels of alpha-carotene and beta-cryptoxanthin are associated with a lower risk of lung cancer death in US adults.

Validation of an FFQ to assess short-term antioxidant intake against 30 d food records and plasma biomarkers.

OBJECTIVE: To validate a brief FFQ developed for capturing short-term antioxidant intake in a sample of US college students. DESIGN: A seventy-four-item antioxidant FFQ was developed based on major antioxidant sources in the American diet. The FFQ was validated against 30 d food records (FR) and plasma antioxidant concentrations. The reliability of the FFQ was evaluated by two FFQ administered at a 1-month interval. Settings University of Connecticut, CT, USA. SUBJECTS: Sixty healthy college students. RESULTS: Estimates of dietary antioxidants from the FFQ were moderately to highly correlated with those estimated from the 30 d FR (r = 0·29-0·80; P < 0·05) except for γ-tocopherol and ß-cryptoxanthin. Total antioxidant capacity from diet only or from diet and supplements estimated by the 30 d FR and FFQ were highly correlated (r = 0·67 and 0·71, respectively; P < 0·0001). The FFQ categorized 91 % of participants into the same or adjacent tertiles of antioxidant intake as the 30 d FR. Most dietary carotenoids estimated from the FFQ were correlated with plasma levels (P < 0·05). Correlation coefficients for test-retest reliability ranged from 0·39 to 0·86. More than 94 % of the participants were classified in the same or adjacent tertiles between the two administrations of the FFQ. CONCLUSIONS: The brief FFQ demonstrated reasonable validity for capturing a comprehensive antioxidant intake profile. This FFQ is applicable in epidemiological or clinical studies to capture short-term antioxidant intake or to simply document the variations of antioxidant intake in intervention trials. Cross-validation studies are warranted in other target populations.

Inverse associations between serum concentrations of zeaxanthin and other carotenoids and colorectal neoplasm in Japanese.

BACKGROUND: To investigate the associations between serum concentrations of carotenoids and the presence of colorectal polyps and cancers in Japanese using a cross-sectional study. METHODS: 893 subjects who underwent colorectal endoscopy between 2001 and 2002 provided serum samples and information on lifestyle factors. Serum concentrations of six carotenoids were compared among patients with polyps, cancers, and controls. RESULTS: In males, high serum zeaxanthin was associated with decreased rates of polyps [odds ratio (OR) = 0.48, 95 % confidence interval (CI) 0.27-0.87] and cancer (OR = 0.35, 95 % CI 0.12-1.06), adjusting for age, body mass index, serum cholesterol, smoking status, and alcohol intake. In females, zeaxanthin (OR = 0.25, 95 % CI 0.07-0.82), lutein (OR = 0.30, 95 % CI 0.10-0.94), alpha-carotene (OR = 0.30, 95 % CI 0.10-0.90), and beta-carotene (OR = 0.27, 95 % CI 0.09-0.85) showed significant inverse associations with cancer development. These associations were consistent with findings of inverse associations between the ingestion of green-yellow vegetables (OR = 0.44, 95 % CI 0.23-0.84), carrots and pumpkins (OR = 0.46, 95 % CI 0.25-0.86), and fruits (OR = 0.53, 95 % CI 0.30-0.94) and polyp in males, and between carrots and pumpkins (OR = 0.30, 95 % CI 0.09-0.99), legumes (OR = 0.14, 95 % CI 0.04-0.44), and seaweed (OR = 0.23, 95 % CI 0.07-0.75) and cancer development in females. CONCLUSIONS: These results provide further support for the protective effects of carotenoids contained in green-yellow vegetables and fruits against colorectal neoplasm in Japanese.

Age-related macular degeneration: Effects of a short-term intervention with an oleaginous kale extract--a pilot study.

OBJECTIVE: Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the retina, which accounts for slowly progressive visual impairment in the elderly. An increased dietary intake of xanthophylls is suggested to be inversely related to the risk of macular disease. METHODS: The present study was designed as a randomized, double-blind, placebo-controlled, parallel trial examining the influence of a short-term intervention with an oleaginous extract of Brassica oleracea var. sabellica L. (kale) on plasma xanthophyll concentrations and the optical density of the macular pigment xanthophylls (MPOD). Twenty patients with non-exudative AMD were recruited for a 10-wk study period (2-wk run-in, 4-wk intervention, 4-wk washout). All participants received 50 mL of a beverage containing either an oleaginous extract of kale (kale) or refined rapeseed oil (placebo). The verum product provides 10 mg lutein and 3 mg zeaxanthin per day. RESULTS: The concentrations of the xanthophylls in plasma and the MPOD increased significantly in the kale group after 4 wk of intervention. The successive washout period resulted in a significant decline of the values in plasma and macula. The values at the end of the study were still significantly higher than the initial values. Nevertheless, the improvements did not persist over 4 wk of washout. CONCLUSION: The distribution of the xanthophylls in the macula seems to be more dynamic than originally assumed.

Dietary fiber intake modifies the association between secondhand smoke exposure and coronary heart disease mortality among Chinese non-smokers in Singapore.

OBJECTIVE: Secondhand smoke (SHS) exposure increases the risk for coronary heart disease (CHD) by an estimated 25% to 30% via oxidative stress and inflammatory mechanisms that may be ameliorated by dietary components. The aim of this study was to evaluate the hypothesized modifying role of nutrients with known antioxidant and/or anti-inflammatory properties on the relationship between SHS exposure and CHD mortality. METHODS: Detailed SHS exposure and dietary information was collected among 29,579 non-smokers in the Singapore Chinese Health Study, a prospective population-based cohort. The evaluation of whether or not dietary factors (ß-cryptoxanthin, lutein, ω-3 polyunsaturated fatty acids, fiber, isothiocyanates, and soy isoflavones) modified the relationship between SHS exposure and CHD mortality was conducted within multivariable Cox proportional hazards models by creating an interaction term between the potential dietary effect modifier (lowest quartile of intake versus the second through fourth quartiles of intake) and the SHS exposure (none versus living with at least one smoker[s]). RESULTS: Evidence for a main-effects association between SHS exposure and risk for CHD mortality was not observed. In stratified analyses by levels of selected dietary nutrient intake, fiber modified the effects of SHS exposure on risk for CHD mortality (P for interaction = 0.02). The adjusted hazards ratio for SHS exposure (living with at least one smoker[s] versus living with no smokers) and CHD mortality was 1.62 (95% confidence interval, 1.00-2.63) for those with low-fiber intake. In contrast, among those with high-fiber intake, there was no association with SHS exposure. CONCLUSION: We provide evidence that a diet high in fiber may ameliorate the harmful effects of SHS exposure on risk for CHD mortality.

Association of blood antioxidants and vitamins with risk of age-related cataract: a meta-analysis of observational studies.

BACKGROUND: Observational studies have been inconsistent regarding the association between blood antioxidants or vitamins and risk of age-related cataract. OBJECTIVE: We performed a meta-analysis to determine whether an association exists between blood levels of antioxidants or vitamins and age-related cataract in observational studies. DESIGN: We searched PubMed, EMBASE, and the Web of Science for relevant studies from inception to October 2012. Study-specific risk estimates were combined by using a random-effects model. RESULTS: A total of 13 studies with 18,999 participants were involved in this meta-analysis. A pooled estimate showed vitamin E (OR: 0.75; 95% CI: 0.58, 0.96), α-carotene (OR: 0.72; 95% CI: 0.59, 0.88), lutein (OR: 0.75; 95% CI: 0.65, 0.87), and zeaxanthin (OR: 0.70; 95% CI: 0.60, 0.82) were inversely associated with age-related cataract. Vitamins A (OR: 0.69; 95% CI: 0.58, 0.83) and C (OR: 0.67; 95% CI: 0.57, 0.78) were inversely associated with age-related cataract in Asian populations but not in Western populations. ß-Carotene (OR: 0.90; 95% CI: 0.78, 1.05), lycopene (OR: 0.86; 95% CI: 0.65, 1.15), and ß-cryptoxanthin (OR: 0.83; 95% CI: 0.68, 1.02) had no significant association with risk of cataract. CONCLUSIONS: This meta-analysis provides additional evidence supporting the view that blood levels of certain antioxidants are inversely associated with risk of age-related cataract. However, the role of antioxidant or vitamin supplement intake in preventing cataract should be further investigated in interventional studies.

Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4.

IMPORTANCE: Age-related cataract is a leading cause of visual impairment in the United States. The prevalence of age-related cataract is increasing, with an estimated 30.1 million Americans likely to be affected by 2020. OBJECTIVE: To determine whether daily oral supplementation with lutein/zeaxanthin affects the risk for cataract surgery. DESIGN, SETTING, AND PATIENTS: The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, double-masked clinical trial, enrolled 4203 participants, aged 50 to 85 years, at risk for progression to advanced age-related macular degeneration. INTERVENTIONS: Participants were randomly assigned to daily placebo; lutein/zeaxanthin, 10mg/2mg; omega-3 long-chain polyunsaturated fatty acids, 1 g; or a combination to evaluate the effects on the primary outcome of progression to advanced age-related macular degeneration. MAIN OUTCOMES AND MEASURES: Cataract surgery was documented at annual study examination with the presence of pseudophakia or aphakia, or reported during telephone calls at 6-month intervals between study visits. Annual best-corrected visual acuity testing was performed. A secondary outcome of AREDS2 was to evaluate the effects of lutein/zeaxanthin on the subsequent need for cataract surgery. RESULTS: A total of 3159 AREDS2 participants were phakic in at least 1 eye and 1389 of 6027 study eyes underwent cataract surgery during the study, with median follow-up of 4.7 years. The 5-year probability of progression to cataract surgery in the no lutein/zeaxanthin group was 24%. For lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratios for progression to cataract surgery was 0.96 (95% CI, 0.84-1.10; P = .54). For participants in the lowest quintile of dietary intake of lutein/zeaxanthin, the hazard ratio comparing lutein/zeaxanthin vs no lutein/zeaxanthin for progression to cataract surgery was 0.68 (95% CI, 0.48-0.96; P = .03). The hazard ratio for 3 or more lines of vision loss was 1.03 (95% CI, 0.93-1.13; P = .61 for lutein/zeaxanthin vs no lutein/zeaxanthin). CONCLUSIONS AND RELEVANCE: Daily supplementation with lutein/zeaxanthin had no statistically significant overall effect on rates of cataract surgery or vision loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

Comparison of high-performance liquid chromatography/tandem mass spectrometry and high-performance liquid chromatography/photo-diode array detection for the quantitation of carotenoids, retinyl esters, α-tocopherol and phylloquinone in chylomicron-rich fractions of human plasma.

RATIONALE: Bioavailability of essential lipophilic micronutrients and carotenoids is of utmost interest for human health, as the consumption of these compounds may help alleviate major nutritional deficiencies, cardiovascular disease, and cancer. High-performance liquid chromatography/photo-diode array detection (HPLC-PDA) and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) were compared for the quantitative analysis of α- and ß-carotene, ß-cryptoxanthin, lutein, lycopene, α-tocopherol, phylloquinone, and several retinyl esters from chylomicron-containing triglyceride rich lipoprotein (TRL) fractions of human plasma obtained from two clinical trials. METHODS: After selecting an efficient extraction method for the analytes, both the HPLC/PDA and the HPLC/MS/MS methods were developed and several parameters validated using an HP 1200 series HPLC system interfaced with a HP 1200 series diode-array detector (Agilent Technologies, Santa Clara, CA, USA) and a QTRAP 5500 (AB Sciex, Foster City, CA, USA) via an atmospheric pressure chemical ionization (APCI) probe operated in positive ion mode. RESULTS: For lycopene, α- and ß-carotene, HPLC/MS/MS was up to 37 times more sensitive than HPLC-PDA. PDA detection was shown to be up to 8 times more sensitive for lutein. MS/MS signals were enhanced by matrix components for lutein and ß-cryptoxanthin, as determined by referencing to the matrix-independent PDA signal. In contrast, matrix suppression was observed for retinyl palmitate, α-carotene, and ß-carotene. Both detectors showed similar suitability for α-tocopherol, lycopene and retinyl palmitate (representing ~73% of total retinyl esters). MS/MS exclusively allowed the quantitation of minor retinyl esters, phylloquinone, and (Z)-lycopene isomers. CONCLUSIONS: HPLC/MS/MS was more sensitive than HPLC-PDA for six of the eight analytes and represents a powerful tool for the analysis of chylomicron samples and potentially other biological samples of limited sample size. When internal standards are available for the target carotenoid, employing MS/MS detection may reduce the necessary blood sample volume, which is particularly advantageous for minimizing risk and discomfort to human subjects during clinical studies.

Race-ethnicity is a strong correlate of circulating fat-soluble nutrient concentrations in a representative sample of the U.S. population.

Sociodemographic and lifestyle factors exert important influences on nutritional status; however, information on their association with biomarkers of fat-soluble nutrients is limited, particularly in a representative sample of adults. Serum or plasma concentrations of vitamin A, vitamin E, carotenes, xanthophylls, 25-hydroxyvitamin D [25(OH)D], SFAs, MUFAs, PUFAs, and total fatty acids (tFAs) were measured in adults (aged ≥ 20 y) during all or part of NHANES 2003-2006. Simple and multiple linear regression models were used to assess 5 sociodemographic variables (age, sex, race-ethnicity, education, and income) and 5 lifestyle behaviors (smoking, alcohol consumption, BMI, physical activity, and supplement use) and their relation to biomarker concentrations. Adjustment for total serum cholesterol and lipid-altering drug use was added to the full regression model. Adjustment for latitude and season was added to the full model for 25(OH)D. Based on simple linear regression, race-ethnicity, BMI, and supplement use were significantly related to all fat-soluble biomarkers. Sociodemographic variables as a group explained 5-17% of biomarker variability, whereas together, sociodemographic and lifestyle variables explained 22-23% [25(OH)D, vitamin E, xanthophylls], 17% (vitamin A), 15% (MUFAs), 10-11% (SFAs, carotenes, tFAs), and 6% (PUFAs) of biomarker variability. Although lipid adjustment explained additional variability for all biomarkers except for 25(OH)D, it appeared to be largely independent of sociodemographic and lifestyle variables. After adjusting for sociodemographic, lifestyle, and lipid-related variables, major differences in biomarkers were associated with race-ethnicity (from -44 to 57%), smoking (up to -25%), supplement use (up to 21%), and BMI (up to -15%). Latitude and season attenuated some race-ethnicity differences. Of the sociodemographic and lifestyle variables examined, with or without lipid adjustment, most fat-soluble nutrient biomarkers were significantly associated with race-ethnicity.

Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids.

OBJECTIVE: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). DESIGN: A cross-sectional study of healthy adults aged 20 to 70. PARTICIPANTS: We recruited 302 participants after local advertisement. METHODS: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts. MAIN OUTCOME MEASURES: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender. RESULTS: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10(-4)), an SNP in high linkage disequilibrium with rs11057841 (r(2) = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. CONCLUSIONS: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Self-report of fruit and vegetable intake that meets the 5 a day recommendation is associated with reduced levels of oxidative stress biomarkers and increased levels of antioxidant defense in premenopausal women.

BACKGROUND: Oxidative stress has been associated with a variety of chronic diseases and reproductive disorders. Fruits and vegetables (F/V) may contribute to antioxidant vitamin and micronutrient levels and reduce oxidative stress. OBJECTIVE: To investigate the effect of meeting the 5 A Day For Better Health Program recommendation for F/V consumption on biomarkers of oxidative damage and antioxidant defense. DESIGN: In this longitudinal study, healthy premenopausal women (n=258) were followed for ≤2 menstrual cycles with ≤16 oxidative stress measures timed to cycle phase. MAIN OUTCOME MEASURES: Plasma concentrations of F2-isoprostane, 9-hydroxyoctadecadieneoic acid, 13-hydroxyoctadecadieneoic acid, erythrocyte activity of superoxide dismutase, glutathione reductase, and glutathione peroxidase, as well as blood micronutrient concentrations were measured. Dietary intake was assessed by food frequency questionnaires (FFQs) (1 per cycle), and 24-hour recalls (≤4 per cycle). STATISTICAL ANALYSES PERFORMED: Fruit and vegetable servings were dichotomized based on the recommendation to consume five servings of F/V each day. Linear mixed models with repeated measures were used to analyze lipid peroxidation markers, antioxidant vitamins, and antioxidant enzymes by cycle phase and in association with usual F/V intake. RESULTS: For both 24-hour recall (timed to cycle phase) and cycle-specific FFQ, meeting the recommendation to consume five servings of F/V each day was associated with decreased F2-isoprostanes (24-hour recall ß=-.10 [95% CI, -0.12 to -0.07]; FFQ ß= -.14 [95% CI, -0.18 to -0.11]). Glutathione reductase was lower in association with typical consumption of five or more servings of F/V by FFQ but not in the phase-specific analysis. Higher levels of ascorbic acid, lutein, beta carotene, and beta cryptoxanthin were observed with both intake measures. CONCLUSIONS: Meeting the 5 A Day For Better Health Program recommendation was associated with lower oxidative stress and improved antioxidant status in analyses of typical diet (via FFQ) and in menstrual cycle phase-specific analyses using 24-hour recalls. Green salads were commonly eaten and increasing intake of salads may be a useful strategy to influence oxidation in reproductive aged women.

Effects of lutein supplementation on biological antioxidant status in preterm infants: a randomized clinical trial.

OBJECTIVE: To test the hypothesis that lutein, compared to the placebo, would enhance the total antioxidant status (TAS) in the preterm infants. METHODS: Infants with gestational age (GA) ≤34 weeks were randomly assigned to receive a daily dose of lutein and zeaxanthin (0.5 mg + 0.02 mg/kg/d) or placebo from the 7th day of life until 40th week of postmenstrual age or until discharge. RESULTS: Seventy-seven preterm infants were randomized (38 in the Lutein group and 39 in the Placebo group) with mean GA of 30.4 (±2.3) weeks and the mean birth weight of 1415 (±457) grams. The TAS did not result statistically different between the two groups during all the study period, but a significant linear correlation was evidenced between plasma lutein concentration and TAS (r = 0.14, p = 0.012) and between plasma zeaxanthin concentration and TAS (r = 0.13, p = 0.02). CONCLUSIONS: Supplementation of preterm infants with orally lutein was ineffective in enhancing biological antioxidant capacity. Further studies need to better understand the bioavailability of lutein in the neonatal period in order to identify any best form of supplementation. TRIAL REGISTRATION NUMBER: UMIN000007041.

Effective inhibition of skin cancer, tyrosinase, and antioxidative properties by astaxanthin and astaxanthin esters from the green alga Haematococcus pluvialis.

Astaxanthin mono- (AXME) and diesters (AXDE) were characterized and examined for anticancer potency with total carotenoids (TC) and astaxanthin (AX) against UV-7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer model in rat. At 200 µg/kg bw, AXDE and AXME reduced UV-DMBA-induced tumor incidences up to 96 and 88%, respectively, when compared to AX (66%) and TC (85%). UV-DMBA has been known to generate high levels of free radicals and tyrosinase enzyme, leading to characteristic symptoms of skin pigmentation and tumor initiation. Intriguingly, ~7-fold increase in tyrosinase and 10-fold decrease in antioxidant levels were normalized by AXDE and AXME as opposed to only ~1.4-2.2-fold by AX and TC, respectively. This result together with the appearance of 72 and 58 ng/mL of retinol in the serum of respective AXE-treated (AXDE + AXME) and AX-treated animals suggested that better anticancer potency of AXEs could be due to increased bioavailability.

Low levels of plasma carotenoids are associated with an increased risk of atrial fibrillation.

Systemic inflammation, oxidative stress, and atrial fibrosis are identified as the main mechanisms for atrial fibrillation (AF). Antioxidant micronutrients may have antiarrhythmic benefit in humans. We studied whether plasma carotenoids are related to the risk of AF in elderly subjects. The study population consisted of 1,847 Finnish subjects (620 women and 1,227 men) aged 61-82 years from the Kuopio Ischaemic Heart Disease Risk Factor study cohort. Plasma concentrations of carotenoids were measured by high-performance liquid chromatography. The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of plasma carotenoids were analyzed using the Cox proportional hazard's model. During a median follow-up of 2.8 years a total of 105 subjects developed incident AF. The HRs of AF among subjects with levels in the highest through the lowest tertile after adjustment for age, examination year, gender, systolic blood pressure, smoking, alcohol consumption, education, diabetes, use of antihypertensive medication, congestive heart failure, recurrent AF, prevalent coronary heart disease and baseline prevalence of myocardial infarction were 1.70 (95% CI: 1.01-2.86, p = 0.047) for lutein, 1.99 (95% CI: 1.14-3.48, p = 0.016) for zeaxanthin. Risk of AF was borderline significant for ß-carotene (HR = 1.69, 95 % CI: 1.00-2.87, p = 0.050). Results remained unchanged, when season was added to the multivariable model. Lycopene, ß-cryptoxanthin, α-carotene and total carotenoids were not associated with the risk of AF. Results of the present study suggest that low plasma concentrations of lutein and zeaxanthin were associated with an increased risk of AF in elderly population.

Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies.

BACKGROUND: Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. METHODS: We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. RESULTS: Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, P(trend) = .04), ß-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, P(trend) = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, P(trend) = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, P(trend) = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, P(trend) = .01). ß-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER(-)) than for ER(+) tumors (eg, ß-carotene: ER(-): top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, P(trend) = .001; ER(+): RR = 0.83, 95% CI = 0.66 to 1.04, P(trend) = .06; P(heterogeneity) = .01). CONCLUSIONS: This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, ß-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.