Associations of serum carotenoids with all-cause and cardiovascular mortality in adults with MAFLD.

BACKGROUND AND AIMS: The associations between serum carotenoids and mortality are contradictory in various metabolic-associated diseases. This study aimed to examine the associations of five major serum carotenoids with mortality among adults with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS AND RESULTS: This analysis included 3040 individuals with MAFLD from the Third National Health and Nutrition Examination Survey (NHANES III). All-cause and cardiovascular mortality were ascertained by linkage to the National Death Index through December 31, 2019. Cox proportional hazards regression models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and restricted cubic spline (RCS) analyses were performed to assess the linearity of the associations. During a follow-up period of 826,547 person-years, 1325 all-cause and 429 cardiovascular deaths occurred. For all-cause mortality, compared with those in the lowest quartiles, the multivariable-adjusted HRs (95% CIs) in the highest quartiles were 0.63 (0.49-0.81) for α-carotene; 0.65 (0.52-0.80) for ß-carotene; 0.64 (0.51-0.81) for ß-cryptoxanthin; 0.73 (0.56-0.95) for lycopene; and 0.69 (0.52-0.91) for lutein/zeaxanthin. For cardiovascular mortality, the multivariable-adjusted HRs (95% CIs) in the highest quartiles were 0.51 (0.33-0.78) for α-carotene; 0.54 (0.35-0.82) for ß-carotene; 0.52 (0.34-0.80) for ß-cryptoxanthin; 0.63 (0.44-0.90) for lycopene; and 0.62 (0.39-0.99) for lutein/zeaxanthin. Besides, serum α-carotene, ß-cryptoxanthin, and lycopene exhibited linear correlations with all-cause mortality in MAFLD adults, and four serum carotenoids, except ß-carotene, were linearly correlated with cardiovascular mortality. CONCLUSIONS: Lower serum α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin concentrations were associated with higher risk of all-cause and cardiovascular mortality in US adults with MAFLD.

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.

(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.

Higher dietary and serum carotenoid levels are associated with lower carotid intima-media thickness in middle-aged and elderly people.

Several studies have suggested that higher carotenoid levels may be beneficial for atherosclerosis patients, but few studies have examined this relationship in the Chinese population. This cross-sectional study examined the association between the levels of carotenoids in diet and serum and carotid intima-media thickness (IMT) in Chinese adults aged 50-75 years in Guangzhou, China. Dietary intake was assessed using a FFQ. HPLC was used to assay the serum concentrations of α-carotene, ß-carotene, lutein+zeaxanthin, ß-cryptoxanthin and lycopene. The IMT at the common carotid artery (CCA) and bifurcation of the carotid artery was measured by B-mode ultrasound. A total of 3707 and 2947 participants were included in the analyses of dietary and serum carotenoids. After adjustment for demographic, socio-economic and lifestyle factors, all the serum carotenoids levels except lycopene were found to be inversely associated with the IMT at the CCA and bifurcation (P trend<0·001 to 0·013) in both men and women. The absolute mean differences in the IMT between the subjects in the extreme quartiles of serum carotenoid levels were 0·034 mm (α-carotene), 0·037 mm (ß-carotene), 0·032 mm (lutein+zeaxanthin), 0·030 mm (ß-cryptoxanthin), 0·015 mm (lycopene) and 0·035 mm (total carotenoids) at the CCA; the corresponding values were 0·025, 0·053 0·043, 0·050, 0·011 and 0·042 mm at the bifurcation. The favourable associations were also observed between dietary carotenoids (except lycopene) and the CCA IMT. In conclusion, elevated carotenoid levels in diet and serum are associated with lower carotid IMT values (particular at the CCA) in Chinese adults.

Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults.

PURPOSE: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit. METHODS: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire. RESULTS: Significant baseline correlations were found between MPOD and Beck anxiety scores (r = -0.28; P = 0.032), MPOD and Brief Symptom Inventory scores (r = 0.27; P = 0.037), and serum cortisol and psychological stress scores (r = 0.46; P < 0.001). Supplementation for 6 months improved psychological stress, serum cortisol, and measures of emotional and physical health (P < 0.05 for all), versus placebo. These outcomes were either maintained or improved further at 12 months. CONCLUSIONS: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.

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.

Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults.

OBJECTIVES: It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance. METHODS: Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures. RESULTS: Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions. CONCLUSIONS: To the authors' knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017, 23, 11-22).

Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study.

Carotenoid bioavailability from plant and animal food is highly variable depending on numerous factors such as the physical deposition form of carotenoids. As the carotenoid zeaxanthin is believed to play an important role in eye and brain health, we sought to compare the human bioavailability of an H-aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated into identical formulation matrices. A randomised two-way cross-over study with sixteen participants was designed to compare the post-prandial bioavailability of an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation, both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich lipoprotein fractions were analysed over 9·5 h after test meal consumption. Bioavailability from the J-aggregated formulation (AUC=55·9 nmol h/l) was 23 % higher than from the H-aggregated one (AUC=45·5 nmol h/l), although being only marginally significant (P=0·064). Furthermore, the same formulations were subjected to an internationally recognised in vitro digestion protocol to reveal potential strengths and weaknesses of simulated digestions. In agreement with our human study, liberation of zeaxanthin from the J-aggregated formulation into the simulated duodenal fluids was superior to that from the H-aggregated form. However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin dipalmitate was lower than that of the H-aggregated zeaxanthin, being contradictory to our in vivo results. An insufficient ester cleavage during simulated digestion was suggested to be the root cause for these observations. In brief, combining our in vitro and in vivo observations, the effect of the different aggregation forms on human bioavailability was lower than expected.

Status of Vitamin A and Related Compounds and Clinical Outcomes in Maternal-Infant Pairs in the Midwestern United States.

BACKGROUND: Vitamin A is an essential nutrient for pregnant women, and other vitamin A-related compounds, including lutein and lycopene, have been associated with maternal-infant outcomes. The objective of this study was to quantify the status of vitamin A and related compounds in maternal-infant pairs at the time of delivery, and to determine its impact on clinical outcomes. METHODS: Maternal and cord blood samples were collected in 189 mother-infant pairs. Concentrations of lutein + zeaxanthin, ß-cryptoxanthin, lycopene, carotenes, and retinol were measured using high-performance liquid chromatography. Descriptive statistics was calculated and Spearman coefficients were used to assess correlations between maternal and cord measurements. Kruskal-Wallis and independent samples t test were used to compare measures between retinol groups. Linear and logistic regression models were used to adjust for relevant confounders. p < 0.05 was considered statistically significant. RESULTS: Ten percent of mothers had serum retinol concentrations ≤0.70 µmol/L; 80% of infants had serum retinol concentrations ≤0.70 µmol/L. Low maternal retinol concentrations were associated with maternal anemia (p = 0.04) and a trend toward low birth weight (p = 0.06). Maternal and infant concentrations of vitamin A compounds were highly correlated. After adjustment for confounders, maternal lutein was associated with a C-section (p = 0.03) and a diagnosis of respiratory distress syndrome in the infant (p = 0.02). Maternal lycopene was associated with growth parameters in the infant. CONCLUSIONS: As vitamin A-related compounds are modifiable by diet, future research determining the clinical impact of these compounds is warranted.

Carotenoids as biomarkers of fruit and vegetable intake in men and women.

High fruit and vegetable (FAV) intake is associated with a lower prevalence of chronic diseases. Identifying the ideal number of FAV servings needed to reduce chronic disease risk is, however, difficult because of biases inherent to common self-report dietary assessment tools. The aim of our study was to examine the associations between daily FAV intake and plasma carotenoid concentrations in men and women enrolled in a series of fully controlled dietary interventions. We compiled and analysed data from a group of 155 men and 109 women who participated in six fully controlled dietary interventions and compared post-intervention fasting plasma carotenoid (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, lycopene, zeaxanthin) concentrations with regard to the daily FAV servings consumed by the participants. We found that plasma ß-cryptoxanthin, lutein and zeaxanthin concentrations were positively associated with daily FAV servings (P≤0·005). However, daily FAV intake was negatively associated with plasma α-carotene (P<0·0005) and lycopene (P<0·0001) concentrations, whereas no association was noted with plasma ß-carotene. When men and women were analysed separately, we found that for any given number of FAV servings consumed women had higher circulating lutein concentrations compared with men (P<0·01). Significant sex×FAV (P<0·0001) and sex×dietary ß-cryptoxanthin (P<0·0005) interactions were also noted favouring higher plasma ß-cryptoxanthin concentrations in women than in men for a given FAV consumption. Results from these fully controlled dietary feeding studies indicate that plasma ß-cryptoxanthin and lutein concentrations can be used as robust biomarkers of FAV consumption. They also suggest the existence of sex differences influencing circulating ß-cryptoxanthin and lutein concentrations following FAV consumption.

Increasing fruit and vegetable intake has no effect on retinal vessel caliber in adults at high risk of developing cardiovascular disease.

BACKGROUND AND AIM: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk. METHODS AND RESULTS: Following a 4 week washout period, participants were randomized to consume either 2 or 4 or 7 portions of FV daily for 12 weeks. Retinal vessel caliber was measured at baseline and post-intervention. A total of 62 participants completed the study. Self-reported FV intake indicated good compliance with the intervention, with serum concentrations of zeaxanthin and lutein increasing significantly across the groups in a dose-dependent manner (P for trend < 0.05). There were no significant changes in body composition, 24-h ambulatory blood pressure or fasting blood lipid profiles in response to the FV intervention. Increasing age was a significant determinant of wider retinal venules (P = 0.004) whereas baseline systolic blood pressure was a significant determinant of narrower retinal arterioles (P = 0.03). Overall, there was no evidence of any short-term dose-response effect of FV intake on retinal vessel caliber (CRAE (P = 0.92) or CRVE (P = 0.42)). CONCLUSIONS: This study demonstrated no effect of increasing FV intake on retinal vessel caliber in overweight adults at high risk of developing primary CVD. CLINICAL TRIAL REGISTRATION: NCT00874341.

Effect of dietary α-tocopherol on the bioavailability of lutein in laying hen.

Lutein and its isomer zeaxanthin have gained considerable interest as possible nutritional ingredient in the prevention of age-related macular degeneration (AMD) in humans. Egg yolk is a rich source of these carotenoids. As an oxidative sensitive component, antioxidants such as α-tocopherol (T) might contribute to an improved accumulation in egg yolk. To test this, chickens were fed lutein esters (LE) with and without α-tocopherol as an antioxidant. After depletion on a wheat-soya bean-based lutein-poor diet for 21 days, laying hens (n = 42) were equally divided into three groups and fed the following diets for 21 days: control (basal diet), a LE group (40 mg LE/kg feed) and LE + T group (40 mg LE plus 100 mg T/kg feed). Eggs and blood were collected periodically. Carotenoids and α-tocopherol in yolk and blood plasma were determined by HPLC. Egg yolk was also analysed for total carotenoids using a one-step spectrophotometric method (iCheck((™)) ). Lutein, zeaxanthin, α-tocopherol and total carotenoids in egg yolk were highest after 14 days of feeding and decreased slightly afterwards. At the end of the trial, eggs of LE + T group contained higher amount of lutein (13.72), zeaxanthin (0.65), α-tocopherol (297.40) and total carotenoids (21.6) compared to the LE group (10.96, 0.55, 205.20 and 18.0 mg/kg, respectively, p < 0.05). Blood plasma values of LE + T group contain higher lutein (1.3), zeaxanthin (0.06) and tocopherol (20.1) compared to LE group (1.02, 0.04 and 14.90 mg/l, respectively, p < 0.05). In conclusion, dietary α-tocopherol enhances bioavailability of lutein reflecting higher content in egg yolk and blood plasma. Improved bioavailability might be due to increased absorption of lutein in the presence of tocopherol and/or a greater stability of lutein/zeaxanthin due to the presence of α-tocopherol as an antioxidant.

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.

PURPOSE: Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated. DESIGN: Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. PARTICIPANTS: Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). METHODS: Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively. MAIN OUTCOME MEASURES: AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD. RESULTS: The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. CONCLUSIONS: Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype.

Prediction of fruit and vegetable intake from biomarkers using individual participant data of diet-controlled intervention studies.

Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258.0 g, the correlation between observed and predicted intake was 0.78 and the mean difference between observed and predicted intake was - 1.7 g (limits of agreement: - 466.3, 462.8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201.1 g, the correlation was 0.65 and the mean bias was 2.4 g (limits of agreement: -368.2, 373.0 g). The prediction models which include the biomarkers and subject characteristics may be used to estimate average intake at the group level and to investigate the ranking of individuals with regard to their intake of fruit and vegetables when validating questionnaires that measure intake.

High serum carotenoids associated with lower risk for the metabolic syndrome and its components among Japanese subjects: Mikkabi cohort study.

Recent epidemiological studies show the association of carotenoids with the metabolic syndrome (MetS), but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk of developing the MetS and its components in Japanese subjects. We conducted a follow-up study on 1073 men and women aged 30-79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 men and 615 women) took part in the follow-up survey at least once. Over a mean follow-up period of 7·8 (sd 2·9) years, thirty-six men and thirty-one women developed new MetS. After adjustments for confounders, the hazard ratio (HR) for the MetS in the highest tertile of serum ß-carotene against the lowest tertile was 0·47 (95 % CI 0·23, 0·95). On the other hand, significantly lower risks for dyslipidaemia were observed in the highest tertiles of serum α- and ß-carotene and ß-cryptoxanthin (HR 0·66; 95 % CI 0·46, 0·96; HR, 0·54; 95 % CI 0·37, 0·79; and HR 0·66; 95 % CI 0·44, 0·99, respectively). Other significant associations between the risks for obesity, high blood pressure and hyperglycaemia with serum carotenoids were not observed. Our results further support the hypothesis that eating a diet rich in carotenoids might help prevent the development of the MetS and its complications in Japanese subjects.

Carotenoid consumption is related to lower lipid oxidation and DNA damage in middle-aged men.

The present cross-sectional study assessed the potential relationships of carotenoid intake with lipid and oxidative stress markers in middle-aged men. A total of 296 apparently healthy middle-aged men (mean age 50.5 (SD 5.0) years, BMI 25.8 (SD 3.5) kg/m(2)) were recruited to participate in the study. Dietary intake, anthropometry, blood pressure, lifestyle features, blood and urine biomarkers were assessed using validated procedures. The lipid markers included NEFA, Castelli index, and TAG:HDL ratio; oxidative stress markers included urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-PGF2α and plasma oxidised-LDL (ox-LDL). We observed a significant inverse association (P < 0.05) between NEFA concentrations and consumption of lutein plus zeaxanthin, ß-carotene, α-carotene and total carotenoid, while Castelli index was negatively associated with daily intake of lycopene, ß-carotene and total carotenoids. Regarding oxidative stress biomarkers, urinary 8-OHdG and ox-LDL concentrations were also inversely associated (P < 0.05) with consumption of lycopene, lutein plus zeaxanthin, ß-carotene, α-carotene and total carotenoids, regardless of confounding variables. Moreover, there was a negative association of urinary 8-iso-PGF2α concentration with dietary lutein plus zeaxanthin (ß - 0.135, 95% CI - 0.268, - 0.001), ß-carotene (ß - 0.156, 95% CI - 0.277, - 0.034) and with the sum of all carotenoids (ß - 0.189, 95% CI - 0.333, - 0.046). In conclusion, total daily carotenoid intake based on five investigated carotenoid types (ß-cryptoxanthin, lycopene, lutein plus zeaxanthin, ß-carotene and α-carotene) was inversely associated with relevant lipid and oxidative stress markers in middle-aged men, with emphasis on ß-carotene that was negatively associated with five of the six lipid and oxidative stress markers evaluated in the present study.

Independent positive association of plasma ß-carotene concentrations with adiponectin among non-diabetic obese subjects.

PURPOSE: Many epidemiological studies find an inverse correlation between carotenoids intake or carotenoids plasma concentrations and body mass index (BMI), insulin resistance or metabolic syndrome in the general population. However, it is not clear whether these relationships occur in obese population. METHODS: We conducted a cross-sectional study in 108 obese non-diabetic patients. RESULTS: There was an inverse correlation between plasma levels of pro-vitamin A carotenoids (α-carotene, ß-carotene and ß-cryptoxanthin) and both BMI and insulin resistance (estimated by the HOMA-IR). No correlation between plasma concentrations of lycopene or lutein/zeaxanthin and BMI or insulin resistance was found. The inverse association between the three pro-vitamin A carotenoids and HOMA-IR disappeared after adjustment for BMI and waist circumference. Interestingly, we identified a positive association between concentrations of ß-carotene and adiponectin in plasma that was independent of sex, age, smoking status, BMI and waist circumference. To our knowledge, such association has never been described in obese patients. CONCLUSION: These results suggest the existence of a favourable effect of ß-carotene on insulin sensitivity in obese individuals that could involve a positive regulation of adiponectin, either directly or via its pro-vitamin A activity. The demonstration of the potential benefits of ß-carotene towards insulin sensitivity would open the way to dietary strategies to prevent metabolic syndrome.

Effects of lutein-enriched egg yolk in buttermilk or skimmed milk on serum lipids & lipoproteins of mildly hypercholesterolemic subjects.

BACKGROUND AND AIMS: Earlier studies in our group suggested that traditionally prepared buttermilk influences cholesterol metabolism. We therefore designed a study to evaluate whether traditionally prepared buttermilk lowers serum low-density lipoprotein cholesterol (LDL-C) and/or prevents the LDL-C raising effect of egg yolks. METHODS AND RESULTS: Mildly hypercholesterolemic subjects were randomly allocated to one of four diet groups consuming daily at lunch 80 ml skimmed milk with (n = 23) or without (n = 25) lutein-enriched egg yolk (28 g from 1.5 eggs providing 323 mg cholesterol) or traditionally prepared buttermilk with (n = 23) or without (n = 21) lutein-enriched egg yolk during a 12 week period. Fasting blood samples were taken to measure concentrations of serum lipids, (apo)lipoproteins, liver and kidney function markers, and plasma lutein, zeaxanthin and high-sensitive C-reactive protein (hsCRP). Egg yolk consumption significantly increased serum total cholesterol (total-C) (p = 0.035) and LDL-C concentrations (p = 0.022). Buttermilk did not change the effects of egg yolk on serum lipids and (apo)lipoproteins. There was a trend towards significant lower total-C (p = 0.077), but not LDL-C (p = 0.204) concentrations in the buttermilk groups. Plasma lutein and zeaxanthin concentrations increased significantly (p < 0.001) in the egg yolk groups. CONCLUSION: In mildly hypercholesterolemic subjects, daily consumption of traditionally prepared buttermilk for 12 weeks did not lower serum total-C or LDL-C concentrations, nor did it prevent the serum total-C and LDL-C raising effect of daily egg yolk consumption. REGISTRATION NUMBER: This study is registered at www.clinicaltrials.gov as NCT01566305.

Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration.

PURPOSE: Our aim was to investigate the macular response to three different supplements containing lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) in normal subjects and those with age-related macular degeneration (AMD). MATERIALS AND METHODS: Macular pigment optical density (MPOD) and serum xanthophyll concentrations were measured in normal (n = 31) and AMD subjects (n = 32), randomly assigned to: group 1 (20 mg L, 2 mg Z, 0.3 mg MZ), group 2 (10 mg L, 2 mg Z, 10 mg MZ) or group 3 (3 mg L, 2 mg Z, 17 mg MZ). MPOD was measured at baseline, 2, 4, 6 and 8 weeks and at 0.25°, 0.5°, 1.0° and 1.75° of eccentricity using customised heterochromatic flicker photometry and serum xanthophylls by HPLC. RESULTS: MPOD increased significantly at all eccentricities in each group (p < 0.05), except at 1.75° in group 3 (p = 0.242). There was no difference in MPOD measurements between AMD and normal subjects, except for group 2, where AMD subjects exhibited a greater response at 1.75° (p = 0.012). Final serum concentrations of MZ were positively and significantly related to final MPOD values at each eccentricity in all subjects. Targeted analysis of those subjects receiving the MZ-containing supplements exhibited stronger relationships between serum MZ concentrations and MPOD at 0.25° in group 3 than group 2; in group 2 all associations were positive, but only significant at 1.75°. CONCLUSIONS: Serum concentrations of MZ were strongly correlated with MPOD after 8 weeks of supplementation with the group 3 formulation, but the inclusion of L in the group 2 formulation may result in greater MPOD augmentation across the spatial profile.

Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer's disease mortality in older adults.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD). Accumulating evidence shows that antioxidant-rich food reduces the risk of AD by inhibiting oxidative stress. This study investigates whether serum levels of carotenoids were associated with the risk of AD mortality in a nationally representative sample of US adults. METHODS: We used data from the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. A total of 6,958 participants aged older than 50 years were included in this study. RESULTS: We found that high serum levels of lycopene and lutein+zeaxanthin at baseline were associated with a lower risk of AD mortality after adjustment for potential covariates. The reduction in the mortality risk was progressively raised by increasing serum lycopene (HR = 0.26, 95% CI 0.10-0.69) and lutein+zeaxanthin (HR = 0.43, 95% CI 0.22-0.85) levels. In contrast, no associations with AD mortality were observed for other serum carotenoids, including alpha-carotene, beta-carotene, and beta-cryptoxanthin. CONCLUSION: High serum levels of lycopene and lutein+zeaxanthin are associated with a lower risk of AD mortality in adults. Our findings suggest that a high intake of lycopene- or lutein+zeaxanthin-rich food may be important for reducing the AD mortality risk.