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The aim of this study was to perform a systematic review and meta-analysis on randomized controlled trials investigating the effects of carotenoids on selected inflammatory parameters. PubMed, SCOPUS, and Web of science were searched from inception until April 2021. The random-effect model was used to analyze data and the overall effect size was computed as weighted mean difference (WMD) and corresponding 95% of confidence interval (CI). A total of 26 trials with 35 effect sizes were included in this meta-analysis. The results indicated significant effects of carotenoids on C-reactive protein (CRP) (WMD: ‒0.54 mg/L, 95% CI: ‒0.71, ‒0.37, P < 0.001), and interleukin-6 (IL-6) (WMD: ‒0.54 pg/mL, 95% CI: ‒1.01, ‒0.06, P = 0.025), however the effect on tumor necrosis factor-alpha (TNF-α) was not significant (WMD: ‒0.97 pg/ml, 95% CI: ‒1.98, 0.03, P = 0.0.059). For the individual carotenoids, astaxanthin, (WMD: ‒0.30 mg/L, 95% CI: ‒0.51, ‒0.09, P = 0.005), lutein/zeaxanthin (WMD: ‒0.30 mg/L, 95% CI: ‒0.45, ‒0.15, P < 0.001), and β-cryptoxanthin (WMD: ‒0.35 mg/L, 95% CI: ‒0.54, ‒0.15, P < 0.001) significantly decreased CRP level. Also, only lycopene (WMD: ‒1.08 pg/ml, 95%CI: ‒2.03, ‒0.12, P = 0.027) led to a significant decrease in IL-6. The overall results supported possible protective effects of carotenoids on inflammatory biomarkers.

Carotenoids are increasingly being implicated to have an important role in brain and eye development. This study aimed to quantify the content and profile of carotenoids in human breast milk, maternal plasma and neonatal umbilical cord plasma in Chengdu, an urban area in Southwest China. In this study, fifty-four healthy mothers were enrolled. Maternal blood, umbilical cord blood, colostrum, transitional milk and mature milk were collected. Concentrations of carotenoids (lutein, zeaxanthin, β-cryptoxanthin, β-carotene and lycopene) were analysed by HPLC. We found that carotenoid concentrations decreased from colostrum to mature milk. Hydrocarbon carotenoids with weaker polarity decreased more than the polar carotenoids. Lycopene concentrations dropped by 99 %, β-carotene by 92 %, β-cryptoxanthin by 83 %, lutein by 32 % and zeaxanthin by 22 %. Lycopene and β-carotene accounted for 70 % of the total carotenoids in colostrum, and lutein predominated amongst carotenoids in transitional milk and mature milk (51–55 %). Carotenoid concentrations in maternal plasma were much higher than that in cord plasma. Lutein predominated in cord plasma. The concentrations of all carotenoids in maternal plasma were correlated with those of cord plasma and human milk. These results are consistent with selective transport mechanisms in the mammary gland related to the polarity of carotenoids, and each carotenoid has its own implications, which may have different priorities in the early life development of infants. These findings may help guide dietary recommendations for carotenoid inclusion in infant formulas.

The efficacy of β-cryptoxanthin (BCX), a high-protein diet (HPD), or both in reducing oxidative stress and inflammation in nonalcoholic fatty liver disease (NAFLD) has never been examined within a randomized controlled trial (RCT). Thus, we aimed to assess the efficacy of an energy-restricted HPD supplemented with BCX in alleviating these conditions in NAFLD in an RCT design. We hypothesized that this combination may improve oxidative stress and inflammation in NAFLD as compared to a standard energy-restricted diet. Ninety-two ultrasonographically confirmed overweight/obese adult NAFLD patients attending an outpatient clinic in Ahvaz, Iran, were recruited for this 12-week, single-center, parallel-group, double-blind RCT from 2017 to 2018. Subjects were randomized into 4 equal groups (n = 23): HPD-BCX (energy-restricted HPD + BCX), HPD (energy-restricted HPD + placebo), BCX (standard energy-restricted diet + BCX), and control (standard energy-restricted diet + placebo). Serum levels of oxidative stress- and inflammation-related markers, as primary outcome measures, were determined at baseline and at the study end point. The 1-way analysis of covariance models in the intention-to-treat population (N = 92) showed that the HPD-BCX group achieved greater 12-week reductions in malondialdehyde, high-sensitivity C-reactive protein, interleukin-6, and total cytokeratin-18 (CK18-M65) but higher increases in total antioxidant capacity and adiponectin compared to the control group (mean differences for malondialdehyde, high-sensitivity C-reactive protein, interleukin-6, total cytokeratin-18, total antioxidant capacity, and adiponectin were -1.9 nmol/mL, -1.0 mg/L, -2.0 ng/L, -270.9 ng/L, 2.5 U/mL, and 1.9 mg/L, respectively; all P .001). These results show that an energy-restricted HPD supplemented with BCX more efficaciously alleviates oxidative stress and inflammation in NAFLD as compared to a standard energy-restricted diet.

Citrus fruits are known for their beneficial health effects associated with the prevention of metabolic syndrome/type 2 diabetes that is mainly attributed to flavonoids. Few investigations have reported the potential anti-diabetic effects of retinoids from the bioconversion of β-cryptoxanthin (bcx), a citrus carotenoid. Therefore, the present study explored the anti-diabetic effect of a citrus functional food, obtained by membrane eco-technology of a citrus clementina juice, especially enriched in bcx but also in flavonoids and pectin. We assessed the in vivo effect of citrus bcx absorption and its bioconversion into retinoids in metabolic syndrome/type 2 diabetic fructose rats. Fructose-fed rats were used as a prediabetic control, and a prediabetic group was treated with the citrus concentrate for 8 weeks. The citrus-based food treatment improved glucose tolerance, dyslipidemia and blood pressure, in prediabetic rats. Although these effects were in part due to the synergy between enriched phytonutrients (bcx, hesperidin, pectin) of the citrus matrix, the role of bcx and its bioconversion into retinoids were highlighted. We showed that prediabetic rats absorbed less bcx and the bioconversion was less efficient. Bcx from citrus-based food was able to restore vitamin A status in prediabetic rats suggesting that the absorption/bioconversion of bcx may have a key role in improvement of metabolic syndrome/type 2 diabetes.

Most of the maize (Zea mays L.) varieties in developing countries have low content of micronutrients including vitamin A. As a result, people who are largely dependent on cereal-based diets suffer from health challenges due to micronutrient deficiencies. Marker assisted recurrent selection (MARS), which increases the frequency of favorable alleles with advances in selection cycle, could be used to enhance the provitamin A (PVA) content of maize. This study was carried out to determine changes in levels of PVA carotenoids and genetic diversity in two maize synthetics that were subjected to two cycles of MARS. The two populations, known as HGA and HGB, and their advanced selection cycles (C1 and C2) were evaluated at Ibadan in Nigeria. Selection increased the concentrations of β-carotene, PVA and total carotenoids across cycles in HGA, while in HGB only α-carotene increased with advances in selection cycle. β-cryptoxanthine increased at C1 but decreased at C2 in HGB. The levels of β-carotene, PVA, and total carotenoids increased by 40%, 30% and 36% respectively, in HGA after two cycles of selection. α-carotene and β-cryptoxanthine content improved by 20% and 5%, respectively after two cycles of selection in HGB. MARS caused changes in genetic diversity over selection cycles. Number of effective alleles and observed heterozygosity decreased with selection cycles, while expected heterozygosity increased at C1 and decreased at C2 in HGA. In HGB, number of effective alleles, observed and expected heterozygosity increased at C1 and decreased at C2. In both populations, fixation index increased after two cycle of selections. The greatest part of the genetic variability resides within the population accounting for 86% of the total genetic variance. In general, MARS effectively improved PVA carotenoid content. However, genetic diversity in the two synthetics declined after two cycles of selection.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10–18 and h2 = 0.58, P = 1 × 10–7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (− 0.22), waist circumference (− 0.25), triglycerides (− 0.18), fat mass (− 0.23), fasting glucose (− 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (− 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Mandarin juice is a rich source of antioxidant bioactive compounds. While the content and profile of bioactives are known, the impact of high-pressure processing (HPP) on their stability and bioaccessibility (BA) is unknown, but may allow obtaining safe, nutritious, and fresh-tasting juices with highly extractable bioactive compounds. The stability and BA of bioactive antioxidant compounds in untreated and HPP-treated (400 MPa/40 °C/1 min) Clementine mandarin juices, and the cytoprotective effect of its bioaccessible fractions (BF) obtained after simulated gastrointestinal digestion against H2O2-induced oxidative stress in differentiated Caco-2 cells were investigated. The BF of HPP-treated juices showed a better retention of carotenoids, flavonoids, ascorbic acid, total polyphenols and FRAP value, and slightly higher cytoprotection (mitochondrial membrane potential and ROS) than untreated juices. Therefore, HPP can be recommended as a suitable technology to retain or indeed increase antioxidant bioactives and their cytoprotective activity in mandarin juices after gastrointestinal digestion., This study has been funded by the Spanish Ministry of Economy and Competitiveness (MINECO) by the Program Consolider-Ingenio 2010 Fun-C-Food (CSD2007-00063 project) throughout the Biocitrus consortium and by the projects AGL2013-46326-R, AGL2015-70218, AGL2016-76817-R and RTI-2018-095131-B-I00. MJR and LZ are members of Eurocaroten (COST Action CA15136). MJR and LZ belong to CaRed (Spanish Carotenoid Network BIO2017-90877-REDT, Ministerio de Ciencia, Innovación y Universidades, Spain).

Background Despite promising animal data, there is no randomized controlled trial (RCT) on the effects of high protein (HP)-diet and/or β-cryptoxanthin in non-alcoholic fatty liver disease (NAFLD). Aims: Safety and efficacy assessment of a hypocaloric HP-diet supplemented with β-cryptoxanthin in NAFLD. Methods Ninety-two Iranian NAFLD outpatients were recruited for this 12-week, single-center, parallel-group, double-blind RCT and randomized into 4 arms (n = 23): HP-diet and β-cryptoxanthin (hypocaloric HP-diet + β-cryptoxanthin), HP-diet (hypocaloric HP-diet + placebo), β-cryptoxanthin (standard hypocaloric diet + β-cryptoxanthin), and control (standard hypocaloric diet + placebo). Serum levels of liver enzymes and grade of hepatic steatosis were assessed at baseline and study endpoint as outcome measures. Results In the intention-to-treat population (N = 92), HP-diet and β-cryptoxanthin group experienced greater 12-week reductions in serum levels of liver enzymes than control group (mean difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase: − 27.2, − 7.2, − 39.2, and − 16.3 IU/L, respectively; all p p Conclusion A hypocaloric HP-diet supplemented with β-cryptoxanthin safely and efficaciously improves NAFLD. Trial registration number This trial was registered at https://www.irct.ir as IRCT2017060210181N10.

We investigated the effects of &beta, cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or &beta, cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. &beta, cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice, however, &beta, cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice, cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. &beta, cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, &beta, cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the &beta, cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that &beta, cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

The present study aimed to explore the function and molecular mechanism of β-cryptoxanthin on myocardial ischaemia-reperfusion injury (MIRI). Left anterior descending coronary artery ligation with reperfusion was utilised to establish a MIRI rat model. The results indicated that β-cryptoxanthin decreases infarct size and ameliorates signs of pathological histology in MIRI. TNF-α, IL-1β, and IL-6 levels in the serum were attenuated in response to β-cryptoxanthin treatment, serum LDH and CK-MB activities were also decreased. Immunohistochemical analysis and western blot results suggested that p65 was translocated to the nucleus in the I/R injury rat model. However, in the β-cryptoxanthin administration group, p65 expression and activity in the nucleus were decreased in a dose-dependent manner. Furthermore, p-p38 MAPK levels in response to β-cryptoxanthin were decreased, indicating that MAPK is involved in NF-κB signalling pathway regulation. In conclusion, β-cryptoxanthin alleviates myocardial ischaemia/reperfusion injury by inhibiting NF-κB-mediated inflammatory signalling in rats.

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

Objective. This research is aimed at determining the vascular health characteristics of carotenoids by evaluating their effect on excessive inflammatory response in endothelial and monocyte cells, the main factors of atherosclerosis. Methods. Human umbilical vein endothelial cells (HUVECs) or U937 monocytes were treated with escalating concentrations (0.1, 0.5, and 1 μM) of five most common carotenoids in human plasma, i.e., α-carotene, β-carotene, β-cryptoxanthin, lutein, and lycopene prior to stimulation with 2 mM fructose. We examined the monocyte adhesion to endothelial cells (ECs) and relevant endothelial adhesion molecules. Chemokine and proinflammatory cytokine production as well as intracellular oxidative stress were also assessed in fructose-stimulated ECs and monocytes. Results. Carotenoids repressed monocyte adhesion to fructose-stimulated ECs dose dependently via decreasing primarily the expression of endothelial VCAM-1. In ECs and monocytes, three carotenoids, i.e., β-cryptoxanthin, lutein, and lycopene, suppressed the fructose-induced expression of chemokines MCP-1, M-CSF, and CXCL-10 and inflammatory cytokines TNF-α and IL-1β, with CXCL-10 being the most repressed inflammatory mediator. β-Cryptoxanthin, lutein, and lycopene dramatically downregulated the fructose-induced CXCL-10 expression in vascular cells. The reduction in the inflammatory response was associated with a slight but significant decrease of intracellular oxidative stress. Conclusions. Our results show that carotenoids have a variety of anti-inflammatory and antiatherosclerosis activities, which can help prevent or reduce fructose-induced inflammatory vascular diseases.

At present, cancer is one of the major diseases in the world affecting numerous lives. There have been various approaches to combat the disease, particularly involving chemical interventions (chemotherapy). However, owing to serious side effects of chemotherapy, employment of natural supplements in cancer therapy has been long desired. Nutraceuticals are currently being studied as a medicament, to act as both preventive and curative measure. Nutraceuticals provide both nutrition and therapeutic benefits; besides, they are natural and biocompatible, and therefore pose no side effects. This facilitates their ready acceptance as dietary supplements with no requirements of special dosage and concerns over long-term usage. Nutraceuticals can be derived from the natural resources such as spices, fruits, vegetables, and plants. However, nutraceuticals are vulnerable to environmental stresses that necessitate encapsulation for long-term storage and required bioavailability. The review collates the findings on encapsulated nutraceuticals in liposomes for cancer therapy. The article provides a coherent overview of the research conducted on liposomal administration of nutraceuticals to target various forms of cancer, explaining the advances made.

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-β-carotene, cis- β-carotene, β-cryptoxanthin and combined Lutein/zeaxanthin were positively and significantly associated with TL (all p

Background: Previous evidence supports that vitamin A decreases the risk of several types of cancer. However, the association between vitamin A and liver cancer is inconclusive. Aim: This systematic review and meta-analysis summarizes the existing literature, discussing the association between vitamin A intake, serum vitamin A, and liver cancer in adult populations. Methods: A systematic literature review was performed by searching the EMBASE, PubMed, Scopus and International Pharmaceutical Abstract databases using terms related to vitamin A (e.g. retinol, α-carotene, β-carotene, and β-cryptoxanthin) and hepatic cancer without applying any time restriction. A meta-analysis was performed using random effect models. Results: The meta-analysis of five studies showed no association between serum retinol and liver cancer (pooled risk ratio = 1.90 (0.40–9.02); n = 5 studies, I2 = 92%). In addition, the systematic review of studies from 1955 to July 2017 found studies that indicated no association between the intake and serum level of α-carotene ( n = 2) and β-cryptoxanthin ( n = 1) and the risk of liver cancer. Further, the associations between retinol intake ( n = 3), β-carotene intake ( n = 3), or serum β-carotene ( n = 3) and liver cancer were inconclusive. Conclusions: Current information on the association between vitamin A intake and liver cancer or serum vitamin A and liver cancer are limited. Most studies demonstrated no association between dietary vitamin A and the risk of liver cancer. However, the finding was based on a small number of studies with potential publication bias. Therefore, large observational studies should be conducted to confirm these associations.

Beta-cryptoxanthin (β-CX), a carotenoid abundant in Satsuma mandarin (Citrus unshiu Marc), is suggested to suppress visceral fat accumulation in animal models. Therefore, the aim of this study was to investigate whether daily intake of a beverage containing β-CX for 12 weeks reduces body mass index (BMI) and abdominal visceral fat. For this purpose, two double-blind, placebo-controlled parallel trials were conducted. In the first pilot trial, pre-obese and obese men who consumed a beverage containing 1 mg β-CX showed a smaller increase in BMI in the β-CX group than in the placebo group. In the second main trial, pre-obese men in the β-CX group who consumed a beverage containing 2 mg β-CX showed a larger decrease in BMI and visceral fat area compared with those in the placebo group, without notable side effects. These findings suggest that this β-CX-containing beverage may exert an anti-obesity effect in pre-obese men.

β-cryptoxanthin, a xanthophyll carotenoid, exerts preventive effects on various lifestyle-related diseases. Here, we found that daily oral administration of β-cryptoxanthin significantly ameliorated the development of tactile allodynia following spinal nerve injury but was ineffective in mechanical allodynia in an inflammatory pain model in mice. Our results suggest that β-cryptoxanthin supplementation would be beneficial for the prophylaxis of neuropathic pain.

Coffee consumption has been inversely associated with various diseases, however, the underlying mechanisms are not entirely clear. We used data of 17,752 Third National Health and Nutrition Examination Survey participants to investigate the association of 245 metabolites, nutrients, and lifestyle factors with coffee consumption. We used data from the first phase (n = 8825) to identify factors with a false discovery rate of &lt, 5%. We then replicated our results using data from the second phase (n = 8927). Regular coffee consumption was positively associated with active and passive smoking, serum lead and urinary cadmium concentrations, dietary intake of potassium and magnesium, and aspirin intake. In contrast, regular coffee consumption was inversely associated with serum folate and red blood cell folate levels, serum vitamin E and C, and beta-cryptoxanthin concentrations, Healthy Eating Index score, and total serum bilirubin. Most of the aforementioned associations were also observed for caffeinated beverage intake. In our assessment of the association between coffee consumption and selected metabolites, nutrients, and lifestyle factors, we observed that regular coffee and caffeinated beverage consumption was strongly associated with smoking, serum lead levels, and poorer dietary habits.

While β-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of β-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% β-cryptoxanthin for 12 weeks. β-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the β-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that β-cryptoxanthin reduces body fat and body weight gain and that β-cryptoxanthin increases the expression of UCP1 via the RAR pathway.

Beta-cryptoxanthin (β-CRX, (3R)-β, β-caroten-3-ol) is an oxygenated carotenoid and a potent antioxidant that is abundant in Satsuma mandarin orange (Citrus unshiu MARC.), which is the most popular fruit in Japan. Since our preliminary data suggested that the ingestion of β-CRX had an anti-stress effect in female participants, the effect was evaluated in another set of female participants. The study design was a double-blind group comparison and participants (n = 23) were randomly assigned to β-CRX-rich orange juice or placebo (β-CRX was removed from orange juice) groups. β-CRX or placebo juice (125 mL, after breakfast) were consumed from 1 week prior to pharmacy practice and continued for 5 d into the practice period. Salivary α-amylase activity (sAA), a marker of sympathetic nervous system activity, was significantly higher in the evening than in the morning in the placebo-group during pharmacy practice, but not in the β-CRX-group. This result supports the anti-stress effect of β-CRX. The dose-dependency of β-CRX was observed in male mice that were loaded with stress. These results indicate that the ingestion of β-CRX is helpful to reduce stress.

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Oxidative stress is thought to be a major mechanism, and previous epidemiological studies found higher serum levels of antioxidant carotenoids were associated with reduced risk for development and progression of NAFLD. The objective of this analysis is to examine cross-sectional associations between dietary and serum levels of carotenoids in relation to NAFLD among a nationally representative sample of US adults. We used data from the 2003&ndash, 2014 National Health and Nutrition Examination Survey (NHANES). Dietary carotenoid intake was estimated from a 24-hour recall, while serum carotenoids were measured from 2003 to 2006. The NAFLD status was determined based upon US Fatty Liver Index (FLI) value &ge, 30. Regression models were used to estimate associations between carotenoids and NAFLD by controlling for covariates and adjusting for survey design variables. Overall, 33% of participants were classified as having NAFLD. Intake of all carotenoids, with the exception of lycopene, was lower among those with NAFLD. This association was significant for the highest quartiles of intake of &alpha, carotene, &beta, cryptoxanthin, and lutein/zeaxanthin. For serum measures, the highest level of all carotenoids was associated with significantly reduced odds of NAFLD. In conclusion, higher intake and serum levels of most carotenoids were associated with lower odds of having NAFLD. Identification of such modifiable lifestyle factors provide an opportunity to limit or prevent the disease and its progression.

Epidemiological and clinical studies have suggested that β-cryptoxanthin (β-CX) has health benefits in humans. To understand the health benefits of β-CX, it is important to examine its in vivo kinetics and identify a convenient noninvasive biomarker for serum β-CX level. However, to date, there have been few studies of β-CX kinetics in humans. We hypothesized that simultaneous consumption of fat-containing food would stimulate absorption of β-CX. We conducted 2 in vivo kinetics studies, one after a single intake and the other after daily intake of β-CX in healthy adults, to examine whether simultaneous consumption of fat-containing food stimulates absorption of β-CX and whether palmar b* value (yellowness) is a suitable biomarker. After a single intake of 1.1 or 2.2 mg of β-CX, the serum level increased dose-dependently and returned to the baseline level after 14 to 17 days. The simultaneous consumption of fat-containing food enhanced the absorption of β-CX by 1.8-fold. During daily intake of 2.0 mg/day β-CX with fat-containing food for 12 weeks, both serum β-CX level and palmar b* value measured with a colorimeter increased continuously. After intake was halted, both serum β-CX level and palmar b* value decreased. There was a positive correlation between serum β-CX level and palmar b* value during the trial (R = 0.55, P .001). These results suggest that intake of β-CX with fat-containing food stimulates the absorption of β-CX and increases palmar yellowness.

BACKGROUND β-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by β-carotene-15,15'-oxygenase (BCO1) to generate vitamin A, and by β-carotene-9',10'-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals. OBJECTIVES We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2. METHODS Six-week-old male wild-type (WT) and BCO1-/-/BCO2-/- double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA. RESULTS Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33‒43% and hepatic total cholesterol by 43‒70% in both WT and DKO mice (P

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, β-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.

β-Cryptoxanthin, which is primarily obtained from citrus fruits such as Satsuma mandarins, is a major carotenoid routinely found in human serum. Recently, we demonstrated that daily oral intake of β-cryptoxanthin prevented ovariectomy-induced bone loss and ameliorated neuropathic pain in mice. Although β-cryptoxanthin exerts preventive effects on various lifestyle-related diseases, there have been no studies on the effect of β-cryptoxanthin on the development of osteoarthritis, the most common degenerative joint disease, which frequently leads to loss of ability and stiffness in the elderly. Here we showed that daily oral administration of β-cryptoxanthin significantly prevented the development of osteoarthritis developed by surgically inducing knee joint instability in mice in vivo. Furthermore, in vitro experiments revealed that β-cryptoxanthin markedly inhibited the expression of inflammatory cytokines and enzymes critical for the degradation of the extracellular matrix in primary chondrocytes. Our results suggest that oral supplementation of β-cryptoxanthin would be beneficial for the maintenance of joint health and as prophylaxis against osteoarthritis.

Despite the consistent association between a higher intake of the provitamin A carotenoid β-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-1-[3-pyridyl]-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. BCX supplementation was given daily to the mice starting 2 weeks prior to the injection of NNK and continued 16 weeks after NNK injection. BCX supplementation resulted in a dose-dependent increase of BCX concentration in both serum and lungs of the mice without a significant alteration of vitamin A (retinol and retinyl palmitate) concentration. BCX significantly reduced the multiplicity of the NNK-induced lung tumor by 52% to 63% compared with the NNK-treated mice without BCX supplementation. The protective effect of BCX in the lungs was associated with reductions of both mRNA and protein of the homopentameric neuronal nicotinic acetylcholine receptor α7 (α7-nAChR), which has been implicated in lung tumorigenesis. We then conducted an in vitro cell culture study and found that BCX treatment suppressed α7-nAChR expression and inhibited the migration and invasion of α7-nAChR-positive lung cancer cells but not in cells lacking α7-nAChR. The activities of BCX were significantly attenuated by activators of α7-nAChR/PI3K signaling or by overexpression of constitutively active PI3K. Collectively, the results suggest that BCX inhibits lung tumorigenesis and cancer cell motility through the downregulation of α7-nAChR/PI3K signaling, independent of its provitamin A activity. Therefore, BCX can be used as a chemopreventive agent or a chemotherapeutic compound against lung cancer. Cancer Prev Res; 9(11); 875–86. ©2016 AACR.

Findings of observational studies suggest cardioprotective effects of antioxidant vitamins and carotenoids. However, recent meta-analyses failed to show the beneficial effects of supplemental intake of antioxidants on cardiovascular disease (CVD). We aimed to assess the association between CVD risk and β-cryptoxanthin in Japan, where Satsuma mandarin, a major source of β-cryptoxanthin, is widely consumed.This was part of the Mikkabi cohort study. Surveys were conducted at baseline, in 2003 and 2005, and on follow-up in 2006, 2009, and 2013. We examined brachial-ankle pulse wave velocity (baPWV) with a high cut-off value set at 18.3 m s(-1). Hazard ratios (HR) and 95% confidence intervals for high baPWV were estimated using a Cox proportional hazards model with adjustment for potential confounders. A total of 635 participants with baPWV of less than 18.3 m s(-1) at baseline were included in the analysis. During the follow-up period of 57,921 person-months, 99 subjects developed high baPWV. After multivariate adjustment, the HR for high baPWV in the highest tertile compared with the lowest tertile was significantly low for β-cryptoxanthin, β-carotene, and total carotenoids. Serum concentrations of β-cryptoxanthin and β-carotene were higher in people who ate Satsuma mandarin frequently. Compared with1/d intake of Satsuma mandarin, 3-4/d was associated with a low risk of high PWV.This study indicated that β-cryptoxanthin and β-carotene derived from Satsuma mandarin are candidate micronutrients for preventing arteriosclerosis development. Further longitudinal and interventional studies will be required to validate the effect on CVD.

β-cryptoxanthin (CX), a major carotenoid pigment, can inhibit inflammatory gene expression in mice with nonalcoholic steatohepatitis. In the present study, we examined the anti-inflammatory effects of CX on lipopolysaccharide (LPS)-induced inflammation in mouse primary Sertoli cells and the possible molecular mechanisms behind its effects. The results showed that CX significantly inhibited LPS-induced decreases in cell viability and in the percentage of apoptotic cells. Moreover, CX inhibited the LPS-induced up-regulation of tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in Sertoli cells. In addition, CX significantly limited the LPS-induced down-regulation of AR, HSF2, CREB, FSHR, INHBB and ABP in Sertoli cells. Western blot analysis showed that CX significantly suppressed NF-κB (p65) activation as well as MAPK phosphorylation. All the results suggested that CX suppressed inflammation, possibly associated with the NF-κB activation and MAPK of phosphorylation. Thus, CX may possess therapeutic potential against inflammation-related diseases.

Biofortified maize, designed as an intervention strategy to prevent vitamin A deficiency, can provide upwards of 15 μg β-carotene per g dry weight. Some varieties also have elevated concentrations of other carotenoids. We conducted a cluster randomized, controlled feeding trial in rural Zambia to test the impact of daily consumption of biofortified maize over a 6-month period on vitamin A status. Serum concentrations of retinol and carotenoids were assessed by high-performance liquid chromatography. Data on circulating carotenoids by intervention group in 679 children are reported here. As previously shown, consumption of this β-carotene-rich maize significantly improved serum β-carotene concentrations (0.273 vs. 0.147 μmol/L, p

Carotenoids form an important part of the human diet, consumption of which has been associated with many health benefits. With the growing global burden of liver disease, increasing attention has been paid on the possible beneficial role that carotenoids may play in the liver. This review focuses on carotenoid actions in non-alcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD). Indeed, many human studies have suggested an association between decreased circulating levels of carotenoids and increased incidence of NAFLD and ALD. The literature describing supplementation of individual carotenoids in rodent models of NAFLD and ALD is reviewed, with particular attention paid to β-carotene and lycopene, but also including β-cryptoxanthin, lutein, zeaxanthin, and astaxanthin. The effect of beta-carotene oxygenase 1 and 2 knock-out mice on hepatic lipid metabolism is also discussed. In general, there is evidence to suggest that carotenoids have beneficial effects in animal models of both NAFLD and ALD. Mechanistically, these benefits may occur via three possible modes of action: 1) improved hepatic antioxidative status broadly attributed to carotenoids in general, 2) the generation of vitamin A from β-carotene and β-cryptoxanthin, leading to improved hepatic retinoid signaling, and 3) the generation of apocarotenoid metabolites from β-carotene and lycopene, that may regulate hepatic signaling pathways. Gaps in our knowledge regarding carotenoid mechanisms of action in the liver are highlighted throughout, and the review ends by emphasizing the importance of dose effects, mode of delivery, and mechanism of action as important areas for further study. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

&beta, carotene, &alpha, carotene and &beta, cryptoxanthin are greater contributors to vitamin A intake than retinol in the human diet for most people around the world. Their contribution depends on several factors, including bioavailability and capacity of conversion into retinol. There is an increasing body of research showing that the use of retinol activity equivalents or retinol equivalents could lead to the underestimation of the contribution of &beta, cryptoxanthin and of &alpha, carotene. The aim is to assess their apparent bioavailability by comparing concentrations in blood to their dietary intakes and identifying the major food contributors to their dietary intake. Dietary intake (3-day 24-h records) and serum concentrations (by HPLC) were calculated in normolipemic subjects with adequate retinol status (&ge, 1.1 &micro, mol/L) from our studies (n = 633) and apparent bioavailability calculated from 22 other studies (n = 29,700). Apparent bioavailability was calculated as the ratio of concentration in the blood to carotenoid intake. Apparent bioavailabilities for &alpha, cryptoxanthin were compared to those for &beta, carotene. Eating comparable amounts of &alpha, carotene, &beta, cryptoxanthin and &beta, carotene foods resulted in 55% greater &alpha, carotene (95% CI 35, 90) and 686% higher &beta, cryptoxanthin (95% CI 556, 1016) concentrations than &beta, carotene in blood. This suggests differences in the apparent bioavailability of &alpha, cryptoxanthin and even larger differences with &beta, cryptoxanthin, greater than that of &beta, carotene. Four fruits (tomato, orange, tangerine, red pepper) and two vegetables (carrot, spinach) are the main contributors to their dietary intake (&gt, 50%) in Europeans.

&beta, Cryptoxanthin (BCX) is a major dietary pro-vitamin A carotenoid, found mainly in fruits and vegetables. Several studies showed the beneficial effects of BCX on different aspects of human health. In spite of the evidence, the molecular mechanisms of action of BCX need to be further investigated. The Caenorhabditis elegans model was used to analyze in vivo the activity of BCX on fat reduction and protection to oxidative stress. Dose-response assays provided evidence of the efficacy of BCX at very low dose (0.025 &micro, g/mL) (p &lt, 0.001) on these processes. Moreover, a comparative analysis with other carotenoids, such as lycopene and &beta, carotene, showed a stronger effect of BCX. Furthermore, a transcriptomic analysis of wild-type nematodes supplemented with BCX revealed upregulation of the energy metabolism, response to stress, and protein homeostasis as the main metabolic targets of this xanthophyll. Collectively, this study provides new in vivo evidence of the potential therapeutic use of BCX in the prevention of diseases related to metabolic syndrome and aging.

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, &beta, cryptoxanthin, &alpha, carotene, and &beta, 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 &lt, 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.

Previous observational studies have suggested that β-cryptoxanthin, a micronutrient present in yellow and orange fruit and vegetables, may help delay the onset of menopause. Given the widespread social trend of delaying pregnancy, the possibility that β-cryptoxanthin supplementation may delay age-related loss of fertility and onset of menopause is of significant interest. In a parallel study, either saline or β-cryptoxanthin (5 µg/kg rat/day) was delivered to Wistar albino rats via an osmotic pump from 4 to 7 months of age. All control and β-cryptoxanthin-treated dams were fertile at 7 months of age, with no differences in litter size, sex ratio, or pup viability at the time of mating at 7, 9, 11, and 15 months of age (p ≥.05 for all). As expected, over time there was a pronounced decrease in litter size and serum anti-Müllerian hormone (AMH), but with no significant differences between the two groups at any time point. Overall, there was a positive correlation between litter size and AMH (r = 0.324, p =.012), confirming a link between this serum marker of ovarian reserve status and fertility potential. At 16 months, bilateral oophorectomies were performed at necropsy, before conducting follicle density assessments of ovarian reserve. The total number and stage of follicle development were similar between the β-cryptoxanthin and control groups (13.8 ± 3.2 cf 10.2 ± 4.8, respectively, p >.05). β-cryptoxanthin supplementation for 3 months early in reproductive life was not effective in delaying ovarian senescence or enhancing fertility in rats later in life, contrary to the association suggested by observational studies in humans Refereed/Peer-reviewed

s Background Excessive hepatic fat is associated with increased metabolic risk factors, production of inflammatory factors, and oxidative stress. High protein intake might trigger an increased hepatic lipid oxidation through an increase in hepatic energy expenditure. Furthermore, the majority of randomized controlled trials (RCT) in humans have failed to show whether carotenoids can be used to prevent and treat non-alcoholic fatty liver disease (NAFLD). However, it is notable and contradictory that NAFLD is rapidly escalating in Iran and other countries with lower intakes of fruit and vegetables (as sources of β-cryptoxanthin [β-CX] and carbohydrates) and higher intake of carbohydrates (as an agent of NAFLD); and the effects of β-CX and a high protein diet (HPD) on NAFLD need to be investigated further. Methods/design This study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for 12 weeks to receive daily β-CX 6 mg supplementation combined with a HPD on levels of metabolic factors, β-CX, glycemic and lipid profiles, inflammatory factors, adipocytokines, and body composition. Ninety-two eligible patients, aged 18–60 years, of both genders, who are obese and overweight (body mass index [BMI] 25–40 kg/m2) will be randomly assigned to four groups as follow: HPD + placebo; normal protein diet + β-CX (NPD + β-CX); HPD + β-CX; and NPD + placebo (control group). Two populations will be analyzed in this work. The intention-to-treat (ITT) population includes all patients who will be randomized, while the per-protocol (PP) population includes all individuals who complete the 12- week intervention (i.e. study completers). Discussion Our findings from this trial will contribute to the knowledge of the relationship between β-CX supplementation and a HPD on NAFLD patients and determination of optimal macronutrient ratios without energy restriction. Trial registration Iran clinical trials registry, IRCT2017060210181N10. Registered on 20 June 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3014-8) contains supplementary material, which is available to authorized users.

Carotenoids are phytochemicals with strong antioxidant activity against reactive oxygen species that are widely distributed in fruits and vegetables. The beneficial effects of carotenoids on human health have attracted considerable attention. The plasma carotenoid profile in humans is generally recognized to reflect the dietary carotenoid composition. Although carotenoid profile in plasma is believed to correlate well with that in other tissues, the data for tissue accumulation of carotenoids in humans is very limited and poorly understood. In order to test the hypothesis that blood carotenoids reflect tissue accumulation of dietary carotenoids, the cynomolgus monkey was used as a model to determine it's suitable for extrapolation of data on tissue accumulation of carotenoids to humans. Herein, plasma carotenoids were measured in cynomolgus monkeys given a dietary mixture of carotenoids. The findings indicate that cynomolgus monkeys and humans are similar with regard to preferential accumulation of β-cryptoxanthin in the blood and brain. These results suggested that cynomolgus monkeys could be used to collect data on tissue accumulation of carotenoids for extrapolation to humans. The tissue accumulation of carotenoids in other tissues of cynomolgus monkeys that have not yet been evaluated in humans were also investigated, revealing marked differences in carotenoid levels and composition among plasma and various monkey tissues. These results suggest that accumulation of carotenoids in plasma does not reflect necessarily that in tissues, so that predicting the tissue accumulation of carotenoids from plasma carotenoid levels and profiles alone could lead to errors.

BACKGROUND: Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. OBJECTIVE: We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. METHODS: We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. RESULTS: Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 ± 28.9 and 138.7 ± 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of β-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant. CONCLUSIONS: These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.

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, β-carotene, lutein+zeaxanthin, β-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 (Ptrendα-carotene), 0·037 mm (β-carotene), 0·032 mm (lutein+zeaxanthin), 0·030 mm (β-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.

This cross-sectional study has been performed to investigate the relationship between serum carotenoids and bone mineral density (BMD) in Chinese population. We found that women with higher serum β-cryptoxanthin, lycopene, or α-carotene exhibited higher BMD at various bone sites. Similar association was observed between α-carotene and BMD in men. Carotenoids may positively regulate bone metabolism through their antioxidant properties; however, few studies have examined the relation between serum carotenoids and bone health. We aimed to determine the associations between the serum concentration of several carotenoid subclasses and BMD in a Chinese population. This study was a community-based cross-sectional study. We measured 1898 women and 933 men aged 59.6 years who completed serum β-cryptoxanthin, zeaxanthin + lutein, lycopene, and α-carotene concentration analyses and BMD assessments. Serum individual carotenoids were assessed by the methods of reverse-phase high-performance liquid chromatography. Dual-energy X-ray absorptiometry was applied to determine BMD at whole body, lumbar spine, total hip, femur neck, and trochanter. ANCOVA was used to examine the correlations between categorized individual carotenoids and BMD at measured sites. After adjusting for potential covariates, a monotonic dose–response positive correlation between circulating levels of β-cryptoxanthin, lycopene, and α-carotene and BMD at various skeletal sites was observed in women. Women in the top (vs. bottom) quartiles of serum β-cryptoxanthin, lycopene, or α-carotene exhibited 1.8–2.3, 1.5–2.0, or 1.3–2.7 % higher BMD at the bone sites with significant results (P-trend

Recent epidemiological studies show that antioxidant vitamins and carotenoids might be beneficial to the maintenance of bone health. Recently, we found that serum carotenoids were inversely associated with the risk of developing osteoporosis in post-menopausal Japanese female subjects. However, little is known about the vitamin alone and/or the combination of the vitamin and carotenoid with the risk of osteoporosis. The objective of this study was to investigate longitudinally whether antioxidant vitamins and their combination with carotenoids are associated with the risk of developing of osteoporosis. We conducted a follow-up study on 187 post-menopausal female subjects from the Mikkabi prospective cohort study. Those who participated in previous bone mineral density (BMD) surveys and completed four years of follow-up were examined longitudinally. During a four-year follow-up, fifteen of the post-menopausal female subjects developed new-onset osteoporosis. After adjustment for confounders, the odds ratios (OR) for osteoporosis in the highest tertiles of vitamins C and E and retinol intakes against the lowest tertiles were 0.15 (95% confidence interval (CI): 0.02-0.99), 0.50 (CI: 0.08-3.23), and 1.49 (CI: 0.36-6.22), respectively. Furthermore, a significantly lower odds ratio was observed in the higher vitamin C intake group (169-625 mg/d) with higher serum β-cryptoxanthin (1.88-10.53 μM) against the lower vitamin C intake group (47-168 mg/d) with lower serum β-cryptoxanthin (0.24-1.84 μM) used for the reference group (p

β-cryptoxanthin (CRY), a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride (CdCl 2 )-induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal (i.p.) injections of corn oil and physiological saline. The other rats were i.p. injected with CRY (10 μg kg-1 ) every 8 h, beginning 8 h before CdCl 2 (2.0 mg kg-1 ) treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats. Furthermore, the Cd-induced decrease in the testicular testosterone (T) level was attenuated after CRY administration (P < 0.05). The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide (LPO) and malondialdehyde (MDA) levels (P < 0.01). The testicular antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.

Beta-cryptoxanthin [β-CRX, (3R)-β, β-caroten-3-ol] is a provitamin A and a potent antioxidant that is abundant in Satsuma mandarin orange (Citrus unshiu MARC.), which is the most popular fruit in Japan. The anti-stress effect of β-CRX on humans was evaluated in fifth-year university students during both routine daily life at the university and at pharmacy practice. The study design was a double-blind group comparison and participants (n=20; female 12, male 8) were randomly assigned to β-CRX-rich orange juice or placebo (β-CRX was removed from orange juice) groups. β-CRX or placebo juice (125 mL, once a day, after breakfast) were consumed from 10 d prior to the pharmacy practice and continued for 10 d into the practice period. To assess participants' anxiety, the state-trait anxiety inventory test was carried out before the pharmacy practice. Salivary α-amylase activity (sAA) was measured as a marker of sympathetic nervous system activity. In the placebo-group, sAA in the evening (post-practice sAA) tended to be higher than sAA in the morning (pre-practice sAA) during both routine daily life at the university and during pharmacy practice. In the β-CRX-group, the increase of post-practice sAA was suppressed in females. These results suggested that β-CRX has an anti-stress effect, at least, in females.

BACKGROUND: Biofortification of staple crops with β-carotene is a strategy to reduce vitamin A deficiency, and several varieties are available in some African countries. β-Cryptoxanthin (BCX)-enhanced maize is currently in field trials. To our knowledge, maize BCX bioavailability has not been assessed in humans. Serum retinol (13)C content and xanthophyll concentrations are proposed effectiveness biomarkers for biofortified maize adoption. OBJECTIVE: We determined the relative difference in BCX and zeaxanthin bioavailability from whole-grain and refined BCX-biofortified maize during chronic feeding compared with white maize and evaluated short-term changes in (13)C-abundance in serum retinol. DESIGN: After a 7-d washout, 9 adults (mean ± SD age: 23.4 ± 2.3 y; 5 men) were provided with muffins made from BCX-enhanced whole-grain orange maize (WGOM), refined orange maize (ROM), or refined white maize (RWM) for 12 d in a randomized, blinded, crossover study followed by a 7-d washout. Blood was drawn on days 0, 3, 6, 9, 12, 15, and 19. Carotenoid areas under the curve (AUCs) were compared by using a fixed-effects model. (13)C-Abundance in serum retinol was determined by using gas chromatography/combustion/isotope-ratio mass spectrometry on days 0, 12, and 19. Vitamin A status was determined by (13)C-retinol isotope dilution postintervention. RESULTS: The serum BCX AUC was significantly higher for WGOM (1.70 ± 0.63 μmol ⋅ L(−1) ⋅ d) and ROM (1.66 ± 1.08 μmol ⋅ L(−1) ⋅ d) than for RWM (−0.06 ± 0.13 μmol ⋅ L(−1) ⋅ d; P

The eryptotic and hemolytic effects of a phytosterol (PS) mixture (β-sitosterol, campesterol, stigmasterol) or β-cryptoxanthin (β-Cx) at physiological serum concentration and their effect against oxidative stress induced by tert-butylhydroperoxide (tBOOH) (75 and 300 μM) were evaluated. β-Cryptoxanthin produced an increase in eryptotic cells, cell volume, hemolysis, and glutathione depletion (GSH) without ROS overproduction and intracellular Ca2+influx. Co-incubation of both bioactive compounds protected against β-Cx-induced eryptosis. Under tBOOH stress, PS prevented eryptosis, reducing Ca2+influx, ROS overproduction and GSH depletion at 75 μM, and hemolysis at both tBOOH concentrations. β-Cryptoxanthin showed no cytoprotective effect. Co-incubation with both bioactive compounds completely prevented hemolysis and partially prevented eryptosis as well as GSH depletion induced by β-Cx plus tBOOH. Phytosterols at physiological serum concentrations help to prevent pro-eryptotic and hemolytic effects and are promising candidate compounds for ameliorating eryptosis-associated diseases.

Adulteration of Mozzarella di Bufala Campana with cow milk is a common fraud because of the high price and limited seasonal availability of water buffalo milk. To identify such adulteration, this work proposes a novel approach based on the use of species-specific, low-molecular-weight biomarkers (LMWBs). Liquid chromatography–tandem mass spectrometry screening analyses identified β-carotene, lutein, and β-cryptoxanthin as LMWBs of cow milk, while ergocalciferol was found only in water buffalo milk. Adulterated mozzarellas were prepared in the laboratory and analyzed for the four biomarkers. Combined quantification of β-carotene and ergocalciferol enabled the detection of cow milk with a sensitivity threshold of 5% (w/w). The method was further tested by analyzing a certificated water buffalo mozzarella and several commercial products. This approach is alternative to conventional proteomic and genomic methods and is advantageous for routine operations as a result of its simplicity, speed, and low cost.

Age-related bone loss is a major public health problem. This cross-sectional study examined the association between the dietary intake of carotenoids and bone mineral density (BMD). Data from 8022 subjects (3763 males and 4259 females) aged 30–75 years included in the Korean National Health and Nutrition Examination Survey (2008–2011) were analyzed. BMD was measured by dual-energy X-ray absorptiometry. Intake of carotenoids was estimated using 24-h dietary recall. In multiple linear analysis, after adjusting for covariates, lutein + zeaxanthin and β-cryptoxanthin intake was positively associated with total hip BMD in males and premenopausal women respectively, while β-carotene intake was positively correlated with femoral neck, total hip, and whole-body BMD in postmenopausal women. Postmenopausal women in the highest quintile of daily β-carotene intake, showed a lower risk of osteopenia at the lumbar spine (odds ratio (OR): 0.35, 95% CI: 0.16–0.79, P for trend = 0.009) than those in the lowest quintile, after adjusting for covariates. Daily β-cryptoxanthin intake was significantly associated with a lower risk of osteopenia at the total hip (OR per 1 mg/day increase: 0.76; 95% CI: 0.59–0.97), and lumbar spine (OR per 1 mg/day increase: 0.79; 95% CI: 0.70–0.89) in postmenopausal women. These results suggest that the dietary intake of β-carotene and β-cryptoxanthin may have a positive effect on bone health.

Diet quality indices can predict nutritional adequacy of usual intake, but validity should be determined. The aim was to assess the validity of total and sub-scale score within the Australian Recommended Food Score (ARFS), in relation to fasting plasma carotenoid concentrations. Diet quality and fasting plasma carotenoid concentrations were assessed in 99 overweight and obese adults (49.5% female, aged 44.6 ± 9.9 years) at baseline and after three months (198 paired observations). Associations were assessed using Spearman’s correlation coefficients and regression analysis, and agreement using weighted kappa (Kw). Small, significantly positive correlations were found between total ARFS and plasma concentrations of total carotenoids (r = 0.17, p < 0.05), β-cryptoxanthin (r = 0.18, p < 0.05), β-carotene (r = 0.20, p < 0.01), and α-carotene (r = 0.19, p < 0.01). Significant agreement between ARFS categories and plasma carotenoid concentrations was found for total carotenoids (Kw 0.12, p = 0.02), β-carotene (Kw 0.14, p < 0.01), and α-carotene (Kw 0.13, p < 0.01). In fully-adjusted regression models the only signification association with ARFS total score was for α-carotene (β = 0.19, p < 0.01), while ARFS meat and fruit sub-scales demonstrated significant relationships with α-carotene, β-carotene, and total carotenoids (p < 0.05). The weak associations highlight the issues with self-reporting dietary intakes in overweight and obese populations. Further research is required to evaluate the use of the ARFS in more diverse populations.

cope β-Cryptoxanthin is an abundant carotenoid in fruits and vegetables that can be quantified in human blood-serum. Yet, contrary to other carotenoids, its effects on endothelial cells and angiogenesis remain unknown. Methods and results Human umbilical-vein endothelial cells (HUVEC) were treated with 0.01, 0.1 or 1 μM of β-cryptoxanthin. Antioxidant activity was determined by its free radical scavenging and oxygen-radical absorbance capacity (ABTS and ORAC assays). Effect on migration and formation of tubular structures was studied. Additionally, effect on angiogenesis was also analyzed using an in vivo model. β-Cryptoxanthin exhibited scavenging ability, having antioxidant effect on HUVEC. Interestingly, β-cryptoxanthin reduced their migration and angiogenesis, even in presence of vascular endothelial growth-factor (VEGF). Additionally, such carotenoid inhibited in vivo angiogenesis induced by VEGF. Besides, treatment of HUVEC with LE540 [retinoic-acid receptor (RAR) panantagonist] inhibited β-cryptoxanthin antiangiogenic effect on HUVEC. Conclusion β-Cryptoxanthin inhibits angiogenesis through RAR. Thus, this carotenoid and food containing it may be useful for prevention and treatment of angiogenic pathologies. That includes tumoral growth and wet macular-degeneration associated to aging. To the best of our knowledge, this is the first report of the antioxidant effect and antiangiogenic activity of such carotenoid on HUVEC, both in vitro and in vivo. This article is protected by copyright. All rights reserved

We investigated the transcriptional regulation of six genes involved in carotenoid biosynthesis, together with the carotenoid accumulation during postharvest ripening of three different papaya genotypes of contrasting pulp color. Red-pulp genotype (RPG) showed the lowest content of yellow pigments (YP), such as β-cryptoxanthin, zeaxanthin, and violaxanthin, together with the lowest relative expression levels (REL) of CpLCY-β2 and CpCHX-β genes. On the contrary, the yellow-pulp genotype (YPG) showed the highest content of YP and the highest REL of CpLCY-β2 and CpCHX-β genes. Interestingly, the orange-pulp genotype (OPG) showed intermediate content of YP and intermediate REL of CpLCY-β2 and CpCHX-β genes. The highest content of β-carotene shown by OPG despite having an intermediate REL of the CpLCY-β2 genes, suggests a post-transcriptional regulation. Thus, the transcriptional level of the genes, directing the carotenoid biosynthesis pathway, can partially explain the accumulation of carotenoids during the postharvest ripening in C. papaya genotypes of contrasting pulp color.