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β-Cryptoxanthin (BCX) possesses potential therapeutic and health benefits. However, BCX absorption is low because of its poor aqueous solubility. In this study, a complex between BCX and casein (Cas) was prepared to improve the water dispersibility and bioavailability of BCX. BCX was recovered quantitatively from freeze-dried kumquat powder through solid–liquid extraction and saponification. The complexation significantly improved the apparent solubility of BCX under acidic and neutral conditions. A cell membrane permeation test using a Caco-2 cell monolayer was performed to evaluate the bioavailability of the BCX–Cas complex. This complex and a blank sample were digested in vitro and added to the apical side of the Caco-2 cell membrane. The quantity of BCX that permeated using the BCX–Cas complex after 24 h was 22.7 times greater than that of the blank. Thus, complexation of BCX with Cas improved dramatically the bioavailability of BCX from a kumquat extract.

In this study, to investigate the xanthophyll accumulation in citrus fruits, the major fatty acid esters of β-cryptoxanthin and β-citraurin were identified, and changes in their contents were investigated in two Satsuma mandarin varieties, 'Miyagawa-wase' and 'Yamashitabeni-wase', during the ripening process. The results showed that β-cryptoxanthin and β-citraurin were mainly esterified with lauric acid, myristic acid, and palmitic acid in citrus fruits. During the ripening process, β-cryptoxanthin laurate, myristate, and palmitate were accumulated gradually in the flavedos and juice sacs of the two varieties. In the flavedo of 'Yamashitabeni-wase', β-citraurin laurate, myristate, and palmitate were specifically accumulated, and their contents increased rapidly with a peak in November. In addition, functional analyses showed that CitCCD1 and CitCCD4 efficiently cleaved the free β-cryptoxanthin, but not the β-cryptoxanthin esters in vitro. The substrate specificity of CitCCDs towards free β-cryptoxanthin indicated that β-cryptoxanthin esters might be more stable than free β-cryptoxanthin in citrus fruits.

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

β-Cryptoxanthin has been associated with reduced-risk of some cancers. However, the mechanisms of β-cryptoxanthin still remain unclearly understood in gastric cancer (GC). In this study, we examined the effect of β-cryptoxanthin on AMPK signal in human gastric cancer cells. AGS and SGC-7901 cells were treated with β-cryptoxanthin (0-40 μM) and AGS cells were injected in BALB/c (nu/nu) mice to analyze the effect of β-cryptoxanthin on GC. We found that β-cryptoxanthin induced inhibitory effect on the cell viability in a time- and concentration-dependent manner. The number of migrated cells and protein levels of matrix metalloproteinase (MMP) −2 and MMP-9 were obviously decreased. β-Cryptoxanthin treatment induced G0/G1 arrest, and reduced the expression of Cyclin E, Cyclin D1, cyclin-dependent kinases (CDK) of CDK4 and CDK6, and increased the expression of p53 and p21 in the two GC cells. Additionally, β-cryptoxanthin induced apoptosis and increased the expression of cleaved caspase-3, -8, -9 as well as cytochrome C (cyt C). β-Cryptoxanthin induced AMP-activated protein kinase (AMPK) signal inactivation by the down-regulation of protein kinase A (PKA), p-AMPK, eukaryotic elongation factor 2 kinase (eEF2k). Furthermore, β-cryptoxanthin inhibited tumor growth through suppressing the tumor volume and weight, inducing apoptotic cells. Besides, β-cryptoxanthin induced significant reductions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In conclusion, our data provide the novel evidence to understand the mechanism of anti-pcancer of β-cryptoxanthin and indicate that β-cryptoxanthin can serve as a promising chemopreventive agent against gastric cancer.

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.

To better understand the potential function of carotenoids in the chemoprevention of cancers, mechanistic understanding of carotenoid action on genetic and epigenetic signaling pathways is critically needed for human studies. The use of appropriate animal models is the most justifiable approach to resolve mechanistic issues regarding protective effects of carotenoids at specific organs and tissue sites. While the initial impetus for studying the benefits of carotenoids in cancer prevention was their antioxidant capacity and pro-vitamin A activity, significant advances have been made in the understanding of the action of carotenoids with regards to other mechanisms. This review will focus on two common carotenoids, provitamin A carotenoid β-cryptoxanthin and non-provitamin A carotenoid lycopene, as promising chemopreventive agents or chemotherapeutic compounds against cancer development and progression. We reviewed animal studies demonstrating that β-cryptoxanthin and lycopene effectively prevent the development or progression of various cancers and the potential mechanisms involved. We highlight recent research that the biological functions of β-cryptoxanthin and lycopene are mediated, partially via their oxidative metabolites, through their effects on key molecular targeting events, such as NF-κB signaling pathway, RAR/PPARs signaling, SIRT1 signaling pathway, and p53 tumor suppressor pathways. The molecular targets by β-cryptoxanthin and lycopene, offer new opportunities to further our understanding of common and distinct mechanisms that involve carotenoids in cancer prevention. 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.

OBJECTIVES: Skin Carotenoid Content (SCC) is a validated biomarker of vegetable intake. The objective of this study is to compare SCC to self-reported diet and supplement intake. METHODS: This cross-sectional study used baseline data from 61 participants in an ongoing intervention trial (Nutrition Interventions for Cognitive Enhancement). Participants were cognitively normal older adults (≥65 years, MMSE score >25). SCC was determined non-invasively by Resonance Raman spectroscopy (VEGGIE METER®; Longevity Link Corporation). Three measurements were taken on the fingertip and averaged. Dietary intake was obtained by 3-day diet records. A dietitian reviewed the diet records and entered the records into the Nutrition Data System for Research (version 2019). Linear regression was used to assess relationships between self-reported carotenoid intake and SCC measurement. RESULTS: The mean SCC was 279 ± 72.1. Correlations for self-reported individual carotenoid intake and SCC scores were beta-carotene (r2 = 0.15, β̞ = 0.38, P = 0.002), alpha-carotene (r2 = 0.10, β̞ = 0.32, P = 0.01), and lutein + zeaxanthin (r2 = 0.16, β̞ = 0.41, P = 0.001). Correlations for self-reported combined diet and supplement intake and SCC scores were beta-carotene (r2 = 0.15, β̞ = 0.38, P = 0.002), alpha carotene (r2 = 0.10, β̞ = 0.32, P = 0.01), and lutein + zeaxanthin (r2 = 0.07, β̞ = 0.26, P = 0.04). Neither reported diet nor diet and supplement intakes of beta-cryptoxanthin, lycopene, and retinol were related to SCC scores. Correlations for food group and SCC scores were dark vegetables (r2 = 0.15, β̞ = 0.39, P = 0.002), deep yellow vegetables (r2 = 0.09, β̞ = 0.30, P = 0.02), and total vegetable intake (r2 = 0.16, β̞ = 0.40, P = 0.001). CONCLUSIONS: Within older adults, the SCC is a good indicator of dietary lutein + zeaxanthin, beta-carotene, and alpha-carotene intake. The finding that lutein + zeaxanthin relationship decreases when accounting for combined diet and supplement intake suggests need to investigate bioavailability of supplemental lutein + zeaxanthin. FUNDING SOURCES: National Institutes of Health.

&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.

The carotenoid profiles of citrus fruit have been well studied, but knowledge about the xanthophylls esters pattern is more limited. In this study, the native carotenoid profiles of mandarin and orange juices were studied. Xanthophylls in oranges were esterified with lauric, myristic, palmitic and stearic acids. The fatty acids esterifying β-cryptoxanthin in mandarins were lauric, myristic, palmitic and capric acid. In oranges, the average relationships of total free carotenoids to the sum of mono-esters and di-esters were 0.82 and 1.67, respectively, and the average relationships total mono-esters to total of di-esters was 2.51. In general, the mono-ester fraction was the most significant quantitatively. In mandarins, the average relationship of total free carotenoids to the sum of mono-esters was 0.17, which is in line with the fact that β-cryptoxanthin was mostly esterified and not free (unesterified).

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.

27 Páginas.-- 3 Figuras.-- 2 Tablas, Among the nutritional properties of microalgae, this study is focused in the presence of carotenoid esters in prokaryote microalgae, an event that has not been shown so far. Three carotenoid esters that accumulate in non-stressful culture conditions are identified in Aphanotece microscopica Nägeli and Phormidum autumnale Gomont, what may provide an extra value to the quality attributes of the carotenoid profile in cyanobacteria as functional foods. In addition, new data on the carotenoid characterization added quality criteria for the identification of the esterified metabolites, enabling the monitoring of these food components. Specifically, the metabolomic approach applied to the food composition analysis, has allowed to differentiate between the esters of zeinoxanthin and β-cryptoxanthin, which were undifferentiated to date during the MS characterization of carotenoids in other food sources. We propose a new qualifier product ion specific for zeinoxanthin ester, which it is not present in the MS2 spectrum of β-cryptoxanthin esters., This work was supported by the Comisión Interministerial de Ciencia y Tecnología (CICYT-EU, Spanish and European Government, grant number AGL 2015-63890-R). MM was supported with a fellowship from CAPES.

Carotenoids constitute a large group of lipophilic pigments whose health-promoting benefits have been widely recognized. Hydroxy-containing carotenoids can be found in both free form or esterified with fatty acids in several plant matrices, but the native carotenoid profile is overall poorly explored due to the difficulty of analyzing carotenoid esters. One of the main natural sources of carotenoids is the marigold flower, which has been extensively used by the industry for the production of food colorants or supplements, both often manufactured with no saponification process. Although lutein esters are well established as the major compounds naturally found in marigold petals and their products, carotenoid esters other than the lutein ones have not been extensively examined. We carried out a comprehensive identification of carotenoids and carotenoid esters from marigold petals by LC-DAD-(APCI+)MS/MS. Whereas 18 carotenoids were identified in the saponified extract, 56 were identified when no saponification procedure was carried out: 6 free carotenoids, 20 monoesters and 30 diesters. This is the first time that esters of zeaxanthin, violaxanthin, auroxanthin, zeinoxanthin and β-cryptoxanthin are identified in marigold. The structural information obtained through characteristic fragmentation patterns and diagnostic fragments in MS and MS/MS spectra (APCI+) sustained the differentiation between carotenoid esters with similar characteristics. Therefore, the separation of carotenoids by reversed-phase liquid chromatography using C30 columns in combination with DAD and APCI-MS/MS detection allowed high sensitivity and selectivity for carotenoid ester analysis.

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.

Vitamin A serves essential functions in mammalian biology as a signaling molecule and chromophore. This lipid can be synthesized from more than 50 putative dietary provitamin A precursor molecules which contain at least one unsubstituted β-ionone ring. We here scrutinized the enzymatic properties and substrate specificities of the two structurally related carotenoid cleavage dioxygenases (CCDs) which catalyze this synthesis. Recombinant BCO1 split substrates across the C15,C15' double bond adjacent to a canonical β-ionone ring site to vitamin A aldehyde. Substitution of the ring with a hydroxyl group prevented this conversion. The removal of methyl groups from the polyene carbon backbone of the substrate did not impede enzyme activity. Homology modeling and site-directed mutagenesis identified amino acid residues at the entrance of the substrate tunnel, which determined BCO1's specificity for the canonical β-ionone ring site. In contrast, BCO2 split substrates across the C9,C10 double bond adjacent to assorted ionone ring sites. Kinetic analysis revealed a higher catalytic efficiency of BCO2 with substrates bearing 3-hydroxy-β-ionone rings. In the mouse intestine, the asymmetric carotenoid β-cryptoxanthin with one canonical and one 3-hydroxy-β-ionone ring site was meticulously converted to vitamin A. The tailoring of this asymmetric substrate occurred by a stepwise processing of the carotenoid substrate by both CCDs and involved a β-apo-10'-carotenal intermediate. Thus, opposite selectivity for ionone ring sites of the two mammalian CCDs complement each other in the metabolic challenge of vitamin A production from a chemically diverse set of precursor molecules.

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.

The objective of this study was to develop straightforward processes that could be applied to the large-scale production of β-cryptoxanthin in an attempt to facilitate investigation of its biological activity. An oleoresin obtained from crude extracts of marigold flowers (Tagetes erecta) with approximately 24% total lutein fatty acid ester content was directly used as starting material for partial synthesis of (3 R)-β-cryptoxanthin under mild reaction conditions at ambient temperature. Therefore, acid-catalyzed deoxygenation of lutein esters from marigold oleoresin followed by hydrogenation in the presence of catalytic amount of platinum (Pt) supported on alumina (5%) at ambient temperature gave a mixture of (3 R)-β-cryptoxanthin fatty acid esters (major) and (3 R,6'R)-α-cryptoxanthin fatty acid esters (minor). Saponification and Z-to-E isomerization of the product followed by crystallization gave a mixture of (3 R)-β-cryptoxanthin as the major product. Similarly, acid-catalyzed hydrogenation of unesterified (3 R,3'R,6'R)-lutein with Pt/alumina in ethyl acetate gave a mixture of (3 R,6'R)-α-cryptoxanthin acetate (minor) in a one-pot reaction. Alkaline hydrolysis and Z-to-E isomerization of the mixture followed by crystallization provided (3 R)-β-cryptoxanthin.

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

24 Páginas.-- 3 Tablas.-- 1 Figura, Carotenoids, especially β-cryptoxanthin, exert multiple biological activities in the organism. Various processing techniques can improve carotenoid bioavailability in relation to the food matrix. The study objective was to compare the bioavailability of carotenoids from orange juice (OJ) with that from a beverage obtained by alcoholic fermentation of orange juice (FOB). Seven volunteers were recruited for a randomized, controlled, and crossover study. Post-intake plasma carotenoid concentrations were measured by HPLC in the subjects at 0–8 h after their consumption of OJ or FOB. β-Cryptoxanthin and lutein absorption was significantly higher from FOB than from OJ, but no significant difference in zeaxanthin absorption was found. The mean baseline-corrected area under the concentration curve (AUC0-8 h) for β-cryptoxanthin, lutein and zeaxanthin was 24.6-, 1.3- and 4.65-fold larger, respectively, after FOB versus OJ consumption. This fermented orange beverage could be an abundant source of bioavailable carotenoids, and its regular consumption may exert healthy effects., The authors thank the Spanish Government (projects AGL2010-14850/ALI and AGL2014-53195R) and Junta de Andalucía (projects P09-AGR4814M and P08-AGR-03477, and group PAI BIO311) for financial support. DHM is member of CaRed Network funded by MINECO (BIO2015-71703-REDT) and participates in EUROCAROTEN COST Action (CA15136). They are also grateful to Grupo Hespérides Biotech S.L. for supplying the fermented orange beverage.

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.

Provitamin A carotenoids (ß-carotene, α-carotene, and ß-cryptoxanthin) contribute to the dietary intake of vitamin A and are associated with decreased risk of many chronic diseases. Besides their contents in foods, their bioaccessibility is of great interest since it represents the amount that will be absorbed in the gut. The aim of this study was to adopt, for the first time, the in vitro digestion model suitable for food, proposed in a consensus paper by Minekus et al. (2014), to assess the bioaccessibility of carotenoids from the fruits that are the major contributors to the intake of ß-cryptoxanthin in Spain (orange, tangerine, red pepper, peach, watermelon, and persimmon) and loquat. The highest ß-cryptoxanthin content and the lowest bioaccessibility was found in mandarin and loquat (13331.6 and 929.2 μg per 100 g respectively), whereas the highest contents of ß-carotene and α-carotene were recorded in red pepper (1135.3 and 90.4 μg per 100 g respectively). The bioaccessibility of ß-cryptoxanthin was similar to that of ß-carotene (0.02-9.8% and 1-9.1%, respectively) and was higher than that of ß-carotene in red pepper, watermelon and peach. α-Carotene bioaccessibility ranged between 0% and 4.6%. We discuss the critical factors for comparing our data: the form of the food being analyzed (raw/cooked/previously frozen, in the presence or absence of oil/fat) and the protocol for bioaccessibility assessment. Different food processing techniques may increase carotenoid bioaccessibility compared to raw food. However, given the difficulties encountered when comparing the results of studies on bioaccessibility, it seems logical to propose the application of the previously mentioned standardized in vitro protocol., Rocío Estévez-Santiago is the recipient of a JAE-Predoc grant from the Spanish Consejo Superior de Investigaciones Científicas (CSIC), awarded under the program of the Junta para la Ampliación de Estudios, cofinanced by the European Social Fund (ESF). The support of the program for international connection iLINK+ (I-LINK0770) of the CSIC and the AZ Mercadante’s (Sao Paulo Research Foundation (FAPESP, proc. 13/50789-0), E Murillo’s (Universidad de Panamá) and AA Durant’s (INDICASAT, Panamá) critical contributions are acknowledged. The authors wish to thank Milagros Sánchez-Prieto for technical support and the financial support from ALIMNOVA-UCM951505.

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.