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Background: Although diets rich in carotenoids are associated with muscle health and a reduced risk of disability, the relationship between carotenoids and low lean body mass has not been fully elucidated., Objectives: This study aimed to clarify the relationship between serum carotenoid concentrations and low lean body mass over 4 y in older Japanese community-dwellers., Methods: A total of 750 adults aged ≥60 y participated in the National Institute for Longevity Sciences-Longitudinal Study of Aging. Individuals with a low lean body mass and muscle strength or gait speed at baseline were excluded. Baseline serum α-carotene, β-carotene, β-cryptoxanthin, zeaxanthin, lutein, and lycopene were measured. Low lean body mass was defined as appendicular lean mass relative to the measured height (ALM/ht 2 ) of <7.0 kg/m 2 in males and <5.4 kg/m 2 in females, according to the criteria of the Asian Working Group for Sarcopenia 2019. A generalized estimating equation was used to estimate the odds ratio and 95% confidence interval for low lean body mass according to tertiles of total and individual carotenoids at baseline, adjusted for sex, age, season, follow-up months, education years, economic status, current smoking status, a history of ischemic heart disease, stroke, hypertension, dyslipidemia, diabetes mellitus, and metabolic equivalents., Results: Low serum total carotenoids were associated with low ALM/ht 2 , and the odds ratios of low ALM/ht 2 in the third tertile of total carotenoids were significantly lower than those in the first tertile after adjusting for covariates. The odds ratios of low ALM/ht 2 in the third tertile of β-cryptoxanthin were significantly associated with those in the first tertile after adjusting for covariates (P = 0.03); however, no trend was observed for this relationship., Conclusions: These findings indicate that low serum total carotenoids and serum β-cryptoxanthin are associated with low lean body mass in older Japanese community-dwellers., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The associations between serum carotenoids and mortality are contradictory in various metabolic-associated diseases. This study aimed to examine the associations of five major serum carotenoids with mortality among adults with metabolic dysfunction-associated fatty liver disease (MAFLD)., Methods and Results: This analysis included 3040 individuals with MAFLD from the Third National Health and Nutrition Examination Survey (NHANES III). All-cause and cardiovascular mortality were ascertained by linkage to the National Death Index through December 31, 2019. Cox proportional hazards regression models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and restricted cubic spline (RCS) analyses were performed to assess the linearity of the associations. During a follow-up period of 826,547 person-years, 1325 all-cause and 429 cardiovascular deaths occurred. For all-cause mortality, compared with those in the lowest quartiles, the multivariable-adjusted HRs (95% CIs) in the highest quartiles were 0.63 (0.49-0.81) for α-carotene; 0.65 (0.52-0.80) for β-carotene; 0.64 (0.51-0.81) for β-cryptoxanthin; 0.73 (0.56-0.95) for lycopene; and 0.69 (0.52-0.91) for lutein/zeaxanthin. For cardiovascular mortality, the multivariable-adjusted HRs (95% CIs) in the highest quartiles were 0.51 (0.33-0.78) for α-carotene; 0.54 (0.35-0.82) for β-carotene; 0.52 (0.34-0.80) for β-cryptoxanthin; 0.63 (0.44-0.90) for lycopene; and 0.62 (0.39-0.99) for lutein/zeaxanthin. Besides, serum α-carotene, β-cryptoxanthin, and lycopene exhibited linear correlations with all-cause mortality in MAFLD adults, and four serum carotenoids, except β-carotene, were linearly correlated with cardiovascular mortality., Conclusions: Lower serum α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin concentrations were associated with higher risk of all-cause and cardiovascular mortality in US adults with MAFLD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Carotenoids are a group of tetraterpenoid lipophilic pigments linked to depression, but studies on individual carotenoid components are lacking. We aimed to assess the association between each serum carotenoids and depressive symptoms in adults., Methods: This cross-sectional study included 7264 adults from the National Health and Nutrition Examination Survey (NHANES). Serum carotenoid levels (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin) were measured using high-performance liquid chromatography. Participants with a Patient Health Questionnaire score ≥ 10 were considered to have depressive symptoms. The association between each carotenoid and depressive symptoms was investigated using multivariable-adjusted logistic regression, restricted cubic spline, and weighted quantile sum regression models., Results: The participants' average age was 46.0 (interquartile range: 34.0-60.0) years (50.9 % females), and 545 participants (7.5 %) were diagnosed with depressive symptoms. The logistic regression model demonstrated that high serum α-carotene, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin levels were associated with a lower likelihood of depressive symptoms. The restricted cubic spline model revealed that the significantly inverse relationships between serum carotenoid levels and the risk of depressive symptoms were nonlinear for α-carotene, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin and were linear for lycopene. The threshold effect analysis further identified the inflection points were 12.1, 35.7, 5.9, and 7.7 μg/dL for α-carotene, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin, respectively. The weighted quantile sum regression model revealed that β-cryptoxanthin (35.2 %) and α-carotene (34.5 %) were the top-weighted carotenoids correlated with depressive symptoms., Conclusions: The present results suggested an association between higher levels of each serum carotenoids and a decreased risk of depressive symptoms in adults., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The study focuses on the association between serum carotenoids and cancer-related death. Using data from the National Health and Nutrition Examination Survey (2001-2006 and 2017-2018), the study encompasses 10,277 participants older than age 20 years, with recorded baseline characteristics and serum carotenoid concentrations (including α-carotene, trans-β-carotene, cis-β-carotene, β-cryptoxanthin, trans-lycopene, and lutein/zeaxanthin). We hypothesized that serum carotenoid concentrations were negatively associated with cancer-related death. The weighted chi-square analyses indicate significant negative correlations between higher serum concentrations of α-carotene, β-cryptoxanthin, trans-lycopene, and total carotenoids, and the risk of cancer-related deaths. Using weighted Cox regression analysis, this study confirms that α-carotene, β-cryptoxanthin, trans-lycopene, and total carotenoids, as continuous or categorical variables, are inversely related to cancer mortality (P < .0001). Furthermore, considering competitive risk events, lower concentrations of serum β-cryptoxanthin (Fine-Gray P = 1.12e-04), trans-lycopene (P = 5.68e-14), and total carotenoids (P = .03) are associated with an increased risk of cancer-related deaths. The research reveals a crucial inverse relationship between serum carotenoid concentrations and cancer-related death., Competing Interests: Author Declarations The authors declare no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, β -cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (OR total carotenoids = 0·61, 95% CI: 0·41-0·89, OR β -cryptoxanthin = 0·67, 95% CI: 0·49-0·92), chronic bronchitis (OR β -cryptoxanthin = 0·66, 95% CI: 0·50-0·87) and asthma (Q2: OR lutein/zeaxanthin = 0·78, 95% CI: 0·62-0·97); participants in the highest tertiles of total carotenoids, α -carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR) total carotenoids = 0·62, 95% CI: 0·42-0·90, HR α -carotene = 0·54, 95% CI: 0·36-0·82, HR lutein/zeaxanthin = 0·48, 95% CI: 0·33-0·71, HR lycopene = 0·66, 95% CI: 0·45-0·96) than those in the lowest tertiles. Higher serum total carotenoids and β -cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α -carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.

Purpose: Current literature on the roles of α-, β-carotene and β-cryptoxanthin in neurocognitive function has largely focused on preventing cognitive decline in older people, and less on neuro-development in children. We examined the relations of maternal plasma carotenoids concentrations with offspring cognitive development up to age 4.5 years in the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study., Methods: Maternal plasma α-, β-carotene and β-cryptoxanthin concentrations at delivery were determined by ultra-performance liquid chromatography. Children's cognition was assessed at ages 2 (Bayley Scales of Infant and Toddler Development) and 4.5 (Kaufman Brief Intelligence Test) years. Associations were examined in 419 mother-offspring pairs using linear regressions adjusting for key confounders., Results: Median and interquartile range of maternal plasma concentrations (mg/L) were: α-carotene 0.052 (0.032, 0.081), β-carotene 0.189 (0.134, 0.286), and β-cryptoxanthin 0.199 (0.123, 0.304). In 2 years old children, higher maternal carotenoids [per standard deviation (SD) log-concentration] were positively associated with neurocognitive functions: β-cryptoxanthin with higher scores in cognitive [β = 0.18, (0.08, 0.28) SD], receptive language [β = 0.17 (0.07, 0.27) SD], fine motor [β = 0.16 (0.05, 0.26) SD], and gross motor [β = 0.16 (0.06, 0.27) SD] scales; β-carotene with higher cognitive score [β = 0.17 (0.05, 0.29) SD]. No significant associations were observed with neurocognitive functions at age 4.5 years., Conclusion: Our study provides novel data suggesting a potential role of prenatal carotenoids, particularly β-cryptoxanthin, on early offspring cognitive and motor development. Whether the prenatal influences sustain beyond early childhood requires further investigation in longer term studies.

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 [h 2  = 0.98, P = 7 × 10 -18 and h 2  = 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.

β-carotene, α-carotene and β-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 β-cryptoxanthin and of α-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 (≥1.1 µmol/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 α-carotene and β-cryptoxanthin were compared to those for β-carotene. Eating comparable amounts of α-carotene, β-cryptoxanthin and β-carotene foods resulted in 55% greater α-carotene (95% CI 35, 90) and 686% higher β-cryptoxanthin (95% CI 556, 1016) concentrations than β-carotene in blood. This suggests differences in the apparent bioavailability of α-carotene and β-cryptoxanthin and even larger differences with β-cryptoxanthin, greater than that of β-carotene. Four fruits (tomato, orange, tangerine, red pepper) and two vegetables (carrot, spinach) are the main contributors to their dietary intake (>50%) in Europeans.

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 <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., Competing Interests: The authors declare no conflict of interest.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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, β-cryptoxanthin, α-carotene, and β-carotene). This Institutional Review Boardapproved cross-sectional study enrolled 82 mother-infant pairs. Placenta, maternal serum, and umbilical cord blood samples were analyzed for carotenoids concentrations. Mothers completed a food frequency questionnaire and demographic/birth outcome data were collected. L + Z were present in placenta, median 0.105 micrograms/gram (mcg/g) and were significantly correlated with maternal serum ( r = 0.57; p < 0.001), umbilical cord blood levels ( r = 0.49; p = 0.001), but not dietary intake ( p = 0.110). L + Z were the most prevalent in placenta (49.1%) umbilical cord blood (37.0%), but not maternal serum (18.6%) or dietary intake (19.4%). Rate of transfer was 16.0%, the highest of all carotenoids. Conclusively, L + Z were identified as the two most prevalent in placenta. Results highlight unique roles L + Z may play during pregnancy.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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

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 13C 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 13C-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. 13C-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 13C-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 < 0.003). A greater increase occurred in serum BCX from WGOM muffins (131%) than from ROM muffins (108%) (P ≤ 0.003). Zeaxanthin AUCs were higher for WGOM (0.94 ± 0.33) and ROM (0.96 ± 0.47) than for RWM (0.05 ± 0.12 μmol ⋅ L-1 ⋅ d; P < 0.003). The intervention did not affect predose serum retinol 13C-abundance. Vitamin A status was within an optimal range (defined as 0.1-0.7 μmol/g liver)., Conclusions: BCX and zeaxanthin were highly bioavailable from BCX-biofortified maize. The adoption of BCX maize could positively affect consumers' BCX and zeaxanthin intakes and associated health benefits. This trial is registered at www.clinicaltrials.gov as NCT02800408.

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 (AUC 0-8 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

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 < 0.001)., Conclusions: Our findings support a possible positive association between serum concentrations of lipophylic antioxidant and TL. The implications of this association deserve further investigation.

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, I 2 = 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.

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 (P trend<0·001 to 0·013) in both men and women. The absolute mean differences in the IMT between the subjects in the extreme quartiles of serum carotenoid levels were 0·034 mm (α-carotene), 0·037 mm (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 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 Ca 2+ influx. Co-incubation of both bioactive compounds protected against β-Cx-induced eryptosis. Under tBOOH stress, PS prevented eryptosis, reducing Ca 2+ 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.

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 < 0.001, in this subset of children). Here we show significant increases in α-carotene, β-cryptoxanthin, and zeaxanthin (p < 0.001). There was no impact on lutein or lycopene concentrations. Consumption of biofortified maize can have broader implications beyond the control of vitamin A deficiency (Trial registration: NCT01695148).

Paprika oleoresin is obtained by solvent extraction from Capsicum annuum L. fruits and contains multiple carotenoids, such as capsanthin, β-carotene, zeaxanthin, and β-cryptoxanthin, which are considered protective against various diseases. Herein, we investigated the effect of paprika oleoresin supplementation on plasma carotenoid accumulation and evaluated the safety of the oleoresin. We used a double-blinded, placebo-controlled comparative clinical study design and tested the effects of varying doses in healthy adult subjects. In total, 33 subjects were randomly divided into three groups to take capsules containing 0, 20, or 100 mg of paprika oleoresin daily for 12 consecutive weeks. Plasma carotenoid concentrations were measured at 0, 4, 8, and 12 weeks, and the safety of paprika oleoresin capsules was investigated using analyses of blood biochemistry, hematology, and urine contents. In these experiments, β-cryptoxanthin and zeaxanthin dose-dependently accumulated in plasma within the dose range of the study over 12 consecutive weeks of paprika oleoresin supplementation. Moreover, β-cryptoxanthin accumulated to higher levels than the other paprika oleoresin carotenoids. In contrast, capsanthin was not detected in plasma before or during the 12-week treatment period. Finally, no adverse events were associated with intake of paprika oleoresin (20 and 100 mg/day) in safety evaluations. Paprika oleoresin is a suitable source of carotenoids, especially β-cryptoxanthin.

Scope: Previous epidemiological studies on the association between circulating carotenoids and the risk of colorectal cancer drew inconclusive conclusions. This study aimed to examine serum carotenoids in relation to colorectal cancer risk in a Chinese population., Methods and Results: One case-control study beginning from July 2010, consecutively recruited 538 eligible colorectal cancer cases and 564 age (5-year interval) and sex frequency-matched controls. Serum levels of α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin were detected by HPLC. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI) after adjusting for various confounders. Serum levels of α-carotene, β-cryptoxanthin and lycopene were found to be inversely associated with colorectal cancer risk. The adjusted ORs of the highest quartile relative to the lowest quartile serum level were 0.49 (95% CIs 0.33-0.72) for α-carotene, 0.44 (95% CIs 0.29-0.66) for β-cryptoxanthin, and 0.36 (95% CIs 0.24-0.54) for lycopene, respectively. The association between serum β-carotene, lutein/zeaxanthin and colorectal cancer risk was not statistically significant., Conclusion: The results indicated that the incidence of colorectal cancer was associated with lower serum levels of α-carotene, β-cryptoxanthin and lycopene among Chinese population residing in Guangdong., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., Competing Interests: The authors declare no conflict of interest.

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 (K w ). 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 (K w 0.12, p = 0.02), β-carotene (K w 0.14, p < 0.01), and α-carotene (K w 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., Competing Interests: The authors declare no conflict of interest.

Birds are an anomaly among vertebrates as they are remarkably long-lived despite having naturally high blood glucose and metabolic rates. For mammals, hyperglycemia leads to oxidative stress and protein glycation. In contrast, many studies have shown that domestic and wild birds are relatively resistant to these glucose-mediated pathologies. Surprisingly very little research has examined protein glycation in birds of prey, which by nature consume a diet high in protein and fat that promotes gluconeogenesis. The purpose of this study was to evaluate protein glycation and antioxidant concentrations in serum samples from several birds of prey (bald eagle (BAEA), red-tailed hawk (RTHA), barred owl (BAOW), great horned owl (GHOW)) as protein glycation can accelerate oxidative stress and vice versa. Serum glucose was measured using a commercially available assay, native albumin glycation was measured by mass spectrometry and various antioxidants (uric acid, vitamin E, retinol and several carotenoids) were measured by high performance liquid chromatography. Although glucose concentrations were not significantly different between species (p=0.340), albumin glycation was significantly higher (p=0.004) in BAEA (23.67±1.90%) and BAOW (24.28±1.43%) compared to RTHA (14.31±0.63%). Of the antioxidants examined, lutein was significantly higher in BAOW (p=0.008). BAEA had the highest beta-cryptoxanthin and beta-carotene concentrations (p<0.005). The high concentrations of antioxidants in these birds of prey relative to other birds likely helps protect from complications that may otherwise arise from having high glucose and protein glycation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (© 2017 S. Karger AG, Basel.)

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

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/β-carotene and higher β-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene ( r = -0.248), α-tocopherol ( r = 0.208), α-carotene ( r = -0.112), and β-cryptoxanthin ( r = 0.125; all p < 0.001). Age was inversely associated with lycopene (-6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m²)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher β-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (-4.8% vs. -3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene., Competing Interests: The authors declare no conflict of interest.

Background and Aims: 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., Methods and Results: 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 with <1/d intake of Satsuma mandarin, 3-4/d was associated with a low risk of high PWV., Conclusion: 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., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Several studies suggest that β-cryptoxanthin has a greater plasma response from its common food sources than other carotenoids such as β-carotene and lycopene. The hypothesis of this study is that changes in plasma β-cryptoxanthin concentrations will be greater than changes in plasma β-carotene or lycopene concentrations even if these carotenoids are fed in a similar food matrix, such as citrus fruit. We tested this hypothesis by measuring changes in plasma concentrations of β-cryptoxanthin, lycopene, and β-carotene after feeding measured amounts of canned tangerines and pink grapefruit to healthy nonsmoking adult humans. Volunteers served as their own controls and received both citrus fruit treatments randomly. In the first study, 8 subjects ate single meals of 234-304g of tangerines or 60-540g of pink grapefruit. The second study compared changes in plasma carotenoid concentration caused by feeding 234g of tangerines or 540g of pink grapefruit to 11 subjects. Blood was collected 5 times within 24hours after each citrus meal. Carotenoid concentrations were analyzed by reversed-phase high-performance liquid chromatography. Plasma β-cryptoxanthin concentrations increased within 5hours and then stabilized, remaining high throughout the 24hours measured. Plasma concentrations of lycopene and β-carotene did not change. These results show that β-cryptoxanthin concentrations increased after a citrus fruit meal, but lycopene and β-carotene concentrations did not change after a similar citrus fruit meal. These results support our hypothesis that changes in plasma β-cryptoxanthin are greater than changes in plasma lycopene or β-carotene, even when these carotenoids are fed in a similar food matrix., (Published by Elsevier Inc.)

Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

Unlabelled: 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., Introduction: 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., Methods: 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., Results: 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 <0.05), respectively. For men, the corresponding values were 2.6-4.0 % for α-carotene at the whole body and hip regions (P-trend <0.001-0.023)., Conclusion: These results suggest that serum carotenoids have a favorable association with bone health in the study population, especially in women.

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<0.05). The combination of β-cryptoxanthin and vitamin C is inversely associated with the risk of developing osteoporosis in post-menopausal Japanese female subjects.