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A better understanding of the factors contributing to systemic concentrations of carotenoids is necessary given the weak correlations between circulating levels and dietary intake of carotenoids. Although genetic variation may play a key role in the interindividual variability in carotenoid concentrations, few genome-wide association studies (GWAS) have focused on carotenoids. We used a random sample (n = 519) of postmenopausal participants in the Sister Study with data on genotypes and plasma carotenoid levels to conduct GWAS for each of five carotenoids (mcg/mL): alpha-carotene, beta- carotene, cryptoxanthin, lycopene, and lutein/zeaxanthin. We used linear regression models and an additive genetic model to evaluate associations between 371,532 variants and inverse normal transformed carotenoid concentrations. We found evidence for one genome-wide statistically significant association with the combined carotenoids of lutein and zeaxanthin for rs6564851-C (beta = −0.377, se = 0.059, p = 4.6×10−10) and rs6420424-A (beta = −0.334, se = 0.059, p = 2.2×10−8), upstream of beta-carotene oxygenase 1 (BCO1) gene on chromosome 16. No other variant was associated with any of the remaining four carotenoids. Our results for the common rs6564851 and rs6420424 variants correspond to previous findings. Although biologic mechanisms explain the association between beta-carotene and the variants, the inverse association with lutein/zeaxanthin will require further investigation.

Purpose: To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. Materials and Methods: This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community- dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. Results: The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Conclusions: Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels.

Purpose: To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. Materials and Methods: This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community-dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. Results: The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Conclusions: Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels. [ABSTRACT FROM AUTHOR]

A better understanding of the factors contributing to systemic concentrations of carotenoids is necessary given the weak correlations between circulating levels and dietary intake of carotenoids. Although genetic variation may play a key role in the interindividual variability in carotenoid concentrations, few genome-wide association studies (GWAS) have focused on carotenoids. We used a random sample ( n  = 519) of postmenopausal participants in the Sister Study with data on genotypes and plasma carotenoid levels to conduct GWAS for each of five carotenoids (mcg/mL): alpha-carotene, beta- carotene, cryptoxanthin, lycopene, and lutein/zeaxanthin. We used linear regression models and an additive genetic model to evaluate associations between 371,532 variants and inverse normal transformed carotenoid concentrations. We found evidence for one genome-wide statistically significant association with the combined carotenoids of lutein and zeaxanthin for rs6564851-C (beta = -0.377, se = 0.059, p  = 4.6×10 -10 ) and rs6420424-A (beta = -0.334, se = 0.059, p  = 2.2×10 -8 ), upstream of beta-carotene oxygenase 1 (BCO1) gene on chromosome 16. No other variant was associated with any of the remaining four carotenoids. Our results for the common rs6564851 and rs6420424 variants correspond to previous findings. Although biologic mechanisms explain the association between beta-carotene and the variants, the inverse association with lutein/zeaxanthin will require further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Von Holle, Shi, O’Brien, Weinberg, Sandler and Park.)

A Gram-stain-negative, yellow-pigmented, strictly aerobic, non-flagellated, motile by gliding, rod-shaped bacterium, designated strain YSD2104 T , was isolated from a coastal sediment sample collected from the southeastern part of the Yellow Sea. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain YSD2104 T was closely related to three type strains, Lutimonas vermicola IMCC1616 T (97.4 %), Lutimonas saemankumensis SMK-142 T (96.9 %), and Lutimonas halocynthiae RSS3-C1 T (96.8 %). Strain YSD2104 T has a single circular chromosome of 3.54 Mbp with a DNA G+C content of 38.3 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain YSD2104 T and the three type strains ( L. vermicola IMCC1616 T , L. saemankumensis SMK-142 T , and L. halocynthiae RSS3-C1 T ) were 74.0, 86.2 and 73.6 %, and 17.9, 30.3 and 17.8 %, respectively. Growth was observed at 20-30 °C (optimum, 30 °C), at pH 6.5-8.5 (optimum, pH 7.0), and with NaCl concentrations of 1.5-3.5 % (optimum, 2.5 %). The major carotenoid was zeaxanthin, and flexirubin-type pigment was not produced. The major respiratory quinone was menaquinone-6. The major fatty acids (>10 %) were iso-C 15 : 0 , iso-C 15 : 1 G, iso-C 17 : 0 3-OH, summed feature 3 (C 16 : 1  ω 6 c and/or C 16 : 1  ω 7 c ), and summed feature 9 (iso-C 17 : 1  ω 9 c and/or 10-methyl C 16 : 0 ). The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, two unidentified aminolipids, and eight unidentified lipids. Conclusively, based on this polyphasic approach, we classified strain YSD2104 T (=KCTC 102008 T =JCM 36287 T ) as representing a novel species of the genus Lutimonas and proposed the name Lutimonas zeaxanthinifaciens sp. nov.

Background: Previous studies mainly concentrated on examining the correlation between single carotenoids and Chronic obstructive pulmonary disease (COPD). However, these findings have been inconsistent., Objectives: This study aimed to evaluate both the individual and overall associations of carotenoids with the prevalence of COPD., Methods: This study comprised 2,939 participants chosen from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. The logistic regression, quantile-based G-computation regression (qgcomp), and Bayesian kernel machine regression (BKMR) models were employed to explore the association between carotenoids and the prevalence of COPD. Mediation analyses were also conducted to explore the underlying mechanism of carotenoids on COPD., Results: Individuals diagnosed with COPD had significantly lower serum carotenoid concentrations than those without COPD. We found a negative relationship between combined carotenoids and the prevalence of COPD, and lutein and zeaxanthin and alpha cryptoxanthin were identified as the main contributors to this negative association. Moreover, eosinophil acted as a mediator in the relationship between lutein and zeaxanthin, alpha cryptoxanthin, and the prevalence of COPD, with mediating proportions of 2.75 % and 3.67 %., Conclusion: A negative association was observed between combined carotenoids and COPD prevalence, with lutein and zeaxanthin, and alpha cryptoxanthin identified as the main contributors. Eosinophils could potentially mediate the association between carotenoids and COPD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

The development of integrated co-production of multiple high-purity carotenoids from microalgal cells holds considerable significance for the valorization of microalgae. In this study, the economical microalga Nannochloropsis oceanica was identified as an accumulator of violaxanthin cycle carotenoids, including violaxanthin, antheraxanthin, and zeaxanthin. Notably, a novel and competent approach for the integrated co-production of violaxanthin cycle carotenoids was explored, encompassing four steps: microalgal cultivation, solvent extraction, octadecylsilyl open-column chromatography, and ethanol precipitation. Under optimal co-production conditions, the purities of the obtained violaxanthin, antheraxanthin, and zeaxanthin all exceeded 92%, with total recovery rates of approximately 51%, 40%, and 60%, respectively. Utilizing nuclear magnetic resonance techniques, the purified violaxanthin, antheraxanthin, and zeaxanthin were identified as all-trans-violaxanthin, all-trans-antheraxanthin, and all-trans-zeaxanthin, respectively. This method held significance for the multiproduct biorefinery of the microalga N. oceanica and carried potential future implications for the violaxanthin cycle carotenoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Glycans in corn silk could interact with co-existing small molecules during its absorption, digestion, and biological process. In order to understand the exact mechanism of action of zeaxanthin, it is critical to investigate the biomolecular interactions, which were necessary to form a glycan-small molecule complex and yet produce the bioactive effect. So far, the in-depth study of these natural interactions has not been fully elucidated. Here, we probed that the molecular interaction between zeaxanthin (ZEA) and glycans from corn silk (CSGs) was driven by enthalpy. More importantly, it was the first time found that CSGs can bind to lipid-soluble ZEA could be binded with CSGs. It was the first report on the thermostability of insulin structure and natural glycans. This study should facilitate our understanding of the interaction between lipid soluble molecules and glycans, and provide a more comprehensive understanding of the nutrient base in food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Flavobacterium can synthesize xanthophyll, particularly the pigment zeaxanthin, which has significant economic value in nutrition and pharmaceuticals. Recently, the use of carotenoid biosynthesis by bacteria and yeast fermentation technology has shown to be very efficient and offers significant advantages in large-scale production, cost-effectiveness, and safety. In the present study, JSWR-1 strain capable of producing xanthophyll pigment was isolated from a freshwater reservoir in Wanju-gun, Republic of Korea. Based on the morphological, physiological, and molecular characteristics, JSWR-1 classified as belonging to the Flavobacterium species. The bacterium is strictly aerobic, Gram-negative, rod-shaped, and psychrophilic. The completed genome sequence of the strain Flavobacterium sp. JSWR-1 is predicted to be a single circular 3,425,829-bp chromosome with a G+C content of 35.2% and 2,941 protein-coding genes. The optimization of carotenoid production was achieved by small-scale cultivation, resulting in zeaxanthin being identified as the predominant carotenoid pigment. The enhancement of zeaxanthin biosynthesis by applying different light-irradiation, variations in pH and temperature, and adding carbon and nitrogen supplies to the growth medium. A significant increase in intracellular zeaxanthin concentrations was also recorded during fed-batch fermentation achieving a maximum of 16.69 ± 0.71 mg/l, corresponding to a product yield of 4.05 ± 0.15 mg zeaxanthin per gram cell dry weight. Batch and fed-batch culture extracts exhibit significant antioxidant activity. The results demonstrated that the JSWR-1 strain can potentially serve as a source for zeaxanthin biosynthesis.

The objective of study was to investigate the relationships between maize kernel properties and carotenoid release during simulated gastrointestinal digestion of 103 hybrids of dent type. Commercial maize hybrids significantly differed in kernel hardness, chemical composition and carotenoid profile. Across all hybrids, the amount of digestible individual carotenoids increased as follows: β-carotene < α-cryptoxanthin < β-cryptoxanthin < lutein < zeaxanthin. The amount of digested carotenoids correlated negatively with amylose content and amylose-to-amylopectin ratio, while it correlated positively with the content of neutral detergent fibres and amylopectin as well as the Stenvert index. However, the content of endosperm lipids could not be related to carotenoid digestibility. Findings clearly indicate that the carotenoid release from the kernel during digestion is related to specific physical and chemical properties, leading to a better understanding of the effects of kernel matrix structure on carotenoid digestibility in dent-type maize hybrids., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Osteoporosis constitutes a serious challenge for public health. Dietary patterns belong to important, modifiable risk factors of this disease. Therefore, what and in what quantities we consume on a daily basis are extremely relevant. It is commonly known that bone health is positively affected by vitamins (e.g., vitamin D and vitamin K) as well as mineral components (e.g., calcium and magnesium). However, the human diet consists of many other groups of compounds that exhibit a potential antiosteoporotic and supporting bone-building effect. These dietary components include carotenoids. This paper presents a broad review of studies on the influence of particular carotenoids (β-carotene, lutein, zeaxanthin, β-cryptoxanthin, and lycopene) on bones. The paper discusses up-to-date in vitro experiments and research on animal models and presents how the results translate into clinical effect in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The performance and acclimation strategies of Chlamydomonas reinhardtii under stress conditions are typically studied in response to single stress factors. Under natural conditions, however, organisms rarely face only one stressor at a time. Here, we investigated the impact of combined salt and high light stress on the photoprotective response of C. reinhardtii. Compared to the single stress factors, the combination of both stressors decreased the photosynthetic performance, while the activation of energy dissipation remained unaffected. However, the PsbS protein was strongly accumulated and the conversion of violaxanthin to zeaxanthin was enhanced. These results support an important photoprotective function of PsbS and zeaxanthin independently of energy dissipation under combined salt and high light stress in C. reinhardtii., (© 2024 The Authors. Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

This study aimed to evaluate the association between dietary carotenoid intake and periodontitis in diabetic patients. Data on diabetic patients were collected from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 for this cross-sectional study. Dietary intake of carotenoids was assessed through the first 24-hour dietary recall interview. Full-mouth periodontal examinations were conducted by trained dental examiners. Subgroup analysis was conducted in terms of age, gender, the number of missing teeth, cardiovascular disease, smoking, and anti-diabetic drugs. Totally 1914 diabetic patients were included, with 1281 (66.93%) in the periodontitis group. After adjusting for age, gender, race, education, smoking, dental implants, hepatitis, and the number of missing teeth, α-carotene intake ≥55.82 mcg was associated with lower odds of periodontitis than α-carotene intake <55.82 mcg [OR = 0.70, 95% CI: 0.53-0.91, P = 0.010]; lutein and zeaxanthin intake ≥795.95 mcg was associated with decreased odds of periodontitis than lutein and zeaxanthin intake <795.95 mcg (OR = 0.75, 95%CI: 0.57-0.98, P = 0.039). The association between carotenoid intake and periodontitis varied across different subpopulations. In diabetes, dietary intake of α-carotene and lutein and zeaxanthin was inversely associated with the odds of periodontitis, which may facilitate clinical periodontitis management., Competing Interests: None., (© The Author(s) 2024.)

Purpose: Measurements of macular pigment optical density (MPOD) using the autofluorescence spectroscopy yield underestimations of actual values in eyes with cataracts. Previously, we proposed a correction method for this error using deep learning (DL); however, the correction performance was validated through internal cross-validation. This cross-sectional study aimed to validate this approach using an external validation dataset., Methods: MPODs at 0.25°, 0.5°, 1°, and 2° eccentricities and macular pigment optical volume (MPOV) within 9° eccentricity were measured using SPECTRALIS (Heidelberg Engineering, Heidelberg, Germany) in 197 (training dataset inherited from our previous study) and 157 eyes (validating dataset) before and after cataract surgery. A DL model was trained to predict the corrected value from the pre-operative value using the training dataset, and we measured the discrepancy between the corrected value and the actual postoperative value. Subsequently, the prediction performance was validated using a validation dataset., Results: Using the validation dataset, the mean absolute values of errors for MPOD and MPOV corrected using DL ranged from 8.2 to 12.4%, which were lower than values with no correction (P < 0.001, linear mixed model with Tukey's test). The error depended on the autofluorescence image quality used to calculate MPOD. The mean errors in high and moderate quality images ranged from 6.0 to 11.4%, which were lower than those of poor quality images., Conclusion: The usefulness of the DL correction method was validated. Deep learning reduced the error for a relatively good autofluorescence image quality. Poor-quality images were not corrected., Competing Interests: A patent application on the deep learning-based correction technology was filed by Seirei Hamamatsu General Hospital and Hamamatsu Photonics K. K., a patent application number: WO2021/171788. There are no further patents, products in development, or marketed products to declare. The remaining authors declare no competing financial interests., (Copyright: © 2024 Obana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study was to examine whether higher dietary carotenoid intake levels were associated with a lower prevalence of kidney stones., Materials and Methods: This study analyzed data from 2007 to 2018 National Health and Nutrition Examination Survey (NHANES) project. Dietary carotenoid intake (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin) was assessed using two 24-h dietary recall interviews. Multiple logistic regression and weighted quantile sum (WQS) regression were applied to examine the associations between five dietary carotenoids alone, compounds, and the prevalence of kidney stones. The dose-response relationships were analyzed by restricted cubic spline regression., Results: A total of 30,444 adults (2909 participants with kidney stones) were included in the analysis. The mean age of the participants was 49.95 years and 49.2% of the participants were male. Compared with the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.82 [0.73-0.92]), β-carotene (OR = 0.79 [0.70-0.89]), β-cryptoxanthin (OR = 0.88 [0.79-0.99]), and lutein/zeaxanthin (OR = 0.80 [0.71-0.91]) were significantly and inversely associated with the prevalence of kidney stones after adjusting for confounders. The dose-response analysis showed a linear relationship between five dietary carotenoid intake levels and the prevalence of kidney stones. Further WQS analysis revealed that the combination of all five dietary carotenoids was negatively associated with and the prevalence of kidney stones, with the largest effect coming from β-carotene (weight = 0.538)., Conclusion: Our findings indicated that higher dietary carotenoid intake levels were associated with decreased prevalence of kidney stones, and increasing the intake of foods rich in β-carotene may prevent the development of kidney stones., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Abdominal aortic calcification (AAC) is an important marker of subclinical atherosclerosis and a predictor of cardiovascular disease. This study aims to explore the association between carotenoid intakes and AAC., Methods: We included 2889 participants from the National Health and Nutrition Examination Survey (NHANES). Dietary carotenoid intakes were obtained through 24-h dietary recall interviews. Severe AAC was defined as a Kauppila score > 5. The main analysis utilizes logistic and restricted cubic spline models., Result: Severe AAC was detected in 378 (13.08%) participants. In fully adjusted models, the odds ratios (OR) with 95% confidence intervals (CI) of α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein with zeaxanthin and total carotenoid intakes for individuals with severe AAC were 0.53 (0.23-0.77), 0.39 (0.19-0.80), 0.18 (0.05-0.62), 0.40 (0.20-0.78), 0.53 (0.32-0.88) and 0.38 (0.18-0.77) in the highest versus lowest quartile intake, respectively. Dose-response analyses revealed that all of the carotenoids were associated with decreased risk of severe AAC in a nonlinear trend. Total carotenoid intakes of at least 100ug/kg/day were associated with decreased odds for severe AAC., Conclusion: α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein with zeaxanthin and total carotenoids were inversely associated with the risk of severe AAC in adults., (© 2024. The Author(s).)

Background and aims: Experimental studies showed that carotenoids had anti-carcinogenic properties, but epidemiological studies on the association between dietary carotenoids and esophageal squamous cell carcinoma (ESCC) risk were limited, and the findings were inconsistent. This study aimed to investigate the roles of intake of dietary carotenoids in the development of ESCC among a rural Chinese population. Methods: A population-based case-control study was conducted in Southwest China. A total of 915 incident ESCC cases and 925 community-based controls were included. A validated food frequency questionnaire with 76-item was adopted to collect information about dietary consumption. Intake of dietary calories and each carotenoid was calculated according to the China food composition tables. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by a logistic regression model, with adjustments for age, gender, body mass index, family cancer history, cigarette smoking, alcohol drinking, education, marital status, prudent pattern score, and total calories. Results: In comparison to the highest with lowest intake quartiles, intake of total carotenes (OR: 0.70, 95% CI: 0.52-0.96, P trend : 0.024), α-carotene (OR: 0.62, 95% CI: 0.46-0.83, P trend : 0.014), β-carotene (OR: 0.63, 95% CI: 0.46-0.86, P -trend : 0.005), and the sum of lutein and zeaxanthin (OR: 0.41, 95% CI: 0.29-0.56, P trend <0.001) was significantly associated with a decreased risk of ESCC after adjustment for confounders. Conclusions: The results indicated that a higher intake of total carotene, α-carotene, β-carotene, and the sum of lutein and zeaxanthin was associated with a lower risk of ESCC.

Habitual dietary intake measurement of carotenoids lutein and zeaxanthin (L/Z) has often been omitted or attempted with tools of unknown validity in past research. It was hypothesized that the dietary assessment tool, the L/Z screener, developed as part of this study, would be valid with agreement within 0.25 mg/day when compared against multiple 24-hour diet recalls in healthy Australian and United Kingdom adults. Two screeners with 91 food items were developed, 1 with a recall timeframe of a month and the other a week. Over 4 weeks, 56 Australian and 47 United Kingdom participants completed 4 weekly screeners, 2 monthly screeners, and eight 24-hour diet recalls. Validity was assessed through Bland-Altman plot analysis. L/Z intake measured by all tools was significantly correlated, with correlation coefficients from 0.58 to 0.83. Despite these correlations, the screeners were not valid, with poor Bland-Altman plot agreement when compared with the diet recalls. The Australian weekly screener performed best, demonstrating a mean difference of 0.51 mg/day and 95% limits of agreement between -1.46 mg/day and 2.49 mg/day of L/Z intake. Baby spinach, broccoli, and pumpkin provided the greatest proportion of L/Z intake. The low validity may be explained by high rates of misestimation or missed capture of moderate to high L/Z containing foods such as baby spinach. Prior research reliant on correlational statistics for L/Z tool validity should be interpreted with caution, and future screener development should prioritize accurate capture of high contribution foods., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Previous research has associated high dietary cholesterol intake with raised low-density lipoprotein cholesterol (LDL-C) and thus increased risk for cardiovascular disease (CVD). Emerging research suggests that it is saturated fat, not dietary cholesterol, associated with increased CVD risk. Despite being high in cholesterol, eggs, low in saturated fat, are not adversely associated with blood lipids or CVD risk. This paper describes a randomised controlled counter-balanced, cross-over trial assessing the effects of a high-cholesterol/low-saturated fat (egg) diet and a low-cholesterol/high-saturated fat diet (egg free) on blood lipids and lipoproteins, while accounting for physical activity levels which can also influence these parameters. The primary aim is to demonstrate that high cholesterol intake (from eggs) within a healthy, low-saturated fat diet does not adversely affect blood lipid levels and lipoprotein profiles. Instead, we propose that adverse effects on these parameters are mediated by saturated fat intake. The secondary aim is to explore relationships between changes in blood lutein and zeaxanthin concentrations and alterations in physical activity, examining whether changes in physical activity mediate effects on blood lipids and lipoproteins., Methods and Analysis: Fifty-two adults aged 18-60 years with LDL-C less than 3.5 mmol/L will be randomly allocated to three isocaloric diets for 5 weeks each: a high-cholesterol (600 mg)/low-saturated fat (6%) (egg) diet, a low-cholesterol (300 mg)/high-saturated fat (12%) (egg free) diet and a control diet that is high in both cholesterol (600 mg) and saturated fat (12%). Lipid and lipoprotein levels, lipoprotein size and concentrations, blood pressure, blood glucose, physical activity levels, and plasma lutein and zeaxanthin concentrations will be measured. Treatment effects will be analysed using linear mixed effects models., Ethics and Dissemination: Ethics approval was obtained from the University of South Australia Human Research Ethics Committee no. 204 327. Results will be disseminated through peer-reviewed journals and national and international presentations., Trial Registration Number: NCT05267522., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lutein and its isomer zeaxanthin serve as antioxidants and preserve cognitive function during aging. However, whether lutein/zeaxanthin (L + Z) exposure early in life improves cognitive development of children is rarely explored. It is also unknown whether gestational diabetes mellitus (GDM), characterized by heightened oxidative stress, affects lutein metabolism. This prospective longitudinal cohort study examined the differences in L + Z intake and metabolism, as well as the association between maternal L + Z intake and children's cognitive development in GDM versus non-GDM pregnancies. Seventy-six pregnant women ( n = 40 with GDM) were recruited between 25 and 33 weeks of gestation and dietary intakes were recorded. At delivery, cord blood was collected, and 2 years later, the Bayley III developmental test was conducted on a subset of children ( n = 38). The results suggest that GDM reduced cord blood lutein levels at birth; L + Z intake during pregnancy was associated with better cognitive (β = 0.003, p = 0.001) and language (β = 0.002, p = 0.038) scoring of children at 2 years regardless of GDM status. In conclusion, maternal L + Z intake was positively associated with children's developmental scores, regardless of GDM. More studies are needed to confirm such associations.

Background: Crocin, a glycosylated apocarotenoid pigment predominantly found in saffron, has garnered significant interest in the field of biotechnology for its bioactive properties. Traditional production of crocins and their aglycone, crocetin, typically involves extraction from crocin-producing plants. This study aimed to develop an alternative biosynthetic method for these compounds by engineering the metabolic pathways of zeaxanthin, crocetin, and crocin in Escherichia coli strains., Results: Employing a series of genetic modifications and the strategic overexpression of key enzymes, we successfully established a complete microbial pathway for synthesizing crocetin and four glycosylated derivatives of crocetin, utilizing glycerol as the primary carbon source. The overexpression of zeaxanthin cleavage dioxygenase and a novel variant of crocetin dialdehyde dehydrogenase resulted in a notable yield of crocetin (34.77 ± 1.03 mg/L). Further optimization involved the overexpression of new types of crocetin and crocin-2 glycosyltransferases, facilitating the production of crocin-1 (6.29 ± 0.19 mg/L), crocin-2 (5.29 ± 0.24 mg/L), crocin-3 (1.48 ± 0.10 mg/L), and crocin-4 (2.72 ± 0.13 mg/L)., Conclusions: This investigation introduces a pioneering and integrated microbial synthesis method for generating crocin and its derivatives, employing glycerol as a sustainable carbon feedstock. The substantial yields achieved highlight the commercial potential of microbial-derived crocins as an eco-friendly alternative to plant extraction methods. The development of these microbial processes not only broadens the scope for crocin production but also suggests significant implications for the exploitation of bioengineered compounds in pharmaceutical and food industries., (© 2023. The Author(s).)

Background: Retinol, tocopherols, and carotenoids (RTC) have physiological roles as vitamins, pro-vitamins, and antioxidants, and provide biomarkers of dietary vegetable and fruit intake. The goal was to investigate RTC in multiple sclerosis (MS)., Methods: This exploratory study included 106 people with MS (71 relapsing-remitting MS or RR-MS; and 35 progressive MS or PMS) and 31 healthy controls (HC) at baseline and 5-year follow-up (5YFU). Serum retinol, α-carotene, β-carotene, α-tocopherol, δ-tocopherol, γ-tocopherol, β-cryptoxanthin, lutein/zeaxanthin, and lycopene were measured using high performance liquid chromatography. Serum neurofilament light chain (sNfL) levels were measured using the single molecule array method. Expanded Disability Status Scale (EDSS) and low contrast letter acuity (LCLA) were used as disability measures., Results: Retinol in MS was positively correlated with α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, and α-tocopherol but negatively correlated with δ-tocopherol. EDSS was associated with α-tocopherol, δ-tocopherol, and lycopene. Greater retinol levels were associated with greater LCLA in RR-MS and PMS; high contrast visual acuity was not associated. Greater γ-tocopherol levels were associated with lower LCLA and high contrast visual acuity in PMS., Conclusions: RTC exhibit distinctive associations with LCLA and EDSS in MS., Competing Interests: Declaration of Competing Interest Ms. Nasim Nehzat and Dr. Richard Browne have nothing to disclose. Dr. Dejan Jakimovski is an Associate Editor for Clinical Neurology and Neurosurgery, and Frontiers in Cardiovascular Medicine. Bianca Weinstock-Guttman participated in speaker's bureaus and/or served as a consultant for Biogen, EMD Serono, Novartis, Genentech, Celgene/Bristol Meyers Squibb, Sanofi Genzyme, Bayer, Janssen, and Horizon. Dr. Weinstock-Guttman also received grant/research support from the agencies listed. She serves on the editorial board for BMJ Neurology, Children, CNS Drugs, MS International and Frontiers Epidemiology. Dr. Robert Zivadinov received speaker honoraria and consultant fees from Sanofi, Bristol Myers Squibb, Janssen, Mapi Pharma, CorEvitas, 415 Capital, and EMD Serono. He has received research support from Mapi-Pharma, Protembis, Bristol Myers Squibb, CorEvitas, Octave and Novartis. Dr. Murali Ramanathan received research funding from the National Multiple Sclerosis Society, Department of Defense and National Institute of Neurological Diseases and Stroke. He receives royalty from a self-published textbook., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the retina, retinoids involved in vision are under constant threat of oxidation, and their oxidation products exhibit deleterious properties. Using pulse radiolysis, this study determined that the bimolecular rate constants of scavenging cation radicals of retinoids by taurine are smaller than 2 × 10 7 M -1 s -1 whereas lutein scavenges cation radicals of all three retinoids with the bimolecular rate constants approach the diffusion-controlled limits, while zeaxanthin is only 1.4-1.6-fold less effective. Despite that lutein exhibits greater scavenging rate constants of retinoid cation radicals than other antioxidants, the greater concentrations of ascorbate in the retina suggest that ascorbate may be the main protectant of all visual cycle retinoids from oxidative degradation, while α-tocopherol may play a substantial role in the protection of retinaldehyde but is relatively inefficient in the protection of retinol or retinyl palmitate. While the protection of retinoids by lutein and zeaxanthin appears inefficient in the retinal periphery, it can be quite substantial in the macula. Although the determined rate constants of scavenging the cation radicals of retinol and retinaldehyde by dopa-melanin are relatively small, the high concentration of melanin in the RPE melanosomes suggests they can be scavenged if they are in proximity to melanin-containing pigment granules., Competing Interests: The authors declare no conflicts. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Astaxanthin (ASTA) and zeaxanthin (ZEA) are xanthophyll carotenoids showing a wide spectrum of health-promoting properties. However, their utilization is limited, mostly due to poor water solubility, limited bioavailability, and a tendency to oxidate, as well as photo- and thermal instability. The aim of this work was to develop ASTA- and ZEA-loaded nano-structured lipid carriers (NLCs) that would protect them against degradation and improve their intestinal stability/permeability. Obtained NLCs were characterized by an effective diameter of 294 nm for ASTA-NLC and 280 nm for ZEA-NLC; polydispersity index ( PDI ) lower than 0.2; and zeta potential of -29.4 mV and -29.0 mV, respectively. Interestingly, despite similar physicochemical characteristics, our investigation revealed differences in the encapsulation efficiency of ASTA-NLC and ZEA-NLC (58.0 % vs . 75.5 %, respectively). Obtained NLCs were stable during a 21 day-storage period in the dark at room temperature or at 4 °C. Investigation of gastrointestinal stability showed no change in effective diameter and PDI under gastric conditions while both parameters significantly changed under intestinal conditions. Our results showed for the first time that both ASTA- and ZEA-NLCs intestinal absorption investigated in the in vitro model is significantly increased (in relation to pure compounds) and is affected by the presence of mucus. This study provides useful data about the advantages of using NLC as a delivery system for ASTA and ZEA that might facilitate their applications in the food and pharmaceutical industry., (© 2023 Kristina Radić et al., published by Sciendo.)

Carotenoids have been recognized for their potential health benefits due to their antioxidant properties. There is limited research on the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and carotenoids. This study aimed to investigate the effect of carotenoid intake on the risk of MAFLD. We retrospectively analyzed 2722 adults aged ≥ 18 from the National Health and Nutrition Examination Survey 2017-2018. Hepatic steatosis was identified by elastography, and carotenoid consumption was evaluated through two 24-hour dietary recall interviews. Weighted logistic regression models, subgroup analyses, and restricted cubic splines were used for analyses. The weighted prevalence of MAFLD was 51.90%. Weighted logistic regression analysis demonstrated that intake of β-carotene, lutein/zeaxanthin, and lycopene was associated with a lower risk of MAFLD after adjusting for various covariates. Compared to the lowest tertile, a significant inverse correlation was observed between the highest total lycopene intake and MAFLD among females in the gender subgroup analysis. Restricted cubic spline regression analysis revealed a U-shaped association between lycopene consumption and MAFLD risk (P < .001), with an inflection point of approximately 9.48 mg/day. Moreover, the nonlinear relationship was particularly significant in females and absent in males. In summary, increased β-carotene, lutein/zeaxanthin, and lycopene consumption was associated with a decreased risk of MAFLD. The relationship between total lycopene intake and MAFLD was nonlinear, primarily in females. These findings have significant implications for the potential prevention and management of MAFLD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Context: Xanthophyll intake is known to improve eye health; however, its benefits on visual outcomes have not been systematically studied, particularly in a population with eye diseases., Objective: A systematic review, meta-analysis, and meta-regression were conducted to investigate the effect of xanthophyll intake on visual outcomes, and further subgroup analysis was performed on the basis of eye disease status., Data Sources: The PubMed, Scopus, Embase, CINAHL, Cochrane, and Web of Science databases were searched, and relevant randomized controlled trials were identified., Data Extraction: For systematic review, meta-analysis, and meta-regression, 43, 25, and 21 articles were selected, respectively., Data Analysis: Xanthophyll intake enhanced macular pigment optical density (MPOD) for both heterochromatic flicker photometry (weighted mean difference [WMD], 0.05; 95% confidence interval [CI], 0.03-0.07) and autofluorescence imaging (WMD, 0.08; 95%CI, 0.05-0.11) measurements and decreased photostress recovery time (WMD, -2.35; 95%CI, -4.49 to -0.20). While enhancement in visual acuity logarithm of the minimum angle of resolution was observed in response to the xanthophyll-rich food and supplement intake only for patients with eye disease (WMD, -0.04; 95%CI, -0.07 to -0.01). Meta-regression showed a positive correlation between change in MPOD (heterochromatic flicker photometry) and the corresponding change in serum lutein levels (regression coefficient = 0.068; P = 0.00)., Conclusion: Intake of xanthophyll-rich food or supplements can improve eye health. Additional improvement in visual acuity was observed in patients with eye disease. A positive association between MPOD and serum lutein level, while absent with dietary xanthophyll intake, suggests the importance of bioavailability when examining the effect of xanthophyll on eye health., Systematic Review Registration: PROSPERO registration no. CRD42021295337., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the relationship between dietary carotenoid intake and sleep duration., Methods: Adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007-2018 without missing information on dietary carotenoid intake (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin), sleep duration, and covariates were included. Participants' carotenoid consumption was divided into three groups by quartiles and sleep duration was grouped as short (< 7 h/night), optimal (7-8 h/night), and long (> 8 h/night). Multinominal logistic regression was constructed to examine the association between dietary carotenoid intake and sleep duration. Restricted cubic spline (RCS) regression was further utilized to explore their dose-response relationship. The weighted quantile sum (WQS) model was adopted to calculate the mixed and individual effect of 5 carotenoid sub-types on sleep duration., Results: Multinominal logistic regression presented that people with higher intakes of α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin were less likely to sleep too short or too long. Consistent with the findings from multinominal logistic regression, the RCS models suggested a reverse U-shaped relationship between sleep duration and carotenoid intakes. The mixed effects were also significant, where β-cryptoxanthin and lutein + zeaxanthin were the top 2 contributors associated with the decreased risks of short sleep duration, while β-carotene, α-carotene, and β-cryptoxanthin were the main factors related to the lower risk of long sleep duration., Conclusion: Our study revealed that the American adults with optimal sleep duration were associated with more dietary carotenoid intake, in comparison to short or long sleepers., (© 2023. The Author(s).)

Chicken oil is prone to oxidation due to the high content of unsaturated fatty acids. The interaction of antioxidants was affected by their concentration, ratio, and reaction system. In this article, mixtures of zeaxanthin and tocopherols (α-tocopherol and γ-tocopherol) were chosen to enhance the oxidative stability of chicken oil. The antioxidation of zeaxanthin with tocopherols was analyzed using the Rancimat test, the free radical scavenging capacity and the Schaal oven test (the variation of antioxidant content, PV and shelf life prediction). The optimal concentration of zeaxanthin determined by Rancimat in chicken oil was 20 mg/kg. The binary mixtures have a strong synergistic effect in the ABTS experiment, and the clearance rate was up to 99%, but antagonistic effect in ORAC. The degree of synergism between zeaxanthin and tocopherols was determined by ratio. The interaction between zeaxanthin and α-tocopherol was synergistic, while the types of interaction between zeaxanthin and γ-tocopherol were affected by concentration. The main synergistic interaction mechanism was the regeneration of tocopherol by zeaxanthin. Synergistic combinations of zeaxanthin with α-tocopherol and γ-tocopherol played a key role in the primary oxidation stage of the lipid. The best synergistic combination was A3 (zeaxanthin+α-tocopherol: 15+50 23 mg/kg), which could extend the shelf life of chicken oil (92.46 d) to 146.93 days. This work provides a reference for zeaxanthin and tocopherol to improve the oxidative stability of animal fat.

Introduction. Macula lutea is the central part of the retina and it houses carotenoid macular pigments - lutein, zeaxanthin, and meso-zeaxanthin. It is considered that carotenoids can prevent or slow down the progression of the early age-related macular degeneration in some patients. Therefore, the aim of this study was to examine the effects of supplementation with all three macular pigments on vision quality in patients with early agerelated macular degeneration. Material and Methods. This prospective study included 15 patients (25 eyes in total) with early age-related macular degeneration. All visual tests - visual acuity, glare sensation and contrast sensitivity, were performed at baseline and after 6 months of continuous supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg mesozeaxanthin. Results. The results showed that glare sensitivity improved in 20% of cases. Most of the examined eyes (76%) presented without visual acuity deterioration. Similar results were obtained for the contrast sensitivity test, where in 80% of cases vision quality remained stable or improved. There were no statistically significant differences between average values of examined parameters at baseline and after 6 months of supplementation. Conclusion. In most of the examined eyes (over 75%) visual quality remained stable or improvement of measured parameters was observed. This type of supplementation may improve visual performance or its preservation in patients with early age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Background: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are comprehensive indicators to evaluate visceral fat and determine the metabolic health of individuals. Carotenoids are a group of naturally occurring antioxidants associated with several diseases. The purpose of this investigation was to explore the association between serum carotenoid concentration and VAI or LAP., Methods: The data were obtained from the National Health and Nutrition Examination Survey between 2001 and 2006. The levels of serum carotenoids were evaluated using high-performance liquid chromatography. Multivariate linear regression models were employed to investigate the relationship between levels of serum carotenoids and VAI or LAP. The potential non-linear relationship was determined using threshold effect analysis and fitted smoothing curves. Stratification analysis was performed to investigate the potential modifying factors., Results: In total, 5,084 participants were included in this population-based investigation. In the multivariate linear regressions, compared to the lowest quartiles of serum carotenoids, the highest quartiles were significantly associated with VAI, and the effect size (β) and 95% CI was - 0.98 (- 1.34, - 0.62) for α-carotene, - 1.39 (- 1.77, - 1.00) for β-carotene, - 0.79 (- 1.18, - 0.41) for β-cryptoxanthin, - 0.68 (- 0.96, - 0.39) for lutein/zeaxanthin, and - 0.88 (- 1.50, - 0.27) for trans-lycopene. Using piece-wise linear regression models, non-linear relationships were found between β-carotene and trans-lycopene and VAI with an inflection point of 2.44 (log2-transformed, ug/dL) and 3.80 (log2-transformed, ug/dL), respectively. The results indicated that α-carotene, β-cryptoxanthin, and lutein/zeaxanthin were linearly associated with VAI. An inverse association was also found between serum carotenoids and LAP after complete adjustments., Conclusion: This study revealed that several serum carotenoids were associated with VAI or LAP among the general American population. Further large prospective investigations are warranted to support this finding., (© 2023. The Author(s).)

Plasma carotenoid concentrations are associated with antioxidant defense which might be disturbed in people with excessive body weight (EBW). This study aimed at evaluating the effect of a 6-week weight reduction program on plasma concentration of β-carotene, lycopene, and lutein/zeaxanthin in adults with EBW. A total of 130 adults were recruited for the study; 75 completed the program. Data on food consumption were collected with a 3-day recording method and a semi-quantitative FFQ. Body height, body weight (BW), waist circumference (WC), fat mass (FM), fat-free mass (FFM), abdominal subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were measured. Lipid profile, β-carotene, lycopene, and lutein/zeaxanthin were analyzed in blood. The AntioxObesity program resulted in a significant reduction in BW, WC, FM, SAT, and VAT. The mean plasma concentrations of β-carotene, lycopene, and lutein/zeaxanthin increased significantly after intervention. A reduction in FM above 4 kg significantly increased the concentration of β-carotene, lutein/zeaxanthin, and total carotenoids. An increase in carotenoid levels correlated with FM reduction, as fruit and vegetable intake remained unchanged. However, this effect may vary due to gender, HDL-cholesterol, body fat content, and obesity status in the weight loss process.

Lutein, zeaxanthin, and β-cryptoxanthin are polar oxygenated carotenoids found to be detectable in more than 95% of the population in the United States. Research has linked these carotenoids with lower coronary heart disease prevalence. This study investigates the association of serum lutein/zeaxanthin and β-cryptoxanthin with erectile dysfunction (ED) among middle-aged and older men in the United States. Serum lutein/zeaxanthin and β-cryptoxanthin were independent variables. The outcome variable was ED. Analyzed data from 1,302 men (≥40 years old) who participated in the National Health and Nutrition Examination Survey 2001-2002 cross-sectional study were included. After adjusting for all covariates, serum lutein/zeaxanthin negatively correlated with ED (odds ratio [OR]: 0.972, 95% confidence interval [CI]: [0.951, 0.994], p = .011). However, a U-shaped association between serum lutein/zeaxanthin and ED was detected in men with diabetes or prevalent cardiovascular disease. A U-shaped non-linear association was observed between β-cryptoxanthin levels and ED. These findings suggest that while both lutein/zeaxanthin and β-cryptoxanthin are recognized as essential antioxidants, maintaining lower serum lutein/zeaxanthin levels and appropriate serum β-cryptoxanthin levels may offer potential benefits for individuals with ED. Further investigations, particularly prospective studies, are warranted to determine the role of serum lutein/zeaxanthin and β-cryptoxanthin in the biological mechanism associated with ED., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Milk carotenoids may support preterm infant health and neurodevelopment. Infants fed human milk often have higher blood and tissue carotenoid concentrations than infants fed carotenoid-containing infant formula (IF). Donor human milk (DHM) is a supplement to mother's own milk, used to support preterm infant nutrition., Objectives: We tested whether tissue and plasma β-carotene concentrations would be higher in preterm pigs fed pasteurized DHM versus premature IF., Methods: This is a secondary analysis of samples collected from a study of the effects of enteral diet composition on necrotizing enterocolitis incidence. Preterm pigs received partial enteral feeding of either DHM (n = 7) or premature IF (n = 7) from 2 to 7 d of age. The diets provided similar β-carotene (32 nM), but DHM had higher lutein, zeaxanthin, and lycopene, whereas IF had higher total vitamin A. Plasma, liver, and jejunum carotenoid and vitamin A concentrations were measured by HPLC-PDA. Jejunal expression of 12 genes associated with carotenoid and lipid metabolism were measured., Results: Liver β-carotene concentrations were higher in DHM- than IF-fed piglets (23 ± 4 compared with 16 ± 2 μg/g, respectively, P = 0.0024), whereas plasma and jejunal β-carotene concentrations were similar between diets. Liver vitamin A stores were higher in piglets fed IF than DHM (50.6 ± 10.1 compared with 30.9 ± 7.2 μg/g, respectively, P=0.0013); however, plasma vitamin A was similar between groups. Plasma, liver, and jejunum concentrations of lutein, zeaxanthin, and lycopene were higher with DHM than IF feeding. Relative to piglets fed DHM, jejunal low density lipoprotein receptor (Ldlr) expression was higher (61%, P = 0.018) and cluster determinant 36 (Cd36) expression (-27%, P = 0.034) was lower in IF-fed piglets., Conclusions: Preterm pigs fed DHM accumulate more liver β-carotene than IF-fed pigs. Future studies should further investigate infant carotenoid bioactivity and bioavailability., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

Aldehyde dehydrogenase-2 (ALDH2) is a crucial enzyme participating in intracellular aldehyde metabolism and is acknowledged as a potential therapeutic target for the treatment of alcohol use disorder and other addictive behaviors. Using previously reported ALDH2 inhibitors of Daidzin, CVT-10216, and CHEMBL114083 as reference molecules, here we perform a ligand-based virtual screening of world-approved drugs via 2D/3D similarity search methods, followed by the assessments of molecular docking, toxicity prediction, molecular simulation, and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. The 2D molecular fingerprinting of ECFP4 and FCFP4 and 3D molecule-shape-based USRCAT methods show good performances in selecting compounds with a strong binding behavior with ALDH2. Three compounds of Zeaxanthin ( q = 0), Troglitazone ( q = 0), and Sequinavir ( q = +1 e ) are singled out as potential inhibitors; Zeaxanthin can only be hit via USRCAT. These drugs displayed a stronger binding strength compared to the reported potent inhibitor CVT-10216. Sarizotan ( q = +1 e ) and Netarsudil ( q = 0/+1 e ) displayed a strong binding strength with ALDH2 as well, whereas they displayed a shallow penetration into the substrate-binding tunnel of ALDH2 and could not fully occupy it. This likely left a space for substrate binding, and thus they were not ideal inhibitors. The MM-PBSA results indicate that the selected negatively charged compounds from the similarity search and Vina scoring are thermodynamically unfavorable, mainly due to electrostatic repulsion with the receptor ( q = -6 e for ALDH2). The electrostatic attraction with positively charged compounds, however, yielded very strong binding results with ALDH2. These findings reveal a deficiency in the modeling of electrostatic interactions (in particular, between charged moieties) in the virtual screening via the 2D/3D similarity search and molecular docking with the Vina scoring system.

Objectives: The association between dietary carotenoid intake and Soluble Klotho (S-Klotho) levels among the elderly population requires further evaluation. The purpose of this study is to evaluate the relationship between the dietary carotenoid intake and the S-Klotho plasma levels in older adults., Methods: Eligible participants aged 60 years or above were selected from the National Health and Nutrition Examination Surveys (NHANES) data, collected between 2007 and 2016. The consumption of carotenoids was determined through two 24-hour dietary recall assessments. Moreover, the S-Klotho levels in the serum were measured using an Enzyme-Linked Immuno-Sorbent Assay (ELISA)., Results: A total of 5,056 participants were included in the study having a median total carotenoid intake of 9775.25 μg (95% confidence interval (CI): 8971.30-10579.21) and a median S-Klotho concentration of 815.59 pg/mL (95% CI: 802.59-828.60). The multivariable regression analysis showed that a single standard deviation increase in total carotenoid intake was significantly associated with an 8.40 pg/mL increase in S-Klotho levels (95% CI: 0.48-16.31). When the carotenoids were divided into quartiles, participants in the third ((4963.5μg/day,11662.5μg/day]) and fourth quartiles ((11662.5μg/day,377178μg/day]) showed higher S-Klotho levels compared to those in the first quartile. Among carotenoid subtypes, increased intake of α-carotene, β-carotene, and lutein with zeaxanthin was associated with elevated S-Klotho levels. These observed associations between carotenoid subtypes and S-Klotho levels remained consistent across male participants, having a normal weight, and a moderate physical activity based on stratified analysis., Conclusion: The total carotenoid intake was positively related to plasma levels of S-Klotho in the elderly population, particularly for α-carotene, β-carotene, and lutein with zeaxanthin. However, further research is needed to confirm these findings and explore the underlying mechanisms behind this relationship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 He, Yin, Chen and Chen.)

Background: As part of a healthy diet, higher carotenoid intakes have been associated with a reduced risk of depression, mainly in adults, while prospective studies on plasma carotenoids in older adults are lacking. The aim of this study was to assess the prospective association between plasma carotenoids and the risk of Depressive Symptomatology (DS) in older adults., Methods: The study sample was based on the Three-City cohort of adults aged 65y+ free from DS at enrollment in 1999. Plasma carotenoids were measured at baseline. DS was assessed every 2-3 years over 17 years and defined by a Center for Epidemiologic Studies-Depression Scale score ≥ 16 and/or by antidepressant use. The association between plasma carotenoids or carotenoid/lipids (cholesterol and triglycerides) ratio and the risk for DS was assessed through multiple random-effect logistic regression., Results: The study sample was composed of 1010 participants (mean age 74 y (±4.9), 58 % of women) followed-up during a median time of 13.4 years. Plasma zeaxanthin and ratios of zeaxanthin/lipids, lutein+zeaxanthin/lipids and β-carotene/lipids were independently associated with a significant reduced risk of DS over time (Odds ratio (OR) = 0.81, 95 % Confidence Interval (CI) [0.67;0.99], OR = 0.79 [0.67;0.98], OR = 0.79 [0.64;0.94] and OR = 0.80 [0.66;0.97] for +1 standard deviation of each exposure respectively)., Limitations: Plasma carotenoids were only available at study baseline., Conclusion: Focusing on circulating carotenoids and considering lipids levels, the present results suggested an association between higher levels of plasma zeaxanthin, combined lutein+zeaxanthin and β-carotene and a decreased risk of DS over time in older adults., Competing Interests: Declaration of competing interest We have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Main Conclusion: Simultaneous genome editing of the two homeologous LCYe and ZEP genes of Nicotiana benthamiana results in plants in which all xanthophylls are replaced by zeaxanthin. Plant carotenoids act both as photoreceptors and photoprotectants in photosynthesis and as precursors of apocarotenoids, which include signaling molecules such as abscisic acid (ABA). As dietary components, the xanthophylls lutein and zeaxanthin have photoprotective functions in the human macula. We developed transient and stable combinatorial genome editing methods, followed by direct LC-MS screening for zeaxanthin accumulation, for the simultaneous genome editing of the two homeologous Lycopene Epsilon Cyclase (LCYe) and the two Zeaxanthin Epoxidase (ZEP) genes present in the allopolyploid Nicotiana benthamiana genome. Editing of the four genes resulted in plants in which all leaf xanthophylls were substituted by zeaxanthin, but with different ABA levels and growth habits, depending on the severity of the ZEP1 mutation. In high-zeaxanthin lines, the abundance of the major photosystem II antenna LHCII was reduced with respect to wild-type plants and the LHCII trimeric state became unstable upon thylakoid solubilization. Consistent with the depletion in LHCII, edited plants underwent a compensatory increase in PSII/PSI ratios and a loss of the large-size PSII supercomplexes, while the level of PSI-LHCI supercomplex was unaffected. Reduced activity of the photoprotective mechanism NPQ was shown in high-zeaxanthin plants, while PSII photoinhibition was similar for all genotypes upon exposure to excess light, consistent with the antioxidant and photoprotective role of zeaxanthin in vivo., (© 2023. The Author(s).)

Introduction: The objective was to analyze associations between dietary intake of multiple nutrients and altered cognitive function and/or decline., Methods: Observational analyses of participants (n = 6334) in two randomized trials of nutritional supplements for age-related macular degeneration: Age-Related Eye Disease Study (AREDS) and AREDS2., Results: In AREDS, for 4 of 38 nutrients examined, higher intake quintiles were significantly associated with decreased risk of cognitive impairment on the Modified Mini-Mental State test (<80): β-carotene, copper, docosahexaenoic acid, and insoluble fiber. In AREDS2, for 13 of 44 nutrients, higher intake quintiles were associated with decreased risk on the Telephone Interview Cognitive Status-Modified (<30). Rate of cognitive decline over up to 10 years was not significantly different with higher intake of any nutrient., Discussion: Higher dietary intake of multiple nutrients, including specific vitamins, minerals, carotenoids, fatty acids, and fiber, was associated with lower risk of cognitive impairment but not slower decline in cognitive function., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Carotenoids are plant pigments with light filtering and antioxidant properties that deposit in human tissues, including retina and skin. Descriptive characteristics and covariates of carotenoid status in macula and skin have been examined in adults; however, similar studies in children are limited. Thus, this study aimed to delineate how factors of age, sex, race, weight status, and dietary carotenoid intake relate to macular and skin carotenoids in children., Methods: Children (7-13 y, N = 375) completed heterochromatic flicker photometry to assess macular pigment optical density (MPOD). Participants underwent anthropometrics to measure weight status (BMI percentile [BMI%]), and parent/guardian provided demographic information. Subsample data were available for skin carotenoids (N = 181), assessed using reflection spectroscopy, and dietary carotenoids (N = 101) using the Block Food Frequency Questionnaire. Relationships between skin and macular carotenoids were assessed using partial Pearson's correlations controlling for age, sex, race, and BMI%. Relationships between dietary carotenoids and macular and skin carotenoids were assessed using stepwise linear regression including age, sex, race, and BMI% in the model., Results: Mean MPOD was 0.56 ± 0.22 and skin carotenoid score was 282 ± 94.6. There was no significant correlation between MPOD and skin carotenoids (r = 0.02, P = 0.76). BMI% was negatively associated with skin (stdβ = -0.42, P < 0.001), but not macular carotenoids (stdβ = -0.04, P = 0.70). Neither MPOD nor skin carotenoids were associated with age, sex, or race (all P > 0.10). MPOD was positively associated with energy-adjusted reported lutein + zeaxanthin intake (stdβ = 0.27, P = 0.01). Skin carotenoids were positively associated with energy-adjusted reported carotenoid intake (stdβ = 0.26, P = 0.01)., Conclusions: The mean MPOD values in children were higher than what has been reported in adult populations. Previous studies in adult samples report an average MPOD of 0.21. Although macular and skin carotenoids were not related, they were associated with dietary carotenoids relevant to the respective tissues; however, skin carotenoids may be more susceptible negative influence from higher weight status., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Zeaxanthin is a carotenoid, a dihydroxy derivative of β-carotene. Zeaxanthin has antioxidant, anti-inflammatory, anticancer, and neuroprotective properties. In this study, Yarrowia lipolytica was used as a host for the efficient production of zeaxanthin. The strain Y. lipolytica PO1h was used to construct the following engineered strains for carotenoid production since it produced the highest β-carotene among the Y. lipolytica PO1h- and Y. lipolytica PEX17-HA-derived strains. By regulating the key nodes on the carotenoid pathway through wild and mutant enzyme comparison and successive modular assembly, the β-carotene concentration was improved from 19.9 to 422.0 mg/L. To provide more precursor mevalonate, heterologous genes mvaE and mvaS MT were introduced to increase the production of β-carotene by 27.2% to the yield of 536.8 mg/L. The β-carotene hydroxylase gene crtZ was then transferred, resulting in a yield of zeaxanthin of 326.5 mg/L. The oxidoreductase RFNR1 and CrtZ were then used to further enhance zeaxanthin production, and the yield of zeaxanthin was up to 775.3 mg/L in YPD shake flask.

Main Conclusion: WHIRLY1 deficient barley plants surviving growth at high irradiance displayed increased non-radiative energy dissipation, enhanced contents of zeaxanthin and the flavonoid lutonarin, but no changes in α-tocopherol nor glutathione. Plants are able to acclimate to environmental conditions to optimize their functions. With the exception of obligate shade plants, they can adjust their photosynthetic apparatus and the morphology and anatomy of their leaves to irradiance. Barley (Hordeum vulgare L., cv. Golden Promise) plants with reduced abundance of the protein WHIRLY1 were recently shown to be unable to acclimatise important components of the photosynthetic apparatus to high light. Nevertheless, these plants did not show symptoms of photoinhibition. High-light (HL) grown WHIRLY1 knockdown plants showed clear signs of exposure to excessive irradiance such as a low epoxidation state of the violaxanthin cycle pigments and an early light saturation of electron transport. These responses were underlined by a very large xanthophyll cycle pool size and by an increased number of plastoglobules. Whereas zeaxanthin increased with HL stress, α-tocopherol, which is another lipophilic antioxidant, showed no response to excessive light. Also the content of the hydrophilic antioxidant glutathione showed no increase in W1 plants as compared to the wild type, whereas the flavone lutonarin was induced in W1 plants. HPLC analysis of removed epidermal tissue indicated that the largest part of lutonarin was presumably located in the mesophyll. Since lutonarin is a better antioxidant than saponarin, the major flavone present in barley leaves, it is concluded that lutonarin accumulated as a response to oxidative stress. It is also concluded that zeaxanthin and lutonarin may have served as antioxidants in the WHIRLY1 knockdown plants, contributing to their survival in HL despite their restricted HL acclimation., (© 2023. The Author(s).)

Lutein, zeaxanthin, and meso -zeaxanthin (a steroisomer of zeaxanthin) are macular pigments. They modify the physical properties of the lipid bilayers in a manner similar to cholesterol. It is not clear if these pigments are directly present in the lipid phase of the membranes, or if they form complexes with specific membrane proteins that retain them in high amounts in the correct place in the retina. The high content of macular pigments in the Henle fiber layer indicates that a portion of the lutein and zeaxanthin should not only be bound to the specific proteins but also directly dissolved in the lipid membranes. This high concentration in the prereceptoral region of the retina is effective for blue-light filtration. Understanding the basic mechanisms of these actions is necessary to better understand the carotenoid-membrane interaction and how carotenoids affect membrane physical properties-such as fluidity, polarity, and order-in relation to membrane structure and membrane dynamics. This review focuses on the properties of lutein.

Cyanobacterial blooms are increasing in frequency and intensity globally, impacting lake ecosystem health and posing a risk to human and animal health due to the toxins they can produce. Cyanobacterial pigments preserved in lake sediments provide a useful means of understanding the changes that have led to cyanobacterial blooms in lakes. However, there is some uncertainty as to whether specific carotenoids are unique to certain genera or types of cyanobacteria. To fill this knowledge gap, we analyzed pigments in 34 cyanobacteria cultures and applied the findings to sediments from three New Zealand lakes. The cyanobacterial carotenoids canthaxanthin, echinenone and zeaxanthin were detected in all cultures, whereas myxoxanthophyll was only detected in ten cultures (Microcoleus, Planktothrix and the picocyanobacteria cultures; Synechococcaceae). The sum of the individual carotenoid concentrations provided the strongest relationship with cyanobacterial biomass (R 2  = 0.58) and could be used in paleolimnology studies to evaluate general cyanobacterial abundance. Ratios of canthaxanthin, zeaxanthin and myxoxanthophyll relative to echinenone indicated that carotenoid ratios could be used to differentiate picocyanobacteria and bloom-forming cyanobacteria, to some degree. High zeaxanthin/echinenone ratios were measured in picocyanobacteria and low zeaxanthin/echinenone ratios were measured in bloom-forming cyanobacteria. The zeaxanthin/echinenone ratio was applied to sediment core samples where the cyanobacterial community was also evaluated by 16S rRNA gene metabarcoding, with the zeaxanthin/echinenone ratios showing similar patterns to those observed in the cultures. The preliminary assessment described here suggests that zeaxanthin/echinenone ratios could provide a valuable paleoecological proxy for evaluating historical shifts in cyanobacterial communities and warrants further exploration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Aims: Oral lutein (L) and zeaxanthin (Z) supplementation enhances macular pigment optical density (MPOD) and plays a protective role in the development of age-related macular degeneration (AMD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel in vivo retinal imaging method that has been shown to correlate to classical MPOD measurements and might contribute to a metabolic mapping of the retina in the future. Our aim was to show that oral supplementation of L and Z affects the FLIO signal in a positive way in patients with AMD., Methods: This was a prospective, single center, open label cohort study. Patients with early and intermediate AMD received oral L and Z supplementation during three months, and were observed for another three months after therapy termination. All visits included measurements of clinical parameters, serum L and Z concentration, MPOD measurements using heterochromatic flicker photometry, dual wavelength autofluorescence imaging, and FLIO. Correlation analysis between FLIO and MPOD were performed., Results: Twenty-one patients completed the follow up period. Serum L and Z concentrations significantly increased during supplementation (mean difference 244.8 ng/ml; 95% CI: 81.26-419.9, and 77.1 ng/ml; 95% CI: 5.3-52.0, respectively). Mean MPOD units significantly increased (mean difference 0.06; 95% CI: 0.02-0.09; at 0.5°, 202; 95% CI: 58-345; at 2°, 1033; 95% CI: 288-1668; at 9° of eccentricity, respectively) after three months of supplementation with macular xanthophylls, which included L and Z. Median FLIO lifetimes in the foveal center significantly decreased from 277.3 ps (interquartile range 230.2-339.1) to 261.0 ps (interquartile range 231.4-334.4, p = 0.027). All parameters returned to near-normal values after termination of the nutritional supplementation. A significant negative correlation was found between FLIO and MPOD (r 2  = 0.57, p < 0.0001)., Conclusions: FLIO is able to detect subtle changes in MPOD after L and Z supplementation in patients with early and intermediate AMD. Our findings confirm the previous described negative correlation between FLIO and MPOD. Macular xanthophylls seem to contribute to short foveal lifetimes. This study is registered at ClinicalTrials.gov (identifier number NCT04761341)., Competing Interests: Declaration of competing interest All authors received nonfinancial support for this study as indicated above: Heidelberg Engineering, DSM Nutritional Products, Théa PHARMA S.A. A. Wyss: Employee of DSM Nutrional Products Ltd. M. Zinkernagel: Bayer, Novartis, Boehringer Ingelheim (all consulting and speakers honoraria, not related to the here presented work). S. Wolf: Roche, Chengdu Kanghong Biotechnology, Zeiss, Heidelberg Engineering (all consulting and speakers honoraria, not related to the here presented work), Bayer, Novartis (both Reading Center Fees, not related to the current work)., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)