UNASSIGNED: Vitamins A and D are essential for the health of pregnant women and infants. Nevertheless, the relationship between umbilical cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants remains uncertain.
UNASSIGNED: This cohort study aims to examine the relationship between cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants aged 0-6 months.
UNASSIGNED: 140 singleton mother-infant pairs were recruited in total. Questionnaires were used to collect maternal and infant information, and liquid chromatography was utilized to quantify the levels of vitamins A and D in the umbilical cord blood. Anthropometric measurements were conducted at birth, at 3 and 6 months of age, and the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HAZ), and BMI-for-age z-score (BMIZ) were calculated. Univariate and multivariate linear regression models were used for the analysis.
UNASSIGNED: The average concentration of vitamins A and D in cord blood was 0.58 ± 0.20 μmol/L and 34.07 ± 13.35 nmol/L, both below the normal range for children. After adjusting for confounding factors, vitamin A levels in cord blood positively correlated with HAZ growth in infants aged 3-6 months (β= 0.75, P < 0.01) while vitamin D levels negatively correlated with LAZ growth (β= -0.01, P = 0.01) and positively correlated with BMIZ growth (β= 0.02, P < 0.01).
UNASSIGNED: Higher Vitamin A levels at birth promote HAZ growth in infants aged 3-6 months while higher vitamin D levels at birth promote BMIZ growth in infants aged 3-6 months.
UNASSIGNED: https://register.clinicaltrials.gov, identifier NCT04017286.

OBJECTIVE: This study focused on the investigation of the correlation between dietary retinol intake and rheumatoid arthritis (RA) using the National Health and Nutrition Examination Survey (NHANES) database.
METHODS: Data from five NHANES cycles from 2003 to 2012 were utilized for this study. Dietary retinol intake was considered as the independent variable, and RA was the dependent variable. A weighted logistic regression method was applied to construct the relational model of the two variables. Stratified analysis without adjusting for confounding factors and subgroup analysis with confounding factors adjusted were conducted to explore the association between dietary retinol intake and RA. The optimal intake of dietary retinol was determined by the restricted cubic splines (RCS) analysis.
RESULTS: 22,971 samples were included in this study. The weighted logistic regression model was employed to construct the relational model of dietary retinol intake and RA (OR: 0.95, 95% CI: 0.91-0.99, p = 0.019). Stratified analysis displayed a great influence on the relational model exerted by the interaction between gender and retinol intake (p for interaction = 0.014). A significant association between retinol intake and RA was also indicated in the model adjusted for demographic characteristics (OR: 0.95, 95% CI: 0.90-1.00, p = 0.029). Subgroup analysis by gender showed that in the female population, unadjusted model (OR: 0.90, 95% CI: 0.84-0.96, p = 0.002), model adjusted for demographic characteristics only (OR: 0.89, 95% CI: 0.83-0.96, p = 0.002), and model adjusted for all confounding factors (OR: 0.91, 95% CI: 0.85-0.99, p = 0.019) indicated dietary retinol intake as a protective factor against RA. RCS analysis demonstrated that in the female population, regardless of the model used (Crude, Model I, and Model II), an intake of dietary retinol > 354.86 mcg was associated with RA disease reduction (OR < 1.0, p-non-linear < 0.05, p-overall < 0.05).
CONCLUSIONS: Increased dietary retinol intake was associated with RA disease reduction, particularly in the female population. Women are recommended to increase their dietary retinol intake (> 354.86 mcg) to reduce the risk of RA.

OBJECTIVE: Oxidative stress is strongly associated with atopic dermatitis (AD), and increased antioxidant intake could potentially reduce the risk of or alleviate its symptoms. However, the argument is disputed. Therefore, we conducted a Mendelian randomization (MR) analysis to explore the causal relationship between dietary antioxidant vitamin intake and AD.
METHODS: We applied MR analysis to examine the causative association between dietary antioxidant vitamin intake (vitamin C, vitamin E, carotene, and retinol) and AD. The genome-wide association study (GWAS) summary data for antioxidant vitamins intake and AD were obtained from the IEU OpenGWAS database and the UK biobank. Our study consisted of two major parts, MR analysis to detect the causal relationship between exposure and outcome, and sensitivity analysis as supplemental evidence to verify the robustness of the results.
RESULTS: The results revealed a suggestive causal relationship between vitamin E intake and AD (p = 0.038, OR 95% CI = 0.745-0.992). However, there was no causal relationship between the other three vitamins (vitamin C, carotene, and retinol) and AD (p = 0.507, OR 95% CI = 0.826-1.099) (p = 0.890, OR 95% CI = 0.864-1.184) (p = 0.492, OR 95% CI = 0.893-1.264). None of the single nucleotide polymorphisms (SNPs) were detected as heterogeneous and pleiotropy in the sensitivity analysis (p > 0.05).
CONCLUSIONS: The analysis suggested that dietary intake of vitamin E may potentially lower the risk of AD. Conversely, intake of vitamin C, retinol, and carotene is not causally related to AD. Although vitamin E intake could be protective against AD, intake of dietary antioxidant vitamins to prevent or treat AD is not necessary.

UNASSIGNED: The relationship between vitamin A levels and gestational diabetes mellitus (GDM) is not well understood, and prospective studies are lacking.
UNASSIGNED: This was a prospective, longitudinal study. A total of 391 women in early pregnancy were recruited between October and December 2018 at Shunyi District Maternal and Child Health Hospital (Beijing, China). Serum vitamin A concentration was measured at enrollment. GDM was diagnosed on the basis of a 75 g oral glucose-tolerance test at 24-28 weeks of follow-up. Logistic regression was used for the analysis.
UNASSIGNED: None of the subjects in the cohort had vitamin A deficiency or excess. At the follow-up, 76 participants had developed GDM. Participants who developed GDM were older and had higher body mass index, fasting insulin, HbA1c, fasting glucose, homeostasis model assessment for insulin resistance, triglyceride, low-density lipoprotein cholesterol, and high-sensitivity CRP levels, as well as higher serum vitamin A levels at baseline. On logistic multivariate analysis, higher vitamin A was positively associated with higher risk of GDM. The adjusted OR was 2.85 (95% CI 1.04-7.80, P=0.042) for Q4 versus Q1 and 1.59 (95% CI 1.11-2.28, P=0.011) for every 1 SD increase in serum vitamin A levels. In participants within the vitamin A reference range (0.33-0.78 mg/L), the positive association also maintained significance.
UNASSIGNED: Higher serum vitamin A levels were associated with higher GDM risks, even within the reference range. The results and possible mechanisms need to be further verified and clarified.

The association between vitamin A and single cardiometabolic diseases has been extensively studied, but the relationship between dietary vitamin A intake and the risk of cardiometabolic multimorbidity (CMM) has not been studied. Therefore, the present study was conducted to explore the association with CMM risk by analyzing different sources of vitamin A. This study utilized 13,603 subjects aged ≥ 18 years from 1997 to 2015 from the China Health and Nutrition Survey (CHNS). Dietary intake was calculated from 3 consecutive 24-h dietary recalls combined with a house hold food inventory. CMM is defined as the development of at least two cardiometabolic diseases. After a median follow-up of 9.0 years, there were 1050 new cases of CMM. The risk of CMM was significantly lower in those with higher vitamin A intake (Q1 vs Q5 HR 0.66, 95% CI 0.54-0.81). β-carotene (Q1 vs Q5 HR 0.82, 95% CI 0.66-1.02) and retinol (Q1 vs Q5 HR 0.59, 95% CI 0.48-0.73) intake had a similarly negative correlation. Using restricted cubic spline found an L-shaped relationship between retinol intake and CMM (p non-linear < 0.001). Negative associations were also found in specific CMD groups (hypertension, cardiovascular disease, stroke and diabetes). Dietary intake of vitamin A was negatively associated with CMM risk, and this protective effect was more pronounced in patients with cardiovascular disease. There was an L-shaped association between retinol intake and CMM risk.

OBJECTIVE: We aim to investigate the association between vitamin A intake and depression among patients with heart failure (HF).
RESULTS: In this cross-sectional study, data of HF patients were extracted from the National Health and Nutrition Examination Survey (NHANES) 2007-2020. The independent variable was vitamin A intake, and the dependent variable was depression. Weighted univariate and multivariate logistic regression models were performed to explore the association of vitamin A intake with depression in HF patients. A total of 999 HF patients were included, with a mean age of 66.19 (0.51) years, and 566 (52.49%) were male. And 197 patients have depression. Vitamin A intake ≥731.38 mcg was associated with lower incidence of depression [odds ratio (OR) = 0.37; 95% confidence interval (CI): 0.18-0.76] in HF patients. Similarly, the relationship between high vitamin A intake and lower odds of depression were also observed in subgroups of those aged >65 years (OR = 0.16; 95% CI: 0.04-0.55), males (OR = 0.35; 95% CI: 0.14-0.86), without hypertension (OR = 0.25; 95% CI: 0.11-0.58), without diabetes (OR = 0.30; 95% CI: 0.11-0.78), with hyperlipidaemia (OR = 0.23; 95% CI: 0.09-0.64), and with chronic kidney disease (CKD) (OR = 0.32; 95% CI: 0.13-0.80).
CONCLUSIONS: High vitamin A intake was associated with lower odds of depression in HF patients. Appropriate vitamin A supplementation may have potential benefit to the prevention of depression in HF patients. Additional prospective large-scale studies are required to confirm whether or not vitamin A could lead to decrease in depression symptoms.

Crocetin (CCT), a natural bioactive compound extracted and purified from the traditional Chinese medicinal herb saffron, has been shown to play a role in neurodegenerative diseases, particularly depression. However, due to challenges with solubility, targeting, and bioavailability, formulation development and clinical use of CCT are severely limited. In this study, we used the emulsification-reverse volatilization method to prepare CCT-loaded nanoliposomes (CN). We further developed a borneol (Bor) and lactoferrin (Lf) dual-modified CCT-loaded nanoliposome (BLCN) for brain-targeted delivery of CCT. The results of transmission electron microscope (TEM) and particle size analysis indicated that the size of BLCN (∼140 nm) was suitable for transcellular transport across olfactory axons (∼200 nm), potentially paving a direct path to the brain. Studies on lipid solubility, micropolarity, and hydrophobicity showed that BLCN had a relatively high Lf grafting rate (81.11 ± 1.33 %) and CCT entrapment efficiency (83.60 ± 1.04 %) compared to other liposomes, likely due to Bor improving the lipid solubility of Lf, and the combination promoting the orderly arrangement of liposome membrane molecules. Microplate reader and fluorescence microscopy analysis showed that BLCN efficiently promoted the endocytosis of fluorescent coumarin 6 into HT22 cells with a maximal fluorescence intensity of (13.48 ± 0.80 %), which was significantly higher than that of CCT (5.73 ± 1.17 %) and CN (12.13 ± 1.01 %). BLCN also exhibited sustained function, remaining effective for more than 12 h after reaching a peak at 1 h in cells, while CN showed a significant decrease after 4 h. The uptake mechanisms of BLCN in HT22 cells mainly involve energy-dependent, caveolae-mediated, and microtubule-mediated endocytosis, as well as micropinocytosis. Furthermore, BLCN displayed a significant neuroprotective effect on HT22 cells in glutamate-, corticosterone-, and H2O2-induced models. Tissue fluorescence image analysis of mice showed that BLCN exhibited substantial retention of fluorescent DiR in the brain after nasal administration for 12 h. These findings suggest that CCT has the potential for cellular uptake, neuroprotection, and targeted delivery to the brain following intranasal administration when encapsulated in Bor and Lf dual-modified nanoliposomes.

BACKGROUND: This study aimed to investigate the impact of Vitamin A (VA) on intestinal glucose metabolic phenotypes.
METHODS: Male C57BL/6 mice were randomized assigned to a VA-normal diet (VAN) or a VA-deficient diet (VAD) for 12 weeks. After12 weeks, the VAD mice were given 30 IU/g/d retinol for 10 days and VAN diet (VADN) for 10 weeks. By using glucose tolerance tests, immunofluorescence staining, quantitative polymerase chain reaction, siRNA transduction, and enzyme-linked immunosorbent assay, the glucose metabolic phenotypes as well as secretory function and intracellular hormone changes of STC-1 were assessed.
RESULTS: VAD mice showed a decrease of glucose-stimulated insulin secretion and a loss of intestinal glucagon-like peptide-1 (GLP-1) expression. Through reintroducing dietary VA to VAD mice, the intestinal VA levels, GLP-1 expression and normal glucose can be restored. The incubation with retinol increased VA signaling factors expression within STC-1 cells, especially retinoic acid receptor β (RARβ). The activation of RARβ restored intracellular incretin hormone synthesis and secretory function.
CONCLUSIONS: VA deficiency leads to an imbalance of intestinal glucose metabolic phenotypes through a mechanism involving RARβ signaling pathway, suggesting a new method to achieve the treatment for VAD induced glucose metabolism impairment.

The oviduct of the Chinese brown frog (Rana dybowskii) expands during pre-brumation rather than the breeding period, exhibiting a special physiological feature. Vitamin A is essential for the proper growth and development of many organisms, including the reproductive system such as ovary and oviduct. Vitamin A is metabolized into retinoic acid, which is crucial for oviduct formation. This study examined the relationship between oviducal expansion and vitamin A metabolism. We observed a significant increase in the weight and diameter of the oviduct in Rana dybowskii during pre-brumation. Vitamin A and its active metabolite, retinoic acid, notably increased during pre-brumation. The mRNA levels of retinol binding protein 4 (rbp4) and its receptor stra6 gene, involved in vitamin A transport, were elevated during pre-brumation compared to the breeding period. In the vitamin A metabolic pathway, the mRNA expression level of retinoic acid synthase aldh1a2 decreased significantly during pre-brumation, while the mRNA levels of retinoic acid α receptor (rarα) and the retinoic acid catabolic enzyme cyp26a1 increased significantly during pre-brumation, but not during the breeding period. Immunohistochemical results showed that Rbp4, Stra6, Aldh1a2, Rarα, and Cyp26a1 were expressed in ampulla region of the oviduct. Western blot results indicated that Aldh1a2 expression was lower, while Rbp4, Stra6, RARα, and Cyp26a1 were higher during pre-brumation compared to the breeding period. Transcriptome analyses further identified differential genes in the oviduct and found enrichment of differential genes in the vitamin A metabolism pathway, providing evidences for our study. These results suggest that the vitamin A metabolic pathway is more active during pre-brumation compared to the breeding period, and retinoic acid may regulate pre-brumation oviductal expansion through Rarα-mediated autocrine/paracrine modulation.

BACKGROUND: To date, clinical laboratories face challenges in quantifying retinol from DBS samples. Disputes arise throughout the whole detection process, encompassing the storage condition, the release strategy as well as the selection of internal standards.
METHODS: We incubated DBS with ascorbic acid solution. Then, retinol-d4 in acetonitrile was introduced to incorporate isotopic internal standard and promote protein precipitation. Afterward, sodium carbonate solution was added to ionize cytochromes (such as bilirubin), which amplified the difference of their hydrophobicity to retinol. Subsequently, cold-induced phase separation could be facilitated to separate retinol from the impurities. In the end, the upper layer was injected for LC-MS/MS analysis.
RESULTS: By comparing the detected retinol content in whole blood and DBS samples prepared from the same volume, we confirmed the established pretreatment was capable to extract most of retinol from DBS (recovery >90 %). Thereafter, we verified that within DBS, retinol possessed satisfying stability without antioxidation. Indoor-light exposure and storage duration would not cause obvious degradation (<10 %). Following systematic validation, the established method well met the criteria outlined in the relevant guidelines. After comparing with detected DBS results to the paired plasma samples, 54 out of 60 met the acceptance limit for cross-validation of ±20 %.
CONCLUSIONS: We realized precise quantification of retinol from one 3.2 mm DBS disc. By circumventing conventional antioxidation, liquid-liquid/solid-phase extraction and organic solvent evaporation, the pretreatment could be completed within 15 min consuming only minimal amounts of low-toxicity chemicals (ascorbic acid, acetonitrile, and sodium carbonate). We expect this contribution holds the potential to significantly facilitate the evaluation of patients\' vitamin A status by using DBS samples in the future.