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.

BACKGROUND: Vitamin A is essential for physiological processes like vision and immunity. Vitamin A\'s effect on gut microbiome composition, which affects absorption and metabolism of other vitamins, is still unknown. Here we examined the relationship between gut metagenome composition and six vitamin A-related metabolites (two retinoid: -retinol, 4 oxoretinoic acid (oxoRA) and four carotenoid metabolites, including beta-cryptoxanthin and three carotene diols).
METHODS: We included 1053 individuals from the TwinsUK cohort with vitamin A-related metabolites measured in serum and faeces, diet history, and gut microbiome composition assessed by shotgun metagenome sequencing. Results were replicated in 327 women from the ZOE PREDICT-1 study.
RESULTS: Five vitamin A-related serum metabolites were positively correlated with microbiome alpha diversity (r = 0.15 to r = 0.20, p < 4 × 10-6). Carotenoid compounds were positively correlated with the short-chain fatty-acid-producing bacteria Faecalibacterium prausnitzii and Coprococcus eutactus. Retinol was not associated with any microbial species. We found that gut microbiome composition could predict circulating levels of carotenoids and oxoretinoic acid with AUCs ranging from 0.66 to 0.74 using random forest models, but not retinol (AUC = 0.52). The healthy eating index (HEI) was strongly associated with gut microbiome diversity and with all carotenoid compounds, but not retinoids. We investigated the mediating role of carotenoid compounds on the effect of a healthy diet (HEI) on gut microbiome diversity, finding that carotenoids significantly mediated between 18 and 25% of the effect of HEI on gut microbiome alpha diversity.
CONCLUSIONS: Our results show strong links between circulating carotene compounds and gut microbiome composition and potential links to a healthy diet pattern.

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.

BACKGROUND: Does preschool height predict adult stature in undernourished settings? The extent to which preschool length or height forecasts young adult stature is unclear in chronically undernourished populations.
METHODS: In 2006-8, we assessed height in a cohort of 2074 young adults, aged 16-23 years, in rural Nepal who, as preschoolers (≤ 4 year), were measured at baseline and again 16 months later during a vitamin A supplementation trial in 1989-91. We assessed by linear regression the ability of preschool length (L, measured < 24 mo) or height (Ht, 24-59 mo), at each year of age to predict 16-23 year old height, adjusted for month of young adult age, interval duration (in months), caste, preschool weight-for-height z-score and, in young women, time since menarche, marriage status and pregnancy history.
RESULTS: Young women were a mean of 0.81, 1.11, 0.82, 0.24, 0.44 cm taller (all p < 0.01) and young men, 0.84, 1.18, 0.74, 0.64 and 0.48 cm taller (all p < 0.001) per cm of attained L/Ht at each successive preschool year of age and, overall, were 2.04 and 2.40 cm taller for each unit increase in preschool L/Ht z-score (L/HAZ) (both p < 0.001). Coefficients were generally larger for 16-month follow-up measurements. The percent of young adult height attained by children with normal L/HAZ (>-1) increased from 38-40% mid-infancy to ∼ 69-74% by 6 years of age. By 3-6 years of age heights of stunted children (L/HAZ<-2) were consistently ∼ 4-7% lower in their young adult height versus normal statured children. There was no effect of preschool vitamin A receipt.
CONCLUSIONS: Shorter young children become shorter adults but predictive effects can vary by sex, age assessed, and may be influenced by year or season of measurement.

Hypertension stands as a pervasive global health challenge, contributing significantly to mortality rates worldwide. Various factors, including lifestyle choices and dietary habits, contribute to the development of hypertension. In recent years, oxidative stress has garnered significant attention as a factor influencing hypertension risk, prompting a shift in research focus towards exploring it as a potential target for prevention and treatment. Antioxidants found in our diet, such as vitamins C, E and carotenoids exhibit the ability to neutralize reactive oxygen species, thereby mitigating oxidative stress. In addition, Vitamin A has an antioxidant effect despite not being an antioxidant itself. Consequently, supplementation or increased intake of these antioxidants has been hypothesized to potentially lower blood pressure levels and aid in the management of hypertension, thereby potentially prolonging life expectancy. Research findings regarding this effect have been diverse. This paper examines the existing literature demonstrating favorable outcomes associated with antioxidant supplementation.

BACKGROUND: Hepatic stellate cells (HSC) have numerous critical roles in liver function and homeostasis, while they are also known for their importance during liver injury and fibrosis. There is therefore a need for relevant in vitro human HSC models to fill current knowledge gaps. In particular, the roles of vitamin A (VA), lipid droplets (LDs), and energy metabolism in human HSC activation are poorly understood.
METHODS: In this study, human pluripotent stem cell-derived HSCs (scHSCs), benchmarked to human primary HSC, were exposed to 48-hour starvation of retinol (ROL) and palmitic acid (PA) in the presence or absence of the potent HSC activator TGF-β. The interventions were studied by an extensive set of phenotypic and functional analyses, including transcriptomic analysis, measurement of activation-related proteins and cytokines, VA- and LD storage, and cell energy metabolism.
RESULTS: The results show that though the starvation of ROL and PA alone did not induce scHSC activation, the starvation amplified the TGF-β-induced activation-related transcriptome. However, TGF-β-induced activation alone did not lead to a reduction in VA or LD stores. Additionally, reduced glycolysis and increased mitochondrial fission were observed in response to TGF-β.
CONCLUSIONS: scHSCs are robust models for activation studies. The loss of VA and LDs is not sufficient for scHSC activation in vitro, but may amplify the TGF-β-induced activation response. Collectively, our work provides an extensive framework for studying human HSCs in healthy and diseased conditions.

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.

The distribution of dietary vitamin A/all-trans retinol (ROL) throughout the body is critical for maintaining retinoid function in peripheral tissues and for generating visual pigments for photoreceptor cell function. ROL circulates in the blood bound to the retinol binding protein 4 (RBP4) as RBP4-ROL. Two membrane receptors, RBPR2 in the liver and STRA6 in the eye are proposed to bind circulatory RBP4 and this mechanism is critical for internalizing ROL into cells. Here, we present a longitudinal investigation towards the importance of RBPR2 and influence of the diet on systemic retinoid homeostasis for visual function. Age matched Rbpr2-KO (Rbpr2 -/- ) and wild-type (WT) mice were fed either a vitamin A sufficient (VAS) or a vitamin A deficient (VAD) diet. At 3- and 6-months, we performed retinoid quantification of ocular and non-ocular tissues using HPLC analysis and complemented the data with visual physiology, rhodopsin quantification by spectrophotometry, and biochemical analysis. At 3-months and compared to WT mice, Rbpr2 -/- mice fed either vitamin A diets displayed lower scotopic and photopic electroretinogram (ERG) responses, which correlated with HPLC analysis that revealed Rbpr2 -/- mice had significantly lower hepatic and ocular retinoid content. Interestingly, with the exception of the liver, long-term feeding of Rbpr2 -/- mice with a VAS diet promoted all-trans retinol accumulation in most peripheral tissues. However, even under VAS dietary conditions significant amounts of unliganded opsins in rods, together with decreased visual responses were evident in aged mice lacking RBPR2, when compared to WT mice. Together, our analyses characterize the molecular events underlying nutritional blindness in a novel mouse model and indicate that loss of the liver specific RBP4-ROL receptor, RBPR2, influences systemic retinoid homeostasis and rhodopsin synthesis, which causes profound visual function defects under severe vitamin A deficiency conditions.