Low plasma 25-hydroxyvitamin D levels are not associated with a high risk of recurrent falls in community-dwelling Japanese adults: the Murakami cohort study.

Reports on the association between vitamin D levels and fall risk have been mixed, and long-term follow-up studies are lacking. This 5-year cohort study of 5,343 community-dwelling Japanese people aged 40-74 years found that low vitamin D levels are not associated with a high risk of recurrent falls. PURPOSE: Findings of cohort studies on the association between plasma 25-hydoxyvitamin D (25[OH]D) levels and fall risk have been mixed, and long-term follow-up studies are lacking. The present study investigated whether low plasma 25(OH)D levels are longitudinally associated with a high risk of recurrent falls in adults. METHODS: This 5-year cohort study included 5,343 community-dwelling Japanese people aged 40-74 years. Baseline blood collection and a questionnaire survey were conducted in 2011-2013. Plasma 25(OH)D levels were determined and divided into quintiles after stratification by season, sex, and age group. Information on recurrent falls occurring in the year before the survey 5 years later was obtained, and participants with two or more falls were considered to have experienced recurrent falls. Covariates were sex, age, marital status, education, occupation, BMI, total physical activity levels, calcium intake, vitamin K intake, smoking, drinking, and disease history. RESULTS: Mean age and 25(OH)D levels were 60.9 years and 50.9 nmol/L, respectively. In the follow-up survey, 209 recurrent falls were reported. Plasma 25(OH)D levels were not significantly associated with the occurrence of recurrent falls in men, women, or men/women-combined (adjusted P for trend = 0.1198, 0.8383, and 0.2355, respectively). In men and men/women-combined, adjusted ORs for recurrent falls in the lowest quintile were significantly lower (adjusted OR = 0.42 and 0.59, respectively) than the middle quintile (reference). CONCLUSION: Low plasma 25(OH)D levels are not associated with a high risk of recurrent falls in middle-aged and older people. Further longitudinal studies will be needed to confirm our findings in other populations.

Role of rs2282679 in 25-hydroxyvitamin D levels and insulin resistance after a sleeve gastrectomy.

BACKGROUND & AIMS: Some studies have reported links between 25-hydroxyvitamin D levels and the presence of obesity and some genetic variants. The aim of our design was to evaluate the effects of rs2282679 genetic variant of CG gene on 25-hydroxyvitamin D levels, weight loss and metabolic parameters after a robotic sleeve gastrectomy in premenopausal females with obesity. METHODS: 76 participants were enrolled. 25-hydroxyvitamin D levels, biochemical evaluation and anthropometric parameters were registered before surgery and after 3, 6 and 12 months follow up. Genotype of rs2282679 CG gene was evaluated. RESULTS: The improvements in anthropometric parameters, blood pressure and lipid profile were similar in both genotypes (TT vs TG + GG). Basal insulin levels and HOMA-IR were greater in G allele carriers than non-carriers (Delta: 6.7 ± 1.2 mUI/L; p = 0.01) and (Delta: 1.3 ± 0.1 units; p = 0.02). 25-hydroxyvitamin D levels were lower in G allele carriers than non-carriers (Delta: 8.1 ± 1.1 ng/dl; p = 0.03). The levels of insulin and HOMA-IR remained greater in G allele carriers than non-carriers throughout all the visits. The levels of 25-hydroxyvitamin D remained lower in G allele carriers than non-G allele. The average level of 25-hydroxyvitamin D at 12 months in non-G allele carriers were above 30 ng/dl (36.0 ± 3.1 ng/dl) and the level in G allele carriers were below (24.9 ± 4.9 ng/dl). CONCLUSIONS: rs 2282679 (GC) was related with low 25 hydroxyvitamin D levels and insulin resistance. In addition, the presence of G allele produced a decrease in the improvement of 25-hydroxyvitamin D levels and insulin resistance after weight loss during 12 months.

The correlation of obesity status with serum 25-hydroxyvitamin D in US Asian adults: NHANES 2011-2018.

BACKGROUND: There is a correlation between obesity and 25-hydroxyvitamin D (25OHD) that tends to be negative. However, this relationship varies among different races. In this study, Asian adults with and without obesity were compared in terms of their levels of 25OHD. METHODS: We carried out a cross-sectional analysis on 2664 non-Hispanic Asian adults who participated in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. To examine the connection between obese status, body mass index (BMI), waist circumference (WC) and weight, and 25OHD, we ran multivariate linear regression models and multivariate logistic regression models. RESULTS: After adjusting for all confounding factors, obesity status shows a significant positive correlation with vitamin D deficiency (model 3: OR = 2.318, 95% CI:1.317, 4.082). This positive correlation remains significant in males (males: OR = 2.713, 95% CI: -13.398, 5.217). In all three models, a negative association was observed between obesity status and 25OHD (model 1: ß = -4.535, 95% CI: -6.987, -2.083; model 2 ß = -4.249, 95% CI: -6.549, -2.039; model 3 ß = -1.734, 95% CI: -7.285, 3.816). After controlling for covariates, there was a significant negative correlation between WC and 25OHD when stratified by gender and obesity status in both males with and without obesity (males with obesity: ß = -1.461, 95% CI: -2.485, -0.436; males without obesity: ß = -0.855. 95% CI: -1.499, -0.210). In males with obesity, there was a very strong positive connection between body weight and 25OHD (ß = 0.912, 95% CI: 0.227, 1.597). In addition, neither gender's obese individuals showed a significant link between BMI and 25OHD. CONCLUSION: This study demonstrated a positive correlation between obesity and vitamin D deficiency and a negative correlation between obesity and 25OHD in Asian American adults. Additionally, among male obese individuals, there was a significant negative correlation between WC and 25OHD, an observation that needs to be validated in further prospective studies.

Impact of particulate-matter air pollution on 25-hydroxyvitamin D levels: a mendelian randomisation study.

OBJECTIVES: In observational studies, the 25-hydroxyvitamin D (25(OH)D) level in body has been found to be closely related to particulate matter (PM) air pollution. In this study, we used the two-sample mendelian randomisation (MR) method to investigate and discuss the potential causal relationship and mode of influence. STUDY DESIGN: MR study. METHODS: PM data (PM10, PM2.5-10, PM2.5, PM2.5 absorbance) came from the UK Biobank database, and 25(OH)D data came from European Bioinformatics Institute (EBI) database. The analysis was conducted utilising three prominent methods (inverse-variance-weighted [IVW], MR-Egger, weighted median, weighted mode, and simple mode). The primary emphasis was placed on IVW, accompanied by heterogeneity and horizontal pleiotropy tests. Furthermore, sensitivity analysis was undertaken. RESULTS: The MR analysis revealed a significant association between exposure to PM10 and a decrease in levels of 25(OH)D (odds ratio [OR]: 0.878, 95% confidence interval [CI]: 0.789-0.977). However, no significant relationship was observed between PM2.5 exposure and 25(OH)D (OR: 0.943, 95%CI: 0.858-1.037). Further analysis indicated that the main contributor to the decline in 25(OH)D levels is linked to PM2.5-10 exposure (OR: 0.840, 95%CI: 0.751-0.940) and PM2.5 absorbance (OR: 0.875, 95%CI: 0.824-0.929). No heterogeneity and horizontal pleiotropy existed. CONCLUSIONS: The MR results suggest that PM (PM10, PM2.5-10 and PM2.5 absorbance) exposure lowers vitamin D (VD) levels, but PM2.5 was not found to have a significant effect on VD in humans.

Differences in Plasma 25-Hydroxyvitamin D Levels at Diagnosis of Celiac Disease and Type 1 Diabetes.

AIM: The aim of this work is to assess the vitamin D levels, evaluated as plasma 25-hydroxyvitamin D of children with a new diagnosis of celiac disease (CD), of children with a new onset of type 1 diabetes (T1D) and in children with CD at diagnosis of T1D (T1D&CD). METHODS: In this single-center observational study, we collected data for four groups of children and adolescents: T1D, CD, T1D&CD, and a control group (CG). The CG included schoolchildren who had negative results during a mass screening campaign for CD and were not diagnosed for T1D, according to RIDI Marche registry data, were considered for the purposes of this study. Plasma 25-hydroxyvitamin D, 25(OH)D2, and 25(OH)D3 were considered as the parameters for evaluating vitamin D nutritional status, and the date of measurement was recorded to analyze vitamin D level seasonality. Vitamin D nutritional status was categorized as follows: severe deficiency (<10 ng/mL), deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), or sufficiency/adequacy (≥30 ng/mL). The Kruskal-Wallis test was used to compare the groups. The association of 25(OH)D levels with health conditions and seasonal differences of 25(OH)D levels was analyzed using a multiple linear regression model. RESULTS: The number of children enrolled for the present study was 393: 131 in the CG, 131 CD, 109 T1D, and 22 T1D&CD. Significantly lower levels of vitamin D were displayed for children with CD, T1D, or both the diseases. Interestingly, severe vitamin D deficiency was detected in no children with CD, 1.5% of children in the CG, in 24.4% with T1D, and 31.8% with T1D&CD (p < 0.001). As expected, the CG children vitamin D levels were significantly influenced by seasonality. Contrarily, no seasonal differences were reported in children with CD, T1D, and T1D&CD. Multiple regression analysis showed that children with T1D and T1D&CD had lower 25(OH)D levels of 9.9 ng/mL (95% CI: 5.4; 14.5) and 14.4 ng/mL (95% CI: 6.2-22.7) compared to CG children (p < 0.001). CONCLUSIONS: Our results showed low levels of vitamin D diagnosis of T1D, CD, and T1D&CD; however, severe deficiency was only reported in children with T1D and T1D&CD. More studies are needed to better understand the role of this deficiency in children newly diagnosed with CD and T1D.

Serum 25-Hydroxyvitamin D Status and Vitamin D Supplements Use Are Not Associated with Low Back Pain in the Large UK Biobank Cohort.

Longitudinal studies assessing the association of vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels < 30 nmol/L, and vitamin D supplement (VDS) use with low back pain (LBP) are sparse. This investigation assessed the cross-sectional and longitudinal association of vitamin D status and VDS use with LBP among 135,934 participants from the UK Biobank cohort. Approximately 21.6% of the participants had vitamin D deficiency, while only 4% regularly took VDS. In the month before study enrollment, 3.8% of the population reported experiencing LBP. An additional 3.3% of the population were diagnosed with LBP by their general practitioners for the first time during a median follow-up of 8.5 years. Vitamin D deficiency and VDS use were cross-sectionally associated with LBP in age- and sex-adjusted models, but these associations were not evident in comprehensively adjusted models. In longitudinal analyses, both vitamin D deficiency and VDS use were not associated with LBP in any model after correction for multiple testing. In conclusion, not unexpectedly due to the fact that LBP is multifactorial, our findings provide no evidence for the role of the vitamin D status in the etiology of LBP.

Effect of air temperature on serum 25-hydroxyvitamin D concentrations: A single institutional large-scale study in Korea.

Vitamin D deficiency is a worldwide health issue especially in women. Serum vitamin D concentrations vary depending on the weather. However, the ideal vitamin D supplementation strategy related to weather remains uncertain. We aimed to investigate the relationship between climate factors and serum 25-hydroxy vitamin D [25(OH)D] concentrations. This study included 11,272 women aged 20-79 who visited a health promotion center for annual checkups between January 2013 and December 2015. We reviewed medical records and collected daily meteorological data. We analyzed the association between serum 25(OH)D concentration and climate factors using simple and multiple regression models and then predicted serum 25(OH)D concentration using multiple fractional polynomial models. The median age of the participants was 51 years (20-79 years), and the mean serum 25(OH)D level was 17.4 ± 8.6 ng/mL. The serum 25(OH)D concentration was lower in young women than in older women. The proportions of women with adequate 25(OH)D levels were 14.9% and 47.0% in the age groups 20-29 and 70-79, respectively. The maximum level of predicted log 25(OH)D was found in September, and the minimum was found in January. In multiple regression analysis, age and monthly mean temperature were associated with 25(OH)D concentrations. Serum 25(OH)D level was predicted using the following formula: log (25(OH)D) = 2.144 + 0.009 × age + 0.018 × ((temperature + 12.4)/10)2 (P < 0.001, adjusted R2 = 0.091). Serum 25(OH)D concentrations changed according to air temperature. An adequate strategy for vitamin D supplementation, based on air temperature, is necessary to maintain healthy serum 25(OH)D levels.

The biological variation of serum 1,25-dihydroxyvitamin D and parathyroid hormone, and plasma fibroblast growth factor 23 in healthy individuals.

BACKGROUND AND AIMS: Measuring 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone 1-84 (PTH 1-84) and intact FGF23 (iFGF23) is crucial for diagnosing a variety of diseases affecting bone and mineral homeostasis. Biological variability (BV) data are important for defining analytical quality specifications (APS), the usefulness of reference intervals, and the significance of variations in serial measurements in the same subject. The aim of this study was to pioneer the provision of BV estimates for 1,25(OH)2D and to improve existing BV estimates for iFGF23 and PTH 1-84. MATERIALS AND METHODS: Serum and plasma-EDTA samples of sixteen healthy subjects have been collected for seven weeks and measured in duplicate by chemiluminescent immunoassay on the DiaSorin Liaison platform. After variance verification, within-subject (CVI) and between-subject (CVG) BV estimates were assessed by either standard ANOVA, or CV-ANOVA. The APSs were calculated according to the EFLM-BV-model. RESULTS: We found the following CVI estimates with 95% confidence intervals:1,25(OH)2D, 22.2% (18.9-26.4); iFGF23, 16.1% (13.5-19.5); and PTH 1-84, 17.9% (14.8-21.8). The CVG were: 1,25(OH)2D, 21.2% (14.2-35.1); iFGF23, 21.1% (14.5-35.8); and PTH 1-84, 31.1% (22.1-50.8). CONCLUSIONS: We report for the first time BV estimates for 1,25(OH)2D and enhance existing data about iFGF23-BV and PTH 1-84-BV through cutting-edge immunometric methods.

Oleanolic acid exerts bone anabolic effects via activation of osteoblastic 25-hydroxyvitamin D 1-alpha hydroxylase.

Oleanolic acid (OA) is previously shown to exert bone protective effects in aged animals. However, its role in regulating osteoblastic vitamin D bioactivation, which is one of major causes of age-related bone loss, remains unclear. Our results revealed that treatment of OA significantly increased skeletal CYP27B1 expression and circulating 1,25(OH)2D3 in ovariectomized mice (p <0.01). Moreover, OA upregulated CYP27B1 protein expression and activity, as well as the vitamin D-responsive bone markers alkaline phosphatase (ALP) activity and osteopontin (OPN) protein expression, in human osteoblast-like MG-63 cells (p<0.05). CYP27B1 expression increased along with the osteoblastic differentiation of human bone marrow derived mesenchymal stem cells (hMSCs). CYP27B1 expression and cellular 1,25(OH)2D3 production were further potentiated by OA in cells at mature osteogenic stages. Notably, our study suggested that the osteogenic actions of OA were CYP27B1 dependent. In summary, the bone protective effects of OA were associated with the induction of CYP27B1 activity and expression in bone tissues and osteoblastic lineages. Hence, OA might be a potential approach for management of age-related bone loss.

Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension.

BACKGROUND: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

Association Between Pretreatment Blood 25-Hydroxyvitamin D Level and Survival Outcomes in Patients With Clinically Localized Prostate Cancer: An Updated Meta-Analysis.

Studies on the prognostic value of the blood 25-hydroxyvitamin D level have yielded controversial results in prostate cancer (PCa) patients. This updated meta-analysis aimed to evaluate the association between pretreatment 25-hydroxyvitamin D level with survival outcomes among patients with clinically localized PCa. PubMed, Web of Science, and Embase databases were searched to identify studies evaluating the association of pretreatment 25-hydroxyvitamin D level with PCSM and all-cause mortality among clinically localized PCa patients. Ten cohort studies with 10,394 patients were identified. The meta-analysis revealed that PCa patients with the lowest 25-hydroxyvitamin D levels had an increased risk of PCSM (adjusted hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.26-1.83; p < 0.001) and all-cause mortality (adjusted HR 1.31; 95% CI 1.00-1.90; p = 0.047) compared to those with higher reference 25-hydroxyvitamin D level. Subgroup analyses based on different sample sizes, follow-up duration, and adjusted times of blood draw also exhibited a significant association of vitamin D deficiency with the risk of PCSM. Lower pretreatment level of 25-hydroxyvitamin D may be an independent predictor of reduced survival in patients with clinically localized PCa. Measuring the pretreatment blood 25-hydroxyvitamin D level can provide valuable information for risk stratification of survival outcomes in these patients.

Association of serum 25-hydroxyvitamin D concentration with all-cause and cause-specific mortality in hypertensive patients.

BACKGROUND AND AIMS: To examine the association of serum 25-hydroxyvitamin D [25(OH)D] with all-cause mortality and disease-specific mortality in patients with hypertension. METHODS AND RESULTS: This cohort study included US adults in the National Health and Nutrition Examination Survey from 2007 to 2018. All-cause mortality and cause-specific mortality outcomes were determined by association with National Death Index records. Cox proportional risk models were used to estimate hazard ratios (HRs) for all-cause mortality and cause-specific mortality and 95% confidence intervals (CIs) for serum 25(OH)D concentrations. The cohort included 10,325 adult participants. The mean serum 25(OH)D level was 65.87 nmol/L, and 32.2% of patients were vitamin D deficient (<50 nmol/L). During a mean follow-up of 77 months, 1290 deaths were recorded, including 345 cardiovascular deaths and 237 cancer deaths. Patients with higher serum 25(OH)D were more likely to have lower all-cause mortality and cardiovascular mortality than those with serum 25(OH)D < 25.00 nmol/L. For cancer mortality in hypertensive patients, vitamin D may not have a predictive role in this. CONCLUSIONS: This study shows that higher 25(OH)D levels are significantly associated with lower all-cause mortality and cardiovascular disease (CVD) mortality. These findings suggest that maintaining adequate vitamin D status may reduce the risk of death in patients with hypertension.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Eldecalcitol protected osteocytes against ferroptosis of D-gal-induced senescent MLO-Y4 cells and ovariectomized mice.

BACKGROUND: Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the protection of osteocytes from senescence and the associated ferroptosis. METHODS: The MLO-Y4 osteocytes were exposed to D-gal inducing senescence. The ovariectomized (OVX) mice treated with D-gal using as an aging inducer were intraperitoneally injected with eldecalcitol. The multiplexed confocal imaging, fluorescence in situ hybridization and transmission electron microscopy were applied in assessing osteocytic properties. Immunochemical staining and immunoblotting were carried out to detect abundance and expression of molecules. RESULTS: The ablation of vitamin D receptor led to a reduction in amounts of osteocytes, a loss of dendrites, an increase in mRNA expression of SASP factors and in protein expression of senescent factors, as well as changes in mRNA expression of ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed senescent phenotypes of MLO-Y4 cells shown by improving cell morphology and density, decreasing ß-gal-positive cell accumulation, and down-regulating protein expression (P16, P21 & P53). Eldecalcitol reduced intracellular ROS and MDA productions, elevated JC-1 aggregates, and up-regulated expression of Nrf2 and GPX4. Eldecalcitol exhibited osteopreserve effects in D-gal-induced aging OVX mice. The confocal imaging displayed its improvement on osteocytic network organization. Eldecalcitol decreased the numbers of senescent osteocytes at tibial diaphysis by SADS assay and attenuated mRNA expression of SASP factors as well as down-regulated protein expression of senescence-related factors and restored levels of ferroptotic biomarkers in osteocytes-enriched bone fraction. It reduced 4-HNE staining area, stimulated Nrf2-positive staining, and promoted nuclear translocation of Nrf2 in osteocytes of mice as well as inhibited and promoted protein expression of 4-HNE and Nrf2, respectively, in osteocytes-enriched bone fraction. CONCLUSIONS: The present study revealed the ameliorative effects of eldecalcitol on senescence and the associated ferroptosis of osteocytes, contributing to its preservation against osteoporosis of D-gal-induced senescent ovariectomized mice.

Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

The causal relationship between 25-hydroxyvitamin D and serum lipids levels: A bidirectional two-sample mendelian randomization study.

Serum vitamin D levels were linked to lipid metabolism in observational studies, but the exact mechanism was unclear. Several studies have attempted to decipher the relationship between 25(OH)D and lipid levels. Conventional observational studies are vulnerable to confounding. Mendelian randomization (MR) analysis can better control for confounding factors and reverse causality, allowing for the inference of causal association. We, therefore, sought to use MR to investigate the possible causal relationship between 25(OH)D and blood lipid levels (HDL cholesterol, LDL cholesterol, triglycerides, and total cholesterol). A bidirectional two-sample Mendelian randomization (MR) was performed on data primarily from European ancestors. In addition, the potential causal effect of lipids on 25(OH)D was assessed by regressor-based multivariate magnetic resonance (MVMR). The single-nucleotide polymorphisms (SNPs) related to 25(OH)D were selected from a large-scale genome-wide association study (GWAS) database named IEU GWAS, and the SNPs associated with the four blood lipids were chosen from UK Biobank (UKB) lipid GWAS. When blood lipids were the outcome, the results of bidirectional two-sample MR demonstrated that 25(OH)D exhibited a negative causal association with TG, TC, and LDL-C: ß = - 0.23, 95% CI = -0.28 to -0.19, P<0.001; ß = - 0.16, 95% CI: - 0.30 to-0.03, P < 0.05; ß = - 0.11, 95% CI: - 0.23 to 0, P < 0.05. There was no causal relationship between 25(OH)D and HDL-C (ß = 0.05, 95% CI: - 0.11 to 0.20, P = 0.56). When setting blood lipids as exposure, TG and 25(OH)D, ß = -0.13, 95% CI: - 0.15 to -0.10, P < 0.05; TC and 25(OH)D, ß = -0.11, 95% CI: - 0.15 to -0.07, P < 0.05; HDL-C and 25(OH)D, ß = 0.02, 95% CI: 0 to 0.03, P = 0.07; LDL-C and 25(OH)D, ß = -0.08, 95% CI: - 0.11 to -0.05, P < 0.05). Our MVMR study also showed a significant relationship between genetically determined lipid traits and 25(OH)D levels (TG and 25(OH)D, P < 0.05; TC and 25(OH)D, P < 0.05). In all MR analyses, there was no horizontal pleiotropy (all P > 0.05), or statistical heterogeneity. The "Leave-one-out" sensitivity analysis confirmed the stability of our results. MR Studies have shown a bidirectional causal relationship between genetically-determined 25(OH)D levels and serum TG and TC levels. The findings have potential implications for etiological understanding and disease prevention.

Seasonal Variations in 25-Hydroxyvitamin D Levels among Pediatric Patients Attending the Healthcare Centre.

Vitamin D plays an essential role in maintaining bone density, building the immune system, and regulating cell growth alongside other key biological functions. Limited data are available about the seasonal variation in vitamin D levels in the pediatric population in Saudi Arabia. This study aimed to investigate the seasonal influence on the pediatric circulating levels of 25(OH)D. A total of 1790 pediatric outpatients who visited the University healthcare centre were included in this study. Overall, there was a noticeably high prevalence (69%) of both combined 25(OH)D deficiency and insufficiency. The highest mean serum concentration of 25(OH)D was recorded in summer (29 ng/mL) and autumn (27 ng/mL). The deficient and insufficient categories were predominant, accounting for 33% and 36%, respectively. Comparable patterns were recorded during autumn, winter, and spring. Interestingly, the 25(OH)D level was significantly associated with the four seasons (p = 0.001), with females having a higher prevalence of 25(OH)D deficiency in the spring and summer than males. Furthermore, only in autumn and winter, we found a significant association between gender and 25(OH)D status (p < 0.001 for both). Another association between nationality and the circulating levels 25(OH)D was found during autumn and winter (p < 0.001 and p = 0.01), respectively. In all seasons, age had a negative impact on serum (OH)D levels. However, this relationship was statistically significant (p < 0.05) only in summer, autumn, and winter. Gender was a significant predictor, with 25(OH)D levels in autumn and winter and an odds ratio of 1.67 in autumn and 2 in winter, indicating that being men had a positive influence on circulating 25(OH)D levels. There were highly significant differences in 25(OH)D concentrations among different age categories. The Saudi population experiences low levels of vitamin D, particularly in autumn and winter periods. This study showed that seasonality, age category, nationality, and gender influence vitamin D status, suggesting the need for tailored intervention and monitoring of 25(OH)D status to reach adequate levels of vitamin D. Healthcare practitioners and policymakers may consider the interplay between age, nationality, gender, and seasonal variations when addressing vitamin D status and a targeted supplementation approach for high-risk groups that may develop health issues.

Association Between Serum 25-Hydroxyvitamin D and Trichomonas vaginalis Infection Among American Adults: NHANES 2013-2016.

BACKGROUND: Previous studies have suggested that vitamin D may possess anti-infection properties, but the relationship between vitamin D and Trichomonas vaginalis infection remains unexplored. METHODS: Using data from the National Health and Nutrition Examination Survey between 2013 and 2016, we conducted multivariate regression analyses and subgroup analyses to investigate the association between 25-hydroxyvitamin D (25[OH]D) levels and T. vaginalis infection, ensuring the robustness of our results. RESULTS: The final sample included data from 4318 individuals aged 20 to 59 years, among which 92 were diagnosed with T. vaginalis infection. For every 10 nmol/L increase in serum 25(OH)D level, there was a 22% reduction in the likelihood of T. vaginalis infection incidence (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69-0.90). Similarly, higher concentration tertiles demonstrated relatively lower infection ratios compared with the tertile with the lowest 25(OH)D concentration (aOR, 0.54 [95% CI, 0.30-0.95; P = 0.030] for T2; aOR, 0.23 [95% CI, 0.09-0.61; P < 0.001] for T3). CONCLUSIONS: Our cross-sectional study indicates a negative association between 25(OH)D levels and the prevalence of T. vaginalis infection. However, further high-quality evidence is needed to establish a causal relationship between 25(OH)D levels and T. vaginalis infection, as well as to evaluate the potential role of vitamin D supplementation in preventing T. vaginalis infection.

Physiological and transcriptomic analysis revealed the alleviating effect of 1,25(OH)2D3 on environmental iron overloading induced ferroptosis in zebrafish.

Iron overload in the aquatic environment can cause damage in fish bodies. Vitamin D3 (VD3) has been proven to have antioxidant and regulatory effects on iron transport. The current research investigated the effects of environmental iron overload on larval zebrafish and explored the effects of 1,25(OH)2D3 on ferroptosis in zebrafish larvae and zebrafish liver cells (ZFL) caused by iron overload in the environment and its possible regulatory mechanisms. The results showed that 1,25(OH)2D3 alleviated liver damage in zebrafish larvae and mitochondrial damage in ZFL after excessive ammonium ferric citrate (FAC) treatment, and improved the survival rate of ZFL. 1,25(OH)2D3 cleared and inhibited excessive FAC induced abnormal accumulation of ROS, lipid ROS, MDA, and Fe2+ in zebrafish larvae and ZFL, as well as enhanced the activity of antioxidant enzyme GPx4. Transcriptomic analysis showed that 1,25(OH)2D3 can regulate ferroptosis in ZFL by regulating signaling pathways related to oxidative stress, iron homeostasis, mitochondrial function, and ERS, mainly including ferroptosis, neoptosis, p53 signaling pathway, apoptosis, FoxO signaling pathway. Validation of transcriptome data showed that 1,25(OH)2D3 inhibits ferroptosis in zebrafish larvae and ZFL caused by excessive FAC via promoting the expression of slc40a1 and hmox1a genes and increasing SLC40A1 protein levels. In summary, 1,25(OH)2D3 can resist ferroptosis in zebrafish caused by iron overload in the environment mainly via regulating antioxidant capacity and iron ion transport.