25OHD Concentrations Research Articles

Vitamin D status and its determinants in pregnant women form the Faroe Islands

Abstract Background In regions like the Faroe Islands, where sunlight may be insufficient for vitamin D synthesis, alternative sources such as diet and supplements become crucial. This study focuses on assessing the vitamin D status of pregnant women in the Faroe Islands during the early second trimester, considering the potential implications for maternal and fetal health. Methods A nationwide cross-sectional study (June 2020-April 2022) with 652 women providing blood samples and a questionnaire on demographics, vitamin D intake, and diet. Binary logistic regression assessed predictors of low 25-hydroxyvitamin D (25OHD) levels (<50nmol/L). Plasma 25OHD concentrations were analysed at the local National Hospital using the Alinity i 25-OH Vitamin D assay, employing chemiluminescence microparticle immunoassay (CMIA) for quantitative determination. Results The mean age was 30.7 (SD, 4.9) years; 86% were locally born; 45% resided in the capital area; 49% were overweight (BMI ≥25.0), with a mean pre-pregnancy BMI of 26.0. Most participants (95%) reported vitamin D intake (median of 10µg/day) and consumed vitamin D-rich foods 5.3 times per week. Low 25OHD concentrations were observed in 26% of participants, associated with residency, vitamin D intake, dietary habits, overweight, and sampling time. Maternal age, education, BMI, smoking, and traditional food showed no significant associations. During winter, vitamin D intake correlated more strongly with plasma 25OHD levels (Spearman’s rho, winter: 0.4, p < 0.001; summer: 0.2, p = 0.002). Conclusions Our study’s findings are essential for the health of Faroese pregnant women. 74% of them had sufficient 25OHD levels, which is encouraging. However, low levels were associated with residence, diet, overweight, and winter. This underscores the need for public health efforts to focus on monitoring vitamin D status, promoting vitamin D-rich foods, especially in winter, and monitoring dietary intake to protect maternal and fetal health. Key messages • No previous data on vitamin D status in Faroese pregnant women. • Seasonal variation is observed.

The Impact of Family Relationship on Serum 25-Hydroxyvitamin D (25OHD) Concentrations in Individuals Residing in Pune, India

The Impact of Family Relationship on Serum 25-Hydroxyvitamin D (25OHD) Concentrations in Individuals Residing in Pune, India

6721 Short-Term Responses of Serum 25-Hydroxyvitamin D to Weekly Calcifediol or Cholecalciferol in Healthy Subjects

Abstract Disclosure: R.B. Caldeira: None. A.S. Nunes: None. F.Z. Cazzetta: None. M.S. Medeiros: None. L.B. Oliveira: None. M.P. Bandeira: None. F.F. Bandeira: None. Introduction: Recent studies have shown that oral calcifediol (CAL) induces faster serum 25-hydroxyvitamin D (25OHD) increases than cholecalciferol (CHO) as demonstrated in some studies on SARS-Cov2 infection. It is hypothesized that this rapid elevation is due to the unique mode of intestinal absorption of CAL to the portal vein system in comparison with CHO which is absorbed mainly by the lymphatic route. Data on weekly administration of calcifediol are still scarce. The aim of the present study was to compare serum 25OHD responses in the short term (30 days) to weekly doses of CAL or CHO in healthy subjects. Methods and Results: We studied 35 subjects (34% men, mean age 24.6 ± 4.6 years, BMI 22.9 ± 2.9 kg/m², waist circumference 74.7 ± 6.5 cm, SBP 111.1 ± 12.7 mmHg, and DBP 73.1 ± 9.1 mmHg) who were randomized to receive weekly oral CAL 70 mcg (18 subjects) or CHO 350 mcg (14,000 IU, 17 subjects). Doses were chosen based on the 2000 IU/day potency equivalence. Patients were matched for age, gender, BMI, and BP. They were contacted weekly to confirm medication adherence. Serum 25OHD concentrations were measured before administration of both agents and 24 hours after the last dose, using an immunochemiluminescent assay (Abbott Diagnostics, Lake Forest, IL, USA) with a detection range from 4.9 to 151.3 ng/ml. At baseline serum 25OHD was 32.1 ±8.8 vs 33.1 ± 6.6 in CAL and CHO groups respectively (p=0.691). In CAL group 8 subjects had serum 25 OHD < 30 ng/mL (1 subject had 14.7 ng/mL) and in the CHO none had serum 25OHD below 20 ng/mL and 5 subjects had levels between 20 and 30 ng/mL. After 1 month, serum 25OHD levels rose significantly 3.3 times more with CAL than with CHO (+29.61 ± 7.39 ng/mL vs. 9.00 ± 3.50 ng/mL; p < 0.001). In CHO group one subject remained with 25OHD below 30 ng/mL after the intervention. Conclusion: We found a rapid and robust elevation of serum 25OHD levels with CAL compared to CHO at similar potency doses. This may have clinical implications for conditions in which there is a need for immediate availability of 25OHD to peripheral tissues. Presentation: 6/2/2024

The Association between Vitamin D Status and the Impact of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Subclinical Hypothyroidism.

Metformin inhibits enhanced secretion of anterior pituitary hormones. Its impact on prolactin and gonadotropin concentrations is absent in individuals with hypovitaminosis D. The aim of this prospective cohort study was to investigate whether vitamin D status determines the effect of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-naïve women. The study included three groups of women of reproductive age with subclinical non-autoimmune hypothyroidism, which were matched for age, thyroid-stimulating hormone (TSH) concentration, and insulin sensitivity: untreated women with vitamin D deficiency/insufficiency (group A), women effectively supplemented with exogenous calciferol (group B), and untreated women with normal 25-hydroxyvitamin D concentrations (25OHD) (group C). Owing to concomitant type 2 diabetes or prediabetes, all subjects were treated with metformin. Concentrations of 25OHD, TSH, total and free thyroid hormones, glucose, insulin, glycated hemoglobin (HbA1c), prolactin, and peripheral markers of thyroid hormone action were assayed before metformin treatment and six months later. Based on hormone concentration, structure parameters of thyroid homeostasis were calculated. Except for 25OHD concentrations, there were no between-group differences in baseline values of the measured variables. Metformin reduced glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), and HbA1c in all study group, but these effects were less pronounced in group A than in the remaining groups. The reduction in TSH and Jostel's index was observed only in groups B and C, and its degree correlated with baseline TSH concentrations, baseline 25OHD concentrations, and the degree of improvement in HOMA1-IR. The drug did not affect circulating levels of 25OHD, free and total thyroid hormones, prolactin, other structure parameters of thyroid homeostasis, and markers of thyroid hormone action. The obtained results allow us to conclude that low vitamin D status in young women mitigates the impact of metformin on thyrotroph secretory function.

The Importance of Determining the Level of Bone Metabolism Markers and Vitamin D in the First Year of Life in the Kazakh Population.

The research aimed to determine the importance of vitamin D and markers of bone metabolism in the overall assessment of bone mineralization during a child's first year of life. The 198 children were selected by screening all infants seen at our pediatric clinic over a 2-year period from 2020-2022 and including those who met the eligibility criteria of being aged 0 to 1 year, healthy with no chronic conditions, and not on vitamin D supplementation. Children were divided into 3 groups depending on the content of vitamin D in the blood serum: sufficient, insufficient, and deficient. The markers of bone tissue status included: markers of mineral metabolism (calcium, phosphorus, parathyroid hormone, calcitonin), a marker of bone formation (osteocalcin), resorption marker (deoxypyridinoline). Laboratory values were obtained at the time of study enrollment during the initial study visit. Labs were not repeated during the course of the study. A quarter of the infants exhibited vitamin D deficiency at enrollment with serum 25OHD concentrations below 20 ng/mL, which showed a positive correlation with serum calcium and phosphorus -concentrations and a negative correlation with PTH, while osteocalcin and deoxypyridinoline concentrations remained consistent regardless of vitamin D status. The study's practical significance allows for the recommendation of using vitamin D -concentrations as a marker to detect bone formation and mineral metabolism disorders in children during their first year of life. By identifying and addressing these issues early on, the health care system aims to ensure better musculoskeletal health for children.

The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status.

Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic-pituitary-gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit.

Vitamin D receptor gene polymorphisms, bioavailable 25-hydroxyvitamin D, and hepatocellular carcinoma survival.

Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was statistically significant only in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS. Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

A Causal Relationship Between Type 1 Diabetes and Risk of Osteoporosis: A Univariable and Multivariable Mendelian Randomization Study.

Objective: This Mendelian randomization (MR) analysis aims to investigate the causal relationship between type 1 diabetes (T1D) and osteoporosis (OP). Methods: Single nucleotide polymorphisms (SNPs) associated with T1D were selected from the summary statistics of the genome-wide association study (GWAS) in European ancestry as instrumental variables (IVs) for univariable MR (UVMR) to explore the causal relationship between T1D and OP. Inverse variance weighting (IVW) was the primary method used to assess possible causality between T1D and OP. MR-PRESSO and MR-Egger intercepts were used to assess the horizontal pleiotropy of the IVs, and Q tests and the "leave-one-out" method were used to test for heterogeneity of MR results. Multivariable MR (MVMR) analysis was used to account for potential confounders such as smoking, obesity, drinking, and serum 25-hydroxyvitamin D (25OHD) concentrations. Result: Inverse variance weighted estimates suggest T1D may increase risk of OP (UVMR: OR = 1.06, 95% CI: 1.02-1.10, p = 0.002) (MVMR: OR = 1.50, 95% CI: 1.07-1.90, p < 0.001). Conclusion: Our findings suggest that T1D can increase the risk of OP.

Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration.

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.

Unraveling the complex interplay between obesity and vitamin D metabolism.

Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

Dietary 25-Hydroxycholecalciferol Supplementation as a Vitamin D3 Substitute Improves Performance, Egg Quality, Blood Indexes, Jejunal Morphology, and Tibia Quality in Late-Phase Laying Hens.

This study aimed to investigate whether a dietary 25-OHD3 addition improved the performance, egg quality, blood indexes, antioxidant status, jejunal morphology, and tibia quality of aged laying hens compared to a dietary VD3 addition. A total of 270 Hy-Line Brown laying hens at 55 wk of age were randomly assigned to three dietary treatments with six replicates (15 birds per replicate with 3 birds per cage). Chickens were fed a corn-soybean meal diet supplementation of 4000 IU/kg VD3 (control group), 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 (experimental group 1), or 50 μg/kg 25-OHD3 and 4000 IU/kg VD3 (experimental group 2) for 12 weeks. The results demonstrated that 25-OHD3 caused a significant increase in the laying rate, especially in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group; the laying rate reached the maximum compared with other groups after 12 weeks (p < 0.05). However, there were no significant effects on the average egg weight, average daily feed intake, or feed-to-egg ratio (p > 0.05). A dietary supplementation of 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 provided an improved eggshell strength, thick albumen height, and Haugh unit after 12 weeks (p < 0.05). Further analysis of the blood indexes showed that alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, calcium, and phosphorus were enhanced significantly in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group, while the content of total bilirubin decreased significantly (p < 0.05). In addition, the 25-OHD3 addition in diets improved the calcium and phosphorus contents in the serum (p < 0.05). The concentrations of 25-OHD3, parathyroid hormones, follicle-stimulating hormone, and progesterone were increased in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group, and the levels of cortisol, calcitonin, bone gla protein, and endotoxin in the serum reached a minimum in the 50 μg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05), which constitutes an advantage for the aged laying hens. The antioxidant enzyme activities and free radical scavenging abilities in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group increased markedly, and the MDA level decreased significantly in the 50 μg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05). Improvements in jejunal morphology and intestinal integrity resulted in an increased villi-length-to-crypt-depth ratio in the 50 μg/kg 25-OHD3 + 2000 IU/kg VD3 group (p < 0.05). Dietary 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 additions improved the tibia quality, including fresh tibia weight, strength, mineral content (Ca), and trabeculae area (p < 0.05). Taken together, compared with the dietary VD3 addition, dietary supplementation of 25-OHD3 supported a stable physiological status for sustained egg production, egg quality, and bone quality in late-phase laying hens, and the addition levels of 50 μg/kg 25-OHD3 and 2000 IU/kg VD3 had the best effect. Therefore, this could provide a theoretical basis for the use of 25-OHD3 as a substitute forVD3.

Reference values for serum calcium in neonates should be established in a population of vitamin D-replete subjects.

Serum calcium is frequently measured during the neonatal period, and is known to be influenced by the vitamin D status. We hypothesized that the 25OHD concentration may influence the lower limit of the serum calcium normal range in neonates. We included in our prospective cohort study 1002 mother-newborn pair recruited from April 2012 to July 2014, in two centers located in the neighborhoods of Paris, France, whose serum calcium was measured at 3 days of life. We established, after exclusion of outliers, a 95% confidence interval (CI) for serum calcium 1) in our whole population of 1002 neonates, 2) in neonates with a cord blood 25OHD concentration ≥ 30 nmol/L, and 3) in those with a 25OHD ≥ 50 nmol/L. The mean serum total calcium was 2.46 ± 0.13 nmol/L [95% CI: 2.19-2.72 mmol/L], 2.47 ± 0.25 mmol/L [95% CI: 2.22-2.72 mmol/L], and 2.50 ± 0.25 mmol/L [95% CI: 2.25-2.75 mmol/L] in the whole group, in the 514 neonates with 25OHD ≥ 30 nmol/L, and in the 202 neonates with 25OHD ≥ 50 nmol/L respectively. The lower limit of the 95% range was significantly higher in neonates with 25 OHD ≥ 30 nmol/L (p<0.05) and ≥ 50 nmol/L (p<0.001) than in the entire cohort. We show that the lower limit of the normal serum calcium range is higher in groups with a higher 25OHD than in unselected subjects. We propose that the reference range for serum calcium in neonates is 2.25 to 2.75 mmol/L.

Wild Alaskan salmon supplementation increases 25-OHD levels in sled dogs

Vitamin D deficiency affects canines and humans alike. Athletes are a particularly high-risk group. Further research regarding optimal intake and supplementation is needed to establish the parameters of vitamin D status in both humans and canines and to create a physiologically-relevant definition for vitamin D sufficiency. The objectives of this study were to (1) compare 25-OHD (25-hydroxy vitamin D) levels in sled dogs before and after receiving a diet supplemented with wild Alaskan salmon and (2) correlate biomarkers associated with vitamin D metabolism to 25-OHD levels in sled dogs. Plasma samples from 14 working sled dogs between 10 months and 7 years of age were collected before and after a 4-week supplementation with »0.45 kg of salmon/day. Samples were analyzed using enzyme-linked immunosorbent assays (ELISA) for parathyroid hormone and vitamin D binding protein (DBP); 25-OHD levels were measured via radioimmunoassay. 25-OHD and DBP in sled dogs significantly increased after a 4-week supplementation with salmon (P=0.0011 and 0.0367, respectively). Additional variations in 25-OHD were observed when separated by sex (P=0.0404) and age (P&lt;0.0001). 57% of the dogs were deficient prior to the salmon supplementation and 14% at the completion of the study. Wild Alaskan salmon is one of the few food sources that provide appreciable amounts of vitamin D. A 4-week salmon supplementation in sled dogs was sufficient to improve 25-OHD concentrations in most sled dogs in this study. Confounding factors such as age and sex affect circulating 25-OHD levels.

Genetic variants and non-genetic factors associated with a high prevalence of vitamin D deficiency in full-term neonates in Malaysia

A high prevalence of vitamin D deficiency has been reported in Malaysian pregnant women, indicating that neonates at birth are at increased risk of vitamin D deficiency. Factors including low dietary vitamin D intake and single nucleotide polymorphisms in the vitamin D metabolism genes have been associated with this deficiency in the population. However, there was limited data available regarding the prevalence of neonatal vitamin D deficiency and the factors associated with it among neonates in Malaysia. Therefore, this study aimed to determine the prevalence of vitamin D deficiency and explore the associations between maternal and neonatal gene polymorphisms, as well as non-genetic factors and neonatal vitamin D deficiency. A total of 217 mother-neonate dyads were recruited for this study. Data on skin type, maternal sun exposure, dietary intake, as well as maternal and neonatal 25-hydroxyvitamin D (25OHD) concentrations were collected. Maternal and neonatal vitamin D Receptor (VDR) SNP (rs2228570) and Group-specific component (GC) SNPs (rs4588 and rs7041) genotypes were determined using high-resolution melting (HRM) and restriction fragment length polymorphism, respectively. The results showed that 60.4%, 71.4% and 95.4% of neonates had cord blood 25OHD levels below 25 nmol/L, 30 nmol/L and 50 nmol/L, respectively. After adjusting for the maternal vitamin D status, the maternal VDR rs2228570 GG genotype was significantly associated with neonatal vitamin D deficiency (25OHD<30 nmol/L) (aOR = 2.63, 95% CI: 1.18–5.87, p = 0.018). Maternal vitamin D supplement intake was found to be a protective factor. However, maternal and neonatal vitamin D binding protein (VDBP) SNPs were not associated with neonatal vitamin D deficiency. The high prevalence of neonatal vitamin D deficiency reported in this study indicates the urgent need for the development and implementation of strategies to improve neonatal vitamin D status. The findings suggest that maternal supplementation may be an effective approach to enhance the vitamin D status of neonates.

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study.

Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage? In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages. Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear. The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n = 417580), vitamin D deficiency (426 cases and 354812 controls), miscarriage (16906 cases and 149622 controls), and the number of miscarriages (n = 78700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis. This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran's Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively. There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, P = 0.927), or the number of miscarriages (β = -0.004, 95% CI: -0.040 to 0.032, P = 0.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, P = 0.624), or the number of miscarriages (β = 0.001, 95% CI: -0.009 to 0.011, P = 0.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found. This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups. These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to the management of miscarriage. This project was supported by the Hubei Provincial Natural Science Foundation Program General Surface Project (2022CFB200), the Key Research & Developmental Program of of Hubei Province (2022BCA042), the Fundamental Research Funds for the Central Universities (2042022gf0007, 2042022kf1210), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001, JCRCYG-2022-009). All authors have no conflicts of interest to declare. N/A.

Histomorphometric analysis of patients with femoral neck fracture and 25-hydroxyvitamin D deficiency: a cross-sectional study.

Vitamin D deficiency causes osteoporosis, bone mineralization disorders, and osteomalacia. Osteomalacia is diagnosed using blood biochemical tests, clinical symptoms, and imaging; however, accurate detection of mineralization disorders requires tissue observation. We investigated the prevalence of bone mineralization disorders and their relationship with serum 25-hydroxyvitamin D (25OHD) levels in patients with untreated osteoporosis with femoral neck fractures. A non-demineralized specimen was prepared from the femoral head removed during surgery in 65 patients. Bone histomorphometry of cancerous bone in the femoral head center was conducted. Osteoid volume per bone volume (OV/BV) and osteoid thickness (O.Th) were measured as indicators of mineralization disorder. The mean serum 25OHD level (11.9 ± 5.7ng/mL) was in the deficiency range (< 12ng/mL). There were no clinically diagnosed cases of osteomalacia (OV/BV > 10% and O.Th > 12.5µm); however, one case of mineralization disorder, considered histologically pre-osteomalacia (OV/BV > 5% and O.Th < 12.5µm), was observed (OB/BV, 17.6%; O.Th, 12.3µm). Excluding this case, those with severe (25OHD < 12ng/mL, at risk of osteomalacia; n = 39) and non-severe deficiency (25OHD ≥ 12ng/mL; n = 25) did not significantly differ in OV/BV (%; 0.77 ± 0.54 vs. 0.69 ± 0.38, p = 0.484) or O.Th (µm; 5.32 ± 1.04 vs. 5.13 ± 0.78, p = 0.410). Further, 25OHD and OV/BV were not significantly correlated (R = -0.124, p = 0.327). This is the first study in the twenty-first century to examine serum 25OHD concentrations and bone mineralization disorders in Japanese patients with osteoporosis. The results indicate that vitamin D deficiency does not necessarily cause bone mineralization disorders and rarely leads to osteomalacia.

Tip 1 Diyabette Serum Vitamin D Bağlayan Protein Düzeylerinin Araştırılması: Glisemik Kontrol ve Hastalık Süresinin Etkisi

Aim: Patients with type 1 diabetes mellitus (T1DM) are known to be more prone to vitamin D deficiency. Vitamin D studies in this&#x0D; patient population have traditionally been performed using serum 25OHD levels. However, vitamin D binding protein (VDBP) has&#x0D; been less studied. This study aims to compare serum VDBP levels in T1DM with healthy controls. It also aims to investigate the factors&#x0D; affecting VDBP levels such as disease duration, HbA1c, insulin dose, and age in diabetic subjects.&#x0D; Material and Methods: A research study was conducted at Çanakkale Onsekiz Mart University Health Practice and Research Hospital.&#x0D; The study included 11-17 years old children with T1DM and healthy controls. Serum VDBP and 25OHD concentrations were compared&#x0D; with appropriate statistical methods according to the normal distribution of relevant parameters. For the diabetic subjects, insulin doses&#x0D; and duration of diabetes were recorded. Spearman’s correlation test was utilized to assess associations between continuous variables, and&#x0D; regression analysis was employed to determine predictors of serum VDBP levels.&#x0D; Results: The study enrolled 89 subjects, including 40 with diabetes. Serum 25OHD levels were similar in the T1DM group and control&#x0D; group (17.03 IQR:12.89-22.08) and (17.62 IQR:11.68-24.48), respectively (p=0.701). However, VDBP levels were significantly lower in&#x0D; the T1DM group (335 μg/ml, IQR: 199.8-517.2 μg/ml) compared to the control group (471.2 μg/ml, IQR: 368.3-533.2 μg/ml) (p &lt; 0.015).&#x0D; In the entire group, only the presence of diabetes affected VDBP levels (B=87.236, SE=34.802, p=0.014). On the other hand, HbA1c,&#x0D; duration of diabetes, and insulin dose had no influence on VDBP in the diabetes group.&#x0D; Conclusion: Serum VDBP levels were significantly lower in T1DM patients but in this group, disease duration, insulin dose, and&#x0D; metabolic control did not affect serum VDBP levels. Serum VDBP concentrations in T1DM may be affected by other parameters rather&#x0D; than metabolic parameters. Therefore, future studies should focus on addressing this knowledge gap.

ASSOCIATION VITAMIN D TO GLAUCOMA: A SYSTEMATIC REVIEW

Background: Glaucoma is a chronic progressive optic neuropathy that causes irreversible damage. Therefore, early diagnosis and appropriate treatment to control various risk factors associated with glaucoma are important. Risk factors associated with the development of glaucoma have been reported by many researchers and include both ocular and non-ocular (systemic) factors such as myopia, central corneal thickness, disc hemorrhage, and genetic factors. The aim: This study aims to show association vitamin D to glaucoma. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 89 articles, whereas the results of our search on SagePub brought up 98 articles. The results of the search conducted for the last year of 2013 yielded a total 13 articles for PubMed and 26 articles for SagePub. The result from title screening, a total 2 articles for PubMed and 18 articles for SagePub. In the end, we compiled a total of 10 papers. We included five research that met the criteria. Conclusion: Decreased serum 25-OHD concentration was associated with the presence but not the severity of POAG. It was suggested that Vitamin D deficiency should be considered a potential risk factor for the development of open-angle glaucoma.

Metabolism of vitamin D, Calcium and Phosphorus and their disorders in goats

The review article presents materials on the metabolism of the mostcommon vitamins of group D ergocalciferol (D2), cholecalciferol (D3), aswell as essential macronutrients Ca and Phosphorus and their disorders ingoats. Since the primary forms of vitamin D (D2 and D3) are biologicallyinactive and must undergo several stages of hydroxylation to be activated,the biological role and importance for the body of active metabolites ofvitamin D3 25OH D3 (synthesised mainly in the liver under the influenceof hepatic cytochromes P450) and 1, 25(OH)2 D3 and 24,25(OH)2 D3 (theirsynthesis occurs via 1α-hydroxylase in the mitochondria of proximal cellsof the convoluted tubules of the kidneys).It is believed that the liver, while playing an important role in themetabolism of vitamin D and its metabolites and producing 25OH D3, isalso the only organ that synthesises DBP, which transports 25OH D3 totissues and maintains its concentration in the circulatory system.Vitamin D becomes biologically active only after the second stageof hydroxylation is completed. Renal 1α-hydroxylase (CYP27B1),regulated by parathyroid hormone (PTH), plays an important role inthe transformation of the extracellular substrate 25OH D3 to 1,25(OH)2D3, which exerts its effect on target cells and tissues by binding to thenuclear vitamin D receptor. Alternatively, 1,25(OH)2 D3 can bind to theplasma membrane VDR and induce non-genomic actions, in particular,stimulation of intestinal calcium transport.Vitamin D is a steroid substance that is essential for all vertebratesto maintain calcium and phosphorus metabolism within optimal limits, ahealthy skeleton, muscle contraction, modulation of cell growth and neuromuscular function. Calciferol also regulates the immune system, inhibits the development of pathological cells, angiogenesis and inflammatoryreactions. The active form of vitamin D, 1,25(OH)2 D3, stimulates intestinal absorption and renal Ca reabsorption and maintains its minimumphysiological level in the blood.Vitamin D deficiency in goats leads to a decrease in productivity, causesa decrease in intestinal and renal calcium reabsorption, which leads to theincrease in parathyroid hormone levels. This process leads to activation ofosteocytes and, as a result, accelerates bone demineralisation, causing thedevelopment of many diseases in adults, including nutritional and fibrousosteodystrophy, secondary osteodystrophy, endocrine dysfunction), as wellas rickets in young animals. The development of non-skeletal pathologies,in particular, inflammatory, neoplastic and autoimmune diseases, is also associated with cholecalciferol deficiency in the body. In addition, disordersof D-vitamin and calcium-phosphorus metabolism in goats cause the development of postpartum hypocalcaemia and postpartum hypophosphatemia.In the animal body, calcium and phosphorus homeostasis is maintained by a coordinated interaction of absorption and reabsorptionthrough the gastrointestinal tract and kidneys, as well as by storage and mobilization from bone tissue and is regulated mainly by biologically active cholecalciferol metabolites - 25OH D3, 1,25(OH)2 D3, as wellas parathyroid hormone (PTH; synthesised by the pineal glands) andcalcitonin (CT; produced by sparafollicular (light) thyroid C cells) andfibroblast growth factor-23 (FGF23).In contrast to monogastric animals, small ruminants do not modulaterenal calcium excretion in response to calcium limitation in the diet. Themobilization of Ca and P from the skeleton is stimulated by PTH throughosteoclast activation mediated by receptor activator of nuclear factor-κB(RANK). Vitamin D maintains Ca (by stimulating CaZB) and P homeostasis (the direct rapid action of 1,25(OH)2 D3 has been proven to have a directeffect on the absorption of these vital elements in the intestine, reabsorptionof these cations in the renal tubules and their mobilization from bone tissue).Phosphorus is a component of adenosine triphosphate (ATP) and nucleotides. Macroergic phosphate compounds, among which the main oneis adenosine triphosphate acid, provide both the accumulation of energyreserves and its consumption (ATP, ADP, creatine phosphate), affectingprotein, lipid, carbohydrate, mineral, and energy metabolism. An interaction between vitamin D and fibroblast growth factor 23 (FGF23), a bonehormone that causes the development of phosphaturia and reduces thesynthesis of 1,25(OH)2 D3, has been identified.Despite the multidirectionality of etiological factors, common to allforms of osteodystrophy is a disruption of the processes of bone formation and renewal, which is manifested by increased mobilization of calcium, phosphorus and other elements from bone tissue, so the pathologyis accompanied by osteomalacia, osteoporosis and osteofibrosis, and aviolation of the mechanism of maintaining their homeostasis.The main factors of osteodystrophy in animals are feeding disordersand physical inactivity, and the leading links in its pathogenesis are theimbalance between bone formation and resorption.The main methods for diagnosing disorders of D-vitamin and calcium-phosphorus metabolism in goats are clinical, physical, biochemical,enzyme-linked immunosorbent assays and pathological and morphological studies. Biochemical analysis in goat serum determines the content oftotal calcium, inorganic phosphorus, activity of alkaline phosphatase andits isozymes, and immunoassay the concentration of 25OH D3, 1,25(OH)2D3, calcitonin and parathyroid hormone. Keywords: goats, vitamin D, metabolites, metabolism, calcium,phosphorus, liver, kidneys.