Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

Delving the vitamin D receptor variation and expression profiles in the context of type 2 diabetes among families.

BACKGROUND: Vitamin D is essential for insulin secretion and sensitivity. Consequently, its inadequacy is linked to higher insulin resistance and Type 2 Diabetes (T2D). The Vitamin D receptor (VDR) gene is one potential candidate for T2D, and multiple polymorphisms in VDR have been examined in various populations, but no conclusive answers have been provided. OBJECTIVES: This study was designed to evaluate the susceptibility of VDR gene polymorphism and its expression in diabetic families in Pakistan. METHODOLOGY: In this family-based study, twenty diabetic families with a positive family history of T2D and at least three T2D patients were recruited from outpatient clinics and public hospitals. The current study comprised 143 individuals with 55 affected and 88 unaffected individuals. Blood samples of the selected families were collected. DNA was extracted from the collected samples and the PCR-RFLP method was followed to identify the genotyping and RT-qPCR for expression. Phenotypic and genotypic pedigrees of the families were developed by the progeny online tool. The association values of SNPs were determined by TDT and DFAM analysis implemented on Plink software. RESULTS: The results explained a significant familial aggregation among phenotypic characters including Age, Gender, BMI (body mass index), age of disease diagnosis, disease duration, and blood pressure in the probands, affected FDRs (First Degree Relatives) and affected SDRs (Second Degree Relatives). A significant association of rs731236 C/T (OR = 1.522), rs2228570 C/T (OR = 1.327) with p < 0.05. Whereas, for rs1544410 G/A (OR = 0.9706) and rs7975232 T/G (OR = 0.7368) no considerable association evidence was seen (p > 0.05) in families. The mRNA expression of VDR increased threefold (p = 0.0204) in patients compared to controls. Variation-based expression analysis exhibited that the rs2228570 genotype influences the expression. CONCLUSION: A linkage was found among the FDRs with probands. Variation in the gene VDR at loci rs731236 and rs2228570 was associated with familial T2D. However further research is required to explore more genetic factors that could influence T2D risks in families.

Maternal vitamin D status and risk of gestational diabetes mellitus in twin pregnancies: a longitudinal twin pregnancies birth cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication of pregnancy, with significant short-term and long-term implications for both mothers and their offspring. Previous studies have indicated the potential benefits of vitamin D in reducing the risk of GDM, yet little is known about this association in twin pregnancies. This study aimed to investigate maternal vitamin D status in the second trimester and examine its association with the risk of GDM in twin pregnancies. METHODS: We conducted a prospective cohort study based on data from the Chongqing Longitudinal Twin Study (LoTiS). Peripheral blood serum was collected from the mothers in the second trimester to measure 25(OH)D concentrations. GDM was diagnosed at 23-26 weeks of gestation using a 75-g 2-h oral glucose tolerance test. We used multivariable logistic regression analyses to examine the correlations between vitamin D status and the risk of GDM. RESULTS: Of the total participants, 93 (29.9%) women were diagnosed with GDM. The mean serum 25(OH)D concentration in the second trimester was 31.1 ± 11.2 ng/mL, and the rate of vitamin D insufficiency and deficiency were 23.5% and 18.7%, respectively. Compared to women with a 25(OH)D concentration < 30 ng/mL, those with a 25(OH)D concentration ≥ 30 ng/mL had a significantly lower risk of GDM (RR 0.61; 95% CI: 0.43, 0.86), especially those who were overweight before pregnancy (RR 0.32; 95% CI: 0.16, 0.64). The restricted cubic splines model showed an inverted J-shaped relationship between vitamin D concentrations and GDM risk. CONCLUSIONS: The risk of GDM was significantly reduced in twin pregnant women with vitamin D concentrations ≥ 30 ng/mL in the second trimester. TRIAL REGISTRATION: ChiCTR-OOC-16,008,203. Retrospectively registered on 1 April 2016.

Dietary intake with supplementation of vitamin D, vitamin B6, and magnesium on depressive symptoms: a public health perspective.

Objective: This study aims to understand the impact of dietary intake through supplementation of vitamins D, B6, and magnesium on elevated depressive symptoms, a mental health illness that is a leading contributor to global disability and a public health concern. Methods: Multiple datasets from the National Health and Nutrition Examination Survey 2017-March 2020 investigated the associations between vitamin D, B6, and magnesium on depression screening scores. A cross-sectional sample of adults over 20 was extracted (n = 9,232). Chi-square tests and logistic regression analyses were used to investigate the associations. Results: Individuals with low amounts of vitamin D (p = 0.0481) were more likely to report elevated depressive symptoms relative to those with low amounts of vitamin B6 (p = 0.0225). These results remained significant among those with high magnesium (p = 0.0133) proportionate to high vitamin B6 (p = 0.0225). In the age-adjusted model, a lower intake of vitamin D, vitamin B6, and magnesium showed a relationship with elevated depressive symptoms (Vitamin D: OR = 0.611, 95% CI 0.382-0.980 Vitamin B6: OR = 0.503, 95% CI 0.291-0.867 Magnesium: OR = 0.458, 95% CI 0.277-0.759). The fully adjusted regression model (gender, race/ethnicity, and household food security) showed that a lower intake of vitamin B6 and magnesium correlated with elevated depressive symptoms (Vitamin B6: OR = 0.439, 95% CI 0.260-0.738 Magnesium: OR = 0.465, 95% CI 0.303-0.714). Conclusion: Preventive measures could be addressed by identifying the risks of vitamin deficiencies. Further epidemiological research is needed for the individual effects of vitamin supplementation and depression screening scores. Future prospective cohort studies exploring these associations, focusing on daily dietary intake, are needed to validate the direction of causation further and understand the underlying mechanisms.

Comparative Performance Assessment of Novel Fluorescence Immunoassay POCTs for Measuring Circulating Levels of Vitamin-D.

Vitamin D (Vit D) is a fat-soluble molecule acting like a hormone, and it is involved in several biological mechanisms such as gene expression, calcium homeostasis, bone metabolism, immune modulation, viral protection, and neuromuscular functions. Vit D deficiency can lead to chronic hypocalcemia, hyperparathyroidism, and many other pathological conditions; in this context, low and very low levels of 25-hydroxy-vitamin D (25-OH-D) were found to be associated with an increased risk of COVID-19 infection and the likelihood of many severe diseases. For all these reasons, it is important to quantify and monitor 25-OH-D levels to ensure that the serum/blood concentrations are not clinically suboptimal. Serum concentration of 25-OH-D is currently the main indicator of Vit D status, and it is currently performed by different assays, but the most common quantitation techniques involve immunometric methods or chromatography. Nevertheless, other quantitation techniques and instruments are now emerging, such as AFIAS-1® and AFIAS-10® (Boditech and Menarini) based on the immunofluorescence analyzer, that guarantee an automated system with cartridges able to give quick and reliable results as a point-of-care test (POCT). This work aims to compare AFIAS-1® and AFIAS-10® (Boditech and Menarini) Vit D quantitation with Ultra High-Performance Liquid Chromatography coupled with tandem mass spectrometry that currently represents the gold standard technique for Vit D quantitation. The analyses were performed in parallel on 56 samples and in different conditions (from fresh and frozen plasma) to assess the reliability of the results. Any statistically significant differences in methods, the fixed error, and the error proportional to concentration were reported. Results obtained in all conditions showed a good correlation between both AFIAS® instruments and LC-MS/MS, and we can affirm that AFIAS-1® and AFIAS-10® are reliable instruments for measuring 25-OH-D with accuracy and in a fast manner.

Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection.

To date, the SARS-CoV-2 pandemic still represents a great clinical challenge worldwide, and effective anti-COVID-19 drugs are limited. For this reason, nutritional supplements have been investigated as adjuvant therapeutic approaches in disease management. Among such supplements, vitamin D has gained great interest, due to its immunomodulatory and anti-inflammatory actions both in adult and pediatric populations. Even if there is conflicting evidence about its prevention and/or mitigation effectiveness in SARS-CoV-2 infection, several studies demonstrated a strict correlation between hypovitaminosis D and disease severity in acute COVID-19 and MIS-C (multisystem inflammatory syndrome in children). This narrative review offers a resume of the state of the art about vitamin D's role in immunity and its clinical use in the context of the current pandemic, specially focusing on pediatric manifestations and MIS-C. It seems biologically reasonable that interventions aimed at normalizing circulating vitamin D levels could be beneficial. To help clinicians in establishing the correct prophylaxis and/or supportive therapy with vitamin D, well-designed and adequately statistically powered clinical trials involving both adult and pediatric populations are needed. Moreover, this review will also discuss the few other nutraceuticals evaluated in this context.

Bone mineral density in adults with arthrogryposis multiplex congenita: a retrospective cohort analysis.

The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than - 2. The mean lumbar spine Z score (- 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than - 2, respectively. The mean femoral neck (- 1.1 ± 1.1) and total hip (- 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p < 0.001). Femoral neck BMD correlated with height (rs = 0.39, p = 0.01), age (rs = - 0.315, p = 0.48); total hip BMD correlated with height (rs = 0.331, p = 0.04) and calcium levels (rs = 0.41, p = 0.04). Twenty-five patients (25/51, 49.0%) reported 39 fractures. Thirty-one (31/36, 86.1%) patients had 25-hydroxyvitamin D levels less than 75 nmol/l, and 6 (6/36, 16.7%) had 25-hydroxyvitamin D levels less than 75 nmol/l. Adults with AMC had lower hip BMD than expected for their age, and they more frequently showed vitamin D insufficiency. Screening for low BMD by DXA and adding vitamin D supplementation when vitamin D status is insufficient should be considered in adults with AMC, especially if there is a history of falls or fractures.

Association between prenatal vitamin D deficiency with dental caries in infants and children: a systematic review and meta-analysis.

Prenatal vitamin D (PVD) is a vital micronutrient for dental caries (DCs). The association between prenatal vitamin D deficiencies (PVDD) and DCs in children has been conflicting in different reports. This meta-analysis aimed to investigate the association between PVDD and DCs in children for the first time. We searched PubMed, Scopus, Web of Sciences, Embase, and Scholar databases to find relevant studies based on mesh terms from 2000 to October 2023. This study was conducted based on the 2020 version of the PRISMA checklist. Cochran's Q and I2 tests were used to evaluate heterogeneity between studies. Egger's test was used to evaluate publication bias. The effect size of the association between PVDD and DCs was reported by the odds ratio (OR) at the 95% confidence interval (95% CI).Twelve studies, including 11,021 participants, were reviewed. The pooled prevalence of PVDD was estimated at 4353 (32%). The prevalence of DCs in children of mothers with and without PVDD was 44% and 25%, respectively. PVDD was significantly associated with an increased risk of DCs in children (OR: 1.35, 95% CI (1.22, 1.47), I2 = 86.6%). The association of DCs with PVDD was different based on gestational age groups, children's age groups, and vitamin D levels. This meta-analysis showed PVDD can be associated with an increased risk of DCs in children, especially in mothers with prenatal vitamin D levels ≤ 35 nmol/L. Adequate vitamin D levels throughout pregnancy can help prevent DCs in children.

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

Prevalence of vitamin D insufficiency in early pregnancies- a Singapore study.

Vitamin D plays an essential role in bone and mineral metabolism. There is increased interest in understanding prevalence of Vitamin D deficiency in pregnancy as many studies report association of low vitamin D levels with obstetric complications and neonatal sequelae. There is a paucity of studies in Singapore evaluating levels of vitamin D levels during the first trimester of pregnancies. We aim to study the prevalence of vitamin D insufficiency in this population. Our study assessed vitamin D levels in these women. Vitamin D (Plasma 25(OH)D concentration) levels in multiracial women during the first trimester were collected via venepuncture at their booking antenatal visit. They were stratified into sufficient ≥30ng/ml, insufficient ≥20ng/ml and <30ng/ml, moderately deficient ≥10ng/ml and <20ng/ml and severely deficient <10ng/ml. 93 women were included in this study. Only 2.2% of our study population had sufficient vitamin D levels. In women who had insufficient levels, the heavier the weight, the more likely to be vitamin D deficient. Interestingly, we also note that the older the patient, the less likely they are to be deficient. In women with periconceptual multivitamin supplementation, the average vitamin D level for those with supplementation was 2.10ng/ml higher than those without. Majority of patients were recruited from a single study member's patient pool who were mostly Chinese. Prevalence of Vitamin D deficiency in general obstetric patients with higher BMI and darker skinned patients may be even lower in Singapore. The high prevalence of Vitamin D insufficiency in our patients prove that it is a prominent problem in our population. We aim to implement screening of vitamin D levels as part of antenatal investigations in the first trimester and recommend supplementation as required. We also hope to evaluate the association of low vitamin D levels with obstetric or neonatal complications further understanding its implications.

Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.

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.

Investigating the role of vitamin D in asthma.

Results in mice suggest that vitamin D reduces the symptoms of asthma by controlling an immune response that leads to inflammation of the airways.

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.

Assessment the awareness of vitamin D deficiency among the general population in Syria: an online cross-sectional study.

BACKGROUND: Vitamin D deficiency is an importance preventable problem in the global and associates with lack levels of awareness about vitamin D. According to prior studies, in the Arab world, there is low of knowledge and awareness toward vitamin D deficiency. The target of our study is evaluating the knowledge level about vitamin D deficiency and determining the associated factors with levels of awareness of its. METHOD: This online cross-sectional study was performed in Syria between 25 February to 29 March 2023 to assess the levels of knowledge about vitamin D deficiency among general Syrian population. The study's survey was obtained from previously published research and we conducted a pilot study to assure the validity and clarity questionnaire. All Syrian individuals aged 18 or older who were able to read and write and willing to participate were included, while, non-Syrian nationality individuals and all medical staff (doctors, nurses, and medical students…), as well, those under 18 age were excluded. The questionnaire consisted of 23 questions separated into four categories. The first section was sociodemographic information of the study population. The second section measured the level awareness of the study population regarding the benefits of vitamin D. In addition, the third and fourth part evaluated knowing of the respondents about sources of and toxicity consequences of vitamin D. The data were analyzed by utilizing multivariate logistic regression in IBM, SPSS V.28 version. RESULTS: Overall, 3172 of the study population accepted to participate in this research and 57.9% the majority of them were aged in the range among 18 and 28. While, the average age of the respondents were 30.80 ± 11.957. Regarding with the awareness toward knowledge of advantages and source of vitamin D and outcomes of vitamin D toxicity. Most of the participants mentioned that vitamin D is used to treat bone disease and rickets and contributes in maintaining calcium and phosphates (91.4% and 84.6%, respectively). Whereas, more than half of them reported that sun exposure does not cause vitamin D poisoning and that vegetarians are more likelihood to have vitamin D than non-vegetarians, (54.1% and 54.9%, respectively). Only, age and occupation out of nine predictors variables were significantly correlated with adequate knowledge of Vitamin D (p-value < 0.05). The respondents aged more than 60 years were high probability to have good recognition of Vitamin D than participants aged between 18 and 28 years. (OR = 7.95). Retired participants have shown lower aware of Vitamin D 0.38 times than students. CONCLUSION: Our research revealed that most of the participated individuals have sufficient comprehension about vitamin D, despite, there were significant gap. Health education via programs by government health-care agencies, NGOs and social workers is necessary to increase the awareness and knowledge toward benefits, source, deficiency and toxicity of vitamin D to avoid injury several diseases such as rickets.

Vitamin D Deficiency Leads to Poorer Health Outcomes and Greater Length of Stay After Total Knee Arthroplasty and Supplementation Improves Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin D deficiency is increasingly identified as a predictor of poorer outcomes in musculoskeletal disease affecting as many as 1 in 4 people. This study aimed to evaluate the effect of vitamin D supplementation on outcomes after primary total knee arthroplasty (TKA). METHODS: A targeted search of terms related to vitamin D and TKA outcomes was performed in PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Academy of Orthopaedic Surgeons, and British Orthopaedic Association databases. The results were analyzed using forest plots with I2 heterogeneity statistics and pooled effects with 95% confidence intervals (CIs) and p values. A p < 0.05 was considered statistically significant. RESULTS: A total of 146,054 patients with 150,107 TKRs were analyzed in 10 studies that complied with the inclusion criteria, of which 3 were suitable for meta-analysis. Of these, 4 of the 10 studies showed that vitamin D deficiency resulted in poorer functional outcome scores (Western Ontario and McMasters Universities Osteoarthritis Index, Knee Society Scoring System, and American Knee Society scores), as well as increased risk of revision surgery, incidence of joint infection, and postoperative stiffness. Meta-analysis of length of hospital stay (LOS) demonstrated a significant increase in LOS in patients with vitamin D deficiency (standardized mean difference, -0.54, 95% CI, -0.69 to -0.38, p < 0.00001). Furthermore, outcomes were improved with vitamin D supplementation in 6 of 10 studies. CONCLUSION: Vitamin D deficiency results in poorer outcomes of primary TKA, with improved outcomes after supplementation. Further studies should examine the role of preoperative vitamin D screening and/or perioperative supplementation in primary TKA and standardize outcome measures to assess their effect. LEVEL OF EVIDENCE: Level I/II. See Instructions for Authors for a complete description of levels of evidence.

The role of interaction between vitamin D and VDR FokI gene polymorphism (rs2228570) in sleep quality of adults.

To evaluate association of vitamin D with sleep quality in adults and the influence of VDR-gene polymorphism FokI (rs2228570;A > G). Cross-sectional population-based study in adults, conducted in Brazil. The outcome was sleep-quality, evaluated by the Pittsburgh Sleep Quality Index. Vitamin D was determined by indirect electrochemiluminescence and classified as deficiency (VDD), 25(OH)D < 20 ng/mL in a healthy population or 25(OH)D < 30 ng/mL for groups at risk for VDD. FokI polymorphism in the VDR-gene was genotyped by qPCR and classified as homozygous wild (FF or AA), heterozygous (Ff or AG), or homozygous mutant (ff or GG). Multivariate logistic analysis was used to estimate the association between vitamin D and FokI polymorphism with sleep-quality. In a total of 1674 individuals evaluated, 53.6% had poor-sleep-quality, 31.5% had VDD, and the genotype frequency of the FokI polymorphism was 9.9% FF, 44.6% Ff, and 45.5% ff. In multivariate analysis, individuals with VDD had 1.51 times the chance of poor-sleep-quality, and individuals with the ff genotype had 1.49 times the chance of poor-sleep-quality (OR:1.49;95%CI:1.05-2.12) when compared to individuals with the FF or Ff genotype. In the combined analysis, individuals with VDD and ff genotype had more chance of poor-sleep-quality than individuals with sufficient vitamin D and genotype Ff or FF (OR:2.19;95%CI:1.27-3.76). Our data suggest that VDD and VDR FokI gene polymorphism are associated with poor-sleep-quality, and combining the two factors increases the chance of poor-sleep-quality compared to separate groups.