Cardioprotective effect of Vitamin D on cardiac hypertrophy through improvement of mitophagy and apoptosis in an experimental rat model of levothyroxine -induced hyperthyroidism.

BACKGROUND: Mitochondria are known to be involved in mediating the calorigenic effects of thyroid hormones. With an abundance of these hormones, alterations in energy metabolism and cellular respiration take place, leading to the development of cardiac hypertrophy. Vitamin D has recently gained attention due to its involvement in the regulation of mitochondrial function, demonstrating promising potential in preserving the integrity and functionality of the mitochondrial network. The present study aimed to investigate the therapeutic potential of Vitamin D on cardiac hypertrophy induced by hyperthyroidism, with a focus on the contributions of mitophagy and apoptosis as possible underlying molecular mechanisms. METHODS AND RESULTS: The rats were divided into three groups: control; hyperthyroid; hyperthyroid + Vitamin D. Hyperthyroidism was induced by Levothyroxine administration for four weeks. Serum thyroid hormones levels, myocardial damage markers, cardiac hypertrophy indices, and histological examination were assessed. The assessment of Malondialdehyde (MDA) levels and the expression of the related genes were conducted using heart tissue samples. Vitamin D pretreatment exhibited a significant improvement in the hyperthyroidism-induced decline in markers indicative of myocardial damage, oxidative stress, and indices of cardiac hypertrophy. Vitamin D pretreatment also improved the downregulation observed in myocardial expression levels of genes involved in the regulation of mitophagy and apoptosis, including PTEN putative kinase 1 (PINK1), Mitofusin-2 (MFN2), Dynamin-related Protein 1 (DRP1), and B cell lymphoma-2 (Bcl-2), induced by hyperthyroidism. CONCLUSIONS: These results suggest that supplementation with Vitamin D could be advantageous in preventing the progression of cardiac hypertrophy and myocardial damage.

Testosterone and resistance training improved physical performance and reduced fatigue in frail older men: 1 year follow-up of a randomized clinical trial.

OBJECTIVE: To improve health conditions among hypogonadal men ≥70 years of age using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium, and protein. METHODS: This study is a 1-year follow-up of a double-blind RCT lasting 20 weeks, including 148 older men ≥70 years old with low testosterone levels and mobility problems. During 52 weeks, 4 groups received either testosterone therapy (TU) or progressive resistance training (Training), both (Combo), or no intervention (Controls). Physiotherapists supported the training groups until week 20, while these participants continued trained on their own during weeks 21 to 52. The main outcome measure was the 30-s chair stand test. RESULTS: The following numbers of participants completed the trial: 20 (Combo), 20 (Controls), 24 (TU), and 14 (Training). When examining 30-s chair stand test performance within each group at baseline, and at weeks 4, 20 and 52, only the Combo group improved (p = 0.001, Friedman Test). Compared to controls, only the Combo group experienced reduced fatigue and tiredness (p < 0.05). CONCLUSIONS: Fifty-two weeks of testosterone supplementation combined with progressive resistance training may enhance physical performance, alleviate fatigue, and had no notable detrimental impacts among males aged ≥70 suffering from mobility issues and testosterone insufficiency.Trial registration - Clinical Trials NCT02873559.

Adequate serum 25-hydroxy-vitamin D levels are correlated with low anti-PF4 levels in mild COVID-19 Patients: An observational study.

The worldwide spread of coronavirus disease 2019 (COVID-19) has resulted in an unparalleled health emergency of global proportions. Around 31% of individuals with COVID-19 experience thrombosis associated with hypercoagulation. COVID-19 patients have shown an increase in platelet activation, but the mechanism has not been fully understood yet. One theory suggests that this could be related to the heparin-induced thrombocytopenia phenomenon, where platelet activation involves anti-PF4 antibodies that are associated with thrombosis. Vitamin D has been established to exert an influence on immunological responses and inflammation. The aim of this study is to analyze the correlation between serum 25-hydroxy-cholecalciferol [25(OH)D] levels and anti-PF4 antibodies among COVID-19 patients. A cross-sectional study was conducted among 160 COVID-19 patients at Cipto Mangunkusumo General Hospital and Wisma Atlit Hospital Jakarta from October 2021 to January 2022. The mean serum 25(OH)D level was 15.1 ng/mL. A significant negative correlation was found between serum 25(OH)D and anti-PF4 levels in mild COVID-19 patients (P = .035; R = -0.236). Remarkably, P-selectin levels were significantly higher in the moderate COVID-19 group compared to the severe group (P = .031). Serum 25(OH)D level had a significant negative correlation with anti-PF4 level in mild COVID-19 patients. Thus, it is highly recommended to ensure that serum 25(OH)D levels are maintained above 30 ng/mL. Remarkably, the P-selectin level was significantly higher in the moderate COVID-19 group compared to the severe group.

Assessment of vitamin D status and associated risk factors in high-altitude populations affected by multiple sclerosis: A case-control study.

Several studies have suggested a correlation between serum vitamin D (VitD) level and multiple sclerosis (MS). MS has a known latitudinal distribution pattern, with greater incidence, prevalence, and mortality rates at higher latitudes. This study aims to assess levels of VitD and serum potassium in subjects with MS and the impact of gender and age as disease risk factors. A cross-sectional case-control study was conducted in a high-altitude region of Saudi Arabia. VitD deficiency was defined as serum 25 (OH)D level of ≤20 ng/mL and insufficiency as a serum level between >20 ng/mL and <30 ng/mL. Two hundred patients with MS volunteered for the study, and 160 healthy participants served as controls. VitD and serum potassium were measured in patients and controls. Student t test and regression analysis were used to analyze the data. The average MS patient age was 37.37 ±â€…10.8 years. Most (73.02%) MS patients suffered from deficient vitamin D, while insufficiency (20-29 ng/mL) was found in 12.17%. Only 6.35% had sufficient vitamin D (30-40 ng/mL). VitD was significantly decreased in MS patients compared to the healthy controls (17.036 vs 25.01 ng/mL, P < .001), while serum potassium was also decreased (4.278 vs 4.329 mmol/L, P = .269). Risk factors found to have a statistically significant association with MS included female gender (odd ratio [OR] = 1.72, 95% confidence interval: 1.016-2.915; P = .044) and patient age < 40 years (OR = 1.04, 95% confidence interval: 1.023-1.054; P = .044). VitD was significantly lower in MS patients. The prevalence of MS was higher among women and younger individuals in a high-altitude population in Saudi Arabia.

Exploring the synergistic effects of vitamin D and synbiotics on cytokines profile, and treatment response in breast cancer: a pilot randomized clinical trial.

This study was designed to investigate the effect of vitamin D and/or synbiotics on the response to treatment, cytokines profile and hormonal biomarkers in breast cancer patients undergoing neoadjuvant therapy. A total of 76 patients were recruited and completed the course of the intervention between 2019 and 2021 in Kerman, Iran. breast cancer patients were randomly enrolled in this study. Patients divided into four groups to receive one of the following regimens: placebo, vitamin D, synbiotics and a combination of vitamin D and synbiotics. clinicopathologic parameters, inflammatory and anti-inflammatory biomarkers and hormonal levels were measured at the baseline and four months after intervention. The study results found no clear link between the interventions and achieving pathological complete response (pCR), and a similar trend was observed in Ki-67 index examination. After neoadjuvant therapy, TNF-α concentrations decreased, with vitamin D supplementation moderating this decline. Vitamin D supplemented groups showed a significant increase in serum IL-6 levels. While IL-10 levels decreased in the placebo group, all intervention groups were protected from this decline. Moreover, there was a notable increase in the anti-inflammatory index, particularly in the group receiving both vitamin D and synbiotic supplementation, suggesting potential synergistic anti-inflammatory effects from their combined administration. The outcomes suggest a potential anti-inflammatory function of this combination. Consequently, more extensive studies with prolonged follow-up periods and substantial sample sizes are warranted to thoroughly evaluate their potential benefits for breast cancer patients.

A pharmacovigilance study on clinical factors of active vitamin D3 analog-related acute kidney injury using the Japanese Adverse Drug Event Report Database.

Acute kidney injury (AKI) due to vitamin D therapy for osteoporosis is encountered in clinical practice, but epidemiological studies are scarce. We aimed to determine the association between AKI and vitamin D therapy and to identify risk factors for AKI using the Japanese Adverse Drug Event Report database. We used reporting odds ratios (RORs) to detect signals and evaluate risk factors using multiple logistic regression analysis. Among 298,891 reports from April 2004 to September 2023, 1071 implicated active vitamin D3 analogs as suspect drugs for adverse events. There was a significant association between AKI and active vitamin D3 analogs (ROR [95% confidence interval {CI}], eldecalcitol: 16.75 [14.23-19.72], P < 0.001; alfacalcidol: 5.29 [4.07-6.87], P < 0.001; calcitriol: 4.46 [1.88-10.59], P < 0.001). The median duration of administration before AKI onset was 15.4 weeks. Multiple logistic regression analysis showed a significant association between AKI and age ≥ 70 years (odds ratio [95% CI], 1.47 [1.04-2.07]; P = 0.028), weight < 50 kg (1.55 [1.12-2.13]; P = 0.007), hypertension (1.90 [1.42-2.54]; P < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.58 [1.10-2.25], P = 0.012) and magnesium oxide (1.96 [1.38-2.78]; P < 0.001). Our results suggest that active vitamin D3 analogs are associated with AKI development. Physicians prescribing these medications to patients with risk factors should consider the possibility of AKI, especially during the first 6 months.

Vitamin D Deficiency after Anterior Cruciate Ligament Reconstruction Associates with Knee Osteoarthritis: A Retrospective Study.

BACKGROUND/OBJECTIVES: The objective of this study was to test the hypothesis that vitamin D deficiency (i.e., serum 25-hydroxyvitamin D (25(OH)D) ≤ 20 ng/mL) associates with the increased occurrence and shortened time to a knee osteoarthritis (OA) diagnosis after anterior cruciate ligament reconstruction (ACLR). METHODS: This study consisted of a retrospective, case-control design. The inclusion criteria consisted of (1) patients (≥18 y) who underwent arthroscopic ACLR with (cases; n = 28) and without (controls; n = 56) a subsequent knee OA diagnosis (≥90 d from the date of ACLR) and (2) with a documented serum 25(OH)D concentration after ACLR (and before a knee OA diagnosis for the cases). Controls were matched (2:1) to cases based on sex, age at ACLR, date of ACLR, and body mass index. After matching, patients were separated into two groups: (1) vitamin D deficient (serum 25(OH)D ≤ 20 ng/mL) or (2) non-vitamin D deficient (serum 25(OH)D > 20 ng/mL). Data were extracted from the medical records. RESULTS: Thirty-one percent (n = 26) of patients included were vitamin D deficient. Fifty percent (n = 13) of the vitamin D deficient and twenty-six percent (n = 15) of the non-vitamin D deficient patients were subsequently diagnosed with knee OA (p = 0.03). Time from ACLR to a knee OA diagnosis was significantly (p = 0.02) decreased in the vitamin D deficient (OA-free interval, 95% confidence interval [CI] = 7.9 to 10.9 y) compared to the non-vitamin D deficient group (OA-free interval, 95% CI = 10.5 to 12.5 y). CONCLUSIONS: Vitamin D deficiency after ACLR may serve as a prognostic biomarker for knee OA following ACLR.

1,25-Dihydroxyvitamin D Enhances the Regenerative Function of Lgr5+ Intestinal Stem Cells In Vitro and In Vivo.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestines without a cure. Current therapies suppress inflammation to prevent further intestinal damage. However, healing already damaged intestinal epithelia is still an unmet medical need. Under physiological conditions, Lgr5+ intestinal stem cells (ISCs) in the intestinal crypts replenish the epithelia every 3-5 days. Therefore, understanding the regulation of Lgr5+ ISCs is essential. Previous data suggest vitamin D signaling is essential to maintain normal Lgr5+ ISC function in vivo. Our recent data indicate that to execute its functions in the intestines optimally, 1,25(OH)2D requires high concentrations that, if present systemically, can cause hypercalcemia (i.e., blood calcium levels significantly higher than physiological levels), leading to severe consequences. Using 5-bromo-2'-deoxyuridine (BrdU) to label the actively proliferating ISCs, our previous data suggested that de novo synthesized locally high 1,25(OH)2D concentrations effectively enhanced the migration and differentiation of ISCs without causing hypercalcemia. However, although sparse in the crypts, other proliferating cells other than Lgr5+ ISCs could also be labeled with BrdU. This current study used high-purity Lgr5+ ISC lines and a mouse strain, in which Lgr5+ ISCs and their progeny could be specifically tracked, to investigate the effects of de novo synthesized locally high 1,25(OH)2D concentrations on Lgr5+ ISC function. Our data showed that 1,25(OH)2D at concentrations significantly higher than physiological levels augmented Lgr5+ ISC differentiation in vitro. In vivo, de novo synthesized locally high 1,25(OH)2D concentrations significantly elevated local 1α-hydroxylase expression, robustly suppressed experimental colitis, and promoted Lgr5+ ISC differentiation. For the first time, this study definitively demonstrated 1,25(OH)2D's role in Lgr5+ ISCs, underpinning 1,25(OH)2D's promise in IBD therapy.

The Effect of Vitamin D Supplementation on Glycemic Control and Cardiovascular Risk Factors in Type 2 Diabetes: An Updated Systematic Review and Meta-Analysis of Clinical Trials.

Background and Aims: The purpose of this meta-analysis was to investigate the effect of vitamin D supplementation on hemoglobin A1C (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), and the total vitamin D level in patients with Type 2 diabetes (T2DM). Methods: A systematic search was conducted in databases such as PubMed (Medline), Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov using relevant keywords from January 1990 to January 2024. After screening and extracting data, a qualitative evaluation of articles was performed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). Results: The findings revealed that vitamin D supplementation significantly decreased the mean HbA1C (SMD: -0.15; 95% CI: -0.29, -0.20; I square: 79.76%; p value < 0.001) and mean FBS (SMD: -0.28; 95% CI: -0.40, -0.15; I square: 70.13%; p value < 0.001), lowered SBP (SMD: -0.06; 95% CI: -0.16, -0.05; I square: 39.63%; p value = 0.23), and reduced LDL (SMD: -0.11; 95% CI: -0.28, -0.05; I square: 73.66%; p value < 0.001). Furthermore, vitamin D supplementation increased the average HDL (SMD: 0.13; 95% CI: 0.04, 0.29; I square: 79.33%; p value < 0.001) and vitamin D levels (SMD: 1.78; 95% CI: 1.53, 2.04; I square: 91.92%; p value < 0.001) in patients with T2DM. Subgroup analyses showed that weight gain, BMI, and duration of the disease could reduce the effect of vitamin D supplementation on diabetes control in affected patients. Conclusion: The results also indicated that taking vitamin D supplements in the amount of 50,000 IU had a significant effect on reducing the indicators related to diabetes control. Based on the combined evidence, the findings of this meta-analysis suggest that vitamin D supplementation can significantly improve glycemic control and reduce the risk of complications associated with T2DM, especially cardiovascular diseases (CVDs).

Metabolic and hormonal profiling in polycystic ovarian syndrome: insights into INSR gene variations.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a hormonal disorder characterized by irregular periods, excess androgen levels, and polycystic ovaries, affecting many women of reproductive age. METHODS AND RESULTS: This study employed statistical and molecular analyses to compare hormone and metabolic markers between PCOS patients and controls. Sanger sequencing identified two INSR gene variants linked to high insulin and pre-diabetic conditions. Statistically, no significant age differences were detected (p = 0.492) between the overall PCOS patient pool and controls. However, a substantial variation in Vitamin D levels was observed within PCOS patients compared to controls (p = 0.0006), suggesting an association with PCOS. Correlations between Vitamin D and insulin, as well as HbA1c levels (R2 = 0.141 and 0.143, respectively), suggest Vitamin D's potential impact on glycemic control. Significant differences were found in HbA1c (p < 0.0001), insulin (p < 0.0001), and LDL (p = 0.0004) levels between PCOS patients and controls, highlighting marked disparities in these metabolic markers. LH levels also showed a significant contrast (p < 0.0001), while progesterone levels displayed a notable difference (p = 0.007) between the two groups. Correlation analyses within PCOS patients demonstrated associations among LDL, HbA1c, and insulin, with no such correlations observed in control cases. Additionally, Sanger sequencing identified two INSR gene variants, c.3614C > T (p.Pro1205Leu) and c.3355C > T (p.Arg1119Trp), associated with high insulin, LH, and pre-diabetic conditions. These amino acid changes may trigger metabolic imbalances and hormonal irregularities, potentially contributing to the development of PCOS. CONCLUSIONS: The findings highlight the multifaceted nature of PCOS, revealing significant metabolic, hormonal, and genetic differences compared to controls. These insights may inform tailored interventions and management strategies for the complex associations characteristic of PCOS.

To what Extent does Vitamin D and its Serum Levels Influence the Severity of Hidradenitis Suppurativa: A Literature Review.

Vitamin D plays a role in inflammatory skin conditions and can improve them. Hidradenitis suppurativa (HS) is an autoinflammatory chronic skin disease in which most patients exhibit a hypovitaminosis D. However, it is uncertain whether vitamin D supplementation could relieve the severity of HS. A systematic literature search of PubMed and Web of Science was conducted on 4 September 2023. Studies that investigated vitamin D and its potential implications for the severity of HS were included. In contrast, studies that focused on the prevalence of vitamin D deficiency were excluded, as well as studies on syndromic HS. Seven studies with a total of 575 patients were included in the qualitative synthesis, of which 3 utilized a cross-sectional design, 2 were pilot studies, 1 a controlled cohort study, and 1 a prospective case-control study. In all included studies, HS patients were vitamin D deficient. There was evidence indicating that serum vitamin D levels negatively correlated with the severity of the disease, and at least suggestive evidence that vitamin D supplementation could have a positive impact on the course of HS. To better understand these correlations, conducting a randomized controlled trial study on vitamin D and its effects on HS severity is imperative.

Association between 25 hydroxyvitamin D and serum uric acid level in the Chinese general population: a cross-sectional study.

BACKGROUD: The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. METHODS: This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. RESULTS: Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). CONCLUSIONS: Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels.

Basal Metabolic Rate Versus Dietary Vitamin D and Calcium Intakes and the Association With Body Composition and Bone Health After Chronic Spinal Cord Injury.

We examined the association among basal metabolic rate (BMR) as well as dietary intakes of vitamin D (Vit D) and calcium on body composition and bone mineral density (BMD) after spinal cord injury (SCI). Cross-sectional design. Veterans Affairs Medical Center, Richmond, VA. About 33 individuals with chronic SCI who recorded their food consumption 3 days per week for 2 weeks. BMR was measured after 10 to 12 h of overnight fast. Average daily vit D and calcium intakes, and total caloric intake were recorded and analyzed using the Nutrition Data System for Research (NDSR) software. Fasting blood analysis for 25-hydroxyvitamin D (25[OH]D) status and Triiodothyronine (T3) status was performed (n = 10). Total and regional BMD, % fat mass (FM), and % lean mass (LM) were measured by dual X-ray absorptiometry scans. Participants consumed less than the Institute of Medicine (IOM) recommended daily allowances (RDA) for vit D (600-800 IU) and calcium (1000-1200 mg) for adults. BMR was positively related to total-lean mass (r = .62, P = .0001; n = 32) and leg-lean mass (r = .51, P = .003; n = 32). Adjusted BMR was negatively related to BMD of the left (r = -.38, P = .047; n = 28) and the right (r = -.41, P = .032; n = 28) proximal tibia. Vit D intake was negatively related to percentage total-FM (r = -.33, P = .07; n = 29) and legs-%FM (r = -.37, P = .047; n = 29). Multivariate regression models indicated that adjusted BMR explained the variance in leg fat mass (34%; P = .002) and percentage fat mass (44%; P < .0001). Persons with SCI are likely to consume less than the RDAs for vit D and calcium. BMR may explain the changes in body composition and bone metabolism. Dietary vit D should be considered as a prophylactic intervention in maintenance of bone health after SCI.

Vitamin D and Gestational Diabetes Mellitus in the IEU OpenGWAS Project: A Two-Sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most prevalent pregnancy problems, and there is still debate over the relationship between vitamin D and GDM. OBJECTIVES: Our objective is to investigate the correlation between vitamin D and GDM by employing Mendelian randomization (MR) with summary data obtained from genome-wide association studies (GWAS). METHODS: Data on exposures and outcomes, namely vitamin D, vitamin D insufficiency, and GDM, were acquired from the IEU OpenGWAS Project. Bidirectional MR analysis was performed utilizing the inverse variance weighted (IVW) method as the principal analytical approach. The complementary approaches employed in this study encompassed weighted median, simple mode, weighted mode, and MR-Egger regression. A series of sensitivity analysis were conducted in order to assess the reliability of the obtained results. RESULTS: The data were acquired from the IEU OpenGWAS Project. Following the application of the three assumptions of MR, 13 single nucleotide polymorphisms (SNPs) were included in the MR analysis for vitamin D levels and vitamin D deficiency on GDM, and 10 and 26 SNPs were included for GDM on vitamin D levels and deficiency, respectively. The findings from the IVW analysis revealed a significant positive correlation between vitamin D levels and GDM (OR = 1.057, 95% CI: 1.011-1.104, p = 0.015). Conversely, a negative correlation was seen between vitamin D deficiency and GDM (OR = 0.979, 95% CI: 0.959-0.999, p = 0.039). The results of the reverse MR study revealed no evidence of reverse causation between GDM and vitamin D. The findings from multiple MR approaches were in line with the direction of IVW analysis. Sensitivity analysis revealed no evidence of heterogeneity, pleiotropy, or outliers, suggesting the robustness of the results. CONCLUSIONS: There exists a causal association between vitamin D and GDM, whereby vitamin D levels serve as a risk factor for GDM.

Effects of High Dose Bolus Cholecalciferol on Free Vitamin D Metabolites, Bone Turnover Markers and Physical Function.

High dose bolus cholecalciferol supplementation has been associated with falls and fracture, and this does not appear to be due to hypercalcaemia. The primary aim of this study was to determine the change in free vitamin D and metabolites after high dose bolus supplementation. This was a single centre, double-blinded, randomised, controlled trial of three different oral bolus doses of vitamin D3 (50,000 IU, 150,000 IU, and 500,000 IU) in otherwise healthy, vitamin D deficient (total 25-hydroxylated vitamin 25(OH)D < 30 nmol/L) postmenopausal women. Thirty-three women were randomized to one of the three treatment groups. Twenty-seven vitamin D sufficient (25(OH)D > 50 nmol/L) postmenopausal women were recruited as a concurrent control group. Participants attended five study visits over three months. We measured total 25(OH)D3 and free 25(OH)D, total and free 1,25(OH)2D, parathyroid hormone, fibroblast-growth factor-23, serum calcium, ionised calcium, urinary calcium excretion, and bone turnover markers (procollagen I N-propeptide (PINP), serum C-telopeptides of type I collagen (CTX-I) and Osteocalcin (OC)). We assessed muscle strength and function with grip strength and a short physical performance battery. Postural blood pressure and aldosterone:renin ratio (ARR) was also measured. Total 25(OH)D3 and free 25(OH)D increased in response to dose, and there were proportionate increases in total and free metabolites. Treatment did not affect serum calcium, postural blood pressure, ARR, or physical function. Bone turnover markers increased transiently one week after administration of 500,000 IU. High dose bolus cholecalciferol supplementation does not cause disproportionate increases in free vitamin D or metabolites. We did not identify any effect on blood pressure regulation or physical function that would explain increased falls after high dose treatment. A transient increase in bone turnover markers one week after a 500,000 IU bolus suggests that very high doses can have acute effects on bone metabolism, but the clinical significance of this transient increase is uncertain.

Vitamin D Deficiency Does Not Affect Cognition and Neurogenesis in Adult C57Bl/6 Mice.

Vitamin D deficiency is a global problem. Vitamin D, the vitamin D receptor, and its enzymes are found throughout neuronal, ependymal, and glial cells in the brain and are implicated in certain processes and mechanisms in the brain. To investigate the processes affected by vitamin D deficiency in adults, we studied vitamin D deficient, control, and supplemented diets over 6 weeks in male and female C57Bl/6 mice. The effect of the vitamin D diets on proliferation in the neurogenic niches, changes in glial cells, as well as on memory, locomotion, and anxiety-like behavior, was investigated. Six weeks on a deficient diet was adequate time to reach deficiency. However, vitamin D deficiency and supplementation did not affect proliferation, neurogenesis, or astrocyte changes, and this was reflected on behavioral measures. Supplementation only affected microglia in the dentate gyrus of female mice. Indicating that vitamin D deficiency and supplementation do not affect these processes over a 6-week period.

The Role of Vitamin D in Hematopoietic Stem Cell Transplantation: Implications for Graft-versus-Host Disease-A Narrative Review.

INTRODUCTION/AIM: Vitamin D plays a crucial role in immune modulation, which may influence the development of graft-versus-host disease (GvHD) in patients undergoing hematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of vitamin D levels and supplementation on the incidence of GvHD in HSCT patients. METHODS: A narrative review was conducted across PubMed/Medline, Cochrane Library, CINAHL, and Embase databases. RESULTS: The reviewed studies indicated widespread vitamin D deficiency among HSCT patients, with baseline levels ranging from 12.8 to 29.2 ng/mL. Supplementation protocols varied significantly, with dosages ranging from 1000 IU/day to 60,000 IU/week. Post-supplementation levels improved in some studies. Studies exploring the relationship between vitamin D and GvHD showed mixed results. Lower baseline vitamin D levels were associated with an increased risk of acute GvHD in some studies, while others found no significant correlation. However, a significant association between low levels of vitamin D and the incidence of chronic GvHD was observed. CONCLUSION: Vitamin D deficiency is prevalent in HSCT patients and may influence the risk of developing chronic GvHD. Future research should focus on larger and more rigorous studies to determine the optimal role of vitamin D as an adjuvant therapy in the context of HSCT.