Efficacy of vitamin D supplementation in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Context: COVID-19 has substantial effects on respiratory health and overall well-being. Recent studies suggest vitamin D as a potential treatment, but the results are inconclusive. Objective: The authors conducted a systematic review of randomized controlled trials (RCTs) to examine the link between vitamin D and patients with COVID-19. Data sources: The authors searched electronic databases PubMed, Cochrane, CINAHL, EMBASE and Google Scholar from their inception till August 2023. Study selection: Inclusion criteria used in our systematic review include: (1) patients who tested positive for COVID-19, (2) intervention was vitamin D supplementation, (3) the comparator was either a placebo, standard care of treatment, or, no treatment, (4) at least one of the clinical outcomes of interest were investigated, (5) study design being RCTs. Data extraction: Two independent reviewers manually extracted information from selected articles, including study characteristics, patient characteristics, and the primary outcomes: all-cause mortality, ICU and hospital stay length and secondary outcomes: mechanical ventilation, supplemental oxygen, ICU admission, and adverse events. Risk ratios or mean differences and 95% CIs were calculated using a random-effects model. Data synthesis: The authors' analysis included 14 RCTs with 2165 patients. Vitamin D significantly reduced ICU admissions and lowered the need for mechanical ventilation compared to placebo. However, it did not significantly affect hospital stay length, ICU stay length, mechanical ventilation duration, mortality, or the need for supplemental oxygen. Conclusion: Vitamin D does not significantly improve certain clinical outcomes, such as hospital and ICU stay length, for patients with COVID-19. However, it still may be significantly beneficial in decreasing the burden on intensive care services.

Vitamin D concentration in the blood of women with twin pregnancies and in the umbilical cord blood of newborns in relation to environmental factors.

Background: There is a huge gap in the knowledge of the body's nutrient resources in women with multiple gestations. Due to the increased demand hypothesis and taking into account common vitamin D deficits in women with singleton pregnancies, this issue should also be investigated in twin pregnancies. This study evaluated blood vitamin D concentration in women with twin pregnancies and in the umbilical cord blood of their newborns as well as analyzed environmental factors that may affect the level of this nutrient. Methods: The study included 56 women with twin pregnancies. Venous blood samples were collected from the women before delivery and umbilical cord blood at delivery to determine the total 25(OH)D concentration. The women were interviewed by a dietitian to collect data on their diet and lifestyle. Results: The average maternal 25(OH)D concentrations were 38.4 ± 11.0 ng/mL vs. 23.7 ± 6.1 ng/mL determined in the umbilical cord blood of the newborns. The concentration of 25(OH)D in the umbilical cord blood was strongly correlated with the concentration in the mother (p < 0.001). Vitamin D deficiency was found in 7% of women and 21% of newborns. Factors increasing the risk of too low 25(OH)D concentration in the mothers were age below 27 years (p = 0.002) and short duration of pregnancy (p = 0.011). In newborns, the risk factors included low maternal concentrations (p < 0.001) and delivery before 36 weeks of gestation (p = 0.008). The mean cord blood 25(OH)D levels were almost identical in both twins and amounted to 24.0 ± 6.1 ng/mL in the first-born and 23.4 ± 6.1 ng/mL in the second-born infant. Vitamin D supplementation was declared by 98% of the women, with 85% taking ≤2,000 IU vitamin D daily. Conclusion: Only a small percentage of women with twin pregnancies presented with vitamin D deficiency, which was probably related to the widespread supplementation of this nutrient. It can therefore be assumed that a dose of 2,000 IU vitamin D currently recommended for pregnant women may also be appropriate for twin gestations, although further research is required to validate this finding.

Cytomegalovirus results in poor graft function via bone marrow-derived endothelial progenitor cells.

Introduction: Poor graft function (PGF), characterized by myelosuppression, represents a significant challenge following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human cytomegalovirus (HCMV) being established as a risk factor for PGF. However, the underlying mechanism remains unclear. Bone marrow endothelial progenitor cells (BM-EPCs) play an important role in supporting hematopoiesis and their dysfunction contributes to PGF development. We aim to explore the effects of CMV on BM-EPCs and its underlying mechanism. Methods: We investigated the compromised functionality of EPCs derived from individuals diagnosed with HCMV viremia accompanied by PGF, as well as after infected by HCMV AD 169 strain in vitro, characterized by decreased cell proliferation, tube formation, migration and hematopoietic support, and increased apoptosis and secretion of TGF-ß1. Results: We demonstrated that HCMV-induced TGF-ß1 secretion by BM-EPCs played a dominant role in hematopoiesis suppression in vitro experiment. Moreover, HCMV down-regulates Vitamin D receptor (VDR) and subsequently activates p38 MAPK pathway to promote TGF-ß1 secretion by BM-EPCs. Discussion: HCMV could infect BM-EPCs and lead to their dysfunction. The secretion of TGF-ß1 by BM-EPCs is enhanced by CMV through the activation of p38 MAPK via a VDR-dependent mechanism, ultimately leading to compromised support for hematopoietic progenitors by BM EPCs, which May significantly contribute to the pathogenesis of PGF following allo-HSCT and provide innovative therapeutic strategies targeting PGF.

Environmental pollution impact on the severity of some rheumatic diseases: a comparative analytical study on inflammatory and non-inflammatory samples.

OBJECTIVE: Environmental pollution of heavy metals is increasingly a problem and has become of great concern due to the adverse effects it causes worldwide. Heavy metal exposure has been implicated in health problems, including fibromyalgia and rheumatoid arthritis. We aim to evaluate the rule of chronic heavy metals toxicity on the induction of vitamin D3 (VD) deficiency and parathyroid hormone (PTH) disturbances in an inflammatory disease like rheumatoid arthritis (RA) and non-inflammatory disease like fibromyalgia syndrome (FMS). METHODS: This comparative analytical study was conducted on sixty adults (age ≥ 18 years). Participants were divided into three groups. Group I: twenty patients diagnosed with RA according to the specific ACR/EULAR criteria for RA. Group II: twenty patients diagnosed with FMS according to the specific 2010 (ACR) criteria for FMS. Group III: twenty healthy adults. All patients and controls were subjected to routine laboratory tests as well as the measurement of PTH, VD and estimation of serum levels of lead, cadmium, and chromium. RESULTS: VD was significantly inversely correlated to PTH, lead, cadmium, chromium, and activity scores in the RA and FMS groups. Lead, Cadmium and Chromium had a significant independent risk on the VD level in RA patients, while lead had a significant independent risk on the VD level in FMS patients. CONCLUSION: Heavy metals may affect VD synthesis, leading to hypovitaminosis D and secondary hyperparathyroidism in RA and FMS patients. Heavy metals play a key role in the pathogenesis of RA, FMS, and their disease activity.

Hypovitaminosis D among Adult Patients Visiting for General Health Check-up in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

INTRODUCTION: Vitamin D deficiency presents a notable public health concern, with reported prevalence rising in hospital and community settings. It's linked to various chronic health issues and most often remains undiagnosed in developing nations. This study aimed to determine the prevalence of hypovitaminosis D among adults attending general health check-ups at a tertiary care hospital. METHODS: This descriptive cross-sectional study was conducted among adult patients visiting for general health checkups in a tertiary care centre. The patients' data from 16 April 2023 to 24 November 2023 was retrieved from the hospital record. Serum 25(OH)D was measured by using the chemiluminescence micro particles immunoassay technique and classified as deficient, insufficient, and sufficient with values <20 ng/ml, 20-29 ng/ml, and 30-100 ng/ml, respectively. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. RESULTS: Out of 357 adult patients, 291 (81.51%; 95% CI: 77.49%-85.54%) Confidence Interval) had hypovitaminosis D. Among them 124 (42.61%) were categorised as vitamin D insufficient and 167 (57.39%) as deficient. The mean age of patients was 43.25±12.99 years, with 205 (70.45%) female and 86 (29.55%) male. A total of 169 (58.08%) individuals were classified as obese. Dyslipidemia was observed in 249 (85.57%) patients, with 94 (32.30%) exhibiting hypercholesterolemia. CONCLUSIONS: The prevalence of hypovitaminosis D was higher than other studies done in similar settings. This higher prevalence necessitates public awareness of vitamin D's importance, urging proactive screening and management by physicians and implementation of cost-effective guidelines by policymakers.

Immunotherapy with Intralesional Vit D injection in Recalcitrant wart at a Tertiary Care Center: A Descriptive Cross sectional Study.

INTRODUCTION: Recalcirant warts are resistant to conventional therapeutic option with high recurrence rate. In recent year, treatment of warts with different immunotherapeutic agent has shown good results, as it regulate epidermal cell proliferation and are involved in the formation of anti microbial peptides. Hence, this study was undertaken to evaluate the efficacy of immunotherapy with intralesional vitamin D in wart. METHODS: A descriptive cross-sectional study was conducted from 1 January 2021 to 2 February 2023 at Kathmandu Medical College after approval from the Institutional Review Committee (Reference number: 0110202002). Ninety - two patients with recalcitrant wart of varying sizes and duration were included in the study. Injection vitamin D ( 600000 IU, 15mg/ ml) was injected about (0.2-0.5 ml) to the base of the wart. Maximum of five warts were injected per month, and was repeated after 4 weeks for 3 sessions. RESULTS: Among 92 patient, complete response was seen in 70 patient (76.08%), partial response was seen in 17 patients ( 18.47%) and 5 patient(5.43%)showed no response. Mild pain as observed at the time of injection. Signs of hypervitaminosis D was not observed. CONCLUSIONS: Intralesional administration of Vitamin D is an effective treatment option for reclacitrant warts and is, highly effective, cost-efficient, with minimal adverse effects, and can be perfomed in our clinical set up.

Vitamin D and hip protectors in osteosarcopenia: a combined hip fracture preventing approach.

Osteosarcopenia is an emerging clinical condition highly prevalent in the older people. Affected subjects due to their intrinsic skeletal fragility and propensity to falls are at elevated risk of hip fractures which can increase morbidity and mortality. Strategies for attenuating the impact of predisposing factors on hip fractures are not yet well defined and should derive from multidisciplinary care and collaborations. Our aim was to narratively review available data on the preventive role of vitamin D and hip protectors on hip fractures in older patients with sarcopenia. Older subjects are at high risk of vitamin D deficiency and of falls due to several concomitant factors besides osteosarcopenia. Vitamin D protective actions against hip fractures may be mediated by both skeletal (increased mineralization) and extra-skeletal (reduced risk of falls) actions. Hip protectors may act downstream attenuating the effects of falls although their use is still not yet enough widespread due to the suboptimal compliance obtained by traditional hard devices. Concomitant use of vitamin D and hip protectors may represent an effective strategy in the prevention of hip fractures which need to be tested in ad hoc designed clinical trials.

Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D). METHODS: We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed. RESULTS: We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] µIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D. CONCLUSIONS: Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients.

Vitamin D3 mitigates myopathy and metabolic dysfunction in rats with metabolic syndrome: the potential role of dipeptidyl peptidase-4.

Metabolic syndrome is associated with vitamin D3 deficiency. This work aims to examine the efficacy of vitamin D3 in inhibiting MetS-induced myopathy and to determine whether the beneficial effects of vitamin D3 are mediated by the inhibition of dipeptidyl peptidase-4 (DPP-4). An in silico study investigated the potential effectiveness of vitamin D3 on the inhibition of the DPP-4 enzyme. An in vitro assay of the DPP-4 inhibitory effect of vitamin D3 was performed. In vivo and over 12 weeks, both diet (with 3% salt) and drinking water (with 10% fructose) were utilized to induce MetS. In the seventh week, rats received either vitamin D3, vildagliptin, a combination of both, or vehicles. Serum lipids, adipokines, glycemic indices, and glucagon-like peptide-1 (GLP-1), muscular glucose transporter type-4 (GLUT-4) content, DPP-4, adenosine monophosphate kinase (AMPK) activities, and Sudan Black B-stained lipids were assessed. Muscular reactive oxygen species (ROS), caspase-3, and desmin immunostaining were used to determine myopathy. MetS-induced metabolic dysfunction was ameliorated by vitamin D3, which also reduced intramuscular glycogen and lipid accumulation. This is demonstrated by the attenuation of MetS-induced myopathy by vitamin D3, decreased oxidative stress, increased desmin immuno-expression, and caspase-3 activity. Our in silico data demonstrated that vitamin D3 is capable of inhibiting DPP-4, which is further supported by biochemical findings. Vitamin D3 increased serum GLP-1, muscular AMPK activity, and GLUT-4 content, whereas the levels of muscular ROS were decreased in MetS. Vildagliptin and its combination with vitamin D3 yielded comparable results. It is suggested that the DPP-4 inhibitory potential of vitamin D3 is responsible for the amelioration of MetS-induced metabolic changes and myopathy.

Vitamin D-Do Diet Recommendations for Health Remain Strong?

How will the scientific community and authoritative bodies define future nutritional requirements for vitamin D? At the International Symposium on Nutritional Aspects of Musculoskeletal Health, the authors debated the strength of current evidence for setting vitamin D intake recommendations from diet: the positive side of the strength of the evidence (PRO) suggests there is a physiological requirement for vitamin D and the opposing view (CON) that in light of negative results from large, recent trials, particularly those with fractures and bone health outcomes, we are left rudderless. Should we provide recommendations based on empiric treatment of vitamin D for most groups and conditions? It is becoming increasingly evident that vitamin D plays a role in many physiological functions and processes associated with long-term human health; however, to what extent are these benefits apparent beyond what is needed for adequate nutritional status, measured as serum 25-hydroxyvitamin D levels, for active calcium absorption? The meeting attendees voted for the PRO vs. CON position at the end of the session.

The effect of active vitamin D supplementation on body weight and composition: A meta-analysis of individual participant data.

BACKGROUND & AIMS: Obesity is associated with vitamin D (VitD) deficiency. However, previous studies showed mixed effects of VitD (25-hydroxyVitD/calcidiol) supplementation on body weight. The biological actions of VitD require the hydroxylation of inactive VitD into active VitD (1.25-dihydroxyVitD/calcitriol). This step is highly regulated; therefore, supplementing with inactive VitD might not be sufficient to overcome the potential adverse health effects of VitD deficiency. The objective of this study was to conduct a systematic review and individual participant data (IPD) meta-analysis of data acquired from randomised placebo-controlled calcitriol trials (RCTs) to determine the effects of calcitriol on body weight and weight-related parameters. METHODS: Studies were identified from MEDLINE, EMBASE, and CENTRAL databases up to January 27, 2024, and excluded those involving dialysis or cancer patients. We obtained IPD from eligible trials and assessed bias using the Cochrane Collaboration risk-of-bias tool and methodological quality using the Heyland Methodological Quality Score. The study was prospectively registered with PROSPERO (CRD42017076202). RESULTS: Although none of the studies reported information regarding our primary objective, we obtained IPD for 411 patients, with 206 randomised to receive calcitriol and 205 to placebo. This dataset enabled us to conduct an IPD meta-analysis with 17,084 person-months of follow-up (median: 11 months). Meta-analysis showed that calcitriol does not alter body weight, BMI, waist circumference, fat mass or lean body mass compared to placebo. Adjusting for age and sex did not alter the outcomes. CONCLUSIONS: In conclusion, this systematic review and IPD meta-analysis indicate that calcitriol does not affect body weight in normal-weight postmenopausal women and lean patients with type 1 diabetes nor in people suffering from obesity, type 2 diabetes and chronic kidney disease. Whether calcitriol lowers body weight in VitD-sufficient people with obesity remains to be elucidated.

The correlation between vitamin D and the occurrence of peripheral neuropathy induced by paclitaxel chemotherapy.

Introduction: Paclitaxel, a widely used chemotherapeutic agent for various cancers, induces peripheral neuropathy (PIPN) in approximately 80% of patients, severely affecting their quality of life. The role of vitamin D in pain perception has gained attention, but its correlation with PIPN remains unclear. Methods: This study included 129 cancer patients who received adjuvant paclitaxel chemotherapy from January to June 2023. Neuropathic pain was assessed using the Douleur Neuropathique 4 Questions (DN4) questionnaire, and serum levels of vitamin D and glutathione (GSH) were measured to explore the correlation between vitamin D levels and neuropathic pain induced by paclitaxel chemotherapy. Results: The results showed a negative correlation between vitamin D deficiency and the occurrence of neuropathic pain (Spearman correlation coefficient of -0.324, P < 0.001). The receiver operating characteristic (ROC) curve analysis revealed that the area under the vitamin D curve for neuropathic pain was 0.681. Furthermore, after paclitaxel chemotherapy, there was a significant decrease in GSH levels in the serum of patients, with a more pronounced decline in the vitamin D-deficient group. Discussion: The findings of this study indicate that higher levels of vitamin D are negatively associated with the occurrence of paclitaxel-induced neuropathic pain, suggesting that vitamin D might protect against oxidative stress. This discovery is significant for clinical treatment as it may help physicians better understand the mechanisms of pain during paclitaxel therapy and provide new strategies for the prevention and treatment of such pain. It also suggests that modulating vitamin D levels could reduce the neurotoxicity of paclitaxel, thereby improving patients' quality of life and treatment compliance.

Triclocarban disrupts the activation and differentiation of human CD8+ T cells by suppressing the vitamin D receptor signaling.

Triclocarban (TCC) is a widely applied environmental endocrine-disrupting chemical (EDC). Similar to most of EDCs, TCC potentially damages the immunity of various species. However, whether and how TCC impacts the adaptive immunity in mammals has yet to be determined. Herein, we discovered that TCC disrupts the activation and differentiation of CD8+ T cells in primary human peripheral blood samples, purified CD8+ T cells, and in mice in vivo. Mechanistically, TCC might block the activation of the vitamin D receptor (VDR) and reduce the synthesis of cholesterol, a precursor of vitamin D, resulting in inhibition of VDR signaling due to the suppression of both its ligand and the receptor itself by TCC. Our findings elucidate the hazard and potential mechanisms of TCC in mammalian adaptive immunity and highlighted VDR as a potential therapeutic target for the immunodeficiency caused by TCC.

Vitamin D combined with whole-body vibration training for the treatment of osteo-sarcopenia: study protocol for a randomized controlled trial.

BACKGROUND: Osteo-sarcopenia (OS) has become a global public health problem and a frontier research problem, as a combination of sarcopenia (SP) and osteoporosis (OP) diseases. The clinical performances include muscle weakness, systemic bone pain, standing difficulty, even falls and fractures, etc., which seriously affect the patient's life and work. The pathological mechanism of the OS may be the abnormal metabolism which disrupts the equilibrium stability of the musculoskeletal system. Therefore, this study combined vitamin D (Vit. D) and whole-body vibration training (WBVT) to intervene in subjects of OS, aiming to evaluate the effectiveness and safety of the diagnosis and treatment protocol and to explore the efficacy mechanism. METHODS: We propose a multicenter, parallel-group clinical trial to evaluate the efficacy and safety of Vit. D combined with WBVT intervention in OS. Subjects who met the inclusion or exclusion criteria and signed the informed consent form would be randomly assigned to the WBVT group, Vit. D group, or WBVT+ Vit. D group. All subjects will be treated for 1 month and followed up after 3 and 6 months. The primary outcomes are lumbar bone mineral density (BMD) and appendicular skeletal muscle mass (ASM) measured by dual-energy X-ray absorptiometry (DXA) and handgrip strength measured by grip strength meter. Secondary outcomes include serum markers of myostatin (MSTN), irisin and bone turnover markers (BTM), SARC-CalF questionnaire, 1-min test question of osteoporosis risk, patient health status (evaluated by the SF-36 health survey), physical performance measurement that includes 5-time chair stand test, 6-m walk, and the short physical performance battery (SPPB). DISCUSSION: If Vit. D combined with WBVT can well relieve OS symptoms without adverse effects, this protocol may be a new treatment strategy for OS. After therapeutic intervention, if the serum marker MSTN/irisin is significant, both have the potential to become sensitive indicators for screening OS effective drugs and treatments, which also indicates that WBVT combined with Vit. D plays a role in improving OS by regulating MSTN/irisin. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400082269 . Registered on March 26, 2024.

Effect of vitamin D supplementation on clinical outcomes in adult patients with COVID-19: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

The COVID-19 pandemic has emerged as a major global health crisis. Vitamin D, a crucial fat-soluble vitamin, has been recommended for COVID-19 patients, though evidence of its effectiveness is inconsistent. This systematic literature review and meta-analysis aimed to evaluate the impact of vitamin D supplementation on COVID-19-related outcomes. A comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Primary outcomes included mortality and hospital length of stay, while secondary outcomes encompassed C-reactive protein (CRP), ferritin, D-dimer, hemoglobin (Hb) concentrations, and lymphocyte, neutrophil, and platelet counts. Data analysis was performed using Stata™ Version 14. A total of 16 trials were analyzed. The meta-analysis revealed that vitamin D supplementation significantly reduced hospital length of stay (mean difference = -1.16; 95% confidence interval [CI]: -2.23, -0.09; p = .033) with significant heterogeneity (I2 = 69.2%, p = .002). Subgroup analysis showed a more pronounced reduction in studies with vitamin D dosages ≤10 000 international units (IU) (mean difference = -1.27; 95% CI: -1.96, -0.57; p < .001) and in patients over 60 years old (mean difference = -1.84; 95% CI: -2.53, -1.14; p < .001). Additionally, vitamin D significantly reduced CRP concentrations in older adults (>60 years) (mean difference = -1.13; 95% CI: -2.07, -0.18; p = .019). No significant changes were found in ferritin, D-dimer, Hb concentrations, or in lymphocyte, neutrophil, and platelet counts (p > .05). In conclusion, while vitamin D supplementation did not significantly affect most COVID-19-related biomarkers, however, it reduces the length of hospital stay.

A Curious Case of Severe Recurrent Hypocalcemia.

Hypocalcemia, characterized by low blood calcium levels, can range from asymptomatic to life-threatening. Common causes include hypoparathyroidism and vitamin D deficiency (VDD). Pseudohypoparathyroidism is a rare metabolic disorder marked by resistance to parathyroid hormone (PTH). This report details a young female presenting with severe hypocalcemia, hyperphosphatemia, and elevated PTH levels. She also had an associated VDD, which complicated the clinical picture. Despite receiving intravenous calcium and oral supplementation, she required extended treatment and readmission. Genetic testing revealed a variant in the CACNA1S gene. Her condition eventually stabilized with a strict, adjusted treatment regimen. This case underscores the importance of a systematic diagnostic approach, prolonged intravenous calcium therapy, and close monitoring. Pseudohypoparathyroidism represents a rare cause of severe hypocalcemia, emphasizing the need for close monitoring and regular follow-up to achieve improved outcomes.

Vitamin D-dependent Rickets Type 1A Mimicking Pseudohypoparathyroidism in Presence of Active Tuberculosis.

Vitamin D-dependent rickets type 1A is caused by pathogenic variants of CYP27B1 gene, which is inherited in autosomal recessive pattern. These variants lead to defective 1α-hydroxylase enzymatic activity, leading to impaired renal formation of 1,25(OH)2 vitamin D. We report a case of a 16-year-old Asian male patient, with short stature and progressive bone deformity, whose biochemical parameters revealed low levels of 1,25(OH)2 vitamin D, low serum calcium levels, along with high phosphorus and raised levels of intact parathyroid hormone. These biochemical parameters suggested the diagnosis of pseudohypoparathyroidism. The patient also had concurrent extrapulmonary tuberculosis during the time of presentation to our endocrine unit. However, on molecular testing, it was revealed that the patient was harboring pathogenic variants of the CYP27B1 gene, in a compound heterozygous manner, with a novel missense mutation in exon 6 of the CYP27B1 gene, c.1136G > C (p.Arg379Thr), suggesting the diagnosis of vitamin D-dependent rickets type 1A. The cause of high phosphorus at the time of presentation, which led to a diagnostic dilemma of pseudohypoparathyroidism, was later explained by presence of active extra pulmonary tuberculosis. This report describes a case of vitamin D-dependent rickets type 1A, mimicking pseudohypoparathyroidism owing to presence of concurrent illness like extrapulmonary tuberculosis.

Predicted vitamin D levels and risk of depression in the SUN Project: A prospective cohort study.

The current study aimed to investigate the association between predicted vitamin D status and depression in a prospective Spanish cohort of university graduates. The SUN Project is a dynamic cohort study designed to investigate multiple aspects of health and lifestyle. Participants were asked to complete a comprehensive questionnaire consisting of 556 items, that included a validated food-frequency questionnaire. Participants initially free of depression were classified as incident cases if they reported a medical diagnosis of depression during follow-up. Serum vitamin D levels were predicted by a previously validated equation. Vitamin D deficiency was defined as vitamin D levels below 20 ng/mL. Cox models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). We included 15,175 Spanish university graduates [mean (SD) age: 36.9 year (11.5)] followed-up for a median of 12.7 years. Among 192,976 person-years of follow-up, we identified 753 incident cases of depression. Participants with vitamin D deficiency had a 27% higher risk of depression as compared to those with vitamin D sufficiency (HR: 1.27, 95% CI: 1.09-1.48; p = 0.002) after adjusting for potential confounders. Furthermore, a significant effect modification by female sex was observed with higher depression risks associated with vitamin D deficiency in women than in men (p for interaction = 0.034). In educated middle-aged Spanish adults, we observed a direct association between vitamin D deficiency and the risk of depression, that was stronger among women.

Modelling the influence of vitamin D and probiotic supplementation on the microbiome and immune response.

The intestinal microbiota play a critical role in human health and disease, maintaining metabolic and immune/inflammatory health, synthesising essential vitamins and amino acids and maintaining intestinal barrier integrity. The aim of this paper is to develop a mathematical model to describe the complex interactions between the microbiota, vitamin D/vitamin D receptor (VDR) pathway, epithelial barrier and immune response in order to understand better the effects of supplementation with probiotics and vitamin D. This is motivated by emerging data indicating the beneficial effects of vitamin D and probiotics individually and when combined. We propose a system of ordinary differential equations determining the time evolution of intestinal bacterial populations, concentration of the VDR:1,25(OH)2D complex in epithelial and immune cells, the epithelial barrier and the immune response. The model shows that administration of probiotics and/or vitamin D upregulates the VDR complex, which enhances barrier function and protects against intestinal inflammation. The model also suggests co-supplementation to be superior to individual supplements. We explore the effects of inflammation on the populations of commensal and pathogenic bacteria and the vitamin D/VDR pathway and discuss the value of gathering additional experimental data motivated by the modelling insights.