Vitamin D Status Research Articles

Vitamin D levels do not cause vitamin-drug interactions with dexamethasone or dasatinib in mice.

Vitamin D3 (VD3) induces intestinal CYP3A that metabolizes orally administered anti-leukemic chemotherapeutic substrates dexamethasone (DEX) and dasatinib potentially causing a vitamin-drug interaction. To determine the impact of VD3 status on systemic exposure and efficacy of these chemotherapeutic agents, we used VD3 sufficient and deficient mice and performed pharmacokinetic and anti-leukemic efficacy studies. Female C57BL/6J and hCYP3A4 transgenic VD3 deficient mice had significantly lower duodenal (but not hepatic) mouse Cyp3a11 and hCYP3A4 expression compared to VD3 sufficient mice, while duodenal expression of Mdr1a, Bcrp and Mrp4 were significantly higher in deficient mice. When the effect of VD3 status on DEX systemic exposure was compared following a discontinuous oral DEX regimen, similar to that used to treat pediatric acute lymphoblastic leukemia patients, male VD3 deficient mice had significantly higher mean plasma DEX levels (31.7 nM) compared to sufficient mice (12.43 nM) at days 3.5 but not at any later timepoints. Following a single oral gavage of DEX, there was a statistically, but not practically, significant decrease in DEX systemic exposure in VD3 deficient vs. sufficient mice. While VD3 status had no effect on oral dasatinib’s area under the plasma drug concentration-time curve, VD3 deficient male mice had significantly higher dasatinib plasma levels at t = 0.25 hr. Dexamethasone was unable to reverse the poorer survival of VD3 sufficient vs. deficient mice to BCR-ABL leukemia. In conclusion, although VD3 levels significantly altered intestinal mouse Cyp3a in female mice, DEX plasma exposure was only transiently different for orally administered DEX and dasatinib in male mice. Likewise, the small effect size of VD3 deficiency on single oral dose DEX clearance suggests that the clinical significance of VD3 levels on DEX systemic exposure are likely to be limited.

COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis.

Background: Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic. Methods: Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates versus D3 blood levels. Mortality rates from clinical studies were corrected for age, sex, and diabetes. Data were analyzed using correlation and linear regression. Results: One population study and seven clinical studies were identified, which reported D3 blood levels preinfection or on the day of hospital admission. The two independent datasets showed a negative Pearson correlation of D3 levels and mortality risk (r(17) = −0.4154, p = 0.0770/r(13) = −0.4886, p = 0.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/mL (17.4–26.8), and a significant Pearson correlation was observed (r(32) = −0.3989, p = 0.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/mL D3. Conclusions: The datasets provide strong evidence that low D3 is a predictor rather than just a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/mL to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.

A revised action spectrum for vitamin D synthesis by suberythemal UV radiation exposure in humans in vivo

Action spectra are important biological weighting functions for risk/benefit analyses of ultraviolet (UV) radiation (UVR) exposure. One important human benefit of exposure to terrestrial solar UVB radiation (∼295 to 315 nm) is the cutaneous synthesis of vitamin D3 that is initiated by the photoconversion of 7-dehydrocholesterol to previtamin D3 An action spectrum for this process that is followed by other nonphotochemical steps to achieve biologically active vitamin D3 has been established from ex vivo data and is widely used, although its validity has been questioned. We tested this action spectrum in vivo by full- or partial-body suberythemal irradiation of 75 healthy young volunteers with five different polychromatic UVR spectra on five serial occasions. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels, as the most accurate measure of vitamin D3 status, were assessed before, during, and after the exposures. These were then used to generate linear dose-response curves that were different for each UVR spectrum. It was established that the previtamin D3 action spectrum was not valid when related to the serum 25(OH)D3 levels, as weighting the UVR doses with this action spectrum did not result in a common regression line unless it was adjusted by a blue shift, with 5 nm giving the best fit. Such a blue shift is in accord with the published in vitro action spectra for vitamin D3 synthesis. Thus, calculations regarding the risk (typically erythema) versus the benefit of exposure to solar UVR based on the ex vivo previtamin D3 action spectrum require revision.

Fresh and cryopreserved semen, minerals, hormones and health characteristics in response to reciprocal combinations of vitamin D3 and 25-hydroxyvitamin D3 in the mature and prepubertal Holstein bulls' diet

The objective of this study was to evaluate the effect of supplementation of 25-hydroxyvitamin D3 (25(OH)VD3) instead of vitamin D3 on the quality and seminal plasma antioxidant indicators of fresh and cryopreserved semen, serum minerals, vitamin D3 status, hormone levels, blood biochemistry, antioxidant and immune function in different age of bulls. Thirty-two Holstein bulls (16 bulls aged 24–36 months and weighted 727 ± 99.0 kg; 16 bulls aged 12 months and weighted 332 ± 24.9 kg) randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement with 2 sources of vitamin D3 (vitamin D3 or 25(OH)VD3) fed at 300 IU/kg dry matter intake and two different age of bull (maturity or prepuberty) through a 60 day period. Bulls were tied in individual pens without access to sunlight. Bulls fed 25(OH)VD3 had greater semen concentration (P = 0.03), sperms motility (P = 0.02), viability (P < 0.001), membrane integrity (P < 0.001) and seminal plasma antioxidant capacity (P < 0.05) at fresh stage compared with bulls fed vitamin D3. In addition, 25(OH)VD3 increased sperms motility (P = 0.02) and membrane integrity (P = 0.04) in cryopreserved semen. Feeding 25(OH)VD3 increased serum total calcium (P = 0.03), total phosphorus (P < 0.001), 25(OH)VD3 (P < 0.001), 1,25-dihydroxyvitamin D3 (P < 0.001) compared with dietary vitamin D3. Feeding 25(OH)VD3 improved concentrations of serum estradiol (P = 0.02), testosterone (P = 0.003) and growth hormone (P < 0.001) and decreased serum cortisol (P = 0.01). Lower blood urea nitrogen (P = 0.005), creatinine (P = 0.02), aspartate aminotransferase (P = 0.005) and higher serum glucose (P = 0.03) were observed in the 25(OH)VD3. Dietary 25(OH)VD3 increased serum glutathione (P = 0.001) and immunoglobulin M (P = 0.03) and decreased malondialdehyde (P = 0.04) compared to those fed vitamin D3. The total antioxidant capacity was affected by interaction of age and vitamin D source (P < 0.001). In conclusion, replacing vitamin D3 with 25(OH)VD3 improved semen quality and benefited health of the mature and prepubertal Holstein bulls.

Влияние обеспечения витамином D на аутоиммунное состояние щитовидной железы

Актуальность. Несмотря на большой объем данных, связывающих витамин D с сердечно-сосудистой заболеваемостью, аутоиммунитетом, раком и практически каждой системой органов, взаимосвязь между витамином D и щитовидной железой остается менее известным аспектом в клинической практике. Причиной активного влияния витамина D является тот факт, что рецепторы витамина D (VDR) размещены практически в каждой ткани и системе органов организма. Цель: осветить данные современной литературы о влиянии витамина D и его обеспечения на аутоиммунитет щитовидной железы. Материалы и методы. Источники этого обзора были определены с помощью поиска в PubMed по статьям, опубликованным с 2015 года по сентябрь 2020 года, с использованием терминов «щитовидная железа» и «витамин D». Результаты. Зарегистрирована достоверная обратная корреляция между антителами к тиреоидной пероксидазе (АТ-ТПО) и содержанием 25-гидроксивитамина D (25(OH)D) в сыворотке крови. Наличие положительных титров АТ-ТПО более распространено у лиц с дефицитом витамина D. В большом объеме медицинской литературы приводятся результаты наблюдательных исследований, связывающих витамин D с аутоиммунитетом щитовидной железы. Также приводятся данные интервенционных исследований, подтверждающих положительное влияние витамина D на аутоиммунитет щитовидной железы. Краткосрочный прием высоких доз пероральных добавок витамина D содействует уменьшению титров АТ-ТПО. Некоторые полиморфизмы гена VDR связаны с увеличением случаев аутоиммунных расстройств щитовидной железы. Данные о том, приводит ли коррекция дефицита витамина D при аутоиммунных расстройствах щитовидной железы к снижению потребности в левотироксине или карбимазоле соответственно при гипотиреозе или болезни Грейвса, отсутствуют. Выводы. Несмотря на большой объем медицинской литературы по обсервационным исследованиям, в которых связывают витамин D с аутоиммунитетом щитовидной железы, отсутствуют важные конкретные клинические данные о влиянии дополнительного назначения витамина D на основные клинические конечные точки при этих расстройствах. Это должно быть основной сферой исследований в следующем десятилетии.

Vitamín D a nealkoholová steatóza pečene u detí

Background: Insulin resistance (IR) plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Hypovitaminosis D is associated with several diseases, including hepatic steatosis and obesity. Vitamin D (VD) affects insulin secretion and improves tissue sensitivity to insulin, suggesting that hypovitaminosis D is also associated with IR. The leptin-to-adiponectin ratio (LAR) was investigated as a new marker of IR. Aim: The aim of our study was to determine the association between the VD status, NAFLD and IR in paediatric overweight or obese patients. Methods: The study ran from January 2018 to August 2020 and included 100 subjects. We measured their anthropometric parameters, determined their basic laboratory parameters and the level of leptin and adiponectin, calculated BMI, WHR, WHtR, LAR and HOMA-IR. We measured the degree of hepatic steatosis by obtaining the hepatorenal index (HRI) using ultrasonography, and used real-time elastography to determine the elasticity of the liver parenchyma (LFI). Subsequently, we compared the groups of patients with and without hepatic steatosis and looked for correlations in relation to the level of VD and IR. Results: 4.4% of patients had a severe VD deficiency, 55% of the children had hypovitaminosis D, 28.6% had VD insufficiency and 12% of patients had sufficient VD levels. Patients with significant hepatic steatosis (HRI 1.5 and more) had the lowest level of VD (16.61 ±5.62 μg/l, P = 0.015). The level of VD in patients with hepatic steatosis was inversely correlated with waist circumference, hip circumference, height, weight, triacylglycerols, GMT, C-peptide, insulin, HOMA-IR, HRI and LFI. Leptin levels were highest in patients with hepatic pre-steatosis. LAR was highest in the group with hepatic steatosis, but we did not observe significant correlations in relation to other parameters. Conclusion: VD levels are inversely associated with the degree of hepatic steatosis in overweight or obese paediatric patients. HOMA-IR inversely correlates with VD levels and positively with LFI. The LAR value was highest in the group of patients with steatosis, although we did not find out any significant correlations in relation to VD status and HRI. Key words: vitamin D – non-alcoholic fatty liver disease – insulin resistance – leptin – adiponectin – obesity – childhood

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model.

Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression.Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated.Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group.Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.

Vitamin D Deficiency and Gender Alter Vasoconstrictor and Vasodilator Reactivity in Rat Carotid Artery.

The vitamin-D-sensitivity of the cardiovascular system may show gender differences. The prevalence of vitamin D (VD) deficiency (VDD) is high, and it alters cardiovascular function and increases the risk of stroke. Our aim was to investigate the vascular reactivity and histological changes of isolated carotid artery of female and male rats in response to different VD supplies. A total of 48 male and female Wistar rats were divided into four groups: female VD supplemented, female VDD, male VD supplemented, male VDD. The vascular function of isolated carotid artery segments was examined by wire myography. Both vitamin D deficiency and male gender resulted in increased phenylephrine-induced contraction. Acetylcholine-induced relaxation decreased in male rats independently from VD status. Inhibition of prostanoid signaling by indomethacin reduced contraction in females, but increased relaxation ability in male rats. Functional changes were accompanied by VDD and gender-specific histological alterations. Elastic fiber density was significantly decreased by VDD in female rats, but not in males. Smooth muscle actin and endothelial nitric oxide synthase levels were significantly lowered, but the thromboxane receptor was elevated in VDD males. Decreased nitrative stress was detected in both male groups independently from VD supply. The observed interactions between vitamin D deficiency and sex may play a role in the gender difference of cardiovascular risk.

Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.

Background. In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. Methods. A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. Results. The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6–27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97–1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. Conclusions. Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.

Correlation between Levels of Vitamins D3 and E in Type 2 Diabetes Mellitus: A Case-Control Study in Serdang, Selangor, Malaysia.

An overview of vitamins D3 and E suggests micronutrient deficiency contributes to type 2 diabetes mellitus (T2DM). A case-control study was conducted to determine the status of plasma vitamins D3 and E isomers amongst diabetic Malaysians. Two groups were recruited for participation, one comprising fifty diabetic subjects (DM) and one comprising fifty non-diabetic (non-DM) subjects, in order to assess their plasma vitamin D3, calcium and vitamin E status. Glycaemic status (haemoglobin A1c, HbA1c; fasting blood glucose, FBG; C-Peptide) and lipid profiles (total cholesterol, TC; triglycerides, TG; low-density lipoprotein-cholesterol, LDL-C; high-density lipoprotein-cholesterol, HDL-C) were assessed, followed by anthropometric measurements. The Mann–Whitney U-test, Kruskal–Wallis and Spearman’s correlation coefficient were used to elucidate the association between levels of plasma vitamins D3 and E and T2DM. The vitamin D3 deficiency group (<20 ng/mL) showed a significant correlation (p < 0.05) with glycaemic status (HbA1c and FBG) and lipid profiles (HDL-C, LDL and TC). Spearman’s correlation demonstrated that vitamin D3 status is strongly correlated with HDL levels (p < 0.05). Similarly, plasma total vitamin E levels >4.9 μg/mL revealed significantly different FBG, HbA1c, C-Peptide, LDL, HDL and TC levels across both groups. Moreover, family history, smoking, waist circumference and HbA1c levels demonstrated a significant association (p < 0.05) with levels of vitamins D and E but not FBG and lipid profiles. This could be because the pre-diabetic status among the non-DM group influenced the outcomes of this study.

Outcome of Infected Nonunion of Long Bones Treated by Single-Stage Bone Grafting and External Fixation at Northwest General Hospital, Peshawar, Pakistan

Background: Infected nonunion of long bones after fractures is one of the most challenging complication to treat in clinical practice. It is commonly treated by a two-stage approach; controlling infection initially and then application of external fixator and bone graft. Treatment with Ilizarov had been the gold standard but is associated with few complications. The objective of the study was to evaluate the clinical, radiological and functional outcomes of infected non-union of long bones treated with single-stage bone grafting and external fixation.Material and Methods: This retrospective study was carried out at Orthopedics Department of Northwest General Hospital, Peshawar Pakistan from 2014 to 2019. Medical records of 17 patients, aged 32 years and treated with Single-stage bone grafting and external fixation were reviewed. Nonunion included 7 humerii, 5 femurs, 3 tibias and 2 radius/ulna. Preoperative plain radiographs for any sequestrum or sclerosed bone margins and baseline investigations (like CBC, ESR, CRP and Vitamin-D status) were reviewed. All patients underwent radical debridement, reaming of intramedullary canals, external fixation and autogenous bone grafting. The outcomes evaluated were union of the bone (clinically and radiologically), resolution of infection, complication rate and number of re-intervention surgeries.Results: Among 17 patients, 10 were males and 7 were females. After treatment, mean follow-up duration was 9.414.48 months (4–18 months). None of the patients were lost to follow-up, had recurrence of infection or required further surgery. The mean duration of bone union was 8.4  4.48 months (range 3 to 17 months) and all of the patients achieved infection free union with satisfactory functional outcome.Conclusions: Single-stage bone grafting and external fixation is an effective technique in terms of resolution of infection and satisfactory bone union without any complications and can be used as an alternative to Ilizarov for treating cases of infected nonunion of long bones.

Daily full spectrum light exposure prevents food allergy-like allergic diarrhea by modulating vitamin D3 and microbiota composition

The importance of sun exposure on human health is well recognized, and a recent trend in the avoidance of sun exposure has led to the risk of missing the beneficial effects such as vitamin D3 biogenesis. Vitamin D3 insufficiency is one of the risk factors for the development of food allergies (FAs), and vitamin D3 status controls gut homeostasis by modulating the microbiota. This study aimed to explore the impact of daily full spectrum light exposure (phototherapy) on the pathogenesis of FAs. Phototherapy ameliorated allergic diarrhea and improved FA-associated vitamin D3 insufficiency and dysbiosis. Fecal microbiota transplantation (FMT) of FA donor feces induced allergic diarrhea with OVA-specific IgE elevation in naïve mice. In contrast, FMT of naïve donor feces ameliorated allergic diarrhea in established FA mice, suggesting the involvement of the microbiota composition in FA. Phototherapy is an alternative approach for the prevention of FA-like allergic diarrhea through the modulation of vitamin D3 status and microbiota composition.

Association Between Population Vitamin D Status and SARS-CoV-2 Related Serious-Critical Illness and Deaths

Background: Vitamin-D population status may have possible unappreciated consequences to the COVID-19 pandemic. Α significant association between vitamin-D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease was recently shown while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Aims: To further elucidate the possible role of vitamin D population status in the COVID-19 pandemic, we examined the associations between published representative and standardized population vitamin D data on European population vitamin D status and the Worldometer COVID-19 data. Methods: Data from the Worldometer on 26 European countries populated >4 million (M) were analyzed. Results: On 19-June-2020, linear regression found no correlation between published representative-standardized population vitamin-D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47-64-80% in serious-critical illnesses/M and of 61-82-102.4% in deaths/M, further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L. On 15-August-2020 these correlations were sustained indicating a truthful association, yet not proving causality. Weighted ANOVA was performed to evaluate serious-critical/M (R2=0.22) by the vitamin-D population status (deficient-D <50, insufficient-IN 50–62.5, mildly insufficient-MIN >62.5–75 and sufficient-S >75 nmol/L) and ANCOVA the deaths/M (R2=0.629) after controlling for life expectancy (R2=0.47). Serious-critical showed a decreasing trend (p<0.001) from population status D (p<0.001) to IN: 9.2%, p<0.001, MIN: 47.6%, p<0.044 and S: 100% (reference). For deaths/M the respective decreasing trend (p<0.001) was 62.9% from D (p<0.001) to IN (p<0.001), 65.15% to MIN (p<0.001) and 78.8% to S (p=0.041). Conclusions: Following the Endocrine Society’s expert committee recommendations, without previous testing being necessary, reaching and maintaining a serum 25(OH)D of 100–150 nmol/L (40–60 ng/ml) could be achieved by an initial supplementation with the upper tolerable daily intake doses (IU/day) for up to two months: <1yr 2000, 1-18yrs 4000 and all adults 10,000 (obese x 2–3 times more) and then with the maintenance proposed doses that do not require medical supervision, practically identical with the IOM’s upper tolerable limits: 1000 <6m, 1500 6m-1yr, 2500 1-3yrs, 3000 4-8yrs, and 4000 >8yrs, with adults and adolescents requiring 4000–5000 (obese x 2). Vitamin D may not prevent SARS-CoV-2 from spreading but may protect, without any risk of toxicity, from serious-critical illness and death from COVID-19 disease. While awaiting well-designed prospective studies, following the proposed approach, the gain for global public health and not only against SARS-CoV-2 may just prove invaluable.

Assessments of Serum 25-Hydroxy Cholecalciferol Levels in Neonates with Physiological Jaundice Candidate for Phototherapy

Background In newborns, jaundice is the most common ailment that necessitates medical treatment and hospital readmission. The aim of this study was to evaluate vitamin D3 status and investigate the role of phototherapy in the treatment of jaundice and the improvement of vitamin D3 status in neonates with physiological jaundice. Materials and Methods: This prospective research included 50 full-term neonates with physiological hyperbilirubinemia who were phototherapy candidates. They came from Egypt's Qena University Hospitals' Neonatal Intensive Care Units. Colorimetric assays of albumin and ionized calcium, as well as daily serum bilirubin and an ELISA assay of vitamin D3 were performed on the included cases before and 5 days after phototherapy, in addition to clinical assessments. Results: The findings revealed a high prevalence of vitamin D3 deficiency (96.7%), and a lower frequency of optimal and insufficient vitamin D3 status (3.3%) with lack of optimal vitamin D3 status among cases. Post-phototherapy total, direct, and indirect bilirubin levels were significantly lower than pre-therapy levels, with substantial improvement in vitamin D3 status (p <0.05 for all). Furthermore, both serum total bilirubin (r=-0.703, p <0.001) and serum indirect bilirubin (r=-0.710, p <0.001) had significantly negative associations with vitamin D3 serum levels. Conclusion Without vitamin D3 supplementation, neonates with low vitamin D and physiological jaundice who were received phototherapy had considerably improved vitamin D status 5 days later.

Vitamin-D status among Egyptian children and adolescents

Background and aim Vitamin D is essential for growth, development, and health. It works as a paracrine and autocrine signaling molecule that affects nearly all systems in the body. Vitamin-D deficiency (VDD) may be overlooked due to the variable clinical presentations. This study was conducted to assess vitamin-D status among children and adolescents, and to find out predictors for its deficiency/insufficiency among the studied groups. Patients and methods A cross-sectional analytical study was conducted on 88 patients (47 children and 41 adolescents). All participants were subjected to history, clinical examination, and estimation of serum vitamin D, alkaline phosphatase, calcium, and phosphorous levels. The patients were divided into four groups according to serum vitamin-D level: severely deficient less than 10 ng/ml, deficient 10–less than 20 ng/ml, insufficient 20–30 ng/ml, and sufficient vitamin D more than 30 ng/ml. Results VDD was prevalent in the studied group, where 58% of them showed VDD and 25% showed insufficiency. Children showed 8.6% severe deficiency, 46.8% deficiency, and 31.9% insufficiencies. The adolescents showed 21.1% severe deficiency, 48.8% deficiency, and 17.7% insufficiency. Muscle cramps were significant among children only. Multivariable linear-regression analysis revealed that BMI (P=0.01) and fast food (P=0.016) were associated with the increased risk of deficiency. Conclusions VDD and insufficiency are prevalent in Egyptian children and adolescents among both sexes. The severity of deficiency is associated with muscle cramps. Vitamin-D status was affected by increased BMI and fast-food intake.

Vitamin D and Insulin Resistance in Polycystic Ovarian Syndrome and Congenital Adrenal Hyperplasia-a Commentary and Natural Expansion

In our previous focused review, the journal emphasized Type 2 diabetes (T2DM), excluding intimately associated disorders that should be considered integral components of the insulin resistance (IR) syndrome e.g., polycystic ovarian syndrome (PCOS), congenital adrenal hyperplasia (CAH), and gout [1]. In this expansion I’ll highlight potential roles of vitamin D in PCOS and CAH. Before discussing these areas, I shall briefly summarize key points from our review: • Low vitamin D levels are strongly and independently associated with IR, impaired insulin secretion, and higher incident T2DM risk, especially in people already at increased risk. • In several species the association of hypovitaminosis D with incident T2DM risk is apparently causal. • Causality of hypovitaminosis D in incident T2DM in humans is not established due to conflicting results of interventional trials and mendelian randomization studies on both incidence and glycemic control indices. Interventional trials varied idely in terms of dosage, preparations used, duration, and demographics. • Low vitamin D status (VDS) is strongly correlated with risk for several micro- and macrovascular T2DM complications including: peripheral neuropathy, erectile dysfunction (ED), retinopathy, kidney disease, and all-cause mortality, but not gastroparesis. The association between serum vitamin D level and diabetic cardiac neuropathy risk is U-shaped. • Interventional studies in people with diabetic kidney disease reported significant therapeutic benefit when combining vitamin D analogues with renin angiotensin aldosterone system (RAAS) inhibitors. Causality of low VDS in T2DM omplications, except for renal damage, remains unconfirmed. • In people with prediabetes (unselected for hypovitaminosis D), vitamin D3 supplementation at 4000 IU/ day did not significantly lower risk of incident diabetes in the much much-anticipated D2d trial [2].

Crosstalk between vitamin D axis, inflammation and host immunity mechanisms: A prospective study.

Tuberculosis (TB) remains a public health burden, after many years at attempts for its eradication. Vitamin D (VD) status has been suggested to be related to TB susceptibility because it has the ability to regulate multiple axes of the innate and adaptive host immune response. VD mediates cathelicidin (LL-37) synthesis, a cationic bactericidal peptide, through the expression of vitamin D receptor (VDR). Host innate defense mechanisms include autophagy and apoptosis of alveolar macrophages. The present study aimed to assess the relationship between VD status, inflammation and host defense mechanisms before and after two months of first-line anti-TB pharmacotherapy. The study included newly diagnosed individuals with pulmonary TB without co-morbidities (HIV infection, diabetes, cancer) and without VD supplementation or other therapies interfering with VD serum levels. We measured serum levels of 25-hydroxyvitamin D (25-(OH)-D), the major circulating form of vitamin D, VDR, LL-37, beclin-1 (an autophagy marker) and M30 (an apoptosis biomarker) before and after two months of anti-TB treatment. Individuals presented lower levels of 25-(OH)-D before receiving first-line anti-TB treatment (T0) in comparison with its plasmatic levels after two-months of therapy (T2). At T2, patients were divided in two subgroups according the results of sputum-culture conversion. After two-months of therapy, decreased values of LL-37, beclin-1 and M30 were observed in the culture-negative patients compared to the culture-positive patients. Control of anti-TB treatment outcome could be improved by appraisal of VD status and host defense mechanisms such as autophagy and apoptosis.

Carbon cloth-based immunosensor for detection of 25-hydroxy vitamin D3.

Vitamin D (VD) deficiency is a global health concern due to its serious health impacts, and at present, the monitoring of VD status is expensive. Here, a novel immunosensor for sensitive and label-free detection of 25-hydroxy vitamin D3 (25VD3) is reported. Nanostructured cerium(IV) oxide (nCeO2) was anchored onto carbon cloth (CC) via electrophoretic deposition to fabricate a nanoplatform (nCeO2/CC). Subsequently, bioactive molecules (anti-25VD3 and BSA) were introduced to fabricate the nanobioplatform BSA/anti-25VD3/nCeO2/CC as an immunosensor. The analytical performance of the developed immunosensor was studied towards 25VD3 detection. The immunosensor provides a broad linear range of 1-200 ng mL-1, high sensitivity of 2.08 μA ng−1 mL cm−2, a detection limit of 4.63 ng mL−1, and a response time of 15 min, which is better than that of previous reports. The biosensor exhibited high selectivity, good reproducibility, and excellent stability for about 45 days. The potential application of the proposed immunosensor was observed for real serum samples towards 25VD3 detection that demonstrated a high correlation with the conventional enzyme-linked immunosorbent assay. Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1007/s00604-021-04751-y.

Level of Vitamin D3 in Women who have Uterine Fibroids

Background: Uterine fibroid are the most common benign pelvic tumors among women in reproductive age group that has multifactorial pathogenesis. Vitamin D has become one of the key elements of modern theories of uterine fibroid pathogenesis.Aim: This work aim to investigate the association between vitamin D3 status and uterine leiomyoma.Materials and Methods: This observational case control study was conducted on 150 women in their reproductive age (20-45 years) at Ain-Shams University Hospital in the department of Obstetrics and Gynecology from March 2019 till August 2019. They were divided into two groups. 75 women with at least one uterine fibroid detected by transvaginal ultrasound to be considered as case group and the other 75 women with normal uterine examination and transvaginal ultrasound representing the control group.Results: In the current study, there was a statistically significant difference between cases group and control group as regard 25(OH) D level (P=0.001), the mean vitamin D level in the case group was 13.39±7.93 ng/ml and in the control group was 21.71±8.95 ng/ml. There was no statistical significant difference between the size of fibroid and vitamin D level. The mean serum vitamin D level in patients with small fibroid (size less than 5 cm) was 14.11ng/ml and 12.76 ng/ml for women with large fibroid (size more than 5 cm) (P=0.457).Conclusion: There is a significant association between vitamin D deficiency in reproductive age women and uterine fibroid. There is no correlation between vitamin D level and the size of uterine fibroid

Effectiveness of eight-week zinc supplementation on vitamin D3 status and leptin levels in a population of postmenopausal women: a double-blind randomized trial

BackgroundThe menopausal period is characterized by hormonal imbalance related to the alteration of parameters involved in lipid metabolism. In addition, menopause increases the risk of deficiencies of key vitamins and minerals such as vitamin D and zinc in such women. The present study investigates the influence of zinc supplementation on the status of vitamin D3 and other lipid parameters in postmenopausal women. MethodsFifty-one healthy postmenopausal women aged 44–76 years from the province of Granada (Spain) were divided into two groups (placebo and zinc) of 25 and 26 women, respectively. The zinc group was supplemented with 50 mg/day of zinc for 8 weeks. Nutrient intake assessment was performed by means of a 24 -h reminder. Zinc was determined by flame atomic absorption spectrophotometry. Vitamin D was analyzed by liquid chromatography - tandem mass spectrometry. Leptin was determined by enzyme immunoassay. ResultsZinc supplementation improved the initial vitamin D3 status of the postmenopausal population (p = 0.049). Plasma levels of 25−OH-D3 increased significantly after Zn supplementation in women with lower age at menopause (p = 0.045). Both intake and plasma zinc levels were inversely correlated to serum leptin levels (p = 0.044 and p = 0.033, respectively), being significantly lower in lower age at menopause (p < 0.001). ConclusionZinc supplementation improved vitamin D3 status and was associated to low leptin levels in the postmenopausal women of the study.