VitD Group Research Articles

TO STUDY THE EFFECT OF TADALAFIL IN IMPROVING URODYNAMIC PARAMETERS IN SPINAL CORD INJURY PATIENTS: A RANDOMIZED CONTROLLED TRIAL

Objectives: The aim of the study was to compare the effect of single dose Tadalafil 20 mg 2 h after administration on Urodynamic study (UDS) parameters and comparison with calcium+vit-D3 (control) in spinal cord injury (SCI). Methods: Sixty-six SCI individuals with lower urinary tract symptoms (LUTS) and upper motor neuron bladder were randomized into Tadalafil group (n=33) and calcium+vitD3 group (n=33). UDS was done and parameters (maximum detrusor filling pressure [MDFP], maximum bladder capacity, and bladder compliance) were recorded at baseline and 2 h after administration of respective drugs in both groups and comparison was done. Results: Statistically significant improvement in mean MDFP from 24.42±6.75 to 21.12±5.72 cm H2O (p < 0.001), mean maximum bladder capacity from 263.94±108.48 to 287.67±112.71 mL (p<0.001), and mean bladder compliance from 11.07±4.31 to 13.94±5.13 mL/cm H2O (p<0.001) was observed in Tadalafil group whereas in calcium+vit-D3 group, no significant improvement was observed. When we compared difference of mean of MDFP, bladder capacity, and bladder compliance between Tadalafil and calcium+vitD3 group, significant improvement (p<0.001) in Tadalafil group was noted as compared to calcium+vitD3 group. Conclusions: Single dose of oral Tadalafil 20 mg has shown significant improvement in MDFP, bladder capacity, and bladder compliance in SCI individuals with LUTS as compared to control.

Quantitative 1H Magnetic Resonance Imaging on Normal and Pathologic Rat Bones by Solid-State 1H ZTE Sequence with Water and Fat Suppression.

Osteoporosis (OP) and osteomalacia (OM) are metabolic bone diseases characterized by mineral and matrix density changes. Quantitative bone matrix density differentiates OM from OP. MRI is a noninvasive and nonionizing imaging technique that can measure bone matrix density quantitatively in ex vivo and in vivo. To demonstrate water + fat suppressed 1H MRI to compute bone matrix density in ex vivo rat femurs in the preclinical model. Prospective. Fifteen skeletally mature female Sprague-Dawley rats, five per group (normal, ovariectomized (OVX), partially nephrectomized/vitamin D (Vit-D) deficient), 250-275 g, ∼15 weeks old. 7T, zero echo time sequence with water + fat (VAPOR) suppression capability, μCT imaging, and gravimetric measurements. Cortical and trabecular bone segments from normal and disease models were scanned in the same coil along with a dual calibration phantom for quantitative assessment of bone matrix density. ANOVA and linear regression were used for data analysis, with P-values <0.05 statistically significant. The MRI-derived three-density PEG pellet densities have a strong linear relationship with physical density measures (r2 = 0.99). The Vit-D group had the lowest bone matrix density for cortical bone (0.47 ± 0.16 g cm-3), whereas the OVX had the lowest bone matrix density for trabecular bone (0.26 ± 0.04 g cm-3). Gravimetry results confirmed these MRI-based observations for Vit-D cortical (0.51 ± 0.07 g cm-3) and OVX trabecular (0.26 ± 0.03 g cm-3) bone groups. Rat femur images were obtained using a modified pulse sequence and a custom-designed double-tuned (1H/31P) transmit-receive solenoid-coil on a 7T preclinical MRI scanner. Phantom experiments confirmed a strong linear relation between MRI-derived and physical density measures and quantitative bone matrix densities in rat femurs from normal, OVX, and Vit-D deficient/partially nephrectomized animals were computed. 2 TECHNICAL EFFICACY: Stage 2.

Selective estrogen receptor modulators (SERMs) with vitamin D composite agent can prevent fracture better than SERMs treatment: based on the National Health Claims Database 2017-2019.

This study compared the potential of the composite agent of selective estrogen receptor modulators (SERMs) and vitamin D (SERM + VitD) with that of SERMs-only for fracture prevention and mortality reduction in women aged ≥ 50years. The incidence of osteoporotic fracture (fractures of the vertebrae, hip, wrist, or humerus) and all-cause death after treatment with SERM + VitD and SERMs were characterized using the Korean National Health Insurance Service database 2017-2019. The participants were divided into two groups (SERM + VitD vs SERMs). After exclusion and propensity score matching, 2,885 patients from each group were included in the analysis. Fracture incidence was compared between groups. Kaplan-Meier curves were used to compare mortality. Cox proportional hazards regression analysis was used to compare the risks of fracture occurrence and mortality between the groups. The incidence rate (138.6/10,000 vs. 192.4/10,000 person-years), and risk of osteoporotic fractures (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.024) were lower in the SERM + VitD group than in the SERMs group. Analysis for specific fractures showed a lower hazard of hip fracture in the SERM + VitD group (HR, 0.25; 95% CI, 0.09-0.71; p = 0.009). No difference was observed between the groups regarding mortality. The risk of osteoporotic fractures, especially hip fractures, was lower in the SERM + VitD group than in the SERMs group. Therefore, the composite agent of SERMs and vitamin D can be considered as a viable option for postmenopausal women with a relatively low fracture risk.

Effects of electro-scalp acupuncture on inflammatory response and microglial polarization in the ischemic cortex of rats with ischemic stroke

To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1β, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke. Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D3 (1,25-VitD3) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1β, and IL-10 in the ischemic cortex. Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD3 group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD3 group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1β, and IL-10 in the ischemic cortex (P<0.01, P<0.05). ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.

A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency-Results from a prospective randomized clinical trial.

Vitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied. We aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults. In study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2. In study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported. Our results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions. clinicaltrials.gov, identifier: NCT05706259.

Additive Effects of Exercise and Vitamin D Supplementation (with and without Calcium) on Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis.

Exercise is a recognized component in the prevention and therapy of osteoporosis. The present systematic review and meta-analysis aimed to determine the effect of Vitamin D (Vit-D) added to exercise versus exercise alone on bone mineral density (BMD) at the lumbar spine (LS) or hip in older adults. A systematic review based on six literature databases according to PRISMA included (a) exercise trials, with an exercise (EX) and a combined exercise + Vit-D group (EX + Vit-D), (b) intervention ≥ 6 months, and (c) BMD assessments at LS or hip. Effects sizes (MD) and 95%-confidence intervals (95%-CI) were calculated using a random-effect model that includes the inverse heterogeneity model (IVhet). Five studies with 281 participants in the EX and 279 participants in the EX + Vit-D were included. No significant differences between EX versus EX + Vit-D were observed for BMD-LS (MD: 0.002, 95%-CI: -0.033 to 0.036) or BMD-hip (MD: 0.003, 95%-CI: -0.035 to 0.042). Heterogeneity between the trial results was moderate-substantial for LS (I2 = 0%) and moderate for hip-BMD (I2 = 35%). The funnel plot analysis suggests evidence for a publication/small study bias for BMD-LS and hip results. In summary, this present systematic review and meta-analysis were unable to determine significant positive interaction of exercise and Vit-D on LS- or hip-BMD. We predominately attribute this finding to (1) the less bone-specific exercise protocols of at least two of the five studies and (2) the inclusion criteria of the studies that did not consequently focus on Vit-D deficiency. This issue should be addressed in more detail by adequately powered exercise trials with promising exercise protocols and participants with Vit-D deficiency. This trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42022309813.

P-332 Standard-dose Vitamin D supplementation as an effective and safe non-hormonal treatment for the prevention of uterine fibroid growth in reproductive-age women: A pilot study

Abstract Study question Could low-dose vitamin D supplementation prevent uterine fibroid growth in reproductive-age women with hypovitaminosis D? Summary answer Six-month low-dose Vitamin D supplementation (≈ 1500 IU/day) in patients with hypovitaminosis D significantly decrease uterine fibroid growth compared to patients not receiving supplementation. What is known already Uterine fibroids (UF) are the most common tumor of the reproductive tract, affecting up to 77% of reproductive-age women. Due to the association between hypovitaminosis D and UF, several studies have evaluated the effect of a high Vitamin D (VitD) dose (3500-8500 IU/day) on UF size, proposing VitD supplementation as a therapeutic option. However, the standard dose recommended for VitD deficiency (800-2000 IU/day) has not been assessed. We aimed to evaluate if the restoration of normal serum levels of 25(OH)D by standard VitD dose in patients with UF and hypovitaminosis D can avoid the growth of UF in reproductive-age women. Study design, size, duration Ambispective observational study carried out at La Fe University Hospital. In the study group, patients (n = 6) were prospectively recruited from 2019 to 2022. Clinical data from the control group (n = 14) was collected retrospectively from 2016 to 2018. The study was approved by the autonomous government ethics committee (CAEPO; Spain) (ISS-COL-2028-01). Participants/materials, setting, methods Twenty women under 45 years old with uterine fibroids and hypovitaminosis D [25(OH)D levels &amp;lt; 30 ng/mL] were included. The study group received VitD for 6 months (25000 IU/2 weeks). Study outcomes: UF size determined by ultrasound, serum levels of 25(OH)D, Calcium, AST, ALT, Bilirubin and Creatinine were determined at 0, 3 and 6 months. Data from control group was obtained retrospectively from patients diagnosed with UF and hypovitaminosis D without VitD supplementation. Main results and the role of chance At the beginning of the treatment, no significant differences were found between patients included in the control and VitD group regarding age (40.57 ± 2.76 vs. 38.73 ± 4.92), BMI (23.6 5 ± 2.96 vs. 25.36 ± 4.25), VitD levels (18.57 ± 7.47 vs. 23.37 ± 37.29) and UF size (67.07 ± 20.68 vs. 56.17 ± 12.56). After treatment, VitD levels significantly increased in the study group (23.37 ± 37.29 vs. 37.02 ± 6.35, p = 0.001). Regarding size, the control group showed a significant UF growth of 17.3 ± 14.31% (p = 0.0005) after 6 months, while in patients treated with VitD UF size slightly decreased (-5.84 ± 2.14 %, p = 0.15). In addition, when comparing % of UF growth in both groups at the end of the treatment, UF growth was significantly lower in patients treated with VitD compared to control (-5.84% vs. 17.3%, p = 0.0002). There were no significant changes in serum parameters analyzed in the study group after 6 months of VitD supplementation: Calcium (9.15 vs. 9.20 mg/dL), AST (15.83 vs. 13 U/L), ALT (17.83 vs. 16 U/L), Bilirubin (0.42 vs. 0.48 mg/dL) and Creatinine (0.69 vs. 0.67 mg/dL). Limitations, reasons for caution This is an observational study and thus possible confounders cannot be completely excluded. More data are needed to draw firm conclusions and it will be critical to increase the sample size to check if the results observed in this work remain in the general population. Wider implications of the findings To our knowledge, this is the first study evaluating the effect of standard VitD dose on UF growth in reproductive-age women with hypovitaminosis D. Our results suggest that low-dose VitD could be a safe non-hormonal therapeutic option in the management of UF in patients willing to preserve their fertility. Trial registration number NCT03991078

Effects of Probiotics and Vitamin D3 Supplementation on Sports Performance Markers in Male Mixed Martial Arts Athletes: A Randomized Trial

BackgroundStrategies targeted at the intestine microbiome seem to be beneficial for professional athletes. The gut–muscle axis is associated with the inflammatory state, glucose metabolism, mitochondrial function, and central nervous system health. All these mechanisms may affect maximal oxygen uptake, muscle strength, and training adaptation. Moreover, the positive effect of certain bacterial strains may be enhanced by vitamin D. Thus, this study aimed to assess and compare the level of selected markers of sports performance of mixed martial arts (MMA) athletes supplemented with vitamin D3 or probiotics combined with vitamin D3.MethodsA 4-week randomized double-blind placebo-controlled clinical trial was conducted with 23 MMA male athletes assigned to the vitamin D3 group (Vit D; n = 12) or probiotics + vitamin D3 group (PRO + VitD; n = 11). Repeated measures of the creatine kinase level, lactate utilization ratio, and anaerobic performance were conducted.ResultsAfter 4 weeks of supplementation, we found lower lactate concentrations 60 min after the acute sprint interval in the PRO + VitD group when compared to the Vit D group (4.73 ± 1.62 and 5.88 ± 1.55 mmol/L; p < 0.05). In addition, the intervention improved the total work (232.00 ± 14.06 and 240.72 ± 13.38 J kg−1; p < 0.05), and mean power following the anaerobic exercise protocol (7.73 ± 0.47 and 8.02 ± 0.45 W kg−1; p < 0.05) only in the PRO + VitD group. Moreover, there was an improvement in the lactate utilization ratio in the PRO + VitD group compared with the Vit D group as shown by the percentage of T60/T3 ratio (73.6 ± 6.9 and 65.1 ± 9.9%, respectively; p < 0.05). We also observed elevated serum 25(OH)D3 concentrations after acute sprint interval exercise in both groups, however, there were no significant differences between the groups.ConclusionFour weeks of combined probiotic and vitamin D3 supplementation enhanced lactate utilization and beneficially affected anaerobic performance in MMA athletes.

Long term dietary vitamin D3 supplementation impacts both microbicidal and inflammatory responses to ex-vivo Mycobacterium bovis BCG challenge in dairy calves

Vitamin D deficiency (VDD) is associated with enhanced susceptibility to multiple respiratory diseases in humans, including tuberculosis. However, the consequences of VDD for disease susceptibility in calves are unknown. Previously we developed a model to drive divergent circulating 25OHD concentrations in cattle, where animals were supplemented with vitamin D3 (vit D3) from birth to 7 months of age. Calves in the control group (Ctl) received a diet containing a standard vit D3 concentration, whereas the vit D group (VitD) received a diet with the highest vit D3 concentration allowed under EU guidelines. Here, we assessed the microbicidal activity and immunoregulatory effect of divergent 25OHD circulating levels to Mycobacterium bovis BCG challenge ex-vivo. Blood samples from Ctl and VitD calves were taken at 1-, 3- and 7-months of age. 25OHD concentrations were significantly different at 7 months (but not at 1 or 3 months) with animals from the VitD group having higher serum levels. Differences in microbicidal activity followed the same pattern, with no significant differences observed at 1 and 3 months, but at 7 months a significant increase in the percentage of bacteria killed was detected. Furthermore, analysis of the reactive oxygen species (ROS) and nitric oxide (NO) in serum showed a higher production of ROS and NO in VitD-supplemented calves. In contrast, serum concentrations of IL-1β and IL-8 were significantly lower. A similar anti-inflammatory profile was observed after gene expression analysis, with a significant downregulation of a cluster of genes including IL1B, IL1R1, CXCL1, CXCL2, CXCL5, MMP9 and COX2 and an upregulation of CXCR1, CX3CR1 and NCF1, in VitD calves after BCG challenge relative to Ctl animals. Collectively, these results suggest that dietary vit D3 boosts antimicrobial and innate immune responses and thereby could improve host anti-mycobacterial immunity.

A prospective randomized controlled study of Mycobacterium Indicus Pranii vaccine, Measles Mumps Rubella vaccine and Vitamin D3 in extragenital cutaneous warts.

Interventional, prospective, four arm randomized control. Outpatient department, Department of Dermatology, Venereology and Leprology, AIIMS Jodhpur (Rajasthan), India. Two hundred patients. The intervention administered in the groups were normal saline (A), vitamin D3 (B), MIP (C), and MMR (D). The injections were given into the largest wart at 2-weekly intervals until complete clearance or for a maximum of seven sittings. Post-treatment clearance of the injected wart and the distant wart was compared on the basis of change in wart number, percentage clearance, and mean time to complete clearance. Side effects were recorded. A total of 197 patients were recruited. The mean percentage improvement in the injected and non-injected warts was 68.4% and 66.8%, respectively. Intention to treat analysis (ITT) showed that complete clearance of lesions in injected wart occurred in placebo, vit D3 , MMR, and MIP arms in 64%, 66%, 58%, and 55% patients, respectively (p > 0.05), while in the non-injected warts in 62%, 64%, 52%, and 53%, respectively (p > 0.05). The mean time to achieve complete clearance of wart was fastest in MIP at 7.1 weeks followed by MMR at 7.2 weeks, VIT D3 at 7.4 weeks and in placebo group 7.8 weeks (p > 0.05). Side effects noted were fever, pain, erythema, and swelling which was highest in VIT D3 group (p < 0.05). The efficacy of immunotherapies was comparable to placebo with minimal side effects.

Effect of Vitamin D on YKL-40: Rat Hypercholesterolemia Model.

YKL-40 is considered to be associated with cardiovascular disease (CVD). In this study, the effect of serum 25(OH) vitamin D [25(OH)VitD] differences between groups on YKL-40 was evaluated on a hypercholesterolemia rat model. Thirty-two male rats (wistar albino) were equally divided into 4 groups. The first group was the control group; the second group was high-cholesterol (H-CH) adequate vitamin D (VitD) group (H-AdeVD). The third group was the H-CH deficient VitD group (H-DefVD), and the last group was designed with the H-CH supplement VitD (H-SupVD). The feeding process consisted of 2 stages. At the first stage (5 months), the H-DefVD group was fed on VitD deficient chow, while the other groups (control, H-AdeVD, H-SupVD) were fed on standard chow. At the second stage (3 months), the H-AdeVD and the H-SupVD groups were fed on the H-CH chow, whereas the H-DefVD group was fed on the H-CH-VitD deficient chow. Moreover, the H-SupVD group was given 100 IU/kg/day VitD along with the H-CH chow. Compared with the control group, interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and YKL-40 values in the H-DefVD groups increased significantly (p<0.001, p<0.001, p=0.009, p=0.005; sequentially). It can be concluded that VitD can suppress the YKL-40, thus, it will prevent CVD development in rat. Therefore, further clinical studies related with human will reveal the effect of VitD and YKL-40 on CVD development.

Effect of acute or subchronic stress on T cell response in peripheral blood: Regulatory role of vitamin D

The immune response, orchestrated by helper (Th1, Th2, and Th17) and regulatory (Treg) T cells, is modulated by stress and Vitamin D (Vit-D). Although the immunomodulatory functions of both are known, their specific roles on Th cells have not been fully clarified, yet. On this background, we aimed to investigate the effect of acute or subchronic stress on the distribution of peripheral T lymphocytes, as well as the immunomodulatory role of Vit-D. Young adult male, Swiss-albino mice (30–40g) were allocated to the control, acute stress (AS), subchronic stress (ChS), control+Vit-D, AS+Vit-D, and ChS+Vit-D groups (n=11/group). The combined cold (2-h at 4°C)-immobilization (2-h in a restrainer) stress protocol was employed as one day in AS groups and five consecutive days in ChS groups. Vit-D (2μg/kg ip) was applied every other day, until the end of the protocol. Serum cortisol, Vit-D and cytokine levels (IL-4, IFN-γ, and IL-17A) were measured, and lymphocytes from blood samples were subtyped by flow-cytometry. Stress exposure caused differential Th and Treg responses, acute stress shifting the response to Th1, and subchronic stress shifting the response to Th2. Th17 and Treg cells were lower in subchronic stress exposed mice. These changes became comparable to control values in Vit-D treated groups. The T cell response, crucial for immune system function, differs on the basis of stress exposure as such the Vit-D treatment. The tolerogenic profile created by Vit-D should be considered for management of stress-related diseases. Our results may help to provide a better understanding of disease pathogenesis.

Synergistic Anti-Cancer Activity of the Combination of 1,25-Dihydroxyvitamin D3 and Retinoic Acid in U937 Cell Line.

MicroRNA is a form of non-coding RNAs that able to regulate gene expression. miR-424 is one of the members of the regulatory family, which plays an important role in the proliferation and differentiation of myeloid cells. Epigenetic changes can change the level of miR-424 under environmental factors. Therefore, the level of expression of miR-424 in U937 cells of the myeloid line was evaluated in this research under the influence of vitamin D3 (VitD3) and retinoic acid (RA). In this study, U937 cells were cultured in the presence of VitD3, and RA to evaluate cell proliferation, viability via the trypan blue exclusion test, and expression level of miR-424 by real-time PCR at specific times. Cell proliferation has shown a significant decrease in the RA group versus other groups during incubation times (P < 0.05). In VitD3 group, there was a significant increase in cell proliferation after 24- and 48-hours incubation periods versus other groups. In the VitD3 and RA groups, the increase of cell proliferation caused the downregulation of miR-424. In addition, the upregulation of VitD3 group and downregulation of the RA group were significant versus the control group (P < 0.05). We concluded that the expression level of miR-424 was critically affected in the dose- and time-dependent of RA and VitD3 treatment in the U937 cell line. Treatment with VitD3 decreased the expression of miR-424 and RA treatment increase miR-424 expression level in physiological doses.

Effect of the administration of different forms of vitamin D on central blood pressure and aortic stiffness, and its implication in the reduction of albuminuria in chronic kidney disease

Background and objectivesVitamin D (vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. Patients and methodsWe studied in 97 patients with CKD stages 3–4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3–4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7±2 months. ResultsIn the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2–12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43–876) mg/g (median (interquartile range)), with no differences between the groups.Serum calcium and phosphorus increased significantly in those treated with cholecal-ciferol (native vitD) and paricalcitol (active vitD). Parathormone (PTH) values ​​decreased in those treated with paricalcitol. bPP and cPP decreased in all groups treated with native and active vitD. No significant changes in bPP and cPP were observed in the control group.Vpc-f did not change significantly in any of the groups, although the variation was quantitatively greater in group 3 (11.2±2 vs. 10.7±1.6 (p:0.06)). No differences were observed in the changes in Vpc-f between the groups when adjusted to the baseline values ​​of estimated glomerular filtration rate (eGFR), albuminuria, PTH, vitD, brachial and central blood pressure parameters, and their changes with treatment.Those who received treatment with native and active vitD presented a significant decrease in albuminuria of 17% (group 2) and 21% (group 3) compared to a 16% increase in the untreated group (group 1) (p:0 .01). A decrease in albuminuria ≥30% was observed more frequently in the groups treated with some form of vitD (group 2: 23%; group 3: 45%) than in the control group (13%) (p:0.03). The decrease in albuminuria observed in the groups treated with any of the forms of vitD did not vary when the baseline values ​​of the biochemical parameters of phosphorus-calcium metabolism, those of arterial function (PPb, PPc, Vpc-f) or its modifications were introduced as covariates. There was no significant correlation between changes in Vpc-f and albuminuria. In logistic regression, changes in arterial function parameters were also not explanatory for the ≥30% decrease in albuminuria. ConclusionsIn patients with CKD stages 3–4, treated with RAS blockers and with residual albuminuria, the administration of or paricalcitol reduces brachial and aortic pulse pressures, and albuminuria. The decrease in albuminuria does not seem to be mediated, at least not decisively, by changes in central hemodynamics or aortic stiffness.

Efficacy of vitamin D supplementation on child and adolescent overweight/obesity: a systematic review and meta-analysis of randomized controlled trials.

The global prevalence of overweight and obesity in children and adolescents has been increasing. Child and adolescent overweight/obesity has been demonstrated to be partially associated with vitamin D deficiency. This systematic review and meta-analysis aims to assess the efficacy of vitamin D supplementation on child and adolescent overweight/obesity. PubMed, Embase, Cochrane Library, and Web of science were searched from inception to June 20th, 2022. Randomized controlled trials (RCTs) assessing the efficacy of vitamin D on child and adolescent overweight/obesity were included. The Cochrane bias risk assessment tool was used to assess the bias risk of included studies, and subgroup analysis was conducted based on different administration dosages. All data-analyses were performed using R 4.2.1. There were 1502 articles retrieved, and 10 eligible studies were finally included, with a total of 595 participants. Meta-analysis showed no differences in LDL, TC, TG, BMI, ALP, Ca, and PTH between vitamin-D (Vit-D) group and placebo, while Vit-D group resulted in improved HOMA-IR[WMD = - 0.348, 95%CI (- 0.477, - 0.219), p = 0.26]. Subgroup-analysis showed no significant difference in the increase of 25-(OH)-D between subgroups (p = 0.39), whereas the serum 25-(OH)-D level was increased under different Vit-D doses [WMD = 6.973, 95%CI (3.072, 10.873)]. High daily dose (≥ 4000IU/d) of Vit-D might decrease CRP and increase HDL levels. Conclusion: High dose of Vit-D supplementation (over 4000IU/d) would reduce several cardiometabolic risk indicators and improve insulin resistance. More high-quality and large-scale RCTs are needed to provide more robust evidence. What is Known: •Vit-D deficiency is common in overweight/obesity (OW/OB) children and adolescents. • Previous randomized studies on the benefit of Vit-D supplementation to OW/OB children and adolescents are inconsistent. What is New: •This is the first meta-analysis conducted to assess the efficacy of Vit-D supplementation on child and adolescent OW/OB. • High dose of Vit-D supplementation is beneficial to cardiovascular metabolism, and improve insulin resistance on child and adolescent OW/OB.

Effect of vitamin D on bone morphometry and stability of orthodontic tooth movement in rats

Vitamin D (VitD) maintains bone health and may influence orthodontic tooth movement (OTM). The objective was to evaluate the VitD effect on bone morphometry and the rate and stability of OTM. Thirty-two male Sprague Dawley rats were assigned into 2 experimental groups, treated with VitD by gavage (systemic) or injection (local), and 2 respective control groups treated with phosphate-buffered saline for 47 days. OTM was performed for 7 days with a nickel-titanium coil bonded between the maxillary first molar and incisors. Microcomputed tomography scanning was performed at 5 time points: before administration of VitD, the start of OTM, the end of OTM, 7 days post-OTM, and 30 days post-OTM. The rate and stability of OTM were assessed. Bone morphometry was analyzed by bone mineral density, bone volume/total volume, total porosity, trabecular pattern factor, structure model index, and connectivity density. The systemic VitD group showed a lower OTM rate and a lower relapse than the control (P<0.05). It also demonstrated increased bone mineral density, bone volume/total volume, and a decrease in total porosity (P<0.05). The bone structure appeared more fragmented and presented a lower connectivity density than the control (P<0.05). No statistical difference was found between VitD local administration and the other groups for the rate and stability of OTM or bone morphometry. The systemic administration of VitD caused a decrease in the OTM rate by generating more bone resistance but also contributed to a lower relapse with a higher bone mineral density.

Vitamin D supplementation at different doses affects the vagal component of the baroreceptor reflex and the Bezold-Jarisch reflex in eutrophic rats.

Vitamin D has been used to prevent several diseases. The 1,25 (OH) 2D3, the active form of vitamin D (VitD), participates in calcium metabolism, and has direct action in various tissues as those of the cardiovascular system binding to the VitD receptor. We investigated whether the supplementation with different doses of VitD affect or not the resting mean arterial pressure (MAP) and heart rate (HR), heart rate variability (HRV), baroreceptor and Bezold-Jarisch reflexes in eutrophic rats. Adult male Wistar rats were randomly assigned in 4 groups (Control, VitD 15, 250, and 3,750 IU/day, n = 6/group). After 3 days of supplementation, MAP and HR recordings were performed in freely moving rats. Baseline (resting) MAP, HR, and HRV showed no difference in Control and VitD groups. Nevertheless, the index of the baroreceptor reflex showed that the bradycardic component of the baroreflex evoked by a pressor dose of phenylephrine (3 μg/kg of b.w.) in bolus injection had a significant increase in rats supplemented with VitD 15 IU/day for 3 days compared to Control animals. No difference was observed in the index of the baroreflex evaluated with phenylephrine in rats treated with VitD 250 and 3,750 IU/day for 3 days in comparison to the Control group. The index of the baroreceptor reflex evaluated with an intravenous bolus injection of a depressor dose of sodium nitroprusside (30 μg/kg of b.w.) showed that the tachycardic component of the baroreflex is not different comparing all groups supplemented with VitD and Control animals. Rats supplemented with VitD 15 IU/day presented exaggerated bradycardic responses to the intravenous injection of phenylbiguanide (PBG, 5 μg/kg of b.w.) compared to Control animals, despite the similar hypotension in both groups. Higher doses of supplementation of VitD (250 and 3,750 IU/day for 3 days) abolished the hypotension and bradycardia induced by PBG. The findings suggest that the supplementation with different doses of VitD (15, 250, and 3,750 IU/day) for 3 days did not affect the resting arterial pressure, heart rate and autonomic modulation on the heart in rats. Despite that, the supplementation with a low dose of VitD (15 IU/day for 3 days) improved the sensitivity of the bradycardic component of the baroreflex, whereas higher doses of supplementation with VitD (250 and 3,750 IU/day for 3 days) were unable to cause such effect. In addition, the Bezold-Jarisch reflex responses can be affected regardless the dose of VitD (15, 250 or 3,750 IU/day) supplementation for 3 days in rats.

A randomized, double-blind, placebo-controlled, 12-week trial of vitamin D augmentation in major depressive disorder associated with vitamin D deficiency

BackgroundRandomized controlled trials (RCTs) of vitamin D (VitD) supplementation for depression have yielded inconsistent results. We conducted the first RCT of VitD supplementation with multipoint serum 25(OH)D assessments in major depressive disorder (MDD) patients with concurrent severe VitD deficiency. MethodsWe randomized antidepressant-free depressed adults with mean baseline 25(OH)D of 11.5 ng/ml to VitD (60,000 IU every 5 days; n = 31) or placebo (n = 28) for 12 weeks. All patients also received escitalopram (10–20 mg/day). Patients were rated at baseline and at the end of weeks 4, 8, and 12. Serum 25(OH)D was estimated at baseline, week 8, and week 12. ResultsIn an intent-to-treat analysis, mean Hamilton Depression Scale scores dropped from 25.7 to 5.7 and from 25.8 to 5.0 in VitD and placebo groups, respectively (primary outcome; P = 0.92). VitD and placebo groups did not differ on other objective and subjective ratings of depression, or on global ratings. Similar findings characterized completer analyses. No significant correlations were observed between 25(OH)D levels and depression ratings across the course of the study. Importantly, endpoint escitalopram doses were 4 mg/day higher in placebo than in VitD patients, and 4 mg/day higher in VitD deficient than in VitD sufficient patients. LimitationsA ceiling effect with escitalopram may have prevented the discovery of benefits with VitD supplementation. ConclusionsVitD supplementation does not improve antidepressant outcomes with flexibly dosed escitalopram. VitD deficient depressed patients may require higher antidepressant doses to experience benefits similar to those whose deficiency is corrected by VitD supplementation.

Efecto de la administración de diferentes formas de vitamina D en la presión arterial y rigidez aórticas, y su implicación en la reducción de la albuminuria en la enfermedad renal crónica

Background and objectivesVitamin D(vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. Patients and methodsWe studied in 97 patients with CKD stages 3-4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3-4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7 ± 2 months. ResultsIn the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2-12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43-876) mg / g (median (interquartile range)), with no differences between the groups.Serum calcium and phosphorus increased significantly in those treated with cholecal-ciferol (native vitD) and paricalcitol (active vitD). Parathormone (PTH) values decreased in those treated with paricalcitol.bPP and cPP decreased in all groups treated with native and active vitD. No significant changes in bPP and cPP were observed in the control group.Vpc-f did not change significantly in any of the groups, although the variation was quantitatively greater in group 3 (11.2±2 vs. 10.7±1.6 (P=.06)). No differences were observed in the changes in Vpc-f between the groups when adjusted to the baseline values of estimated glomerular filtration rate (eGFR), albuminuria, PTH, vitD, brachial and central blood pressure parameters, and their changes with treatment.Those who received treatment with native and active vitD presented a significant decrease in albuminuria of 17% (group 2) and 21% (group 3) compared to a 16% increase in the untreated group (group 1) (P=.01). A decrease in albuminuria ≥30% was observed more frequently in the groups treated with some form of vitD (group 2: 23%; group 3: 45%) than in the control group (13%) (P=.03). The decrease in albuminuria observed in the groups treated with any of the forms of vitD did not vary when the baseline values of the biochemical parameters of phosphorus-calcium metabolism, those of arterial function (PPb, PPc, Vpc-f) or its modifications were introduced as covariates. There was no significant correlation between changes in Vpc-f and albuminuria. In logistic regression, changes in arterial function parameters were also not explanatory for the ≥30% decrease in albuminuria. ConclusionsIn patients with CKD stages 3-4, treated with RAS blockers and with residual albuminuria, the administration of or paricalcitol reduces brachial and aortic pulse pressures, and albuminuria. The decrease in albuminuria does not seem to be mediated, at least not decisively, by changes in central hemodynamics or aortic stiffness.

Relationship between Vitamin D Level and Subclinical Hypothyroidism in Patients with Gestational Diabetes Mellitus.

The aim was to investigate the relationship between the vitamin D (VitD) level and the incidence rate of subclinical hypothyroidism in patients with gestational diabetes mellitus (GDM) in early pregnancy. Ninety eligible patients who underwent physical examination from March 2015 to September 2017 were selected. The levels of serum 25-hydroxyvitamin D (25-OH-VD), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured. The correlations of VitD level with those of thyroid function-related indices were analyzed. The serum 25-OH-VD level was (17.82 ± 3.45) ng/mL in the 90 GDM patients in early pregnancy, including 64.44% patients in VitD deficiency group, 22.22% patients in VitD insufficiency group, and 13.33% in VitD sufficiency group. No significant differences in the levels of serum FT4, FT3, and TSH were found among different VitD groups (p > 0.05), but the level of TPOAb gradually decreased (p < 0.05). There was no significant difference in the incidence rate of subclinical hypothyroidism among different VitD groups (p > 0.05). VitD level was not correlated with those of FT4, FT3, and TSH (p > 0.05), but negatively correlated with that of TPOAb (p < 0.05). An increase of TPOAb level raised the risk of VitD deficiency in pregnant women (p < 0.05). Patients suffered from significant 25-OH-VD deficiency in spring and winter (p < 0.05). GDM patients in early pregnancy display VitD deficiency, and their serum 25-OH-VD level is affected by seasons and not significantly related to subclinical hypothyroidism. However, the increased level of TPOAb may raise the risk of VitD deficiency in pregnant women.