VitD Deficiency Research Articles

VDR and deubiquitination control neuronal oxidative stress and microglial inflammation in Parkinson’s disease

Close correlation between vitamin D (VitD) deficiency and Parkinson’s Disease (PD) risk, VitD as an adjuvant treatment promising to improve PD progression. However, VitD excessive intake could induce hypercalcemia and renal damage. Therefore, upregulation of vitD receptor (VDR) is considered a compensatory strategy to overcome VitD insufficiency and alleviate PD symptoms. In this study, we discovered that VDR played antioxidative roles in dopaminergic neurons by decreasing reactive oxygen species (ROS) and maintaining mitochondrial membrane potential. Further, we newly identified VDR downstream events in C. elegans, including glutathione S-transferase (gst) and forkhead box transcription factor class O (daf-16) mediated oxidative stress resistance. VDR upregulation also mitigated microglial activation through inhibition of NLRP3/caspase-1-mediated inflammation and membrane permeabilization. These findings highlight the multifaceted protective effects of VDR in both neurons and microglia against the development of PD. Importantly, we discovered a novel deubiquitinase DUB3, whose N-terminal catalytic domain interacted with the C-terminal ligand-binding domain of VDR to reduce VDR ubiquitination. Identification of DUB3 as an essential player in the deubiquitinating mechanism of VDR provides valuable insights into VDR regulation and its potential as a therapeutic target for PD.

Highly selective whole-cell 25-hydroxyvitamin D3 synthesis using molybdenum-dependent C25-steroid dehydrogenase and cyclodextrin recycling

BackgroundThe global prevalence of vitamin D (VitD) deficiency associated with numerous acute and chronic diseases has led to strategies to improve the VitD status through dietary intake of VitD-fortified foods and VitD supplementation. In this context, the circulating form of VitD3 (cholecalciferol) in the human body, 25-hydroxy-VitD3 (calcifediol, 25OHVitD3), has a much higher efficacy in improving the VitD status, which has motivated researchers to develop methods for its effective and sustainable synthesis. Conventional monooxygenase-/peroxygenase-based biocatalytic platforms for the conversion of VitD3 to value-added 25OHVitD3 are generally limited by a low selectivity and yield, costly reliance on cyclodextrins and electron donor systems, or by the use of toxic co-substrates.ResultsIn this study, we used a whole-cell approach for biocatalytic 25OHVitD3 synthesis, in which a molybdenum-dependent steroid C25 dehydrogenase was produced in the denitrifying bacterium Thauera aromatica under semi-aerobic conditions, where the activity of the enzyme remained stable. This enzyme uses water as a highly selective VitD3 hydroxylating agent and is independent of an electron donor system. High density suspensions of resting cells producing steroid C25 dehydrogenase catalysed the conversion of VitD3 to 25OHVitD3 using either O2 via the endogenous respiratory chain or externally added ferricyanide as low cost electron acceptor. The maximum 25OHVitD3 titer achieved was 1.85 g L–1 within 50 h with a yield of 99%, which is 2.2 times higher than the highest reported value obtained with previous biocatalytic systems. In addition, we developed a simple method for the recycling of the costly VitD3 solubiliser cyclodextrin, which could be reused for 10 reaction cycles without a significant loss of quality or quantity.ConclusionsThe established steroid C25 dehydrogenase-based whole-cell system for the value-adding conversion of VitD3 to 25OHVitD3 offers a number of advantages in comparison to conventional oxygenase-/peroxygenase-based systems including its high selectivity, independence from an electron donor system, and the higher product titer and yield. Together with the established cyclodextrin recycling procedure, the established system provides an attractive platform for large-scale 25OHVitD3 synthesis.

Prevalence of vitamin D deficiency in patients with COVID-19 admitted to a tertiary hospital in Rio Grande do Sul

Background: Increasing data suggests a connection between vitamin D (vitD) and COVID-19. VitD may impact COVID-19 by affecting innate cellular immunity and exacerbating cytokine storms linked to severe respiratory syndrome from the virus. Objective: To assess the prevalence of vitD deficiency in COVID-19 patients hospitalized at Hospital Ernesto Dornelles and examine its links to in-hospital mortality, the need for Intensive Care Unit (ICU), patient demographics, and hospital stay duration. Methods: A cross-sectional study was performed, in which 3518 hospitalized patients with a confirmed diagnosis of COVID-19 were evaluated to obtain the prevalence of vitD deficiency, from March 2020 to August 2022. Data collection was performed using electronic medical records, excluding patients without serum levels of vitD measured during hospitalization, and including those with the exam in their medical records, which were later placed for statistical analysis. Results: 486 patients had their serum level of vitD measured, with a mean age of 68.3 years, 57.2% female, and 42.8% male. The prevalence of vitD deficiency was 60.1% (292 patients). There was no difference between the groups with and without vitD deficiency when comparing age, gender, and comorbidities. The median length of hospital stay, the need for ICU admission, and the outcome of death were significantly higher in the group with vitD deficiency (p<0.001; p=0.005; p=0.03). After adjusting for confounding factors, only the risk of ICU admission remained 1.38x higher in the group with vitD deficiency than in the group without (p=0.015), as well as age and CRF were factors with a higher risk for ICU admission. Conclusions: The prevalence of vitD deficiency in patients with COVID-19 was 60%, being associated with a higher risk of ICU admission, possibly presenting or not an association with higher mortality rates and length of stay. Therefore, further studies are needed to establish a cause-and-effect association.

Knowledge, attitude, and practice toward pediatric vitamin D deficiency among parents.

To investigate the knowledge, attitude, and practice (KAP) towards pediatric vitamin D deficiency (VitD) among parents and explore the risk factors of their knowledge, attitude, and practice. This cross-sectional study enrolled parents in our Hospital between November 2022 and January 2023. A total of 621 valid questionnaires were collected in this study. The knowledge, attitude, and practice scores were 6.13 ± 3.07 (theoretical score range: 0-13), 31.13 ± 6.20 (theoretical score range: 9-45), and 27.47 ± 4.21 (theoretical score range: 9-45), respectively; the mean knowledge score was <60%, indicating poor knowledge. Commercial and service industry workers and a monthly income ≥5,000 CNY were independently associated with sufficient knowledge (all P < 0.05). The knowledge score, ethnic minorities, divorced/widows, and spouses with a master's degree or above were independently associated with positive attitudes (all P < 0.05). The attitude score, female, non-urban, undergraduate education, commercial and service industry worker, and office worker were independently associated with proactive practice (all P < 0.05). Those characteristics could help design future KAP interventions on vitD deficiency. This study demonstrated poor knowledge, positive attitude, and proactive practice regarding pediatric VitD deficiency among parents. Targeted interventions and educational programs should be developed to improve parental knowledge.

Correlations of IL-1β and vitamin D with CAT score in patients with acute exacerbation of chronic obstructive pulmonary disease.

This study was to analyze the correlations of IL-1β and vitamin D (VitD) with chronic obstructive pulmonary disease assessment test (CAT) score in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). For this purpose, a total of 65 patients with chronic obstructive pulmonary disease (COPD) treated in our hospital between June 2020 and June 2022 were enrolled and assigned to a research group, and 40 healthy individuals who underwent physical examination in our hospital over the same time spanning were enrolled into the control group. The 65 COPD patients were further grouped into a stability group (30 cases) and an exacerbation group (35 cases). The two groups were compared in the levels of 25-hydroxyvitamin D (25(OH)D), interleukin-1β (IL-1β) and blood gas indexes (arterial carbon dioxide partial pressure (PaCO2) and arterial partial pressure of oxygen (PaO2). The modified Medical Research Council Dyspnea Scale (mMRC) and the CAT were adopted for evaluation of the stability group and exacerbation group. The correlations of IL-1β and 25(OH)D with mMRC and CAT scores were analyzed. The diagnostic value of IL-1β and VitD in patients in different stages was analyzed through receiver operating characteristic (ROC) curves. Results showed that the control group showed greatly lower IL-1β and PaCO2 levels and higher 25(OH)D and PaO2 levels than the research group (all P<0.05). The stability group got greatly lower mMRC and CAT scores than the exacerbation group (both P<0.05). IL-1β had positive correlations with mMRC and CAT scores, while 25(OH)D had negative correlations with them (P<0.05). According to ROC curve-based analysis, IL-1β and 25(OH)D had areas under the curves of 0.814 and 0.583, respectively, in diagnosing the acute exacerbation period, and had specificities of 56.67% and 43.33%, respectively and sensitivities of 97.14% and 74.29%, respectively. In conclusion, patients with COPD have increased IL-1 β and VitD deficiency, so VitD can be properly supplemented during treatment, and the levels of inflammatory factors should be paid close attention to at all times. IL-1 β and VitD can be regarded as novel ideas for the diagnosis and treatment of COPD, which may further improve the effect of COPD prevention and treatment.

Multicenter comparison of analytical interferences of 25-OH vitamin D immunoassay and mass spectrometry methods by endogenous interferents and cross-reactivity with 3-epi-25-OH-vitamin D3

BackgroundVitamin D (vit-D) deficiency is highly prevalent in the Korean population, highlighting the need for accurate measurements. In this study, the interferences by endogenous and cross-reactive substances were compared between routine vit-D immunoassays and mass spectrometry (MS) methods. MethodsTwo MS methods and 4 immunoassays from different manufacturers (Abbott, Beckman Coulter, Roche, Siemens) were compared. Residual samples that were icteric, lipemic, hemolyzed, high in rheumatoid factor, from myeloma patients, or patients undergoing hemodialysis were collected. Also, 4 levels of National Institute of Standards and Technology (NIST) Standard Reference Material 972a, and 12 samples serially spiked with 3-epi-25-OH-D3 were prepared. ResultsSignificant interferences were observed in hemolytic (Roche), icteric (Beckman and Siemens) and lipemic samples (all 4 immunoassays). Level 4 NIST material and 3-epi-25-OH-D3-spiked samples induced significant cross-reactivity, yielding higher total vit-D measurements in non-epimer-separating MS methods, and both the Beckman and Roche immunoassays. ConclusionMost observed interferences were consistent with manufacturers’ claims, but overall improvement of immunoassay bias limits is required. Awareness of potential interference is important to increase the accuracy of vit-D measurements. Moreover, care is due when interpreting vit-D results of newborns, infants and less commonly, pregnant women, who are known to have physiologically high levels of the highly cross-reactive 3-epi-25-OH-D3.

Magnetic resonance spectroscopy in the hippocampus of adult APP/PS1 mice following chronic vitamin D deficiency

Vitamin D (VitD) deficiency can exacerbate AD progression and may cause changes in brain metabolite levels that can be detected by magnetic resonance spectroscopy (MRS). The purpose of this study was to determine whether chronic VitD deficiency in an AD mouse model caused persistent metabolite levels changes in the hippocampus associated with memory performance. Six-month-old APPSwe/PS1ΔE9 (APP/PS1) mice (N = 14 mice/group) were fed either a VitD deficient (VitD-) diet or a control diet. Metabolite level changes in the hippocampus were evaluated by 1H MRS using a 9.4 T MRI. Ventricle volume was assessed by imaging and spatial memory was evaluated using the Barnes maze. All measurements were made at 6, 9, 12, and 15 months of age. At 15 months of age, amyloid plaque load and astrocyte number were evaluated histologically (N = 4 mice/group). Levels of N-acetyl aspartate and creatine were lower in VitD- mice compared to control diet mice at 12 months of age. VitD deficiency did not change ventricle volume. Lactate levels increased over time in VitD- mice and increases from 12 to 15 months were negatively correlated with changes in primary latency to the target hole in the Barns Maze. VitD- mice showed improved spatial memory performance compared to control diet mice. VitD- mice also had more astrocytes in the cortex and hippocampus at 15 months than control diet mice. This study suggests that severe VitD deficiency in APP/PS1 mice may lead to compensatory changes in metabolite and astrocyte levels that contribute to improved performance on spatial memory tasks.

The Magic Triangle in Oral Potentially Malignant Disorders: Vitamin D, Vitamin D Receptor, and Malignancy.

OPMDs (oral potentially malignant disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of various diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also suggest a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD and investigate their potential association and ramifications for clinical management of OPMDs.

Correlation between Treatment Outcomes and Serum Vitamin D Levels As Well As Infliximab Trough Concentration among Chinese Patients with Crohn's Disease.

The relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn's disease (CD) remains controversial. To evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD. This was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed. The total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (P < 0.001). CD activity index (CDAI) (120, range, 93-142.75) and simplified endoscopic activity score for CD (SES-CD) (2, range, 0-4) at week 14 were lower than that of enrollment (CDAI, 136.5, range, 101.25-196; SES-CD 13, range, 5-23) (P < 0.001). The biochemical remission (BR), clinical remission (CR), endoscopic remission (ER), and response (ERe) rates of week 38 were 76.1%, 88.5%, 22.4%, and 67.2%, respectively. vit-D levels at enrollment were positively correlated with CDAI at week 38 (P = 0.024). IFX serum TC was related to BR (P = 0.036), CR (P = 0.032) at week 14, and ERe (P = 0.009) at week 38. Among Chinese patients with CD, vit-D levels prior to IFX therapy are related to CDAI scores, and IFX serum TC is associated with BR, CR, and ERe.

THU648 Free Vitamin D And Rs7041 Polymorphism In Vitamin D Binding Protein Gene In Policystic Ovary Syndrome

Abstract Disclosure: P.N. Maidana: None. G.A. Gutierrez: None. M. Rojo: None. G.I. Fernández: None. D. Gonzalez: None. V. Aparicio: None. E. D'Isa: None. S. Demayo: None. L. Maggi: None. B.R. Fabre: None. G.E. Cerrone: None. V. Mesch: None. Introduction: Polycystic ovary syndrome (PCOS) is related with an increased risk of developing metabolic complications, such as vitamin D (VitD) deficiency, which could be in turn associated with insulin resistance and other metabolic risk factors. Most (85-90%) of the circulating VitD is bound to its specific carrier protein (DBP), with a smaller amount (10-15%) bound to albumin and less than 1% exists in a free form, which is the biologically active fraction. So, it should be more useful to determine Free VitD to asses VitD status. Aditionally, the influence of genetic factors on serum VitD levels must be taken into account, such as single nucleotide polymorphisms (SNPs) in the DBP gene, as rs7041 and rs4588. We previously found correlations between VitD and different hormonal and metabolic parameters in PCOS women. In this study our aim is to evaluate if measuring Free VitD in PCOS women gives more information than total VitD, and subsequently, to determine the frequency of SNP rs7041 in the DPB gene. Subjects and methods: 104 women (19-41 years) with PCOS and 64 healthy controls (22-45 years) were initially recruited. In a subgroup of 37 patients and 24 controls, Free VitD was measured by ELISA; in all of them body mass index (BMI) was calculated, waist circumference (WC) was measured as indicator of abdominal obesity, VitD and SHBG were measured by chemiluminescence, triglycerides (TG) and HDL cholesterol (HDL-chol) were determined by enzymatic colorimetric method, total testosterone (To) by electrochemiluminescence and free To (FTo) was calculated from To and SHBG. TG/HDL-chol and Lipid accumulation product (LAP) indexes were calculated, as secondary markers of insulin resistance. The rs7041 variant genotyping was performed in 27 PCOS patients and 27 controls, by PCR real time with TaqMan probes in peripheral blood leucocytes. Statistical analysis was performed by SPSS 22 software. Results: BMI, WC, To, FTo, TG/HDL-chol and LAP were significantly higher in PCOS than controls, while VitD was lower. Free VitD showed no significant differences between patients and controls. VitD levels showed negative correlations with BMI, WC, To, FTo, TG/HDL-chol and LAP. Free VitD only showed a positive correlation with total VitD.No statistical differences in genotype frequencies were observed between patients and controls. Genotype and allelic frequencies analysis could not be performed due to the high presence of heterozygosity in both groups. Conclusions: The fact that we found significant differences between total VitD levels in PCOS and controls but not in Free VitD could be attributed to differences in DBP. The lack of correlations between Free Vit D and the different parameters analyzed suggests that measuring Free VitD in PCOS would not have advantages with respect to total VitD.Variant genotyping analysis must be extended to a larger number of individuals and also other variants could be studied. Presentation: Thursday, June 15, 2023

Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH.

Canagliflozin has been reported to increase the risk of bone fracture-possibly mediated by decreasing 1,25-dihydroxyvitamin D (1,25(OH)2D) and increasing parathyroid hormone (PTH). This work investigated whether baseline vitamin D (VitD) deficiency renders individuals vulnerable to this adverse effect and whether VitD3 supplementation is protective. This community-based, outpatient study had a paired design comparing individual participants before and after VitD3 supplementation. Eleven VitD-deficient (25-hydroxyvitamin D [25(OH)D] ≤ 20 ng/mL) individuals were recruited from the Amish population in Lancaster, Pennsylvania. Participants underwent 2 canagliflozin challenge protocols (300 mg daily for 5 days): the first before and the second after VitD3 supplementation. In the VitD3 supplementation protocol, participants received VitD3 supplementation (50 000 IU once or twice a week depending on body mass index for 4-6 weeks) to achieve 25(OH)D of 30 ng/mL or greater. Two coprimary end points were identified: effects of VitD3 supplementation on canagliflozin-induced changes in 1,25(OH)2D and PTH. Secondary end points included effects of VitD3 supplementation on baseline levels of VitD metabolites and PTH. VitD3 supplementation increased mean 25(OH)D from 16.5 ± 1.6 to 44.3 ± 5.5 ng/mL (P = .0006) and 24,25-dihydroxyvitamin D (24,25(OH)2D) from 1.0 ± 0.1 to 4.3 ± 0.6 ng/mL (P = .0002). Mean 1,25(OH)2D and PTH were unchanged. VitD3 supplementation decreased the magnitude of canagliflozin-induced changes in 1,25(OH)2D (from -31.3%±4.7% to -9.3%±8.3%; P = .04) and PTH (from +36.2%±6.2% to +9.7%±3.7%; P = .005). VitD deficiency rendered individuals more vulnerable to adverse effects of canagliflozin on biomarkers associated with bone health. VitD3 supplementation was protective against canagliflozin's short-term adverse effects on 1,25(OH)2D and PTH.

Impact of vitamin D resistance genes on vitamin D deficiency during pregnancy among the South Indian population

Increasing evidence suggests that vitamin D (Vit-D) could be pivotal in maintaining normal glucose homeostasis. Low levels of Vit-D in early pregnancy are associated with a higher risk of gestational diabetes mellitus (GDM). Though several reports have highlighted the prevalence of vit-D deficiency among pregnant women, its underlying cause has not yet been fully elucidated. In this connection, a few studies have found the development of resistance to Vit-D, including the levels of Vitamin D receptor (VDR) and transcription regulators that modify VDR action, as well as the bioavailability of Vit-D. We aimed to determine the levels of Vit-D resistance genes such as 25-HydroxyVit-D-24-hydroxylase (CYP24A1), VDR repressor genes (SNAIL and SMRT) and their association between Vit-D concentrations in early pregnancy, and the risk of gestational diabetes mellitus (GDM). A prospective observational study was conducted on healthy pregnant women (NGDM; n = 50) and GDM (n = 50) attending routine antenatal care at SRM Medical College Hospital, Chennai, recruited at 12 weeks of gestation. We found that the serum levels of Vit-D were low in GDM subjects and negatively correlated with the fasting glucose levels. Further, increased expressions of Vit-D resistance genes such as CYP24A1, SNAIL, and SMRT were observed in GDM subjects and negatively correlated with the serum levels of Vit-D. Furthermore, we have validated the data using the trophoblast cell line, BeWo, exposed to calcitriol under a hyperglycemic environment. Our finding showed that increased expression of Vit-D resistance genes in pregnancy may be associated with a greater risk of adverse pregnancy outcomes, including GDM.

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.

Correlation of Vitamin D status with TSH levels in postmenopausal women; A pilot study

Vitamin D (VitD) insufficiency is present in over half of population worldwide. Over a billion people worldwide are vitamin D deficient or insufficient. It has been long known that VitD insufficiency contributes to development of osteopenia and osteoporosis. We performed a retrospective review of data of 60 patients in postmenopausal age group (45-75 years) during their routine blood investigation for the first time at Government Medical College and Guru Nanak Dev Hospital Amritsar over a period of 3 months (February 2023 to April 2023). Vitamin D levels were insufficient (10-30 ng/mL) in 35% of the patients, deficient (10 ng/mL) in 18.5%, and normal in the remaining 35%. TSH levels were low (less than 0.3 mIU/L) in 5%, high (more than 4.5 mIU/L) in 18.3%, and normal (0.3-4.5 mIU/L) in the remaining 76.6%. 54% (n-11) of individuals with elevated TSH had vitamin D deficiency, while 18% had insufficient vitamin D. 100%(n-3) patients with low TSH had normal vitamin D levels. TSH and vitamin D levels were normal in 22 individuals. High TSH levels was associated with low vitamin D levels, low TSH levels was associated with normal serum vitamin D level. Hence association was linear between TSH and vitamin D in post-menopausal women.

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.

Six years' experience and trends of serum 25-hydroxy vitamin D concentration and the effect of vitamin D3 consumption on these trends.

Introduction: Vitamin D (vitD) deficiency may have importance in some diseases, but there is a lack of data in our country to clarify the current situation. Our aim was to examine the basic characteristics of patients' vitD status, and the ratio of vitD deficiency and its relation to certain diseases, assess seasonality and trends, and reveal the indirect impact of the COVID-19 pandemic on vitD3 supplementation at the patient population level. Methods: Anonymized data on 25(OH)D test results were obtained from the clinical data registry of a tertiary teaching hospital covering the period between 1 January 2015 and 30 June 2021. VitD consumption (pharmacy sale) data were retrieved from the database of the National Health Insurance Fund of Hungary in order to calculate the defined daily dose (DDD)/1,000 inhabitants/day. Descriptive statistics and odds ratios with their 95% confidence intervals were calculated. The two-sample t-test and F-test were used to analyze our patients' data. Significant differences were considered if p <0.05. Results: Altogether, 45,567 samples were investigated; the mean age was 49 ± 19.1years and 68.4% of them were female subjects. Overall, 20% of all patients had hypovitaminosis D, and just over 7% of patients had vitD deficiency. Male subjects had higher odds for hypovitaminosis or vitD deficiency (65.4 ± 28.2nmol/L vs. 68.4 ± 28.4nmol/L; p <0.0001). The mean 25(OH)D concentration has changed during the year, reaching a peak in September and a minimum in February. Patients with diseases of the circulatory system, genitourinary system, certain conditions originating in the perinatal period, and "sine morbo" (i.e., without a disease; such as those aged over 45years and female teenagers) had statistically higher odds for lower 25(OH)D concentrations (p <0.00001). VitD consumption showed seasonality, being higher in autumn and winter. A slight increase started in the season of 2017/18, and two huge peaks were detected at the beginning of 2020 and 2021 in association with the COVID-19 waves. Conclusion: Our data are the first to describe data concerning vitD in our region. It reinforces the notion of vitD3 supplementation for some risk groups and also in healthy individuals. To prevent the winter decline, vitD3 supplementation should be started in September. This and the results during the COVID-19 pandemic highlight the importance of health education encouraging vitamin D3 supplementation.

Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice.

Overtraining syndrome is a condition resulting from excessive training load associated with inadequate recovery and poor sleep quality, leading to performance decrements and fatigue. Here we hypothesized that vitamin D (VitD) deficiency is a lead factor in the development of the overtraining syndrome. To test this hypothesis, two groups of 60-week-old C57BL/6 mice followed a 16-week excessive eccentric-based overtraining by excessive downhill running with or without dietary VitD depletion (EX and EX-D- groups). Two control groups were trained by uphill running at the same load with or without VitD depletion (CX and CX-D- groups). Handgrip strength decreased throughout the protocol for all groups but the decrease was sharper in EX-D- group (VitD × training, p = 0.0427). At the end of the protocol, the mass of Triceps brachii muscle, which is heavily stressed by eccentric contractions, was reduced in eccentric-trained groups (training effect, p = 0.0107). This atrophy was associated with a lower concentration of the anabolic myokine IL-15 (training effect, p = 0.0314) and a tendency to a higher expression of the atrogene cathepsin-L (training effect, p = 0.0628). VitD depletion led to a 50% decrease of the fractional protein synthesis rate in this muscle (VitD effect, p = 0.0004) as well as decreased FGF21 (VitD effect, p = 0.0351) and increased osteocrin (VitD effect, p = 0.038) concentrations that would lead to metabolic defects. Moreover, the proportion of anti-inflammatory Th2 lymphocytes was significantly decreased by the combination of eccentric training with VitD depletion (vitD × training, p = 0.0249) suggesting a systemic inflammation. Finally, exploratory behavior time of mice was decreased by VitD depletion (VitD effect, p = 0.0146) suggesting a cognitive dysfunction. Our results suggest that VitD deficiency exacerbates the effects of overtraining.

Increased Serum Levels of IL-1β after Ischemic Stroke are Inversely Associated with Vitamin D.

The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1β (IL-1β) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders. To investigate the levels of IL-1β and vitamin D (VitD) in patients with IS compared with controls and their correlation. The serum level of 25-OH VitD and IL-1β was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit. We found a significant increase in IL-1β (80.14±6.8 vs. 60.32±4.1 pg/ml, p<0.05) and a decrease in VitD level (24.3±1.4 vs. 29.9±1.5 ng/ml, p<0.01) in the IS patients compared with the controls. There was a significantly positive correlation between the National Institutes of Health Stroke Scale (NIHSS) and IL-1β according to both the Spearman correlation (r=0.35, p=0.0003) and the linear regression (beta=0.255, p=0.014). Also, a significant negative association between VitD and NIHSS was detected by the Spearman correlation (r=-0.41, p<0.0001) and the linear regression (beta=-0.381, p=0.000). Moreover, we found a significant negative correlation (r=-0.26, p=0.006) between the serum levels of VitD and IL-1β in the patient group. Ischemic stroke correlates positively with IL-1β and negatively with VitD levels. The speculated role of VitD deficiency in the evolution and severity of stroke may be justified by its role in the modification of inflammation.

Changes in choroidal tissue post-supplementation with vitamin D in pediatric patients who are deficient in vitamin D.

To quantitatively assess the choroidal structural parameters of patients in the pediatric age group who were deficient in vitamin D [Vit-D] pre- and post-treatment. Prospective, case-control study. Choroidal structural parameters, including the choroidal thickness (CT) at five points, total choroidal area (TA), luminal choroidal area (LA), stromal choroidal area (SA), and choroidal vascular index (CVI), in patients in the pediatric age group who were deficient in Vit-D, in Group 1, and those who were not, in Group 2, were compared. The patients were divided into 3 different groups according to how deficient in Vit-D they were. This was re-evaluated after treatment. Group 1 consisted of 83 patients and group 2 consisted of 85 patients. CT at all five points, and the TA, SA, LA, and CVI, were lower in Group 1. And for all of these, a significant increase was seen post-treatment. While a significant increase was observed in all of the values in the group with the most severe deficiency in Vit-D, significant changes were observed in the TA, LA, SA, and CVI values in the group that was mildly deficient in Vit-D. There was no significant post-treatment value in the CT values (except for the Temporal 1500 CT [P = 0.012]). Decreases in the CT, TA, LA, SA, and CVI were among the structural changes that were seen to occur in the pediatric patient group that was deficient in Vit-D. Moreover, thinning of the choroid and a decrease in the CVI were the most significant in the group with the greatest Vit-D deficiency.

Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions

BackgroundDiabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid progression to ESRD. Nevertheless, the mechanisms that lead to this process are poorly understood. This study aimed to characterize a model of diabetic nephropathy progression in VitDD and the epithelial-mesenchymal-transition (EMT) role in these processes.MethodsWistar Hannover rats received a diet with or without VitD before type 1 diabetes (T1D) induction. After this procedure, the rats were accompanied for 12 and 24 weeks after T1D induction and the renal function, structure, cell transdifferentiating markers and zinc finger e-box binding homeobox 1/2 (ZEB1/ZEB2) contribution to kidney damage were evaluated during the DKD progression.ResultsThe results showed an increase in glomerular tuft, mesangial and interstitial relative areas and renal function impairment in VitD-deficient diabetic rats compared to diabetic rats that received a VitD-containing diet. These alterations can be associated with increased expression of EMT markers, ZEB1 gene expression, ZEB2 protein expression and TGF-β1 urinary excretion. Decreased miR-200b expression, an important post-transcriptional regulator of ZEB1 and ZEB2 was also observed.ConclusionOur data demonstrated that VitD deficiency contributes to the rapid development and progression of DKD in diabetic rats induced by increase ZEB1/ZEB2 expressions and miR-200b downregulation.