Low Serum Levels Of 25-hydroxyvitamin Research Articles

Alleviation of Diabetic Retinopathy by Glucose-Triggered Delivery of Vitamin D via Dextran-Gated Functionalized Mesoporous Silica Nanoparticles.

Diabetic retinopathy (DR) is the most common retinal disorder, developed in 35% of patients with diabetes mellitus. Lower serum levels of 25-hydroxyvitamin D are associated with the increased risk of developing DR. High doses of the active form of vitamin D (VD), on the contrary, for a long period of time may lead to hypercalcemia and an imbalance in the regulation of bone metabolism. Herein, we studied the efficacy of dextran-gated carboxyphenylboronic acid (CPBA)-functionalized mesoporous silica nanoparticles (MSNs) for glucose-sensitive delivery of 1,25-dihydroxyvitamin D3 to modulate cellular oxidative stress and inflammation for managing DR. The physical adsorption technique was employed to load VD onto nanoparticles (263.63 μg/mg (w/w)). In the presence of glucose, the dextran molecules detach from pores, allowing VD to release since glucose has 1,2-cis diol groups which have very high affinity to CPBA. Approximately 75% of VD was released upon exposure to 25 mM glucose at a time point of 10 h, demonstrating glucose-responsive delivery. Furthermore, MSN-CPBA was able to deliver VD in a glucose-dependent manner and improve the bioavailability of VD. In high-glucose-supplemented human retinal cells, MSN-CPBA increased the bioavailability of VD and reduced cellular oxidative stress and inflammation. The results suggested that the VD-loaded nanocarrier exerted remarkable therapeutic capacity in reducing the risk of developing DR. By using MSN-CPBA as a delivery platform with dextran gating, the research proposes an effective treatment approach for improving the bioavailability and effectiveness of a hydrophobic molecule in the treatment of DR.

THU396 Digital Spatial Profiling Of Human Parathyroid Tumors Reveals Distinct Cellular And Molecular Alterations Linked To Vitamin D Deficiency

Abstract Disclosure: C. Tu: None. W. Chang: None. J.A. Sosa: Advisory Board Member; Self; Novo Nordisk, AstraZeneca, Eli Lilly & Company. Grant Recipient; Self; Exelixis, Inc., Eli Lilly & Company. J. Koh: None. Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population, but the pathophysiological basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from 9 vitamin D-deficient or 34 vitamin D-replete PHPT patients with 12 eucalcemic cadaveric donor parathyroid glands as normal tissue controls. Parathyroid oxyphil cell content is markedly higher in tumors from vitamin D-deficient PHPT patients (Def-Ts) relative to tumors from vitamin D-replete PHPT patients (Rep-Ts) (47.8% vs 17.8%, respectively; p <0.0001) and normal donor parathyroid glands (7.7%). Def-Ts display increased expression of genes encoding electron transport chain (corr. coefficient=0.546), proteasomal catabolism (corr. coefficient=0.587), and oxidative phosphorylation (corr. coefficient=0.982) pathway components. In contrast, Rep-Ts are characterized by upregulation of the ras (corr. coefficient=0.632) and myc (corr. coefficient=0.811) signaling pathways, suggestive of an oncogene-driven etiology. Parathyroid oxyphil cells are comparable to chief cells at the transcriptional level, and vitamin D-status is reflected in the transcriptional profiles of both cell types in a similar manner. Among PHPT patients who did not present as vitamin D deficient, three distinct tumor transcriptional profile clusters showed a dose-dependent relationship to pre-operative 25OHD levels (p <0.0001 by ANOVA). Relative to normal tissue, the abundance of calcium sensing receptor (CaSR) protein is reduced in Def-Ts (mean protein count 253.6 vs 492.3, respectively; p=0.039 for difference), while the type B γ-aminobutyric acid receptor 1 (GABAB1R) is increased (mean protein count 114.5 vs 64.65, respectively; p=0.0099 for difference). These expression changes resulted in a vitamin D dose-dependent reduction in the ratio of CaSR to GABAB1R receptors in Def-T tumor cells (r2 = 0.218, p<0.0001), favoring the formation of calcium sensing-attenuated CaSR:GABAB1R heteromers. The abundance of the amyloid precursor protein (APP) peptide derivative Aβ1-42, a putative GABAB1R ligand, is preferentially increased in Def-Ts compared to normal tissue (mean protein count 5797 vs 4500, respectively; p=0.0318). Collectively, these findings suggest a novel mechanism where chronic vitamin D deficiency can contribute to tonic PTH hypersecretion in PHPT patients by increasing GABAB1R-mediated antagonism of CaSR activity in parathyroid adenomas. Presentation: Thursday, June 15, 2023

Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency.

Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population (1-3), but the basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from vitamin D-deficient or vitamin D-replete PHPT patients. A cross-sectional panel of eucalcemic cadaveric donor parathyroid glands was examined in parallel as normal tissue controls. Here, we report that parathyroid tumors from vitamin D-deficient PHPT patients (Def-Ts) are intrinsically different from those of vitamin D-replete patients (Rep-Ts) of similar age and preoperative clinical presentation. The parathyroid oxyphil cell content is markedly higher in Def-Ts (47.8%) relative to Rep-Ts (17.8%) and normal donor glands (7.7%). Vitamin D deficiency is associated with increased expression of electron transport chain and oxidative phosphorylation pathway components. Parathyroid oxyphil cells, while morphologically distinct, are comparable to chief cells at the transcriptional level, and vitamin D deficiency affects the transcriptional profiles of both cell types in a similar manner. These data suggest that oxyphil cells are derived from chief cells and imply that their increased abundance may be induced by low vitamin D status. Gene set enrichment analysis reveals that pathways altered in Def-Ts are distinct from Rep-Ts, suggesting alternative tumor etiologies in these groups. Increased oxyphil content may thus be a morphological indicator of tumor-predisposing cellular stress.

Genetic Variations of the Vitamin D Metabolic Pathway and COVID-19 Susceptibility and Severity: Current Understanding and Existing Evidence.

The immunomodulatory and metabolic effects of vitamin D receptor (VDR) activation have been considered beneficial in mitigating the susceptibility and severity of COVID-19 infection. Furthermore, vitamin D-binding protein (DBP) has pleiotropic effects on the immune system that may influence inflammation associated with COVID-19. Multiple observational studies have demonstrated an association between low levels of serum 25-hydroxyvitamin D and risk and the severity of COVID-19 infection. However, the impact of vitamin D supplementation as an adjunctive treatment for COVID-19 based on evidence from randomized clinical trials is unclear. Equally important is that certain variations of the genes involved in the vitamin D metabolic pathway have been shown to affect immune function and linked with various clinical outcomes, including cardio-metabolic disorders, autoimmune diseases, infections, and cancers. This indicates inter-individual difference in body response to vitamin D. There is also emerging evidence that common polymorphisms of these genes may influence the susceptibility and severity of COVID-19, although the confidence of these findings is limited by a small number of studies and participants. Further studies are needed to address the potential role of VDR activation and DBP in the pathophysiology of COVID-19 which take into account the genetic variations of vitamin D metabolic pathway.

Normalization of Vitamin D Serum Levels in Patients with Type Two Diabetes Mellitus Reduces Levels of Branched Chain Amino Acids.

Background and Objectives: Vitamin D is involved in pancreatic beta-cell function, insulin sensitivity, and inflammation. Further, elevation in branched-chain amino acids (BCAAs) has been implicated in type 2 diabetes (T2DM) pathology. However, the relationship between vitamin D and BCAAs in T2DM remains unclear. The current study aimed to investigate the relationship between vitamin D and BCAAs in T2DM. Materials and Methods: In total, 230 participants (137 with T2DM and 93 healthy controls) were recruited in a cross-sectional study. Furthermore, an additional follow-up study was performed, including 20 T2DM patients with vitamin D deficiency. These patients were prescribed weekly vitamin D tablets (50,000 IU) for three months. The levels of several biochemical parameters were examined at the end of the vitamin D supplementation. Results: The results showed that patients with T2DM had higher serum levels of BCAAs and lower serum levels of 25-hydroxyvitamin D (25(OH)D) compared with those of the healthy controls (p < 0.01). The serum levels of vitamin D were negatively correlated with BCAA levels in T2DM patients (r = −0.1731, p < 0.05). In the follow-up study, 25(OH)D levels were significantly improved (p < 0.001) following vitamin D supplementation. Vitamin D supplementation significantly reduced the levels of BCAAs, HbA1c, total cholesterol, triglycerides, and fasting glucose (p < 0.01). Conclusion: Overall, these results suggest a role for BCAAs and vitamin D in the etiology and progression of T2DM. Thus, managing vitamin D deficiency in patients with T2DM may improve glycemic control and lower BCAA levels.

An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases.

Vitamin D intervenes in calcium and phosphate metabolism and bone homeostasis. Experimental studies have shown that 1,25-dihydroxyvitamin D (calcitriol) generates immunologic activities on the innate and adaptive immune system and endothelial membrane stability. Low levels of serum 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of developing immune-related diseases such as psoriasis, type 1 diabetes, multiple sclerosis, and autoimmune diseases. Various clinical trials describe the efficacy of supplementation of vitamin D and its metabolites for treating these diseases that result in variable outcomes. Different disease outcomes are observed in treatment with vitamin D as high inter-individual difference is present with complex gene expression in human peripheral blood mononuclear cells. However, it is still not fully known what level of serum 25(OH)D is needed. The current recommendation is to increase vitamin D intake and have enough sunlight exposure to have serum 25(OH)D at a level of 30 ng/mL (75 nmol/L) and better at 40–60 ng/mL (100–150 nmol/L) to obtain the optimal health benefits of vitamin D.

Optimal dosage of vitamin D supplementation in obese patients with low serum levels of 25-Hydroxyvitamin D. A systematic review

The purpose of this study was to assess the evidence for an appropriate dose-response of vitamin D supplementation in patients with obesity with inadequate vitamin D serum levels. We performed a systematic review consulting Medline, Embase and Cochrane Library up to September 2020 to identify studies that included (1) adult obese individuals with vitamin D serum levels below 75 nmol/l, (2) receiving cholecalciferol or calcidiol therapy (3) vitamin D serum levels assessment. The electronic search identified 705 potentially eligible studies, 11 of which were included and analysed. The heterogeneity of the studies did not permit a meta-analysis. Five studies (45.5%) were of high quality. Oral daily cholecalciferol resulted the route of administration that prevailed in most studies. We found that a minimum dose of =>2000UI/day might be needed to normalize 25OHD serum levels. Conversely, oral calcidiol <300IU/day failed to achieve 25OHD sufficiency. Exposed evidence suggests that vitamin D requirements remain higher in patients with obesity compared to lean patients. In order to normalize 25OHD serum levels, patients taking cholecalciferol might need to triple the actual recommended vitamin D doses. In contrast, calcidiol doses are still to be clarified. • Cholecalciferol ’treatment dose in patients with obesity might triple the requirements of non-obese ones. • Calcidiol optimal oral dosage is still to be elucidated. • Recommended dietary allowance for vitamin D may need to take into account patients' body weight and body mass index.

The role of rehabilitation and vitamin D supplementation on motor and psychological outcomes in poststroke patients.

Post-Stroke depression affects between 12% and 72% of patients who have suffered a stroke. The association between low serum levels of 25-hydroxyvitamin D (25(OH) D) and increased risk of depression is reported in both stroke and non-stroke patients. Similarly, high 25(OH) D levels might be associated with greater functional improvement during rehabilitation program.We wanted to investigate the effects of an intensive rehabilitation on poststroke outcomes. We wondered if the daily rehabilitation of motor and cognitive functions could also have an effect on mood and functional abilities in addition to or as an alternative to vitamin D supplementation.We conducted a 12-week, randomized trial, double blind, parallel, monocentric clinical trial of 40 patients undergoing intensive neuro-rehabilitation treatment at a specialized care facility for ischemic or hemorrhagic brain stroke. Participants were randomly assigned, in a 1:1 ratio, to 1 of 2 parallel groups: in the experimental group, 2000 IU/day of oral cholecalciferol was administered; in the control group patients were not taking vitamin D supplementation. Patients underwent a text evaluation to investigate psychological and motor outcomes.Significant intra-group difference in outcomes measures was found but not between control group and experimental group. In the vitamin D group, we highlighted significant differences between T0 and T1 in calcium (P < .001), vitamin D (P < .001), in Montgomery Aasberg Depression Rating Scale (P = .001), and in Functional Independent Measures (P < .001). In the health control group, we found a significant difference in calcium (P = .003), vitamin D (P < .001), Montgomery Aasberg Depression Rating Scale (P = 0.006), in general self-efficacy (P = .009), and in Functional Independent Measures (P < .001).Our results show that the beneficial effect on mood and functional recovery is mainly due to neurorehabilitation rather than vitamin D supplementation.

Association of serum 25-hydroxyvitamin D in COVID-19: A study from India

Background: Novel coronavirus infection 2019 (COVID-19), a pandemic has affected patients irrespective of gender and age. Existing studies have incriminated low levels of serum 25-hydroxyvitamin D to be associated with COVID-19 infection. The present study was to investigate serum 25-hydroxyvitamin D levels in patients with COVID-19 infection.&#x0D; Methods: We recruited prospectively 175 consecutive COVID-19 patients from the Department of Medicine, Yashoda hospital Hyderabad during the study period from May 2020 to December 2020. We measured in all patients, serum levels of 25-hydroxyvitamin D, calcium, phosphorus, alkaline phosphatase, C-reactive protein (CRP), D-Dimer, interleukin-6, procalcitonin, and ferritin.&#x0D; Results: Out of 175 patients 122(69.7%) were men, mean age was 57.2±13.6 years. Clinical symptoms were fever in 175 (100%) dry cough in 110(62.8%), tiredness in 105(60%), shortness of breath in 94(53.7%), and mechanical ventilator support requirement at admission in 40(22.8%). Serum 25-hydroxyvitamin D deficiency was noted in 108(61.7%), CRP was positive in 119(68%), abnormal D-dimer levels in 96(54.8%), abnormal procalcitonin levels in 107(61.1%) abnormal interleukin-6 levels in 98(56%), abnormal serum ferritin levels in 106 (60.5%) and overall mortality in 13(7.4%). Older age (p =0.006) hypertension (p=0.02), diabetes (p=0.01), CRP positivity (p&lt; 0.0001) and mortality (p=0.03) were significantly associated with serum25-hydroxyvitamin D deficiency in COVID-19 patients. Serum 25-hydroxyvitamin D deficiency and age &gt;60 years were significant predictors of mortality with odds of 7.4; (95%CI: 1.10-56.36) and 2.8: (95%CI: 0.81-9.50) respectively.&#x0D; Conclusion: In our study, serum 25-hydroxyvitamin D deficiency was seen in 61.1%, low levels of serum 25-hydroxyvitamin D was independently associated with &gt;60 years age group and mortality in COVID-19.

Single high-dose vitamin D3 injection and clinical outcomes in brain tumor resection: A randomized, controlled clinical trial

Vitamin D is known as a neuroprotective hormone with anti-inflammatory and immune-modulatory properties. We evaluated the effect of vitamin D3 injection on vitamin D status and clinical outcomes in patients with low serum levels of 25-hydroxyvitamin D [25(OH)D] undergoing craniotomy for brain tumor resection. Patients with benign brain tumors and serum 25(OH)D levels ≤20ng/mL were randomized to two groups with an equal number of subjects. The study group (n=30) received intramuscular injection of 300,000 IU vitamin D3 prior to surgery. The control group (n=30) was left without intervention, and both groups underwent routine therapies. On day 5 after craniotomy, the serum 25(OH)D levels increased significantly in the study group (P= <0.001). The length of ICU and hospital stay was significantly lower in the study group compared to the control group (P=0.01 and P=0.008, respectively). It was true when the age, tumor size, tumor type, Karnofsky Performance Scale (KPS) score, and calcium and albumin levels at baseline entered the logistic regression model (OR=0.17 (95%CI=0.04-0.72, P=0.01), and OR=0.19 (95%CI=0.04-0.82, P=0.02), respectively). With and without the application of logistic regression analysis, there was no significant difference in perioperative complications. Intramuscular injection of 300,000 IU of vitamin D3 in patients with low serum levels of 25(OH)D undergoing craniotomy, could rise safely the serum 25(OH)D level. This intervention, significantly reduced the length of ICU stay and hospitalization. Clinicaltrials.gov.identifier no: NCT03248544. Date: 8/14/2017.

Serum 25-Hydroxy-Vitamin D Status and Incident Hip Fractures in Elderly Adults: Looking Beyond Bone Mineral Density.

Observational studies have consistently reported a higher risk of fractures among those with low levels of serum 25-hydroxyvitamin D (25(OH)D). Emerging evidence suggests that low serum 25(OH)D levels may increase the rate of falls through impaired physical function. Examine to what extent baseline measures of volumetric bone mineral density (vBMD), absolute bone mineral content (BMC), and markers of physical function may explain incident hip fractures in older adults with different serum levels of 25(OH)D. A prospective study of 4309 subjects (≥66 years) recruited between 2002 and 2006 into the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study. Hip fractures occurring until the end of 2012 were extracted from hospital records. Prevalence of serum 25(OH)D deficiency (<30 nmol/L), inadequacy (30-<50 nmol/L), and sufficiency (≥50 nmol/L) was 6%, 23%, and 71% for males; and 11%, 28%, and 53% for females, respectively. Female participants had ~30% lower absolute BMC compared to males. Serum 25(OH)D concentrations were positively associated with vBMD and BMC of the femoral neck and markers of physical function, including leg strength and balance. Those who had deficient compared to sufficient status at baseline had a higher age-adjusted risk of incidence hipfractures with hazard ratios (HRs) of 3.1 (95% confidence interval [CI], 1.9-5.2) and 1.8 (95% CI, 1.3-2.5) among males and females, respectively. When adjusting for vBMD and measures of physical function, the association was attenuated and became nonsignificant for males (1.3; 95% CI, 0.6-2.5) but remained significant for females (1.7; 95% CI, 1.1-2.4). Deficient compared to sufficient serum 25(OH)D status was associated with a higher risk of incident hip fractures. This association was explained by poorer vBMD and physical function for males but to a lesser extent for females. Lower absolute BMC among females due to smaller bone volume may account for these sex-specific differences. © 2021 American Society for Bone and Mineral Research (ASBMR).

Clinical correlates of serum 25-hydroxyvitamin D in Parkinson’s disease

ABSTRACT Background Parkinson’s disease (PD) patients have lower levels of serum 25-hydroxyvitamin D (25(OH)D) than the general population. Previous studies have suggested a negative association between 25(OH)D and clinical features of PD, but the data are inconsistent. Materials and Methods We conducted a cross-sectional, observational study. Serum 25(OH)D, disease (Hoehn-Yahr stage [HY]) and clinical symptom (Unified Parkinson Disease Rating Scale [UPDRS]) severity and global cognitive functions (Mini-Mental State Examination [MMSE]) were studied in 500 consecutive PD patients not using vitamin D supplements. Information on sunlight exposure and dietary intakes (using a 66-item food frequency questionnaire) were also collected. A convenient sample of age and sex-matched community healthy controls (N = 100) was included as a control group. Results PD patients had lower 25(OH)D serum levels than controls. Deficiency status (<20 ng/mL) was found in 65.6% of patients. 25(OH)D levels were independently correlated to sunlight exposure (P = .002) and vitamin D intake (P = .009). In multivariate models, using a Mendelian randomization approach, lower serum 25(OH)D was associated with more severe disease (HY, P = .035), worse clinical symptoms (UPDRS Part-III total score [P = .006] and dopaminergic [P = .033] and non-dopaminergic subscores [P = .001]) and greater global cognitive function impairment (P = .041). Neither cognitive functions nor clinical features were associated with reduced intake of vitamin D and sunlight exposure. Conclusion : Serum 25(OH)D was negatively correlated with disease and symptoms severity, as well as with global cognitive functions. Our study adds to the evidence that low 25(OH)D may affect the progression of PD negatively. Intervention studies in this area are required.

Vitamin D Levels in Patients with and without Acne and Its Relation to Acne Severity: A Case-Control Study.

BackgroundVitamin D plays a significant role in the function of the immune system and it influences many dermatological diseases such as psoriasis and atopic dermatitis. The prevalence of vitamin D deficiency is growing globally, with around 30–50% of people are known to have low levels of vitamin D. Acne vulgaris is a common inflammatory disorder of the pilosebaceous unit. Studies about the role of vitamin D in the pathogenesis of acne vulgaris have shown conflicting and nonconclusive results. Thus, the precise purpose of vitamin D has not yet been established.ObjectiveFirst, to evaluate serum levels of vitamin D through a representative sample of patients with acne vulgaris and compare it with matched healthy controls. Second, to investigate if there is a relation between serum vitamin D level and the severity of acne vulgaris.Materials and MethodsThis cross-sectional study included 68 patients with acne vulgaris and 50 matched healthy controls. Serum 25-hydroxyvitamin D [25 (OH) D] levels were measured for both patients and healthy controls.ResultsThe study yielded lower levels of serum 25-hydroxyvitamin D in patients with acne vulgaris than its level in healthy controls. This is statistically significant with P-value = 0.003. Regarding age, gender, and sun exposure, there is no significant variation in serum 25-hydroxyvitamin D level. Also, no significant difference between the severity of acne and serum 25-hydroxyvitamin D levels.ConclusionThis study has shown clearly that vitamin D deficiency is more frequent in patients with acne with P-value = 0.003. However, no significant association between the serum level of 25-hydroxyvitamin D [25 (OH) D] and the severity of acne vulgaris. Further clinical trials on a larger scale are needed to address the importance of vitamin D in acne vulgaris. Specifically, determining whether treatment of acne with both topical vitamin D analogs and vitamin D supplementation is of significant effect.

Immunologic Effects of Vitamin D on Human Health and Disease.

Vitamin D is responsible for regulation of calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. It is also known as an immunomodulatory hormone. Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple components of the innate and adaptive immune system as well as endothelial membrane stability. Association between low levels of serum 25-hydroxyvitamin D and increased risk of developing several immune-related diseases and disorders, including psoriasis, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, tuberculosis, sepsis, respiratory infection, and COVID-19, has been observed. Accordingly, a number of clinical trials aiming to determine the efficacy of administration of vitamin D and its metabolites for treatment of these diseases have been conducted with variable outcomes. Interestingly, recent evidence suggests that some individuals might benefit from vitamin D more or less than others as high inter-individual difference in broad gene expression in human peripheral blood mononuclear cells in response to vitamin D supplementation has been observed. Although it is still debatable what level of serum 25-hydroxyvitamin D is optimal, it is advisable to increase vitamin D intake and have sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve the optimal overall health benefits of vitamin D.

Low serum levels of 25-hydroxyvitamin D in severe preeclampsia: The need for early supplementation

The purpose of this study was to analyze serum 25-hydroxyvitamin D levels in normal pregnant women, severe preeclampsia, and severe preeclampsia with complications. This research was a cross-sectional study; the sample was 86 third-trimester pregnant women consisting of 44 normal pregnant mothers, 30 severe preeclampsia and 12 people severe preeclampsia with complications. The diagnosis based on obstetrics and gynecology physicians who served at the research hospital. Serum levels of 25-hydroxyvitamin D are measured using VD (vitamin D) human Enzyme-Linked Immunosorbent Assay (ELISA) Kit. Serum levels of 25-hydroxyvitamin D showed that there were statistically significant differences in the normal pregnancy group, severe preeclampsia group, and severe preeclampsia group with complications. Low serum 25-hydroxyvitamin D levels were severe in severe preeclampsia, while the highest 25-hydroxyvitamin D serum levels were in complicated severe preeclampsia. Observation on medical records that the majority of severe preeclampsia has received treatment that increases serum levels 25-hydroxyvitamin D. Our study found that serum 25-hydroxyvitamin D levels will decrease as preeclampsia worsens and will increase again after receiving treatment. Earlier treatment in the early period of preeclampsia will be better than if there had been severe preeclampsia.

Active vitamin D activates chondrocyte autophagy to reduce osteoarthritis via mediating the AMPK-mTOR signaling pathway.

Osteoarthritis (OA) is a common joint degenerative disease. Vitamin D (VD) is essential for bone health. We hypothesized that active VD could be used as a therapeutic treatment for OA. Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been found in patients with OA, and thus the serum level of VD could be diagnostic of OA. To test this, we established a mouse model of OA. The results from staining with hematoxylin-eosin and Safranin O - Fast Green indicated that active VD reduced the symptoms of OA in mice. The results from Western blotting indicated that treatment with VD increased the activity of the p-AMPK-AMPK signaling pathway and decreased the p-mTOR-mTOR pathway; it also increased the ratio of LC3II:LC3I antibodies and the protein expression levels of Beclin-1, but decreased the level of p62. Further, treatment with VD reduced the levels of tumor necrosis factor-α and interleukin-6 both in cartilage tissues and in chondrocytes. Administration of the AMPK inhibitor compound C and autophagy inhibitor 3-methyladenine (3-MA) reversed these changes following VD treatment. In addition, the results from transfection with mRFP-GFP-LC3 indicated that active VD led to autophagosome aggregation in OA chondrocytes. 3-MA inhibited cell autophagy and promoted inflammation in OA. This study provides evidence that active VD activate chondrocyte autophagy to reduce OA inflammation via activating the AMPK-mTOR signaling pathway. Treatment with active VD could be a novel therapeutic option for OA.

Vitamin D Receptor Deficiency Does Not Affect Blood Pressure and Heart Function.

Vitamin D is thought to play a role in blood pressure regulation, which in turn can influence cardiovascular risk. Several meta-analyses of cohort studies found low serum levels of 25-hydroxyvitamin D to be associated with increased blood pressure or increased cardiovascular morbidity and mortality in the general population. Active vitamin D mediates its function via the vitamin D receptor (Vdr), which is a ligand-activated transcription factor. A suitable model to examine the causal role of vitamin D in blood pressure regulation and heart function is the Vdr knockout (Vdr–/–) mouse. To elucidate the role of vitamin D on blood pressure, heart function, and cardiac myocyte size, we conducted a long-term study using Vdr–/– mice and well-defined diets. Group 1 comprised Vdr–/– mice that received a high-calcium, high-phosphorus rescue diet to prevent hypocalcemia and a rickets phenotype. Groups 2 and 3 included Vdr+/+ mice that were fed either the rescue diet or a control diet containing normal amounts of these minerals. As Vdr is a nuclear factor that regulates transcription, we analyzed the renal mRNA expression and serum concentration of renin and found that the Vdr–/– group had an almost 50% higher renin mRNA expression in the kidney compared to both groups of Vdr+/+ mice. Additionally, serum concentration of renin in Vdr–/– mice was significantly higher than that of Vdr+/+ mice that received the rescue or control diet (+ 17%,+ 32%; P < 0.05). In contrast, renin activity was lower in Vdr–/– mice than in both groups of Vdr+/+ mice (P < 0.05). However, blood pressure, heart rate, cardiac myocyte sizes, and the expression of renal renin receptor, hepatic angiotensinogen and angiotensin II receptor, type 1, in kidney, liver and heart, did not differ between the three groups of mice. Additionally, data from transthoracic echocardiography did not indicate the role of Vdr on heart function, as the left ventricular ejection fraction, fractional shortening, and velocity of blood flow were comparable between the three groups. To conclude, the roles of Vdr and therefore most probably of vitamin D, in blood pressure regulation and heart function, were not confirmed by our findings.

Comparing the effectiveness of vitamin D plus iron vs vitamin D on depression scores in anemic females: Randomized triple-masked trial.

Background: Low levels of 25-hydroxyvitamin D (25(OH)D) have been related to depression and anxiety. It seems that anemia is associated with vitamin D deficiency. We aimed to evaluate the effects of iron-vitamin D co-supplementation versus vitamin D alone on depression scores in anemic females with low levels of serum 25-hydroxyvitamin D. Methods: This randomized controlled trial was conducted on eighty premenopausal females who were recruited between May 2015 and October 2015 from primary health care centers. Women with anemia and low concentrations of 25(OH)D were randomized to either 1000 IU/d vitamin D plus 27 mg/d iron (D-Fe) or vitamin D plus placebo supplements (D-P) for 12 weeks. Depressive and anxious symptoms were evaluated with the Beck Depression Inventory (BDI) with subscales 1–13 and 14–21 and Beck Anxiety Inventory (BAI). To compare the groups, Mann–Whitney or chi-squared tests were used and within groups comparison was performed using Wilcoxon signed ranks test. The study was registered on www.clinicaltrial.org as NC 01876563. Results: The serum concentrations of 25(OH)D were increased significantly in both groups at the end of the study. In both groups, there was a significant improvement in total BDI, the BDI subscale, and the BAI scores (p<0.001). No differences were found between groups (p>0.05). Conclusion: Although the potential positive effect of vitamin D on mental health was evident, iron plus vitamin D co-supplementation did not demonstrate any significant benefits over vitamin D alone, neither in depression score reduction nor anxiety symptoms.

MON-535 Relationship between Vitamin D and PTH: The Effect of Obesity and Weight Loss after Bariatric Surgery

Obesity is associated with lower serum levels of 25-hydroxyvitamin D (25-OH-D) and higher levels of PTH. There is an inverse relationship between these parameters in the general population, however this relationship is not well established in obesity. The 25-OH-D threshold required to completely suppress PTH has been suggested as a marker of optimal vitamin D status. We evaluated the relationship between 25-OH-D and PTH in obese patients before and after bariatric surgery, and determined the influence of obesity on the threshold for suppression of PTH by 25-OH-D. This was a retrospective study of patients followed between January 2010 and June 2017. We excluded patients with CKD (GFR < 60mL/min/1.73m²), previous history of bone fractures and abnormal levels of calcium, phosphorus and magnesium. Statistical analysis was performed with t, chi-square and linear regression tests. We evaluated 290 patients, 82.4% women, mean age 41.04 ± 10.52 years, BMI 43.57±5.66 kg/m². Before surgery, we observed a significant inverse association between 25-OH-D and PTH (β=-0.644; p<0.001), which is maintained after adjustment for gender, age, BMI and season. At 25-OH-D levels > 20 ng/mL the mean PTH was 53.24±2.68 pg/mL, increasing to 66.4±2.53 pg/mL when 25-OH-D was <10 ng/ml (p <0.001). One year after bariatric surgery, the association between the variables was weaker (β=-0.313, p=0.006), being lost in patients who kept a BMI > 30 kg/m2 (β=-0.154; p=0.434), despite the association between PTH and the presence of obesity (β=5.26, p=0.043). In patients achieving a BMI <30 kg/m², PTH increased from 41.05±1.57 pg/mL to 59.83±7.09 pg/mL for 25-OH-D levels <10 ng/mL (p=0.011) and to 96.1±14.19 pg/mL for 25-OH-D <5 ng/mL (p<0.001). In patients who maintained obesity, PTH increased from 46.66±2.81 pg/mL to 112±18.41 pg/mL from 25-OH-D <5 ng/mL (p=0.001) levels. The relationship between 25-OH-D and PTH in the obese population is modified after bariatric surgery. The PTH suppression threshold, and consequently the optimal vitamin D status, appear to be altered in obese and surgically treated patients. The 25-OH-D assay in the obese population may not be representative of the body's vitamin D reserves.

The Role of Vitamin D Binding Protein, Total and Free 25-Hydroxyvitamin D in Diabetes.

Vitamin D is important for bone health, but may also have extra-skeletal effects. Vitamin D and its binding protein DBP have immunological effects and may therefore be important in the development of type 1 diabetes (T1DM), and low serum levels of 25-hydroxyvitamin D (25(OH)D) are associated with later development of type 2 diabetes (T2DM). However, it has so far been difficult to convincingly show an effect of vitamin D supplementation on prevention or treatment of diabetes. The serum level of 25(OH)D has traditionally been used as a marker of a subject's vitamin D status. This measurement includes both 25(OH)D bound to DBP and albumin as well as the free from of 25(OH)D. However, according to the free hormone hypothesis, the free form is the biologically active. Previously the free form of 25(OH)D had to be calculated based on measurements of 25(OH)D, DBP, and albumin, but recently a method for direct measurement of free 25(OH)D has become commercially available. This is important in clinical conditions where the amount of DBP is affected, and has caused a renewed interest in which vitamin D metabolite to measure in clinical situations. In the present review the relations between DBP, total and free 25(OH)D in T1DM and T2DM are described.