Low Serum 25-hydroxyvitamin Research Articles

Effects of vitamin D supplementation on cardiac biomarkers: Results from the STURDY trial

ObjectivesIn observational studies, older adults with low serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation, possibly because the doses of vitamin D supplements tested were too low. Our objective was to determine if higher doses of vitamin D supplementation reduce high-sensitivity cardiac troponin (hs-cTnI) and N-terminal pro-b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD. MethodsThe Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, 4000 IU/day) on fall risk among older adults with low serum 25-hydroxyvitamin D concentrations (10–29 ng/mL). Hs-cTnI and NT-proBNP levels were measured at baseline, 3-, 12-, and 24-month follow-up visits. For this ancillary study, we used data from the original trial and compared participants by treatment group: low-dose (200 IU/day) or high-dose (1000+ IU/day). The effects of vitamin D dose on biomarkers were assessed via mixed effects tobit models. ResultsAmong 688 participants (mean age of 76.5) hs-cTnI increased in both the low- and high-dose groups by 5.2 % and 7.0 %, respectively; likewise, NT-proBNP increased by 11.3 % and 9.3 %, respectively. Compared to the low-dose, high-dose vitamin D supplementation did not affect hs-cTnI (1.6 %-difference; 95 % CI: -5.3, 8.9) or NT-proBNP (-1.8 %-difference; 95 % CI: -9.3, 6.3). ConclusionsCompared to low-dose vitamin D supplementation, doses ≥1,000 IU/ day did not affect markers of subclinical CVD in older adults with low serum vitamin D levels.

Sustained Reduction of Elevated Intact Parathyroid Hormone Concentrations with Extended-Release Calcifediol Slows Chronic Kidney Disease Progression in Secondary Hyperparathyroidism Patients

Introduction: Chronic kidney disease (CKD) drives onerous human and healthcare costs, underscoring an urgent need to avert disease progression. Secondary hyperparathyroidism (SHPT) develops as CKD advances, and persistently elevated parathyroid hormone (PTH) may be nephrotoxic and associated with earlier dialysis onset. This study examines, for the first time, the hypothesis that sustained reduction of elevated intact PTH (iPTH) with extended-release calcifediol (ERC) reduces the nephrotoxic impact of SHPT and forestalls renal decline. Methods: Changes in estimated glomerular filtration rate (eGFR) were analyzed post hoc in 126 adults with SHPT, stage 3–4 CKD, and low serum 25-hydroxyvitamin D (25D) treated for 1 year with ERC in pivotal trials. ERC was administered at 30 μg/day increasing, as needed, to 60 μg/day to achieve ≥30% reductions in iPTH. Calcium, phosphorus, 25D, 1,25-dihydroxyvitamin D (1,25D), iPTH, eGFR, fibroblast growth factor-23 (FGF23), bone turnover markers (BTMs), and urine albumin-to-creatinine ratio (uACR) were measured at baseline and regular intervals. Participants were categorized by achievement (or not) of sustained ≥30% iPTH reductions over the last 2 quarters of treatment to evaluate differences in eGFR decline. Results: For all participants, 25D increased 58.5 ± 2.3 (SE) ng/mL (p < 0.001) by the end of treatment (EOT), 1,25D increased 10.1 ± 1.8 pg/mL (p < 0.001), iPTH decreased from 143.8 ± 5.8 pg/mL to 108.8 ± 7.2 (p < 0.001), BTMs improved (p < 0.01), and eGFR declined 2.2 ± 0.5 mL/min/1.73 m2 (p < 0.001). The rate of eGFR decline was >5-fold higher (p = 0.014) in participants who did not achieve sustained iPTH reductions of ≥30% (3.2 ± 0.7; 12.7 ± 2.2%) than in those who did (0.6 ± 0.8; 2.9 ± 2.4%). It was highest in the 30 participants who did not exhibit an iPTH lowering response in both of the last 2 quarters of treatment (5.4 ± 0.9; 20.9 ± 3.4%). Duration of iPTH reduction had no impact on safety parameters. Degree of iPTH reduction at EOT was also associated with slower CKD progression. Conclusion: Sustained reduction of elevated iPTH with ERC treatment was associated with slower rates of eGFR decline in patients with SHPT and stage 3–4 CKD without raising safety concerns. A prospective trial is warranted to confirm this finding.

Serum 25-hydroxyvitamin D levels and dermatomyositis: A 2-sample mendelian randomization study.

Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains elusive. Our aim is to confirm the causal relationship between 25(OH)D and DM risk through a Mendelian randomization study. Retrieve genome-wide association study (GWAS) data on 25(OH)D (n = 441 291) and DM (n cases = 201, n controls = 172 834) from the GWAS database (https://gwas.mrcieu.ac.uk/). Select single-nucleotide polymorphisms (SNPs) strongly correlated with 25(OH)D as instrumental variables (IVs). The primary analytical approach involves the use of the inverse-variance weighted method (IVW), supplemented by MR-Egger regression and weighted median methods to enhance the reliability of the results. Heterogeneity and sensitivity analyses were conducted using Cochran's Q and leave-one-out approaches, respectively. The IVW analysis confirmed a positive causal relationship between genetic variation in 25(OH)D levels and DM (OR = 2.36, 95% CI = 1.01-5.52, p = .048). Although not statistically significant (all p > .05), the other methods also suggested a protective effect of 25(OH)D on DM. Based on MR-Egger intercepts and Cochran's Q analysis, the selected SNPs showed no horizontal pleiotropy and heterogeneity. Sensitivity analysis demonstrated the robustness of the results against individual SNPs. We provide the first evidence of a causal relationship between 25(OH)D levels and DM. Our findings support the importance of measuring serum 25(OH)D levels and considering vitamin D supplementation in clinical practice for patients with DM.

Association of serum vitamin D concentration and miscarriage rate in women with first-trimester threatened miscarriage

Research questionIs low serum 25-hydroxyvitamin D (25(OH)D) associated with an increased risk of miscarriage in women who presented with threatened miscarriage to the Early Pregnancy Assessment Clinic (EPAC)? DesignThis was a secondary retrospective analysis using archived serum samples from a randomized, double-blind, placebo-controlled trial. Stored serum samples from 371 women presenting to the EPAC with threatened miscarriage during the first trimester were assayed for 25(OH)D by liquid chromatography–mass spectrometry. ResultsThe overall miscarriage rate was 45/371 (12.1%) in the whole cohort. After grouping vitamin D insufficiency and vitamin D sufficiency together into a ‘non-deficient’ group and excluding participants who underwent termination of pregnancy, there was no difference in the miscarriage rate between those who were vitamin D deficient compared with those who were not (25/205, 12.2% versus 20/157, 12.7%, P= 0.877, odds ratio 0.951, 95% CI 0.507–1.784). When analysed according to the number of gestational weeks, the miscarriage rate was significantly higher in the vitamin D non-deficient group than the vitamin D-deficient group in women who presented at 6 gestational weeks or earlier (13/33 [39.4%] versus 10/58 [17.2%], P= 0.019), but there were no statistically significant differences between the two groups presenting at later gestations. There was no difference in the vitamin D level in women who had a miscarriage compared with those who had a live birth (48 [37–57] versus 47 [37–58] nmol/l, P= 0.725 median [25th–75th percentile]). ConclusionsA low serum vitamin D concentration was not associated with an increased risk of miscarriage in women with threatened miscarriage presenting to the EPAC.

Effect of Low Serum 25 Hydroxyvitamin D3 Level on Prognosis in Neonates with Acute Respiratory Distress Syndrome

Hypovitaminosis D is prevalent among pregnant women and newborns. This study investigates the impact of low serum 25-hydroxyvitamin D3 levels on the prognosis of neonates with acute respiratory distress syndrome. A retrospective analysis was conducted on 120 neonates with acute respiratory distress syndrome admitted between February 2019 and February 2021, compared with 120 healthy neonates born during the same period. Data collected included gender, age, Apgar scores, birth weight, and delivery method. The results indicated that neonates with acute respiratory distress syndrome had significantly lower gestational age, birth weight, and Apgar scores at 1 and 5 min compared to the control group (P &lt; 0.05). Logistic regression analysis revealed that low gestational age, low birth weight, low Apgar scores, and serum 25-hydroxyvitamin D3 deficiency were independent risk factors for acute respiratory distress syndrome (P &lt; 0.05). Low serum 25-hydroxyvitamin D3 levels are associated with a poorer prognosis in affected neonates and should be closely monitored in clinical practice.

Correlation between obesity and serum 25-hydroxyvitamin D levels in patients with type 2 diabetes

[Objective] The paper analyzes the correlation of vitamin D level with obesity degree and serum 25-hydroxyvitamin D level in patients with type 2 diabetes mellitus (T2DM) through clinical case studies, which can provide clinical guidance for obese T2DM patients' weight control to lower their risk of developing metabolic illnesses. [Methods] A total of 249 patients with T2DM were chosen from among those hospitalized at Lanzhou University's First Hospital between April and September of 2023. The serum 25-hydroxyvitamin D level, body fat rate, fasting blood glucose, and fasting insulin of the subjects were detected, and 198 T2DM patients with low serum 25-hydroxyvitamin D levels were selected as the observation group. 51 T2DM patients with normal serum 25-hydroxyvitamin D levels were selected as the control group, and the correlation between type 2 diabetes mellitus and vitamin D levels and obesity was analyzed. [Results] Obesity and serum vitamin D insufficiency are associated with type 2 diabetes. Both vitamin D deficiency and obesity eventually lead to T2D, endocrine disorders, and other common diseases. [Conclusions] Low plasma 25-hydroxyvitamin D (25[OH]D) concentration and high BMI are correlated with an increased risk of diabetes.

High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: A phase 2 RCT.

Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited. A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. The HDVD group (N=29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N=30; p=.03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p=.06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p<.01). Those in the HDVD arm showed significant changes in parathyroid hormone (p<.01), osteoprotegerin (p<0.01), N-terminal telopeptide of type 1 collagen (p<0.01) and C-terminal telopeptide of type 1 collagen (p<0.01). No difference in adverse events or toxicity was noted between the groups. HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.

Association of low serum 25-Hydroxy vitamin D [25(OH) d] with hepatic encephalopathy in patients with decompensated liver cirrhosis

Background and study aimsThe mechanism of hepatic encephalopathy is complex and has not been conclusively established. Recent studies support lower serum 25-Hydroxy Vitamin D [25(OH) D] levels in patients with hepatic encephalopathy. This study aimed to evaluate the association between serum 25(OH) D and hepatic encephalopathy in patients with decompensated cirrhosis of liver. Patients and methodsA total of 70 cirrhosis patients (35 cases of hepatic encephalopathy and 35 patients without encephalopathy as control, mean age 53.07 ± 12.99 years, 67 % male) were recruited for this study. Assessment of the severity of cirrhosis was done by using a model for end-stage liver disease(MELD) and Child Turcotte Pugh (CTP) scores, and assessment of the severity of hepatic encephalopathy was done according to West Haven criteria. Serum 25 (OH) D level was measured by Chemiluminescent Microparticle Immuno Assay(CMIA). ResultsThe mean serum 25(OH) D level among hepatic encephalopathy patients was significantly lower in comparison to the control group without encephalopathy (18.76 ± 8.84 nmol/L vs 31.19 ± 13.9 nmol/L, P<0.0001). 91.4 % of hepatic encephalopathy patients had moderate to severe 25(OH)D deficiency as compared to 51.4 % in the control group. There was a significant correlation observed between the severity of the 25 (OH) D deficiency and the severity of liver disease (r = − 0.35, P = 0.002). No statistically significant difference in serum 25(OH) D levels was found among patients with different hepatic encephalopathy grades (P = 0.416). ConclusionA significant association was found between a low serum 25(OH) D leveland hepatic encephalopathy. It requires further large-scale multicenter studies to establish it as a risk factor and predictor of hepatic encephalopathy.

Searching The New Culprit of Optic Neuritis: The Role of Vitamin D

Abstract&#x0D; Introduction : Low vitamin D status has long been associated in multiple sclerosis patient with higher risk of disease progression and frequent relapses. Vitamin D plays an important role in modulating the immune process responsible for demyelination. To this date, the study on vitamin D deficiency in optic neuritis case is still rare.&#x0D; Case Illustration : Female, 20 years old, presenting with bilateral sudden visual loss since 1 week prior. The patient looked relatively pale and complained of accompanying headache and myalgia. Visual acuity in both eyes were light perception with dilated pupils and posterior segment showing optic disc swelling. CBC, infection and autoimmune screening came within normal limit and brain MRI further confirmed the presence of optic neuritis. The patient was given high dose intravenous steroid but showed no improvement. Later, she was screened for nutrient deficiency and found sign of low serum 25-hydroxyvitamin D. After one week of oral supplementation and neuroprotective agents, her vision drastically improved to 6/6 in both eyes.&#x0D; Discussion : Vitamin D deficiency nowadays is getting more prevalent in high risk individuals with low dietary intake and sunlight exposure. Recent study found that mean serum vitamin D level were significantly lower in autoimmune optic neuritis (ON) and were associated with ON attack severity. Vitamin D sufficiency is associated with better inflammatory outcome and long term neurodegenerative measures in demyelinating diseases, as shown by improvement in RNFL thickness after attack.&#x0D; Conclusion : Screening for vitamin D deficiency is essential to consider in managing patient with atypical optic neuritis.

The effect of three years of vitamin D supplementation on erectile dysfunction: Results from the randomized placebo-controlled D-Health Trial

Background & AimsErectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial. MethodsThe D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N=3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups. ResultsOf the 11,530 men enrolled, 8,920 (77.4%) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p<0.0001). The prevalence of erectile dysfunction was 58.8% and 59.0% in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95% CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses. ConclusionSupplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction. Clinical Trials Registry(ACTRN12613000743763)

The association between serum 25-hydroxyvitamin D levels and psoriasis in a large population-based cohort: across-sectional analysis of The Tromsø Study 2015-16.

Case-control studies indicate an association between lower serum 25-hydroxyvitamin D [25(OH)D] levels and psoriasis. Data from larger population-based cohorts including mild cases are sparse. To investigate the association between 25(OH)D and psoriasis in a large population-based cohort, and assess possible effect modification by overweight. Data from the Tromsø Study 2015-16 (Tromsø7), which included 19 520 participants from the general population aged 40-79 years, were subjected to a cross-sectional analysis. We assessed the shapes of the relationships between 25(OH)D and psoriasis using fractional polynomials. Odds ratios (ORs) for lifetime and active psoriasis were estimated using logistic regression. Adjusted models included month of blood sampling, body mass index (BMI), age and sex. Two-way and additive interaction between BMI and 25(OH)D were explored. From a total of 19 520 participants [10 203 women (52.3%); mean age 56.3 years (SD 10.4); mean 25[OH]D, 63.4 nmol L-1 (SD 21.9)], 2088 (10.7%) reported lifetime psoriasis and 1179 (6.0%) reported active psoriasis the past 12 months. There was no association between 25(OH)D and lifetime psoriasis [OR per 10 nmol L-1 increase in 25(OH)D 1.02, 95% confidence interval (CI) 0.99-1.04]. The relationship between 25(OH)D and active psoriasis was suggested to be nonlinear, but the model was not significant (P = 0.098). There was evidence for a superadditive effect (i.e. larger than the sum of the factors) of BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1 on the odds for active psoriasis (OR 1.92, 95% CI 1.18-3.12), but not for lifetime psoriasis (OR 1.41, 95% CI 0.93-2.15). There was no evidence for two-way interaction between BMI and 25(OH)D. This large population-based study found no significant relationship between 25(OH)D and psoriasis. The analysis may have been underpowered to detect a threshold effect in the lower 25(OH)D spectrum. Interaction analysis indicates that high BMI and vitamin D deficiency combined increase the odds of active psoriasis more than the sum of these factors, with an estimated 92% higher odds for active psoriasis in participants with BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1. Providing advice to prevent vitamin D deficiency may be considered in the follow-up of overweight patients with psoriasis.

Vitamin D and hypophosphatemia in patients with anorexia nervosa and avoidant/restrictive food intake disorder: a case control study

BackgroundRefeeding hypophosphatemia (RH) is a common complication of nutritional restoration in malnourished individuals, yet clear risk stratification remains elusive. Individuals with anorexia nervosa (AN) and avoidant/restrictive food intake disorder (ARFID) may be deficient in vitamin D, an important component of dietary phosphorus absorption in the gut. The relationship between vitamin D and RH in AN and ARFID is unknown. Therefore, the aims of this study were to (1) report rates of low serum 25-hydroxy vitamin D and RH in AN and ARFID; (2) describe associations between phosphorus and variables associated with RH identified in extant literature; (3) examine the relationship between 25-hydroxy vitamin D and RH and (4) investigate moderation by vitamin D between variables of interest and phosphorus level.MethodAnalyses included retrospective chart review of 307 individuals admitted to the ACUTE Center for Eating Disorders and Severe Malnutrition with a diagnosis of AN or ARFID. Variables of interest included admission laboratory values (vitamin D level, comprehensive metabolic panel, hemoglobin, point-of-care blood glucose), anthropometric measures (weight, body mass index [BMI], % ideal body weight [IBW]), age, duration of illness, length of stay, feeding method, and serum phosphorus nadir. Pearson and Spearman rank correlation, one-way ANOVA, and regression analyses were used to determine the relationship between variables and serum phosphorus.ResultsOver 1/3 of the sample (35.3%) had serum phosphorus levels ≤ 2.9 mg/dL. There were no significant differences between groups in phosphorus nadir (p = .17, η2 = 0.12) or hypophosphatemia (p = .16, ϕc = 0.11). Thirty-five (35%) of individuals with ARFID were either deficient or insufficient in vitamin D, compared to 29% of individuals with AN. Individuals with AN had significantly higher mean vitamin D levels compared to those with ARFID (p = .03; η2 = 0.015). Nadir phosphorus showed a positive association with weight, BMI, %IBW, potassium, and calcium on admission, and a negative association with length of stay, hemoglobin, and total number of tube-fed days. Higher levels of 25-hydroxy vitamin D moderated the relationship between serum phosphorus nadir and weight on admission (p = .0004).ConclusionIndividuals diagnosed with ARFID are as nutritionally fragile as those with AN regarding vitamin D and RH. The negative feedback loop involving vitamin D that maintains phosphorus homeostasis may play a role in the development of RH in AN and ARFID.

Correlation between 25-hydroxy-vitamin D and Parkinson's disease

BackgroundPrevious cross-sectional studies have shown that Parkinson’s disease (PD) patients have lower serum 25-hydroxyvitamin D (25(OH)D) concentrations than controls. Other studies have not yet tested whether research findings from other regions are generalizable to Chinese populations. In this case-control study, we examined the correlation between 25-hydroxyvitamin D and Parkinson's disease. MethodsWe established an association between 25-hydroxyvitamin D deficiency and PD in a case-control study of 100 PD patients and 100 control subjects free of neurological disease at the First Affiliated Hospital of Xinjiang Medical University. ResultsTotal 25-hydroxyvitamin D levels were deficient in 21 % of patients with PD compared with 4 % of controls. In univariate analyses, plasma levels of 25-hydroxyvitamin D were associated with PD (p < 0.001). In multivariate analyses, vitamin D deficiency (25(OH)D < 20 ng/mL) was significantly associated with PD (p = 0.008, Odds Ratio =17.13, 95 % CI= 2.082–141.075). Individuals with 25(OH)D levels in the lowest quartile had the highest prevalence of PD (p = 0.026, OR=11.786, 95 % CI =1.342–103.51 compared to individuals with values in the highest quartile). ConclusionsOur study reveals an association between 25-hydroxyvitamin D and PD. Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls. High-risk PD patients with vitamin D deficiency who have not yet developed exercise impairment should undergo vitamin D measurement and any necessary treatment as soon as possible. Limitations of the study: the study needs further assessment of populations with low vitamin D levels in other regions of China; further assessment of the effect of different sources of vitamin D on PD; further study of longitudinal cohorts at different time points.

Low 25-Hydroxyvitamin D [25(OH)D] Levels as a Predictor of Depressive Symptoms: Evidence from Community-Dwelling Older Adults Population in Mexico City

ABSTRACT Objective The purpose of this study was to assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels and depressive symptoms in Mexican older adults 70 years and older. Methods A total of 326 adults aged 70 or older from Coyoacán Cohort Study were included in this study. The depressive symptoms were assessing by Center for Epidemiologic Studies Depression Scale (CES-D) and serum 25-hydroxyvitamin D [25(OH)D] levels were measured by commercially available enzyme-linked immunosorbent assay (ELISA). Results Overall, the prevalence of depressive symptoms was 36.5%. The mean age was 79 years, and 53.4% were women. The total serum 25-hydroxyvitamin D [25(OH)D] levels were lower in older adults with depressive symptoms when compared with older adults without depressive symptoms (p = .006). Logistic regression models showed a significant association between low serum 25(OH)D levels and depressive symptoms even after adjusting for potential confounders (OR = 2.453; 95% CI:1.218–4.939; p = .012). In addition, linear regression model to predict the effect of 25-hydroxyvitamin D [25(OH)D] levels on the CES-D score as a continuous variable, was statistically significant [F(1,324) = 8.54, p = .004], and the R-squared value was .026, indicating that this regression model explains 2.6% of the change in the CES-D score. Conclusion These results suggest that older Mexican adults with lower serum 25-hydroxyvitamin D [25(OH)D] levels are at higher risk of presenting depressive symptoms.

Causal Effect of the 25-Hydroxyvitamin D Concentration on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

Previous observational studies reported that a lower serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with a higher burden of cerebral small vessel disease (cSVD). The causality of this association is uncertain, but it would be clinically important, given that 25(OH)D can be a target for intervention. We tried to examine the causal effect of 25(OH)D concentration on cSVD-related phenotypes using a Mendelian randomization approach. Genetic instruments for each serum 25(OH)D concentration and cSVD-related phenotypes (lacunar stroke, white matter hyperintensity, cerebral microbleeds, and perivascular spaces) were derived from large-scale genome-wide association studies. We performed 2-sample Mendelian randomization analyses with multiple post hoc sensitivity analyses. A bidirectional Mendelian randomization approach was also used to explore the possibility of reverse causation. We failed to find any significant causal effect of 25(OH)D concentration on cSVD-related phenotypes (odds ratio [95% CI], 1.00 [0.87-1.16], 1.01 [0.96-1.07], 1.06 [0.85-1.33], 1.00 [0.97-1.03], 1.02 [0.99-1.04], 1.01 [0.99-1.04] for lacunar stroke, white matter hyperintensity, cerebral microbleeds, and white matter, basal ganglia, hippocampal perivascular spaces, respectively). These results were reproduced in the sensitivity analyses accounting for genetic pleiotropy. Conversely, when we examined the effects of cSVD phenotypes on 25(OH)D concentration, cerebral microbleeds were negatively associated with 25(OH)D concentration (0.94 [0.92-0.96]). Given the adequate statistical power (>0.8) of the analyses, our findings suggest that the previously reported association between 25(OH)D concentration and cSVD phenotypes might not be causal and partly attributed to reverse causation.

Local production of active vitamin D3 metabolites in breast cancer cells by CYP24A1 and CYP27B1

The role of vitamin D3 and its metabolites in cancer and especially as a treatment option has been widely disputed. Clinicians noting low serum 25-hydroxyvitamin D3 [25(OH)D3] levels in their patients, recommend vitamin D3 supplementation as a method of reducing the risk of cancer; however, data supporting this are inconsistent. These studies rely on systemic 25(OH)D3 as an indicator of hormone status, but 25(OH)D3 is further metabolized in the kidney and other tissues under regulation by several factors. This study examined if breast cancer cells also possess the ability to metabolize 25(OH)D3, and if so, whether the resulting metabolites are secreted locally; if this ability reflects ERα66 status; and if they possess vitamin D receptors (VDR). To address this question, estrogen receptor alpha (ERα) positive (MCF-7) and ERα negative (HCC38 and MDA-MB-231) breast cancer cell lines were examined for expression of ERα66, ERα36, CYP24A1, CYP27B1, and VDR as well as for local production of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] after treatment with 25(OH)D3. The results showed that independent of ER status, breast cancer cells express the enzymes CYP24A1 and CYP27B1, which are responsible for converting 25(OH)D3 into its dihydroxylated forms. Moreover, these metabolites are produced at levels comparable to the levels observed in blood. They are positive for VDR, indicating that they can respond to 1α,25(OH)2D3, which can upregulate CYP24A1. These findings suggest that vitamin D metabolites may contribute to the tumorigenicity of breast cancer via autocrine and/or paracrine mechanisms.

The effect of monthly vitamin D supplementation on fractures: a tertiary outcome from the population-based, double-blind, randomised, placebo-controlled D-Health trial

Low serum 25-hydroxy vitamin D concentration is associated with increased fracture risk. It is uncertain whether vitamin D supplementation reduces fractures, or whether intermittent doses are harmful. We aimed to investigate if supplementing adults living in Australia with monthly doses of 60 000 international units (IU) vitamin D3 for 5 years or less altered the rate of fractures. We did a population-based, double-blind, randomised, placebo-controlled trial of oral vitamin D3 supplementation (60 000 IU per month) for up to 5 years in adults aged 60-84 years living in Australia. We randomly assigned (1:1) 21 315 participants to either vitamin D or placebo. We ascertained fractures through linkage with administrative datasets. The main outcome was total fractures. Additional outcomes were non-vertebral, major osteoporotic (hip, wrist, proximal humerus, and spine), and hip fractures. We excluded participants (989 [4·6%]) without linked data, and estimated hazard ratios (HRs) and 95% CIs using flexible parametric survival models. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763, and the trial intervention ended in February, 2020. Between Feb 14, 2014, and June 17, 2015, we recruited 21 315 participants. For the current analysis, we included 20 326 participants (vitamin D 10 154 [50·0%]; placebo 10 172 [50·0%]). 9295 (45·7%) of 20 326 participants were women and the mean age was 69·3 years (SD 5·5). Over a median follow-up of 5·1 years (IQR 5·1-5·1), 568 (5·6%) participants in the vitamin D group and 603 (5·9%) in the placebo group had one or more fractures. There was no effect on fracture risk overall (HR 0·94 [95% CI 0·84-1·06]), and the interaction between randomisation group and time was not significant (p=0·14). However, the HR for total fractures appeared to decrease with increasing follow-up time. The overall HRs for non-vertebral, major osteoporotic, and hip fractures were 0·96 (95% CI 0·85-1·08), 1·00 (0·85-1·18), and 1·11 (0·86-1·45), respectively. These findings do not support concerns that bolus doses of vitamin D administered monthly increase fracture risk. Long-term supplementation might reduce the incidence of total fractures, but additional research is needed to clarify this effect. Australian National Health and Medical Research Council.

Effect of the serum 25-hydroxyvitamin D level on risk for short-term residual dizziness after successful repositioning in benign paroxysmal positional vertigo stratified by sex and onset age.

A low serum 25-hydroxyvitamin D (25(OH)D) level is relevant to both the occurrence and recurrence of benign paroxysmal positional vertigo (BPPV). However, whether it also contributes to residual dizziness (RD) after successful repositioning maneuvers is unknown. Therefore, this study aimed to explore the correlation between the serum 25(OH)D level and short-term RD severity in patients with BPPV after successful repositioning maneuvers. In total, 251 patients with BPPV after successful repositioning were enrolled and prospectively followed up for 1 week (W1). Serum 25(OH)D values were detected by chemiluminescence immunoassay at enrollment (W0). In addition, we explored the relationship between 25(OH)D values at baseline and RD severity at W1 in different subgroups stratified by sex and onset age (early-onset, ≤50 years; late-onset, >50 years). The serum 25(OH)D level of female patients was significantly lower than that of male patients (15.9 ± 6.8 vs. 19.8 ± 6.6 ng/ml, p < 0.001). Its level also decreased in early-onset patients compared to late-onset ones (15.3 ± 5.9 vs. 18.0 ± 7.3 ng/ml, p = 0.003). In addition, early-onset female patients had lower 25(OH)D values than late-onset female patients (14.0 ± 5.5 vs. 17.1 ± 7.2 ng/ml, p = 0.004). However, this difference was not observed between early- and late-onset male patients. Among early-onset female patients, the 25(OH)D values of the moderate-to-severe RD group were lower than those of the minor or no RD group (10.9 ± 3.3 vs. 14.7 ± 5.7 vs. 15.0 ± 5.9 ng/ml, p = 0.046). Multivariate analysis found that decreased 25(OH)D values were related to the occurrence of moderate-to-severe RD in early-onset female patients (OR = 0.801; p = 0.022). This effect did not exist in late-onset female or male patients with BPPV. Age and sex differences in serum 25(OH)D levels exist in patients with BPPV. A decreased 25(OH)D level in early-onset female patients may increase the odds of moderate-to-severe RD 1 week after successful repositioning maneuvers.

“TO ESTIMATE VITAMIN D DEFICIENCY IN OBESE AND NON OBESE FEMALES WITH TYPE 2 DIABETES MELLITUS IN NORTH INDIA”

Background: Vitamin D deciency is prevalent among obese individuals. Some authors have postulated that Vitamin D is sequestered in the excess adipose tissue, leading to less bioavailability, whereas others suggest that low Serum 25-hydroxy Vitamin D may be a result of volumetric dilution of vitamin D in the large adipose stores. Aim: To study and compare the Vitamin D levels in Obese and Non-obese diabetic female with obese and Non-obese nondiabetic females. Method &amp; Materials: The present study was conducted in the Department of Medicine, MLN Medical College &amp; SRN Hospital, Prayagraj to assess Vitamin D levels of diabetic and non-diabetic obese and non-obese females. A total of 115 diabetic female patients attending Clinic fullling the inclusion criteria and giving consent were included as Cases and 115 female non-diabetic patients without active or chronic problems attending different departments were included in the study. Serum samples of all the participants were collected for estimation of 25-hydroxy vitamin D (25-OH vitamin D). Quantitative determination of 25- hydroxy vitamin D (25- OH vitamin D) in human serum is done by chemiluminescent microparticle immunoassay (CMIA). Result: Majority of Controls had Normal Vitamin D levels (52.2%) , on the other hand only 1.7% cases had normal Vitamin D levels. Vast majority of Cases (98.3%) had Vitamin D deciency. Higher percentage of Cases were found to have mild and severe vitamin D deciency as compared to that in controls. [Mild Vitamin D deciency -12.2% vs. 11.3% in cases and controls respectively and severe Vitamin D deciency - 86.1% vs. 36.5% in cases and controls respectively] . Difference in vitamin D status of Cases and Controls was found to be signicant statistically. Serum Vitamin D levels of Controls (29.18±20.31 ng/ml) was found to be signicantly higher as compared to Cases (9.06±6.03 ng/ml). Conclusion- Mean serum vitamin D levels were signicantly lower in Diabetic females as compared to that in Non-Diabetic females.Obesity was associated with a signicantly lower vitamin D levels in both Diabetic females as well as Non-Diabetic females.

Abstract 49: The Effects of Vitamin D Supplementation on Subclinical Cardiovascular Disease: Results From the Sturdy Trial

Background: In observational studies, older adults with insufficient or deficient serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation. This is possibly because the doses of vitamin D supplements tested were too low. Objective: To determine if higher doses of vitamin D supplementation lower high sensitivity cardiac troponin level (hs-cTnI) and N-terminal pro b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD. Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, and 4000 IU/day) on fall risk in adults aged ≥70 years old with low serum 25-hydroxyvitamin D levels (10-29 ng/ml). Hs-cTnI and NT-proBNP levels were measured at baseline and at 3-, 12- and 24-month follow-up visits. For analysis, participants were divided into low (200 IU/day) and high dose (1000+ IU/day) vitamin D treatment groups. The effects of vitamin D dose on hs-cTnI and NT-proBNP were assessed via mixed effects tobit models. Results: Among 688 participants (mean age of 77 ± 5 years, 44% were women, and 18% were Black), 50.7% were in the high-dose treatment group (1000+ IU/day). Hs-cTnI increased in both the low and high dose groups by 5.1% and 5.8%, respectively; likewise, NT-proBNP increased in both groups by 11.3% and 9.3%, respectively ( Figure). Compared to the low-dose group, high-dose vitamin D treatment did not affect hs-cTnI (1.7 % difference; 95% CI: -5.3, 9.3) or NT-proBNP (-1.8 % difference; 95% CI: -9.3, 6.3). Conclusions: Compared to low dose vitamin D supplementation, a higher dose did not affect markers of subclinical CVD in older adults with low serum vitamin D levels. These findings do not support higher doses of vitamin D as an intervention to reduce the risk of CVD in this population.