VitD Levels Research Articles

ODP109 PARATHYROID HORMONE AND 25 OH VITAMINA D IN PREGNANCY: DATA FROM AN ARGENTINEAN COHORT SUPPORTING SUPPLEMENTATION.

Abstract Vitamin D (Vit D) deficiency has become a global health care issue, as it affects a great number of women during pregnancy and lactation. Vit D levels are critical during pregnancy, being the mother the only source of them for the developing fetus; an enzymatic system for conversion of 25OH VitD into 1-25(OH) 2 VitD is present in the placenta, thus reinforcing the importance of VitD during gestation. VitD deficiency has been associated with obstetric complications and adverse outcomes in offspring, affecting skeletal, immunological and respiratory systems. It is known that prenatal supplements available do not contain enough VitD to fulfil requirements. It is generally accepted that elevated PTH is an indicator of VitD deficiency, and Hysaj O et al (2021) showed that 25OH VitD is a statistically significant determinant of PTH levels in early and late pregnancy. Aim To evaluateVitD status and its relationship to parathyroid hormone (PTH) in a cohort of pregnant women representative of multiple Argentinian regions. Subjects and Methods Data from samples of 423 pregnant women in 1st and 2nd trimester were collected between 2016 and 2021. VitD was measured in different platforms: DiaSorin Liaison CLIA (n=184), Roche COBAS ECLIA (n=166), Abbott ARCHITECT CMIA (n=33), Biomérieux VIDAS ELFA (n=18) and Siemens CENTAUR CLIA (n=16). PTH (ng/L) was measured in 162 samples by SIEMENS IMMULITE CLIA and Roche COBAS ECLIA. As VitD is light-exposure dependent, we considered warm and high light-exposure season period from December to March and cold and low light season from April to September. VITD (ng/L) levels were classified as Deficient (<20), Insufficient (between 21 and 29) and Sufficient (>30) (Endocrine Society, 2014). Results From 423 data collected, 102 were excluded because of lacking information on VitD supplementation. From the remaining non supplemented 321 samples, 48% resulted insufficient, 30% deficient and 22% sufficient for VitD (groups comparison: p< 0. 05, Kruskal Wallis-Dunn test). The seasonal period and pregnancy trimester distributions didn't show significant differences. Similar results of VitD insufficiency were found in the major used platforms, regardless the seasonal period considered. PTH results expressed as median and interquartile range were (ng/L): 32. 0 (13.7-169. 0) in Deficient pregnancies (N=92), 23.7(13.3-88. 0) in Insufficient (n=50) and 18.7 (9.8-55.7) in Sufficient (n=20). Conclusions This study shows VitD inadequate levels in 78% in non-supplemented pregnancies, regardless season or measurement platform. Relative elevated levels of PTH were associated to pregnancies with VitD deficiency, evidenciating a regulatory role according to published data. To improve VitD status during pregnancy it would be advisable to pose new strategies for prenatal supplements developed by a multidisciplinary professional team. Presentation: No date and time listed

Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients

BackgroundSeveral studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors’ interplay remains unknown. Methods74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo. Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). Results60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids’ biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). ConclusionsVitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.

Vitamin D enhances type I IFN signaling in COVID-19 patients

The ability of Vitamin D (VitD) to modulate antiviral responses through induction of antimicrobial peptide is well established. However, the effect of VitD on host responses to SARS-CoV-2 is not well investigated. We here report the ability of VitD to enhance host IFN-alpha/beta (a/β) signaling both in vitro and among severe COVID-19 patients treated with VitD. Blood and saliva specimens were obtained from severe COVID-19 patients treated (43 patients), or not (37 patients), with vitD, during their stay in intensive care unit. Patients were followed up to 29 days following admission, and patient survival outcomes were collected. Higher activity levels of RIG-1/MDA-5 and JAK-STAT signaling pathways were observed with significantly higher gene and protein levels of antiviral interferon stimulating genes (ISGs) such as MX-1 and ISG-15; both in vitro, following treatment of PBMCs with vitD, and in whole blood and saliva specimens of VitD treated patients. Moreover, VitD treated patients had lower risk of all-cause mortality by day 29 compared to untreated patients (adjusted hazard ratio, 0.37, 95% confidence interval of 0.14–0.94; P = 0.038). The herein uncovered regulatory role of VitD on type I IFNs suggests the importance of insuring a normal level of VitD for the prevention and probably treatment of SARS-CoV-2 infection. Additional mechanistic studies, however, are needed to fully elucidate the antiviral effects of VitD particularly in the setting of COVID-19 infection.

Serum Vitamin D Among Patients withType 2 Diabetes Mellitus

Vitamin D supplements are a beneficial health issue to benefit from insulin therapy. In those with T2DM, serum vit-D was checked and resuscitated. Serum vit-D was evaluated with its rich content. Serum vit D levels were statistically significantly lower in T2DM patients than in the control group. It was found to be significant in terms of the relationship between fasting blood sugar and vit-D and HbA1C. Vit-D in sugar will be used as a benefit from vit-D in patients with blood T2DM patients. The mean±SD vit-D level was 19.22±9.23 for the whole population with a fasting blood glucose level of 110 mg/dl or less, and 12.21±6.15 for people with a fasting blood glucose level above 130 mg/dl, and p<0.001. The relationship between vit-D level and fasting blood sugar is statistically significant with negative pearson correlation coefficient. Vit-D mean±SD 20.46±8.56 for the entire population with an HbA1C level equal to or lower than 6.5%, and 12.84±6% for individuals with a fasting blood glucose level above 6.5%, is 26 and p<0.001. The strong relationship between vit-D and fasting blood glucose and HbA1C is due to the fact that vit-D tends to specifically stimulate insulin production in β-pancreatic cells via the nuclear vit-D receptor (VDR) and that vit-D minimizes inflammation. Vit-D supplements are a beneficial health challenge to benefit from insulin therapy. Serum vit-D was checked in patients with T2DM. The serum has been evaluated with its rich content of vit-D. Serum vit-D levels were statistically significantly lower in T2DM patients compared to the control group. It was found to be significant in terms of the relationship between fasting blood sugar and vit-D and HbA1C. Vit-D in sugar will be used as a benefit from vit-D in blood T2DM patients.Keywords: Vitamin D, Serum, Type 2 Diabetes Mellitus, Human.

The relationship between subclinical hypothyroidism and vitamin D

Aim: Vitamin D (vitD) is primarily responsible for bone formation and mineralization. However, in recent years, it has been suggested that vitD may play a role as an immune modulator in the development of numerous diseases, including autoimmune diseases. It has been observed that there is an association between chronic autoimmune thyroiditis (AIT) and vitD levels. This study aims to investigate whether there are differences in the levels of 25-hydroxy vitamin D [25(OH)D], calcium, and phosphorus in patients with subclinical hypothyroidism (SCH) due to AIT, in patients with antibody-negative subclinical hypothyroidism (ANSCH), and in healthy control subjects. Material and Method: Data from 50 newly diagnosed patients with SCH (35 of whom AIT) and 50 euthyroid and antibody-negative healthy controls who presented to the Department of Endocrinology and Internal Medicine at our hospital between 2018 and 2020 were retrospectively reviewed. Calcium, phosphorus, and 25(OH)D levels of patients and controls were compared. Results: Serum 25(OH)D levels were significantly lower in patients compared to controls (16.2±7.8 ng/ml and 20.4±8.2 ng/ml, respectively; p=0.024). Serum levels of calcium (p=0.081) and phosphorus (p=0.712) did not differ between groups. In a subgroup analysis, patients with AIT had significantly lower 25(OH)D values than controls (p=0.009). Compared to controls, 25(OH)D levels were comparable in the ANSCH group (p=0.096). 25(OH)D level was higher in the AIT group than in the ANSCH group (p=0.01). Conclusion: Our results show that patients with SCH have lower 25(OH)D levels than healthy controls. However, this difference is significant in patients with AIT. It is recommended to screen for vitD deficiency in patients with SCH due to AIT.

Antibody dynamics post-Comirnaty and CoronaVac vaccination in Malaysia

Several vaccines have been fast-tracked through clinical trials to mitigate the progression of the SARS‑CoV‑2 pandemic. We analyzed sequential blood samples from 314 recipients of Comirnaty and CoronaVac in East Malaysia for the spike-binding IgG (IgG-S), nucleocapsid-binding IgG (IgG-N), spike-binding IgM (IgM-S) and serum vitamin D (VitD). A subset of samples was analyzed for the neutralizing antibodies (Ig-RBD). Results showed that IgG-S due to Comirnaty was significantly higher than CoronaVac. IgM-S was detected in 80.0% Comirnaty and 69.5% CoronaVac recipients, while IgG-N was detected in 58.1% CoronaVac but not in Comirnaty recipients. All IgG-S-positive vaccines possessed detectable Ig-RBD after the second dose but with a weak to moderate correlation. The serum VitD levels did not influence the antibody magnitude in both vaccines. In essence, SARS-CoV-2 vaccination is an IgG-S-dominant event, Comirnaty was more effective than CoronaVac in mounting IgG-S and Ig-RBD responses, independent of the patient’s VitD level.

Association between serum vitamin D status and the anti-seizure treatment in Chinese children with epilepsy.

ObjectiveTo compare the serum 25-OH-VitD levels, the major marker of vitamin D (VitD) status, between healthy children and children with epilepsy before initiation of and during anti-seizure medications (ASMs) treatment and to evaluate the potential influence factors on 25-OH-VitD levels. Another major aim was to assess the potential role of VitD supplementation.MethodsFor comparison, we finally enrolled and collected data from 6,338 healthy children presenting to Health Care Department and 648 children visiting primary care pediatricians with symptoms of epilepsy in Children’s Hospital of Nanjing Medical University from January 2019 to June 2021. The demographic and biochemical characteristics of each child were extracted from the hospital information system.ResultsSerum 25-OH-VitD levels in 648 children with epilepsy were significantly lower than those of 6,338 healthy children (P < 0.0001), and the percentage of VitD insufficiency and deficiency status in pediatric patients was 49.19%. Of note, the serum 25-OH-VitD levels in children with newly diagnosed epilepsy before receiving any ASMs treatment were also significantly lower than those in healthy controls. Interestingly, ASMs therapy, alone or in combination, did not consistently reduce baseline serum VitD levels in children with epilepsy. The lower serum VitD levels in pediatric patients than those in healthy children might be related to the disease itself, rather than the ASMs treatment. As expected, VitD supplementation substantially increased the serum 25-OH-VitD levels (P < 0.0001). More critically, children with epilepsy receiving VitD supplementation achieved good seizure control in our study.SignificanceIn this retrospective study, the childhood epilepsy before initiation of and during ASMs treatment decreased the serum 25-OH-VitD concentrations, suggesting a clear association between epileptic disease and the risk of VitD deficiency. ASMs coadministration and long-term valproic acid treatment did not worse VitD-deficiency status, but in the small group receiving VitD supplementation, there was a significant improvement in reduction of seizure frequency. Therefore, pediatric clinicians are urged to raise public awareness of epilepsy-associated VitD deficiency.

Effect of atorvastatin and rosuvastatin on 25-hydroxy vitamin d levels in newly diagnosed South Indian dyslipidemic subjects

Background: Statins are one of the mainstay treatment modality for the people suffering from dyslipidemia. Statins reduce the cholesterol bio-synthesis by ß-hydroxy-ß-methyl glutaryl Co-A (HMG-CoA) reductase inhibition which is rate-limiting enzyme. It also affects the Vit-D levels as metabolism of cholecalciferol and cholesterol are interrelated. Objectives: Effect of atorvastatin/ rosuvastatin on 25-hydroxy Vitamin-D (25OHD) concentrations among subjects with newly diagnosed dyslipidemia. Materials and Methods: Prospective randomized, open-label, parallel group study. Lipid and 25OHD levels are measured at baseline and end of 6 months after statin treatment. One group received atorvastatin and another study group received rosuvastatin for 6 months. Results: Mean 25OHD concentrations are 32.0±4.7, 31.7±4.8 and 32.9±4.9 in the control, atorvastatin and rosuvastatin groups respectively. Both atorvastatin and rosuvastatin groups, except TGs, all the lipid parameters and 25OHD has showed significant difference (&lt;0.001) from baseline to end-line repeated parameters. All the study participants were well tolerated and no one discontinued the drug due to drug-related adverse reactions. Conclusion: Participants with atorvastatin treated group showed significant reduction in 25OHD concentrations. In addition, 25OHD concentrations are dependent on statin efficacy.

The importance of analyzing the serum C3-epimer level for evaluating vitamin D storage in some special populations.

The serum 25-hydroxyvitamin D [25(OH)D] is recommended by various management agencies for evaluating the nutritional status of vitamin D (VitD). However, 25(OH)D cannot reflect the actual composition and activity of VitD in vivo. This study used UPLC-MS/MS to detect the levels of serum VitD metabolites in some special populations, so as to clarify its importance in accurately evaluating VitD storage in vivo. A total of 2029 subjects were enrolled, including 1204 cases in minor health (MH), 467 in the minor disease (MD), 119 in the adult health (AH) and 239 in adult disease (AD). Serum VitD2 and VitD3 levels were measured by UPLC-MS/MS. Serum C3-epi concentrations were also measured in 144 subjects by a spot check method. There were significant differences in the levels of VitD2, VitD3 and 25(OH)D among groups (all p <0.001). According to serum level of 25(OH)D, percentage of subjects with sufficient VitD in the MH, MD, AH and AD group were 65.4%, 52.7%, 29.4% and 20.9%, respectively. After converting VitD2 activity to AVitD3, subjects with sufficient VitD in MH, MD, AH and AD group accounted for 53.2%, 40.9%, 17.7% and 11.3%, respectively. C3-epi levels in the MH (z = 7.49, p <0.001), MD (z = 7.03, p <0.001) and AD group (z = 4.68, p <0.001) were higher than that in the AH group. Not only the serum 25(OH)D level, but also the simultaneous detection of VitD2 and VitD3 levels will overestimate the VitD storage in some subjects. Accurate evaluation of VitD storage in these individuals also requires detection of C3-epi levels.

A comparative study of vit D3 levels with preterm premature rupture of membranes in pregnant mothers referred to the Bent Alhoda Hospital of Bojnurd city in 2020-2021

A comparative study of vit D3 levels with preterm premature rupture of membranes in pregnant mothers referred to the Bent Alhoda Hospital of Bojnurd city in 2020-2021

Is serum vitamin D associated with diabetic retinopathy and its severity or with diabetes itself ?

ABSTRACT Clinical relevance Vitamin D (VitD) deficiency, which is found in approximately one-third of the population of the world, may play a role in the pathogenesis of diabetic retinopathy. Physicians following diabetes patients should be aware of this relationship and should refer patients to for ophthalmic care for control in a timely manner. Background Diabetic retinopathy is one of the most common complications of diabetic microvascular disease. VitD deficiency has been implicated in the pathogenesis and progression of diabetes and may have a role in development and severity of diabetic retinopathy. The aim of this study was to examine the relationship of serum VitD and some laboratory parameters with the presence of diabetes and retinopathy. Methods In this study, which has a retrospective epidemiological study design, comprehensive ophthalmologic examination data from the eye clinic, laboratory data from fasting blood tests, and internal medicine outpatient clinic examination data were reviewed. All participants were divided into four groups: 109 healthy controls, and 165 patients with type 2 diabetes of whom 54 did not have retinopathy, 64 had proliferative diabetic retinopathy, and 47 had non-proliferative diabetic retinopathy. Participants were also divided into four groups according to their serum VitD levels. Serum 25(OH)D, HbA1C, creatine, calcium, phosphate, triglyceride, low-density lipoprotein, and high-density lipoprotein levels were evaluated. Results In the whole study cohort, 152 (55.5%) were female and 122 (44.5%) were male. A statistically significant difference was observed in VitD between the healthy group and the diabetic and proliferative diabetic retinopathy groups (p ≤ 0.001). However, no significant correlation was observed between the presence of diabetes and retinopathy and serum VitD in logistic regression analyses (p > 0.05). Conclusion Diabetic patients have lower 25(OH)D than non-diabetic patients and there is no direct relationship between 25(OH)D and the development of diabetic retinopathy.

Effect of Replacement of Vit-D in Diabetic Painful Neuropathy among Chronic Type 2 Diabetic Patients

Background: Painful symptoms of diabetic neuropathy are more common in patients having type 2 diabetes. The objective in this trial was assessment of mean change in pain score upon giving Vit-D supplementation in patients with diabetic painful neuropathy.&#x0D; Methodology: This study was conducted from December 2019 to June 2020 in OPD of Fauji Foundation Hospital, Rawalpindi after the ethical approval. A total of 251 diagnosed cases of diabetes (both male and female patients), with high HbA1c and low Vit-D levels were included in the study. Patients having Vit-D deficiency and chronic diabetic neuropathy were given Vitamin supplementation and results were assessed after 1 month through change in pain score according to Douleur Neuropathique 4. A document of consent form was filled by patients who were recruited for this study. Data analysis was done on SPSS version 16.Paired sample t- test, was used to compare pain score where p value less than 0.05 was considered statistically significant.&#x0D; Results: Among the participants mean age was 48.22+17.06. There were 106 (42.2%) males and 145 (57.8%) female patients. A statistically significant (p&lt;0.05)mean reduction in pain score of 2.20±1.19 was observed, upon giving Vit-D supplementation in Vit-D deficient patients having painful diabetic neuropathy.&#x0D; Conclusion: Vit-D supplementation significantly reduced pain in patients having diabetic painful neuropathy.&#x0D; Keywords: Diabetes Mellitus, Diabetic Neuropathy, Vitamin D3

Vitamin D and its Relationship with Female Outfit Dressing Style

Background: Vitamins, minerals, and other important nutrients we get from food can keep our bodies healthy, and to get strong bones, we need calcium and vitamin D. Vit D3 titled the “sunshine vitamin,” is one of the important nutrients needed for a female’s health. Vit D had a constant function in adaptive and inherent immunity. Exposure to sunlight has a major role in providing adequate Vit D for most people in the world. Aim of the study: Our study aims to evaluate Vit D and calcium levels in healthy young females of child-bearing age and to inspect the effects of their outfit dressing. Methods: A total of 108 women were included, those wearing full cover outfit style clothing covering all body leaving the face area and hand exposed group I (74 women), and uncovered women with exposed head, arms, and legs group II (34 women). A quantitative test was used to determine 25-hydroxy Vit D in human serum using minividase and for total calcium measurement atomic absorption spectrophotometry. Results: All women in both groups had a blood test for calcium (Ca) and Vit D3 level levels, and a calculation of body mass index (BMI) was done. Using t-test for the comparison between (group I and group II).A significant difference (p is less than 0.005) was found in serum Vit D3, which was lower in group I with a mean (12.09 ± 7.59), and for group II, it was (16.56 ± 7.61). Serum calcium was slightly elevated in group II than in group I, but there was no significant between the two groups. The mean serum calcium level was (9.41) in group I and (9.56) (p is less than 0.3) in group II. Although body mass index was higher in group I mean (28.73 ± 0.61) than group II mean (27.25 ± 4.88), it was statistically not significant (p is less than 0.2). Conclusion: The finding of this study revealed that many factors could affect Vit D levels, like clothing styles and lifestyle. Inadequate Vit D intake and covered dress style can lead to low Vit D levels. A recommendation that has been suggested when there is no Vit D intake is to expose the face area, arms, and hands for a short duration in the middle of the day many times a week to have normal Vit D levels.

P1513: LOW VITAMIN D LEVELS ARE ASSOCIATED WITH INCREASED CARDIAC IRON UPTAKE IN THALASSEMIA MAJOR.

Background: Decreased vitamin D (VitD) levels stimulate the expression of the transmembrane L-type voltage-dependent calcium channels (LVDCC), which, in addition to calcium, absorb iron. However, there is little and controversial data on the correlation of VitD levels with cardiac iron. Aims: We investigated the association between vitamin D levels and cardiac iron and function in thalassemia major (TM) patients. Methods: We considered 278 TM patients (39.04±8.58 years, 56.8% females), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Myocardial iron overload (MIO) was quantified using a T2* segmental approach. Left ventricular (LV) function parameters were quantified by cine images. Measurement of serum 25(OH)D was carried out using a chemiluminescent immunoassay. Results: Vitamin D supplements were taken by 61.4% of our patients. VitD levels were deficient (<20 ng/dl) in 107 (38.5%) patients, insufficient (20–30 ng/dl) in 96 (34.5%) patients and adequate (>30 ng/dl) in 75 (27.0%) patients. Patients with deficient vitD levels were significantly younger than patients with adequate (36.96±7.64 yrs vs 41.26±8.19 yrs; P<0.0001) as well as insufficient vitD levels (36.96±7.64 yrs vs 39.63±9.39 yrs; P=0.042) while no difference was detected in male to female ratio. MIO (global heart T2*<20 ms) was significantly more frequent in patients with deficient VitD than in patients with adequate and insufficient VitD levels (Figure). Patients with deficient vitD levels had a significant higher risk of MIO than patients with adequate vitD levels (odds ratio-OR=20.62, 95%CI=2.67-153.72; P=0.004) and patients with insufficient VitD levels (OR=8.49, 95%CI=2.46-29.29; P=0.001). At receiver operating characteristic curve analysis, a vitD level≤ 17.3 ng/dl predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (P<0.0001). The area under the curve was 0.79 (95% confidence interval: 0.74–0.84). Compared to patients with normal VitD levels, patients with deficient vitamin levels showed significantly higher LV end-diastolic volume index (87.61±19.19 ml/m2 vs 79.17±14.27 ml/m2; P=0.003) and LV mass index (63.39±13.55 g/m2 vs 57.45±12.90 g/m2; P=0.006). The LV ejection fraction tended to be lower in patients with VitD deficiency, but no statistical difference versus the other groups was detected. Image:Summary/Conclusion: In thalassemia major vitamin D deficiency is associated with and increased risk of cardiac iron overload. Periodic and regular assessment of VitD levels can be useful in the prevention not only of bone disorders but also of cardiac iron accumulation and subsequent overt dysfunction.

Genetically-Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage.

BackgroundThe evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH.Methods and ResultsWe conducted a 2 sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome‐wide association studies of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). We used the inverse‐variance weighted approach to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR‐Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05–2.43]; P=0.029). We found no evidence of horizontal pleiotropy (MR‐Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with P>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18–2.97]; P=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86–2.38]; P=0.17).ConclusionsLower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH.

Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves' Disease Hyperthyroidism During Methimazole Treatment.

Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves’ disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery’s response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated “Thyroid-related Patient-Reported Outcome” questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.

The Association of Vitamin D and Its Pathway Genes' Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study.

Objective: We aimed to explore the effect of single nucleotide polymorphism (SNP) in the genes of the vitamin D (VitD) metabolic pathway and its interaction with VitD level during pregnancy on the development of hypertensive disorders of pregnancy (HDP). Methods: The study was conducted in the Zhoushan Maternal and Child Health Care Hospital, China, from August 2011 to May 2018. The SNPs in VitD metabolic pathway-related genes were genotyped. Plasma 25-hydroxyvitamin vitamin D (25(OH)D) levels was measured at first (T1), second (T2), and third (T3) trimesters. The information of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the diagnosis of HDP were extracted from the electronic medical record system. Multivariable linear and logistic regression models and crossover analysis were applied. Results: The prospective cohort study included 3699 pregnant women, of which 105 (2.85%) were diagnosed with HDP. After adjusting for potential confounders, VitD deficiency at T2, as well as the change of 25(OH)D level between T1 and T2, were negatively associated with DBP at T2 and T3, but not HDP. Polymorphisms in CYP24A1, GC, and LRP2 genes were associated with blood pressure and HDP. In addition, VitD interacted with CYP24A1, GC, and VDR genes’ polymorphisms on blood pressure. Furthermore, participants with polymorphisms in CYP24A1-rs2248137, LRP2-rs2389557, and LRP2-rs4667591 and who had VitD deficiency at T2 showed an increased risk of HDP. Conclusions: The individual and interactive association between VitD deficiency during pregnancy and SNPs in the genes of the VitD metabolic pathway on blood pressure and HDP were identified.

Low baseline vitamin D levels correlate with adverse pathological features and clinical outcomes among patients with breast cancer.

552 Background: Serum vitamin D levels have been linked to breast cancer development; however, the impact on breast cancer features and outcomes remains unclear. The present study aimed at investigating the prognostic value of baseline vitamin D level among non-metastatic breast cancer patients. Methods: In this study; we prospectively assessed female patients presenting to our department with non-metastatic breast cancer during the period from October 2018 to December 2019 for their baseline serum vitamin D levels measured by ELISA test before starting systemic therapy, in addition to other clinicopathological factors. Low Vit-D was defined as Vit-D level less than 30 ng /l. Chi-square test (Fisher’s exact test) was used to examine the relation between qualitative variables. Survival analysis was done using Kaplan-Meier method and comparison between two survival curves was done using log-rank test. Multivariate analysis was done using Cox-regression hazard model for the significant factors affecting survival on univariate analysis. Results: We enrolled 221 patients with non-metastatic breast cancer as they matched our eligibility criteria. Median age at diagnosis was (50.7± 10.9). About two thirds of the patients (64.7%) were post menopause. Median vitamin D level was (23.1 ng/l) with a range of (4-62.46 ng/liter). Around half of the patients (56.5%) had vitamin D level lower than 30 ng/liter, with higher numbers of low vitamin D levels among HER2 positive and triple negative (TNBC) patients compared to hormonal receptor positive (HR+ve) patients (P=&lt;0.001). There was a significant negative correlation between vitamin D levels and tumor size, lymph node positivity and stage at diagnosis (the lower the vitamin D level, the larger the tumor size, and the higher the number of positive lymph nodes and the stage; r= -0.414, r= -0.586, r= -0.674; respectively; p&lt;0.001). On follow up, the number of local recurrences, bone metastases and liver metastases were significantly higher among the low vitamin D level group, however; there was no significant difference between the two groups in terms of development of brain and lung metastases. Disease free survival (DFS) and overall survival (OS) was significantly worse among the low vitamin D level group (p&lt;0.001). Conclusions: Low serum vitamin D in breast cancer patients negatively correlates with tumor size, lymph node positivity and stage at diagnosis. It is linked to HER-2 positive and TNBC, and is significantly associated with worse DFS and OS.

Vitamin D Supplementation Improves Mitochondrial Function and Reduces Inflammation in Placentae of Obese Women.

BackgroundAbout 30% of women entering pregnancy in the US are obese. We have previously reported mitochondrial dysregulation and increased inflammation in the placentae of obese women. Vitamin D (VitD) is a major player in calcium uptake and was shown to modulate mitochondrial respiration and the immune/inflammation system. Studies show decreased VitD levels in obese individuals; however, the effect of maternal obesity on VitD metabolism and its association with placental function remains understudied.MethodsMaternal and cord blood plasma and placental samples were collected upon C-section from normal-weight (NW, body mass index [BMI]<25) and obese (OB, BMI>30) women with uncomplicated pregnancies at term. We measured 25(OH)D3 (calcidiol) levels in maternal and cord blood plasma using ELISA. We assessed the expression of CYP27B1, an activator of calcidiol, and Vitamin D receptor (VDR) in placentae from NW and OB, and women with gestational diabetes and preeclampsia. In addition, we examined the effects of VitD supplementation on mitochondrial function and inflammation in trophoblasts from NW and OB, using the Seahorse Bioanalyzer and Western blot, respectively.ResultsVitamin D levels in blood from OB but not NW women and in cord blood from babies born to NW and OB women showed a significant inverse correlation with maternal pre-pregnancy BMI (r=-0.50, p<0.1 and r=-0.55, p=0.004 respectively). Cord plasma VitD levels showed a positive correlation with placental efficiency, i.e., the ratio between fetal and placental weight, as well as with maternal blood VitD levels (r=0.69 and 0.83 respectively, p<0.00). While we found no changes in CYP27B1 in OB vs. NW women, VDR expression were decreased by 50% (p<0.03) independent of fetal sex. No changes in VDR expression relative to BMI-matched controls were observed in the placentae of women with gestational diabetes or preeclampsia. Cytotrophoblasts isolated from placentae of OB women showed a dose-dependent increase in VDR expression after 24-hour treatment with calcitriol (10 nM and 100 nM), an active form of VitD. Trophoblasts isolated from OB women and treated with calcitriol improved mitochondrial respiration (p<0.05). We also found a two-fold increase in expression of the NLRP3 inflammasome and the pro-inflammatory cytokine IL-18 in trophoblasts isolated from placentae of OB women (p<0.05), with IL-18 expression being reversed by calcitriol treatment (100 nM).ConclusionsWe show that VitD deficiency is at least partially responsible for mitochondrial dysfunction and increased inflammation in the placentae of obese women. Vitamin D supplementation could be beneficial in improving placental dysfunction seen in obese women.

0618 Association between Ambient Light Exposure, Race/Ethnicity, and Vitamin D among Adults in the United States: Analysis of the National Health and Nutrition Examination Survey

Abstract Introduction The prevalence of vitamin D deficiency (VitD) in the United States is 41 percent, with the highest rate among Blacks 82 percent. Vitamin D deficiency has been linked to chronic diseases. The extent to which the association between light exposure and vitamin D serum levels can vary by individual’s race/ethnicity of which has not been studied at a national level. We aim to explore the associations of ambient light exposure between race/ethnicity and vitamin D. Methods The study used data from the National Health and Nutrition Examination Survey (2013-14). For detection of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 nmol/L, ultra-high-performance liquid chromatography-tandem mass spectrometry was performed based on serum samples from adults aged ≥ 18 years. Light levels (lux) data were gathered using 24-hour actigraphic monitoring over /a 7day period. Weighted generalized linear models were fitted examining association between light exposure and VitD adjusting for age, sex, family income/poverty ratio, education, employment, house tenure, marital status, birthplace, number of people in household, smoking, physical activity, and sedentarity. To compare this association across race/ethnicity, a product term between lux and race/ethnicity was included in adjusted models. Results Among 4,251 participants, White adults had the highest levels of VitD (mean=76.0; se=1.3), then other/multiple races (mean=65.1; se=2.2), Asians (mean=62.5; se=1.4); Hispanics (mean=57.4 nmol/L; se=1.6), and Blacks (mean=50.1; se=1.4). Regression analysis revealed estimated mean VitD of 64.9 nmol/L and positive association between light exposure and VitD ( 0.020). Blacks had significantly lower VitD levels ( -19.3) followed by Asians (-12.1) and Hispanics (-12.6) (all p-values &amp;lt;0.001). The association between light exposure and VitD depended on participant’s race/ethnicity Conclusion To our knowledge, this is the first study showing associations between objectively measured light exposure and VitD serum levels using a large representative sample of the US population. Although the study revealed racial/ethnic disparities in VitD levels, light exposure was associated with VitD even when race/ethnicity was adjusted for in the model. Further research on racial/ethnic differences in VitD is warranted. Support (If Any) R01HL142066, R01HL095799, RO1MD004113, R01HL152453, R25HL105444