Low Vitamin D Level Research Articles

Association between vitamin D metabolism gene polymorphisms and schizophrenia.

Schizophrenia (SZ) is a multifactorial and neurodegenerative disorder that results from the interaction between genetic and environmental factors. Notably, hundreds of single nucleotide polymorphisms (SNPs) are associated with the susceptibility to SZ. Vitamin D (VD) plays an essential role in regulating several genes important for maintaining brain function and health. To the best of the authors' knowledge, no studies have yet been conducted on the association between the VD pathway and patients with SZ. Therefore, the present study aimed to assess the potential association between eight SNPs in genes related to the VD pathway, including CYP2R1, CYP27B1, CYP24A1 and VDR among patients with SZ. A case-control study was conducted, involving a total of 400 blood samples drawn from 200 patients and 200 healthy controls. Genomic DNA was extracted and variants were genotyped using the tetra-amplification refractory mutation system-polymerase chain reaction method. The present study revealed statistically significant differences between patients with SZ and controls regarding the genotypes and allele distributions of three SNPs [CYP2R1 (rs10741657), CYP27B1 (rs10877012) and CYP24A1 (rs6013897) (P<0.0001)]. The AA genotype of rs10741657 was identified to be associated with SZ (P<0.0001) and the frequency of the A allele was higher in patients with SZ (P<0.0001) compared with the control group. Similarly, the TT genotype of rs10877012 was revealed to be associated with SZ (P<0.0001) and the T allele was more frequent in patients with SZ (P<0.0001) than in the control group. Moreover, the AA genotype of rs6013897 was revealed to be associated with SZ (P<0.0001), although no significant difference was detected between the two groups regarding the A allele (P=0.055). VDR (rs2228570, rs1544410, rs731236 and rs7975232) and CYP27B1 (rs4646536) gene polymorphisms did not exhibit a significant association with SZ. While the studied SNPs revealed promising discriminatory capacity between patients with SZ and controls, the rs10741657 SNP exhibited the most optimal area under the curve value at 0.615. A logistic model was applied considering only the significant SNPs and VD levels, which revealed that rs6013897 (T/A) and VD may have protective effects (0.267, P<0.001; 0.888, P<0.001, respectively). Moreover, a low serum VD level was highly prevalent in patients with SZ compared with the controls. Based on this finding, an association between serum 25(OH)D and SZ could be demonstrated. The present study revealed that CYP2R1 (rs10741657), CYP27B1 (rs10877012) and CYP24A1 (rs6013897) gene SNPs may be associated with SZ susceptibility.

The Role of Maternal Vitamin D Deficiency in Offspring Obesity: A Narrative Review.

Currently, vitamin D (VD) deficiency during pregnancy is widespread globally, causing unfavorable pregnancy outcomes for both mothers and infants for a longer time than expected, based on the Developmental Origins of Health and Disease (DOHaD) theory. As VD plays a key role in maintaining normal glucose and lipid metabolism, maternal VD deficiency may lead to obesity and other obesity-related diseases among offspring later in life. This review mainly focuses on the effect of maternal VD deficiency on offspring lipid metabolism, reviewing previous clinical and animal studies to determine the effects of maternal VD deficit on offspring obesity and potential mechanisms involved in the progression of offspring obesity. Emerging clinical evidence shows that a low VD level may lead to abnormal growth (either growth restriction or largeness for gestational age) and lipid and glucose metabolism disorders in offspring. Here, we also outline the link between maternal VD deficiency and life-long offspring effects, including the disorder of adipogenesis, the secretion of adipocytokines (including leptin, resistin, and adiponectin), activated systemic inflammation, increased oxidative reactions in adipose tissue, insulin resistance, and abnormal intestinal gut microbiota. Thus, there is an urgent need to take active steps to address maternal VD deficiency to relieve the global burden of obesity.

Influences of Vitamin D Levels and Vitamin D-Binding Protein Polymorphisms on Nonalcoholic Fatty Liver Disease Risk in a Chinese Population

Introduction: Vitamin D-binding protein (VDBP) is correlated with nonalcoholic fatty liver disease (NAFLD) through the biological functions of regulating plasma vitamin D (VD) level and the inflammatory process. Objective: This study aims to investigate the effects of VD level and VDBP gene polymorphisms on the risk of NAFLD in a Chinese population. Methods: Plasma 25-hydroxyvitamin D₃ levels were measured and seven VDBP candidate genetic variants (rs222020, rs2282679, rs4588, rs1155563, rs7041, rs16847024, rs3733359) were genotyped among participants in this case-control study. The control group was frequency-matched to the NAFLD case group by age and gender. Correlation analysis and multiple linear regressions were used to screen determinants of 25-hydroxyvitamin D₃ levels. Multivariable unconditional logistic regression was performed to estimate odds ratio (OR) and 95% confidence interval (95% CI). The prediction capability of models containing independent factors was estimated by the area under the receiver operating characteristic curve and Hosmer-Lemeshow test. Results: Age, body mass index, and triacylglycerol were independent factors influencing VD levels. Participants with low VD levels had significantly higher prevalence of NAFLD compared to subjects with normal VD levels (p < 0.001). A low VD level contributed to increased the risk of NAFLD, independent of metabolic factors known to affect VD levels (adjusted OR = 2.282, 95% CI = 1.422–3.661, p = 0.001). Logistic regression analysis showed that individuals carrying rs7041-G allele had a significantly decreased the risk of NAFLD occurrence compared to T allele (additive model: adjusted OR = 0.814, 95% CI = 0.713–0.929, p = 0.002; codominant model: adjusted OR = 0.623, 95% CI = 0.449–0.866, p = 0.005), after adjusting for age, gender, and overweight. Stratification by multiple metabolic disorders did not alter this relationship. Moreover, we developed a simple model including age, gender, metabolic disorders, and VDBP single nucleotide polymorphism (SNP) to assess NAFLD risk, an AUC of which being 0.817, significantly higher than the model not included VDBP SNP, with Hosmer-Lemeshow test fitting well (p = 0.182). Conclusions: Low plasma VD levels may increase susceptibility to NAFLD, while rs7041-G allele in VDBP contributed to a decreased NAFLD risk among Chinese population. The VDBP variant significantly improved the capability for NAFLD risk assessment, which could be used for early screening and management of NAFLD.

The Interaction between Vitamin D and Diets on Serum Lipids in Chinese Han Adolescents.

Abnormal serum lipids are closely related to cardiovascular disease. Recent studies have shown that vitamin D (VD) and vitamin D receptor (VDR) FokI polymorphism as well as dietary pattern are involved in regulating serum lipids. According to diet pattern, adolescents were divided into high-carbohydrate (high-CHO) and non-high-carbohydrate (non-high-CHO) diet group. Based on VDR FokI polymorphism, they were assigned into TT genotype and C allele carriers. Serum lipids, glucose, and 25-hydroxyvitamin D [25(OH)D] were measured. A linear regression model was established and analyzed. Subjects in the non-high-CHO diet group had higher glucose than those in the high-CHO diet group. With the increasing of VD, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), cholesterol/high density lipoprotein cholesterol (TC/HDL-C), LDL-C/HDL-C decreased. TT genotype subjects had higher TC and HDL-C compared with C allele carriers. As for log triglycerides (TG), TC/HDL-C, logTG/HDL-C, there were interactions between the level of VD and diet pattern. Under the low VD level, subjects in the high-CHO diet group had higher logTG and logTG/HDL-C compared with those in the non-high-CHO diet group. However, under the medium and high level of VD, the results were opposite. In addition, under the low and medium level of VD, subjects in the high-CHO diet group had higher TC/HDL-C. Serum lipids are not only affected by vitamin D, VDR FokI polymorphism and dietary pattern, but also interrelated as well. The impact of diet pattern on lipids may be reversed by the high level of serum VD.

Role of Vitamin D Levels in Venous Thrombosis

Venous thromboembolism (VTE) is a complex condition that impacts over 900,000 people in theUnited States annually. It is estimated that about 100,000 people in the US die from deep veinthrombosis (DVT) or pulmonary embolism (PE) annually. Several biomarkers, includingVitamin D most recently, have been investigated and linked to the risk of developing VTE orrecurrent VTE. Vitamin D is known to control the expression of over 200 genes and it has shownto have anti-thrombotic effects through various mechanisms. There is emerging data regardingits role in the coagulation pathway, platelet activation, inflammatory pathways and endothelialactivation (1). There have been a few international studies linking Vitamin D deficiency toVTE(2). However; no such study has been replicated in the North American population where the prevalence of Vitamin D deficiency is 40%. The focus of this study will be to determine theprevalence of Vitamin D deficiency in patients with VTE. Based on the role of Vitamin D in thepathway for thrombogenesis and antithrombin effects, there is likely a correlation between VTEand Vitamin D levels.This is a retrospective chart review of all patients admitted to Franciscan Health- Olympia Fieldswith VTE between July 2018 and June2020. A total of 181 patients with VTE were reviewed.Data such as age, gender, race, D-dimer, and Vitamin D levels were collected. Vitamin D levels<30ng/mL was defined as deficient. In addition, further data collection, included provoked vsunprovoked VTE, presence of malignancy, and the severity of DVT and PE based on locationand extent of the VTE (severity was scored on a scale of 1-3 with 1 being mild and 3 as severe).A regression analysis was done to find a correlation between several variables and T-test wasused to determine P-value.Of the 181 patients, 110 had a vitamin D level documented at the time of their VTE and datawas specifically analyzed for this subgroup. There were 46 males and 64 females, 53.6%AA,7.3% Hispanic, 38.2% Caucasian, and 0.9% unknown. 25.5% had an unprovoked VTE eventand 74.5% had a provoked event. 39 patients had a known active malignancy and a likelycancer associated thrombosis. 85.7% of patients with unprovoked DVT had a low Vitamin Dlevel. In patients with cancer associated thrombosis there was no significant correlation withvitamin D levels. A strong correlation was noted between vitamin D levels and the severity of PE(p value=0.036).This retrospective chart review from a patient population at a community hospital indicates thatthere is some correlation between venous thromboembolism and Vitamin D levels. Specifically,it appears that patients with an unprovoked VTE have low Vitamin D levels suggesting thatvitamin D deficiency may be a risk factor for VTE development as indicated by previousinternational studies (2). In addition, it appears that there is an inverse relationship between theseverity of PE and vitamin D levels. Perhaps Vitamin D may be used as a biomarker for VTErisk assessment and management. Large scale studies are needed in the future to determinethe exact relationship between VTE and Vitamin D and further studies are needed to test therole of vitamin D supplementation and risk of recurrent VTE. DisclosuresNo relevant conflicts of interest to declare.

Low vitamin D levels in follicular fluid, but not in serum, are associated with adverse outcomes in assisted reproduction.

To assess the relationship between serum/follicular fluid (FF) vitamin D (VD) status and assisted reproductive technology (ART) treatment outcomes among infertile patients. A prospective cohort study, including 132 infertile patients scheduled for their first ART treatment cycle, was carried out in a Reproductive Medical Center. Serum and FF samples were collected to assess 25-hydroxy VD [25(OH)D] levels. Low VD level was defined as 25(OH)D concentration of less than 30ng/mL. Most infertile patients had low VD levels in serum (88%) and FF (90%). We observed a moderately positive correlation between VD levels in serum and FF (r = 0.34, p < 0.0001). Compared to the group of patients with low VD levels in the FF, those with sufficient VD levels had a significantly higher number of retrieved oocytes (p = 0.03), normal fertilization (p = 0.01), and high-quality embryos (p = 0.001). Moreover, patients with sufficient VD levels in the FF also had significantly higher implantation rates than those with low VD levels (76.92% vs. 46.58%, respectively, p = 0.01) and clinical pregnancy rates (92.31% vs. 61.54%, respectively, p = 0.04). These data collectively revealed that low VD levels in serum and FF were common among infertile patients. VD levels in FF, but not in serum, were associated with embryo quality, normal fertilization, implantation rates, and clinical pregnancy rates. Further studies are mandatory to determine the molecular mechanism and VD's potential therapeutic benefits in infertile patients.

Vitamin D in active systemic lupus erythematosus and lupus nephritis: a forgotten player

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disorder associated with immunological abnormalities (Aringer et al., Arthritis Rheumatol 71:1400-1412, 2019). Vitamin D (VD) has an important role in SLE pathogenesis, as it controls cell cycle progression besides its anti-proliferative effects (Liu et al., J Cell Commun Signal 71, 2019). Determining the relationship between VD with SLE activity and lupus nephritis (LN) can establish a new role for VD in SLE management (Liu et al., J Cell Commun Signal 71, 2019). In our study, we aimed to assess the relationship between levels of VD in patients with SLE activity and with LN and to verify the relationship between VD levels with clinical and laboratory parameters in those patients, in order to assess the validity of adding serum VD level in the routine follow-up as a marker that may lead to earlier diagnosis of SLE activity and LN in adult SLE patients.ResultsSerum VD was significantly lower in SLE patients (3.38 ± 2.55 ng/ml) versus healthy controls (5.36 ± 2.88 ng/ml) (P < 0.002). Interestingly, serum VD was significantly lower in patient with active SLE according to SLEDAI (3.00 ± 2.27 ng/ml) versus those with inactive SLE (5.10 ± 3.19 ng/ml) (P < 0.02). Significant negative correlation was found between serum level of VD and each of mucocutaneous, malar rash, and renal manifestations. Significant negative correlation was also noticed among SLEDAI (P value = 0.01) and renal SLEDAI scores (P value = 0.021) with serum level of VD.ConclusionLow levels of VD were found to be frequent in SLE patients especially during phases of SLE activity and nephritis. Potent markers of low serum VD level in SLE patients were found to be mucocutaneous, malar rash, and LN. Our results support that VD levels could act as independent risk factors for activity and LN in SLE patients; moreover, treatment with VD supplementation could decrease the incidence of activity and nephritis in SLE patients.

Vitamin D supplementation improves anxiety but not depression symptoms in patients with vitamin D deficiency.

ObjectiveEpidemiological evidence indicated a relationship between vitamin D (VD) and depression with anxiety, but their therapeutic relationship has not been fully elucidated. This study aimed to examine whether VD supplementation would relieve symptoms in patients with depression and anxiety with low serum 25‐hydroxy VD [25(OH) D] levels.MethodParticipants with low 25(OH)D levels were randomized to control or daily VD group and were followed up for 6 months. Serum concentrations of 25(OH) D were measured using commercial kits. Psychological symptoms were evaluated with the Hamilton Depression Rating Scale‐17 (HAMD‐17), Revised Social Anhedonia Scale (RSAS), Revised Physical Anhedonia scale (RPAS), and Hamilton Anxiety Rating Scale‐14 (HAMA‐14). The trial was listed in the trial registration (http://www.medresman.org.cn/uc/index.aspx; NTR number: ChiCTR2000030130).ResultsIn this clinical population, no significant difference in depression symptoms was detected between VD group and control group at both baseline and at the endpoint of our study. The HAMD‐17, RSAS, and RPAS scores did not change significantly between VD and control groups from baseline to endpoint (all p > .05). However, there was a significant difference in time effect of the total HAMA‐14 scores between the two groups (β [95% Cl] = −2.235 [−3.818, −0.653], p = .006).ConclusionsVitamin D supplementation could improve the anxiety symptoms but not depressive symptoms in depressive patients with low VD level after the 6‐month intervention.

Low bone mineral density in HIV-positive young Italians and migrants.

Human immunodeficiency virus (HIV) infected individuals may have osteoporosis. We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. We conducted a cross-sectional study on 83 HIV patients less than 50 years old. We used the dual-energy X-ray absorptiometry (DXA) within six months from the HIV diagnosis. Participants were categorized as having low BMD if the femoral neck or total lumbar spine Z-score was- 2 or less. MiG showed low BMD more often than ItG (37.5% vs.13.6%), especially for the female gender (16.7% vs. 0.0%). A low CD4 rate (<200 cells/μl) was most often detected in MiG than ItG. In particular, we found most often male Italians with abnormal CD4 than male migrants (67.8% vs. 33.3%) and vice versa for females (30.5% vs. 66.7%). We found an abnormal bone mineral density at the lumbar site. Low BMD at the lumbar site was more frequently observed in female migrants than female Italians. Both male and female migrants had a Z-score value significantly lower than male and female Italians, respectively. By logistic regression low vitamin-D level was positively correlated to low BMD in ItG only. All data were verified and validated using a triple code identifier. Both DXA and vitamin-D evaluation should be offered after the diagnosis of HIV infection. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Vitamin D levels and supplementation may be considered after HIV diagnosis independently of age to improve bone health. This study evaluates the frequency of bone mineral density in HIV positive patients naive to antiretroviral therapy. It compares the density of the native Italian population with that of HIV Migrants upon arrival in Italy. The results show that HIV positive migrants, even if younger than 50 years of age, are at risk for osteoporosis, especially if they are female.

Efficacy of Vitamin-D Supplement on Thyroid Profile in Children with Graves’ Disease

BACKGROUND: Many studies have shown low Vitamin-D level as a risk factor for autoimmune diseases, especially multiple sclerosis and thyroid disease. Graves’ disease (GD) is an autoimmune disease caused by autoantibodies that stimulate thyroid-stimulating hormone (TSH) receptors by increasing thyroid hormone synthesis and secretion. Several studies report that many patients with autoimmune thyroid disease including GD have low Vitamin-D status.&#x0D; AIM: The objective of the study was to evaluate the effect of Vitamin-D supplement on GD patients on improvement in thyroid hormone levels.&#x0D; METHODS: Open random clinical trial was conducted in GD patients to determine changes in thyroid hormone to achieving normal levels between those receiving methimazole plus Vitamin-D supplementation compared with those who only received methimazole. Patients were checked for TSH receptor antibody, thyroid profile and Vitamin-D level before treatment and rechecked for thyroid profile and Vitamin-D level 3 months after treatment. t-test used to compare the drug efficacy (p &lt; 0.05) in two groups.&#x0D; RESULTS: From 25 children with GD accompanied by Vitamin-D deficiency with an average value of Vitamin-D was 16 ng/mL. GD children who receive methimazole with Vitamin-D supplement had elevated TSH levels in the 3rd month of therapy that was significantly different compared to GD children who received methimazole only (p = 0.00), and the increase of TSH was also followed by an increase in Vitamin-D levels.&#x0D; CONCLUSION: All children with GD had Vitamin D deficiency, and the addition of Vitamin-D supplement to GD therapy would improve TSH faster than children who did not receive Vitamin-D supplement.

Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients.

Tenofovir disoproxyl fumarate (TDF) has been associated with renal tubular abnormalities, phosphaturia and proteinuria (retinol binding protein, RBP, loss): vitamin D (VD) and PTH affect these markers. Aim was to understand if some single nucleotide polymorphisms (SNPs) were predictors of renal abnormalities in an Italian cohort of HIV-affected patients. DNA was analyzed through real-time PCR, urinary RBP corrected by creatinine (uRBP/Cr). The majority of patients received TDF. Abnormal uRBP/Cr was more frequent in TDF recipients: eGFR <90 mL/min and TDF were predictors in the whole cohort, whereas eGFR <90 mL/min, TDF concentrations and CYP24A1-3999TT in TDF-treated patients. Phosphate levels were higher low VD level patients: age <50 years, CYP27B1 + 2838CC genotype and non-European ancestry were predictors. PTH levels were border-line higher in TDF patients: non-European ancestry, females, TDF, VD levels < 30 ng/mL and SLC28A2-124CT/TT and ABCC2-24CC were predictors. For the first time, SNPs were associated with PTH, phosphate, calcium and tubular dysfunction in HIV-infected patients.

Association of Maternal Serum Vitamin D Level with Risk of Pregnancy-Related Complications and Neonatal Anthropometric Measures: A Prospective Observational Study.

Background:Body of evidence is increasing about the importance of Vitamin D (VD) for normal development of the fetus and for maternal health. As limited data are available regarding the association between maternal VD level and pregnancy-related complications and neonatal anthropometric measures, the present study aimed to evaluate the neonatal anthropometric measures including weight, high, and head circumference and pregnancy-related complications such as preeclampsia, blood pressure, gestational diabetes mellitus, and nausea and vomiting in pregnancy with 25(OH)VD level.Methods:The current prospective observational study was conducted among 812 Iranian pregnant women during the first trimester in Isfahan, Iran. Needed data were collected using validated questionnaires and biochemical examinations.Results:Overall, this study demonstrated an inverse significant association between VD level and chance of having low-weight infant in the adjusted model (odds ratio [OR]: 0.03, 95% confidence interval [CI]: 0.004–0.26, P < 0.001) in the first VD assessment. The same results were obtained in the second VD assessment (OR: 0.08, 95% CI: 0.01–0.40, P < 0.01). However, such associations were not seen about other neonatal measures and pregnancy-related complications.Conclusions:We found that low maternal VD level might be associated with risk of low-weight infant. Such findings could be considered to implement informative interventional programs to control newborn adverse outcomes. Further studies are required to confirm these findings.

Assessment of long term prognostic value of admission vitamin D level in patients with acute STEMI undergoing primary percutaneous coronary intervention

Objective:&#x0D; Vitamin-D status is very important for optimal function of human body&#x0D; especially cardiovascular system. The aim of this study was to investigate the&#x0D; long term prognostic value of admission vitamin D level in acute ST-segment&#x0D; elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary&#x0D; intervention (PPCI). &#x0D; &#x0D; Methods:&#x0D; One hundred fifty seven consecutive patients, who were admitted to a training&#x0D; and research hospital with a diagnosis of STEMI and underwent PPCI, were&#x0D; recruited in this prospective study. The study patients were divided into 2&#x0D; groups according to their vitamin-D levels as follows: High vitamin-D group&#x0D; (n=80) and Low vitamin-D group (n=77). The severity of coronary artery disease&#x0D; (CAD) was assessed with calculation of the SYNTAX score. &#x0D; &#x0D; Results:&#x0D; There were significant negative correlations between Vitamin-D level and SYNTAX&#x0D; score, serum glucose, and gender, but a positive correlation with hemoglobin&#x0D; level. Cardiovascular mortality was found to be significantly higher in the low&#x0D; vitamin-D group as compared to the high group (p&amp;lt;0.001). In multivariate&#x0D; analysis, low vitamin-D level was found as a significant independent predictor&#x0D; of long term cardiovascular mortality after adjusting for other risk factors. &#x0D; &#x0D; Conclusion:&#x0D; We demonstrated that low admission vitamin-D is related to severity of CAD.&#x0D; Vitamin-D deficiency is an independent predictor for long term cardiovascular&#x0D; mortality in acute STEMI undergoing PPCI.

The role of vitamin D supplementation on erectile function.

In the last few years growing evidence highlighted vitamin D (VD) deficiency is one of the several dynamics that associates with increased atherosclerotic cardiovascular (ASCV) diseases. ASCV diseases and erectile dysfunction (ED) share common risk factors such as diabetes mellitus, hypertension, smoking, hyperlipidemia, and a sedentary lifestyle. The aim of this review was to summarize current progress in VD research by focusing effect of low VD level on different body systems and erectile function. Here we examine research linking VD deficiency and ED and discuss how VD influences ED and its classic risk factors that also associate to increased ED risk. We also summarize research indicating that VD associates with reduced risk of several nonvascular contributing factors for ED. Available literature demonstrates relatively high rates of low VD serum levels in ED patients. Based on the preclinical and clinical data available in the literature, to date, we infer that VD play a critical role in maintaining erectile function in humans. Nevertheless, this should also be tested through randomized controlled studies on the effect of VD supplementation with larger population.

Serum 25‐hydroxyvitamin D and risk of venous thromboembolism: the Atherosclerosis Risk in Communities (ARIC) Study

Some evidence suggests that an inadequate vitaminD level may increase the risk for atherosclerotic cardiovascular disease. Whether a low vitaminD level plays a role in venous thromboembolism (VTE), that is, venous thrombosis and pulmonary embolism, is largely unexplored. We tested prospectively, in the Atherosclerosis Risk in Communities (ARIC) cohort, whether the serum level of 25-hydroxyvitaminD (25[OH]D) is inversely associated with VTE incidence, and whether it partly explains the African American excess of VTE in the ARIC Study. We measured 25(OH)D by using mass spectroscopy in stored samples of 12752 ARIC Study participants, and followed them over a median of 19.7years (1990-1992 to 2011) for the incidence of VTE (n=537). The seasonally adjusted 25(OH)D level was not associated with VTE incidence. In a model adjusted for age, race, sex, hormone replacement therapy, and body mass index, the hazard ratios of VTE across 25(OH)D quintiles 5 (high) to 1 (low) were: 1 (ref.), 0.84 (95% confidence interval [CI]0.65-1.08), 0.88 (95%CI0.68-1.13), 1.04 (95%CI0.78-1.38), and 0.90 (95%CI0.64-1.27). The lowest 25(OH)D quintile contained 59% African Americans, whereas the highest quintile contained 7% African Americans. However, lower 25(OH)D levels explained little of the 63% greater VTE risk of African Americans over whites in this cohort. A low 25(OH)D level was not a risk factor for VTE in this prospective study. However, the totality of the literature (three studies) suggests that a low 25(OH)D level might modestly increase VTE risk in whites, but this needs further confirmation.

Impact Of Vitamin D Level Pre and Post Allogeneic Hematopoietic Stem Cell Transplant

Introduction Allogeneic hematopoietic stem cell transplant (HCT) patients are at risk for having a low Vitamin D (VD) level. VD level has been correlated with cancer incidence, pulmonary disease and infection. VD also has immunomodulatory properties and reports suggest that a low VD level increases the incidence of chronic GVHD and may impact mortality in HCT. HCT morbidity and mortality is attributed to infection, organ system toxicity, GVHD and recurrent disease. Identifying a correctable factor that would reduce the occurrence or severity of these complications would be beneficial. It is possible that VD may have significant effect on outcome after HCT due to its described properties. Normal VD level may infer better outcome for HCT patients by improving response in or preventing infection, protecting organ function, decreasing risk of relapse and/or decrease incidence or severity of GVHD. We hypothesize that there is a relationship between VD level and morbidity and mortality after HCT. We therefore studied VD levels pre- and post-HCT to determine if there was an impact of VD level on these outcomes. Patients and Methods Two hundred and fifty patients underwent myeloblative or non-myeloablative HCT between 3/12/2009 and 10/29/2012 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for VD levels prior to transplant, at day 100 and 1 year post-HCT. Data were collected through day 100 for occurrence of infection and admissions to the ICU. Categories for VD level included normal (≥30 ng/ml) or abnormal (&lt;30 ng/ml). Patient characteristics were compared using the Chi-square test or Wilcoxon rank sum test. The logrank test was used to compare the survival curves between groups, and the Cox proportional hazard model was used to measure the association between outcomes (mortality, relapse, acute or chronic GVHD) and VD level. Results Of the 250 patients undergoing HCT VD level was performed on 180 (72%) patients pre-HCT, 149 (60%) patients at day 100 post-HCT and 81 (32%) patients at 1 year post-HCT. The rate of acute or chronic GVHD was not significantly associated with VD level pre or post-HCT. Overall infection risk was not significant pre or post-HCT but when sorted by type of infection bacterial infection (p=0.01), radiologic evidence of pulmonary nodules/consolidation (p=0.03), and ICU admissions (p=0.0313) within the first 100 days post-transplant were significantly increased in patients who had a low VD level at day 100 post -HCT. Pre-HCT and 1 year post-HCT VD level did not impact mortality or relapse but there was a significant increase in one year mortality (p=0.02, HR = 5.99) and relapse (p = 0.03, HR=9.47) in patients who had a low VD level at day 100 post-HCT. Discussion This study shows that VD may play a significant role in bacterial infection, pulmonary infection, ICU admission, mortality and relapse after HCT. Those patients with a low VD level at day 100 post-HCT had significantly worse outcomes for relapse and mortality. Those patients with a low VD level at day 100 post-HCT had a higher incidence of lung infection, bacterial infection and admission to the ICU. In contrast to previous studies, we found no correlation between VD level and incidence of acute or chronic GVHD. This study is one of the largest reported and the first to our knowledge that reports decreased risk of certain types of infection (bacterial and lung), mortality and relapse in those with an adequate VD level receiving HCT. It is possible that supplementation of VD to keep levels ≥30 would reduce these complications of HCT. Future prospective study of VD is warranted. Finding a low cost and easy to administer therapy (such as VD replacement) that would reduce morbidity, mortality and relapse in the HCT population is needed. Disclosures: Reeder: Celgene: Research Funding; Novartis: Research Funding; Millenium: Research Funding.

Impact of Vitamin D Level After Allogeneic Hematopoietic Stem Cell Transplant

AbstractAbstract 1954 Introduction:Vitamin D (VD) deficiency can cause osteomalacia, aching bone pain, muscle weakness, fatigue, increase risk of fracture and precipitate or exacerbate osteopenia/osteoporosis. Allogeneic hematopoietic stem cell transplant (HCT) patients are susceptible to low VD level secondary to poor oral intake, decreased exposure to sunlight and treatment related malabsorption. VD level has been correlated to cancer incidence and VD metabolites have been used in the treatment of myeloid leukemia. VD shows promising immunomodulatory properties and correction of low VD level may mitigate manifestations of graft versus host disease (GVHD). Reports have suggested that low VD level appears to increase the incidence of GVHD. We hypothesize that there is a relationship between low VD level and morbidity (specifically incidence of acute GVHD), mortality and relapse incidence after HCT. We therefore studied VD levels pre- and post-HCT to determine if VD level impacts these outcomes. Patients and Methods:241 patients underwent myeloblative or non-myeloablative HCT between January 1, 2009 and January 31, 2011 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for pre- and post-transplant VD level. Categories for VD level included normal (>30 ng/ml) or abnormal (<30 ng/ml). Results:131 (54%) of patients who underwent myeloblative or non-myeloablative HCT had their VD level evaluated either pre-transplant, post-transplant or both. Pre-HCT 57 (56%) patients, 100 days post-HCT 55 (59%) patients and 365 days post-HCT 12 (32%) patients had a low VD level. 51 (38%) of patients had a reduced intensity HCT and 80 patients (62%) had an ablative conditioning regimen. 11 (8.4%) patients had acute GVHD. Comparison of VD level among those with acute GVHD did show a higher incidence of acute GVHD between those with a low or normal VD level (HR=3.14, 95% CI: 0.35–28.33) however this association was not statistically significant (p=0.3079). Survival analysis in those with a low VD level pre-HCT showed there was not a higher risk of mortality (HR=1.14, 95% CI: 0.18–7.38) after adjusting for post- VD level, and this association was not statistically significant (p=0.8921). Survival analysis in those with a low VD level post-HCT did show a higher risk of mortality (HR=2.59, 95% CI: 0.26–25) after adjusting for pre-HCT VD level, however, this association was not statistically significant (p=0.4155). The relationship between VD level and relapse at 1 year post-HCT was not able to be examined because the VD level for patients who relapsed was not available. Conclusions:Half of patients undergoing HCT had VD testing pre- or post- HCT. Just over half of the patients tested had a low VD level pre- and 100 days post-HCT. It is notable that 365 days post HCT the number of patients with low VD level had decreased. This could be attributable to less time in the hospital thus increasing sun exposure, increasing performance status allowing better ingestion and absorption of VD in the gastrointestinal tract or proper supplementation of a low level noted previously. There was no significant difference in incidence of acute GVHD by VD level though there was a trend for increased risk. Pre- and post-HCT VD level did not significantly impact mortality but there was a trend toward higher risk in those with a low VD level post-HCT. This is the first study, to our knowledge, to evaluate the impact of VD level on mortality post-HCT. Our study confirms that many patients have a low VD level pre-and post-HCT. These findings, especially the trend towards a higher mortality risk and higher incidence of acute GVHD in those who have a low VD level post-HCT, warrant further prospective investigation. VD supplementation may be a low cost, easy to implement addition to routine post HCT care that might reduce HCT associated mortality. Disclosures:Reeder:Celgene: Research Funding.

Vitamin D Level after Allogeneic Hematopoietic Stem Cell Transplant

Vitamin D (VD) deficiency can cause osteomalacia, bone pain, muscle weakness, fatigue, and increased risk of fracture, and may precipitate or exacerbate osteopenia and osteoporosis. Patients receiving treatment for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) may have limited exposure to sunlight and often experience gastrointestinal side effects that may decrease their ability to maintain an adequate VDlevel. We hypothesized that patients with AML and ALL would have a low VD level after allogeneic hematopoietic cell transplant (HCT), and that these patients would have a high incidence of osteoporosis/osteopenia. We therefore studied the incidence of low VD level and low bone mineral density after HCT. Of 289 patients with AML or ALL undergoing HCT between January 1, 2000, and January 31, 2009, at the Cleveland Clinic, 58 (20.1%) patients had VD testing after HCT. Of these, 52 (89.7%) patients had a low VD level, and 6 (10.3%) had a normal level. Most patients with VD testing had graft-versus-host disease (GVHD) and were taking corticosteroids (94.8% and 98.3%, respectively). Of the 49 patients with VD testing who also had bone mineral density testing, 65% had abnormal (low bone density) results. Only 21% of patients with VD testing were taking VD supplements prior to testing, and 65% had an elevated parathyroid hormone level. We found that most patients did not have VD testing after HCT, but those that did were very likely to have a low level and have low bone mineral density. Those with a low VD level were likely to have received corticosteroids, have GVHD, and have an elevated parathyroid hormone (PTH) level. Given the potential morbidity of low VD level, VD deficiency should be considered after HCT. Prospective study of VD level and its impact on morbidity and mortality after HCT is warranted.