25-hydroxyvitamin D3 Levels Research Articles

Lower levels of 25-hydroxyvitamin D3 are associated with a higher prevalence of microvascular complications in patients with type 2 diabetes

ObjectiveLow levels of serum 25-hydroxyvitamin D [25(OH)D] are commonly found in type 2 diabetes. We examined whether there is an association between circulating 25(OH)D concentrations and the presence of microvascular...

Temporal relationship between vitamin D status and parathyroid hormone in the United States.

BackgroundInterpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.ObjectiveCharacterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OH)D3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OH)D2] levels with PTH levels and total 25(OH)D levels.MethodWe retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D2 and 25(OH)D3] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D2 (≥4 ng/mL).FindingsSeasonal variation was observed for all genders and latitudes. 25(OH)D3 peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D3, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D2 had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D2.Interpretation25(OH)D3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OH)D3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D2, and thus are applicable for patient care.

The Role of FTO and Vitamin D for the Weight Loss Effect of Roux-en-Y Gastric Bypass Surgery in Obese Patients.

BackgroundA recent study in children demonstrated that the rs9939609 single-nucleotide polymorphism in the fat mass and obesity (FTO) gene influences prospective weight gain, however, only in those who were vitamin D-deficient. If this might also be the case for Roux-en-Y gastric bypass (RYGB), surgery-induced weight loss is however unknown. The objective of this study is to examine if the magnitude of RYGB surgery-induced weight loss after 2 years depends on patients’ FTO rs9939609 genotype (i.e., TT, AT, and AA) and presurgery vitamin D status (<50 nmol/L equals deficiency).MethodsBefore and at 24 months after RYGB surgery, BMI was measured in 210 obese patients (mean BMI 45 kg/m2, 72 % females). Serum 25-hydroxyvitamin D3 levels were also repeatedly measured. Following surgery, vitamin D was supplemented. Possible weight loss differences between genotypes were tested with multiple linear regressions.ResultsThe per-allele effect of each FTO A-allele on excessive BMI loss (EBMIL) was 3 % (P = 0.02). When split by baseline status, the EBMIL of vitamin D-deficient patients carrying AA exceeded that of vitamin D-deficient patients carrying TT by ~14 % (P = 0.03). No such genotypic differences were found in patients without presurgery vitamin D deficiency. Post-surgery serum levels of vitamin D did not differ between groups.ConclusionsOur data suggest that presurgery vitamin D levels influence the size of genotype effects of FTO rs9939609 on RYGB surgery-induced weight loss in obese patients.

Vitamin D deficiency in Parkinson's disease patients with orthostatic hypotension.

The purpose of our study was to investigate the associations between serum vitamin D3 levels and orthostatic hypotension (OH) in patients with Parkinson's disease (PD). Fifty-five patients with PD were enrolled in this study. Blood pressure (BP) measurements were gathered while the patients were in the supine position and while standing up. Then, the patients were divided into two groups: PD patients with and without OH. We compared the levels of serum 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 (calcitriol) between the two groups. Serum 25-hydroxyvitamin D and calcitriol levels were significantly decreased in patients with OH compared with those without OH. The systolic and diastolic BPs and symptom severities significantly negatively correlated with the serum 25-hydroxyvitamin D and calcitriol levels. Although the underlying mechanism for this association is not fully understood, our results suggest that low vitamin D status is associated with OH in patients with PD.

Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus

ObjectiveTo investigate the feasibility of bone turnover markers for the assessment of bone metabolism in patients with systemic lupus erythematosus, according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. MethodsThe study included 43 female systemic lupus erythematosus patients. Serum procollagen type I N propeptide, C-terminal telopeptide of type I collagen, osteocalcin, parathyroid hormone, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. ResultsProcollagen type I N propeptide and C-terminal telopeptide of type I collagen levels were elevated in systemic lupus erythematosus patients aged >45 in comparison to those aged <45, although with borderline significance (p=0.05, respectively). Correlations were found between bone turnover markers: the strongest being between procollagen type I N propeptide and osteocalcin (τ=0.69, p<0.05). Procollagen type I N propeptide and osteocalcin were found to be associated with parathyroid hormone (τ=0.3, τ=0.29, respectively, p<0.05). Age correlated with procollagen type I N propeptide (τ=0.23, p<0.05). Elevated procollagen type I N propeptide was found more frequently than elevated osteocalcin or C-terminal telopeptide of type I collagen, both in patients aged <45 (p=0.001) and >45 (p<0.001). No significant difference in procollagen type I N propeptide, osteocalcin or C-terminal telopeptide of type I collagen levels was found with respect to season, neither in the entire systemic lupus erythematosus group nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in bone turnover markers. ConclusionsIncreased bone turnover markers in systemic lupus erythematosus appear to predominantly reflect the pattern of bone remodeling related to age. Increased procollagen type I N propeptide is expected to be the most frequent outcome among bone turnover markers. Better diagnoses of bone disturbances with bone turnover markers performed in accordance with international reference standards need to be included in the approach to systemic lupus erythematosus patients, in addition to bone mineral density assessment.

Correlation between serum 25-hydroxyvitamin D3and the severity of atopic dermatitis in children with allergic or nonallergenic sensitization

Purpose: The aim of this study was to assess the relationship between serum 25-hydroxyvitamin D3 levels and the severity of atopic dermatitis (AD), markers of atopy (total IgE, total eosinophil count, and eosinophil cationic protein) in AD children according to allergen sensitization. Methods: This cross-sectional study was carried out on 160 AD patients aged 1 to 18 years between March 2012 and August 2014. The AD patients (AD group) were subdivided into 2 categories according to the results of the allergic skin prick and Unicap tests: the allergic and nonallergic AD groups. We compared 25-hydroxyvitamin D3 levels between the AD and control groups. We also investigated relationships between serum 25-hydroxyvitamin D3 levels, the severity of AD, and markers of AD (total IgE, total eosinophil count, and eosinophil cationic protein) in the allergic and nonallergic AD groups. Results: The average 25-hydroxyvitamin D3 levels were 30.6±11.7 and 23.7±10.0 ng/mL, respectively, in the control and AD groups (P<0.001). The average 25-hydroxyvitamin D3 levels were 19.7±8.6 and 27.5±9.8 ng/mL, respectively, in the allergic and nonallergic AD groups, with clinical implications (P<0.001). The 25-hydroxyvitamin D3 levels were not significantly associated with SCORing Atopic Dermatitis index in the allergic (P=0.004, r=.0.092) or nonallergic (P=0.610, r=.0.58) AD groups. The 25-hydroxyvitamin D3 levels were not significantly associated with the aforementioned markers of atopy in the AD group. Conclusion: These results suggest that 25-hydroxyvitamin D3 may play a role in the pathogenesis of AD.(Allergy Asthma Respir Dis 2015;3:213-218)

Serum 25-hydroxy vitamin D levels in patients with acne vulgaris and its association with disease severity.

Since vitamin D is a recent known immunoregulatory factor in some diseases which are addressed in immune system disorders such as SLE, [psoriasis] and others. To determine the serum levels of 25-hydroxy vitamin D3 [25(OH)D] in patients with acne vulgaris and its association with clinical features. This cross-sectional study was conducted over months. This study included 39 patients with acne vulgaris and 40 healthy controls. Subjects who did not use alcohol, vitamin D supplements, oral steroids or PUVA and/or NBUVB for more than three months were included. Serum 25(OH)D levels were measured. Baseline demographics, family history and comorbidities like PCO were recorded. Statistical analyses were performed using SPSS 16.0.0. The median concentration of 25(OH)D was 8.4 ng/mL (range: 1.4-99) in patients and 10.4 ng/mL (range: 3.1-56.7) in controls, with no statistical significant difference. PCOS was a significant predictor of the occurrence of acne vulgaris (OR=6.25; 95% CI: 1.52-25.66; p=0.01). There were no significant associations between severity of disease and serum 25(OH)D levels (rs=-0.12, p=0.45), age (rs=-0.28, p=0.09), BMI (rs=-0.12, p=0.46), age at onset of disease (rs=-0.08, p=0.63) and duration of disease (rs=-0.10, p=0.54). Based on the previous studies this is highly suspected that vitamin D would be a prominent factor in acne patients and more performances with bigger sample size could be useful to get positive results.

Is vitamin D deficiency related to accumulation of advanced glycation end products, markers of inflammation, and oxidative stress in diabetic subjects?

Objectives. In diabetes accumulated advanced glycation end products (AGEs) are involved in the striking cardiovascular morbidity/mortality. We asked whether a hypovitaminosis D associates with an increased formation and toxicity of AGEs in diabetes. Methods. In 276 diabetics (160 M/116 F, age: 65.0 ± 13.4; 43 type 1,T1DM, and 233 type 2 patients, T2DM) and 121 nondiabetic controls (60 M/61 F; age: 58.6 ± 15.5 years) routine biochemistry, levels of 25-hydroxyvitamin D3 (25-(OH)D), skin autofluorescence (SAF), plasma AGE-associated fluorescence (AGE-FL), Nε-(carboxymethyl)lysine (CML), soluble receptor for AGEs (sRAGE), soluble vascular adhesion protein-1 (sVAP-1), high sensitive C-reactive protein (hs-CRP), and renal function (eGFR) were determined. Results. In the diabetics SAF and AGE-Fl were higher than those of the controls and correlated with age, duration of diabetes, and degree of renal impairment. In T2DM patients but not in T1DM the age-dependent rise of SAF directly correlated with hs-CRP and sVAP-1. 25-(OH)D levels in diabetics and nondiabetics were lowered to a similar degree averaging 22.5 ng/mL. No relationship between 25-(OH)D and studied markers except for sVAP-1 was observed in the diabetics. Conclusion. In diabetics hypovitaminosis D does not augment accumulation of AGEs and studied markers of microinflammation and oxidative stress except for sVAP-1.

Serum vitamin D₃ does not correlate with liver fibrosis in chronic hepatitis C.

To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive Chinese patients with chronic hepatitis C (CHC). From July 2010 to June 2011, we enrolled 122 CHC patients and 11 healthy controls from Dingxi city, Gansu Province, China. The patients were infected with Hepatitis C virus (HCV) during blood cell re-transfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholinesterase, prothrombin activity, albumin, γ-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HCV RNA levels were measured by real-time PCR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry. Serum levels of 25(OH)D3 but not 24,25(OH)2D3 were significantly lower in CHC patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HCV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation grades. We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive Chinese patient with CHC.

Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC-Germany case-cohort study.

Increased fibroblast growth factor 23 (FGF23) concentrations have emerged as a novel risk factor for heart failure and stroke but not for myocardial infarction (MI). Yet, most studies on MI were conducted in coronary artery disease (CAD) patients and the elderly. Evidence is unclear in subjects without CAD and for stroke subtypes. We investigated the relationships between FGF23 and overall major cardiovascular endpoints, incident MI, ischemic (IS) and haemorrhagic stroke (HS) in middle-aged adults without pre-existing cardiovascular disease. We used a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition-Germany, including a randomly drawn subcohort (n = 1,978), incident MI (n = 463) and stroke cases (n = 359 IS; n = 88 HS) identified during a mean follow-up of 8.2 years. Compared with participants with FGF23 levels in the lowest quartile, those in the highest quartile had a 36% increased risk for cardiovascular events [hazard ratio: 1.36, 95% confidence interval (CI): 1.02-1.82] after adjustment for established cardiovascular risk factors, patahyroid hormone and 25-hydroxyvitamin D3 levels, dietary calcium and phosphorus intake, and kidney function. However, sub-analyses revealed significant relationships with risk of MI and HS, but not IS. Compared with the lowest quartile, individuals in the top two FGF23 quartiles had a 1.62 (95% CI 1.07-2.45) fold increased risk for MI and a 2.61 (95% CI 1.23-5.52) fold increase for HS. Increased FGF23 emerged as a risk factor for both MI and HS. Further studies are warranted to confirm these results and to identify underlying mechanisms.

Evaluating the clinical and physiological effects of long term ultraviolet B radiation on guinea pigs (Cavia porcellus).

Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended.

Diagnostic Challenge

Under natural conditions, guinea pigs (Cavia porcellus) are exposed to ultraviolet B (UVB) radiation. Although the role of UVB radiation in the photobiochemical synthesis of vitamin D is well documented in humans and other vertebrates, to date it has not been evaluated in guinea pigs. The purpose of this study was to determine whether artificial UVB radiation has an effect on serum 25-hydroxyvitamin D3 levels in guinea pigs. A total of 12 juvenile guinea pigs were randomly assigned to 1 of 2 treatment groups: Group A was exposed to 12 hours of artificial UVB radiation (290 to 315 nm) daily and Group B received ambient fluorescent light with no UVB supplementation for 12 hours/day. Blood samples were collected under anesthesia on days 0 and 18 to measure serum 25-hydroxyvitamin D3 levels. Animals in both groups were offered the same diet. There was a significant difference in 25-hydroxyvitamin D3 concentrations over time (F = 399.3, P = 0.0001) and by group (F = 63.6, P = 0.0001), with an average increase between sampling periods of 56.5 nmol/L in Group A (UVB) and 2.33 nmol/L in Group B (no UVB). This study represents the first attempt to measure the effect of UVB radiation on 25-hydroxyvitamin D3 levels in guinea pigs. In vertebrates, vitamin D is an essential hormone that regulates many physiologic functions within the body. These preliminary findings confirm that guinea pigs can obtain vitamin D via photobiochemical synthesis, but additional work is needed to determine the physiologic importance of this finding and potential risks associated with UVB exposure in these rodents.

Low Pre-Transplant Levels of 25-Hydroxyvitamin D3 Predict Relapse and Survival in Male but Not in Female Patients Undergoing Allogeneic Stem Cell Transplantation

Introduction: Vitamin D3 (VitD3) plays a central role in calcium and bone homeostasis and has been shown to exert potent modulatory effects in both innate and adaptive immune responses. VitD3 deficiency is frequent in patients with hematopoietic malignancies undergoing allogeneic transplantation (alloSCT), and it has been implicated in the development of graft-versus-host disease (GVHD). However, the prognostic relevance of VitD3 in the context of alloSCT has not been fully delineated. This retrospective study investigates the prognostic impact of pre-transplant VitD3 levels on outcome parameters after alloSCT.Patients and methods: Between 2001 and 2012, a total of 650 patients undergoing alloSCT at our institution (61% male, 39% female, median age 53 years) provided informed consent to participate in this observational study. 223 patients (34%) received transplants from related donors (RD), 281 patients (43%) from matched unrelated donors (MUD) and 139 (21%) from mismatched unrelated donors (MMUD). Diagnoses were acute myeloid leukemia in 202 patients (32%), lymphoid malignancies (lymphoma, chronic and acute lymphoid leukemia) in 228 patients (35%), multiple myeloma in 110 patients (17%) and other myeloid malignancies (including myelodysplastic syndrome, myelofibrosis and chronic myeloid leukemia) in 110 patients (17%). A total of 285 patients (44%) received statin treatment post alloSCT. Pre-transplant serum samples for VitD3 were collected between 0 and 2 months before alloSCT and cryopreserved at -80°C. VitD3 (25-hydroxyvitamin D3) concentrations were measured by an enzyme-linked immunosorbent assay (DiaSorin Deutschland GmbH, Dietzenbach, Germany). A total of 497 patients had serum samples prior to alloSCT available. In order to consider 153 missing VitD3 data sets multiple imputation (k=20) was applied. Cox regression analysis with cause specific hazard models was applied for overall survival (OS), non-relapse mortality (NRM) and time to relapse (TTR). As confounding prognostic factors we included tumour entity, statin treatment, VitD3, age, recipient’s sex and donor as well as the interaction between VitD3 and donor, sex and statin treatment into the models. Survival times were measured from date of alloSCT.Results: Estimated median follow-up time was 47.1 months. Median pre-transplant 25-hydroxyvitamin D3 level was 11.9 ng/mL (range 1-46.3 ng/mL). In multivariate analysis of the entire cohort, a significant interaction between recipient’s sex and VitD3 level for OS (p=0.04) and TTR (p=0.03) could be observed. There was no interaction effect for NRM. Consequently, separate models for OS and TTR in male and female patients were performed.For female patients, no influence of VitD3 with regard to OS and TTR was observed. In contrast, Cox regression analysis of male patients revealed that lower VitD3 levels were significantly associated with inferior OS (HR=0.71 95%CI 0.55-0.91, p=0.008; hazard ratios were computed for an increase from the lower to the upper quartile of the distribution of VitD3). In male patients VitD3 was also significantly associated with TTR (HR=0.68 95%CI 0.50-0.93, p=0.015), i.e. longer time to relapse with higher VitD3 levels. Since guidelines recommend a VitD3 level of 20 ng/mL for the normal population, VitD3 levels were stratified at 20 ng/mL. In both sexes lower VitD3 levels did not affect NRM incidence. In male but not in female patients VitD3 levels below 20 ng/mL resulted in shorter TTR (p=0.001). Accordingly, VitD3 levels lower than 20 ng/mL were significantly associated with inferior OS in male (p<0.001) (Figure 1A) but not in female patients (Figure 1B).Conclusion: This single center study suggests that male patients with lower pre-transplant VitD3 levels have higher relapse rates translating into a survival disadvantage across all diagnostic entities. Prospective studies investigating VitD3 in the alloSCT setting are highly warranted. [Display omitted] DisclosuresRadujkovic:DiaSorin Deutschland GmbH: 25-Hydroxyvitamin D3 ELISA kits were kindly provided by DiaSorin Deutschland GmbH, Dietzenbach, Germany. Other.

Relationships among the metabolic syndrome, bone mineral density, bone turnover markers, and hyperglycemia.

This study investigated the possible effects of metabolic syndrome on bone mineral density (BMD) and bone turnover markers in Turkish postmenopausal women. This prospective case-control study included a total of 230 postmenopausal women, between 45 and 65 years old, including 63 with metabolic syndrome and 167 without metabolic syndrome on the basis of the International Diabetes Federation criteria. The height, weight, body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio of each subject were measured. Fasting and nonfasting blood glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), calcium, phosphorus, glycated hemoglobin (HbA1c), bone-specific alkaline phosphatase (ALP), 25-hydroxyvitamin D3 [25(OH) D], osteocalcin, and the β-isomerized form carboxy-terminal telopeptide of type I collagen (β-CTx) were measured. Bone mineral densities in the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. The mean age was 58.49±5.7 years in metabolic syndrome patients and 56.13±5.0 years in patients without metabolic syndrome. There was a statistically significant difference in the age of the patients. The mean BMI was 33.96±5.3 and 30.867±3.8 kg/m(2) in metabolic syndrome patients and patients without metabolic syndrome, respectively, indicating a statistically significant difference. Serum calcium, osteocalcin, and β-CTx were statistically significantly lower in metabolic syndrome patients. There was no significant difference in the levels of phosphorus, 25-hydroxyvitamin D3, and bone-specific ALP, TSH, and PTH among the patients with metabolic syndrome and without metabolic syndrome. The statistical analysis, after adjusting for age and BMI, revealed no significant difference between the two groups in terms of lumbar and femoral BMD. When the patients in the metabolic syndrome group were split into two groups on the basis of those with a T score -2.5 or less and those with a normal score, a statistically significant difference was identified between the two groups in terms of the fasting blood glucose (FBG) and HbA1c values (P<0.05). Furthermore, a negative correlation was identified between the lumbar T score and the FBG and HbA1c values (P<0.05). After adjusting for age and BMI in a comparison of BMD between postmenopausal women with and without metabolic syndrome, it was revealed that metabolic syndrome has no positive or negative effect on BMD. In contrast, a negative correlation was identified between FBG and HbA1c levels and lumbar BMD, suggesting that poor glycemic control may have a negative effect on lumbar BMD in this group of patients.

Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men.

AimsTo study the effect and time profile of different doses of testosterone enanthate on the blood lipid profile and gonadotropins.Experimental designTwenty-five healthy male volunteers aged 27–43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses of Testoviron® Depot. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), blood lipid profile (total cholesterol, plasma [p-] low-density lipoprotein, p-high-density lipoprotein [HDL], p-apolipoprotein A1 [ApoA1], p-apolipoprotein B, p-triglycerides, p-lipoprotein(a), serum [s-] testosterone, and 25-hydroxyvitamin D3) were analyzed prior to, and 4 and 14 days after dosing. Testosterone and epitestosterone in urine (testosterone/epitestosterone ratio) were analyzed prior to each dose after a washout period of 6–8 weeks.Results and discussionAll doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic–pituitary–gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg) did not have any effect on the lipid profile.ConclusionThe single doses of testosterone produced a dose-dependent increase in serum testosterone concentrations together with suppression of s-LH and s-FSH. Alterations in ApoA1 and HDL were observed after the two highest single doses. It is possible that long-time abuse of anabolic androgenic steroids will lead to alteration in vitamin D status. Knowledge and understanding of the side effects of anabolic androgenic steroids are important to the treatment and care of abusers of testosterone.

Modified-release oral calcifediol corrects vitamin D insufficiency with minimal CYP24A1 upregulation

Vitamin D insufficiency is prevalent in chronic kidney disease (CKD) and associated with secondary hyperparathyroidism (SHPT) and increased risk of bone and vascular disease. Unfortunately, supplementation of stage 3 or 4 CKD patients with currently recommended vitamin D2 or D3 regimens does not reliably restore serum total 25-hydroxyvitamin D to adequacy (≥30ng/mL) or effectively control SHPT. Preclinical and clinical studies were conducted to evaluate whether the effectiveness of vitamin D repletion depends, at least in part, on the rate of repletion. A modified-release (MR) oral formulation of calcifediol (25-hydroxyvitamin D3) was developed which raised serum 25-hydroxyvitamin D3 and calcitriol levels gradually. Single doses of either bolus intravenous (IV) or oral MR calcifediol were administered to vitamin D deficient rats. Bolus IV calcifediol produced rapid increases in serum 25-hydroxyvitamin D3, calcitriol and FGF23, along with significant induction of CYP24A1 in both kidney and parathyroid gland. In contrast, oral MR calcifediol produced gradual increases in serum 25-hydroxyvitamin D3 and calcitriol and achieved similar hormonal exposure, yet neither CYP24A1 nor FGF23 were induced. A 10-fold greater exposure to bolus IV than oral MR calcifediol was required to similarly lower intact parathyroid hormone (iPTH). Single doses of oral MR (450 or 900μg) or bolus IV (450μg) calcifediol were administered to patients with stage 3 or 4 CKD, SHPT and vitamin D insufficiency. Changes in serum 25-hydroxyvitamin D3 and calcitriol and in plasma iPTH were determined at multiple time-points over the following 42 days. IV calcifediol produced abrupt and pronounced increases in serum 25-hydroxyvitamin D3 and calcitriol, but little change in plasma iPTH. As in animals, these surges triggered increased vitamin D catabolism, as evidenced by elevated production of 24,25-dihydroxyvitamin D3. In contrast, MR calcifediol raised serum 25-hydroxyvitamin D3 and calcitriol gradually, and meaningfully lowered plasma iPTH levels. Taken together, these studies indicate that rapid increases in 25-hydroxyvitamin D3 trigger CYP24A1 and FGF23 induction, limiting effective exposure to calcitriol and iPTH reduction in SHPT. They also support further investigation of gradual vitamin D repletion for improved clinical effectiveness.This article is part of a Special Issue entitled "17th Vitamin D Workshop".

Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women.

This study aims to prospectively assess the incidence of hypercalciuria and hypercalcemia with different doses of vitamin D and with a calcium intake of approximately 1,200 mg/day. This was a 1-year randomized placebo-controlled study of vitamin D (400-4,800 IU/d) in 163 white women aged 57 to 90 years. Calcium citrate tablets (200 mg) were added to the diet to achieve a total calcium intake of approximately 1,200 mg/day in all groups. All women had vitamin D insufficiency at baseline, with serum 25-hydroxyvitaminD levels lower than 20 ng/mL (50 nmol/L). Serum and 24-hour urine calcium were collected every 3 months on supplementation, any test result above the upper reference range represented an episode of hypercalcemia or hypercalciuria. Mixed-effects models and multivariate logistic regression were used in the analysis. Hypercalcemia (>10.2 mg/dL [2.55 mmol/L]) occurred in 8.8% of white women. Hypercalciuria (>300 mg/d [7.5 mmol]) occurred in 30.6% of white women. Episodes of hypercalciuria were transient in half of the group and recurrent in the other half. No relationship between hypercalcemia or hypercalciuria and vitamin D dose was found, and hypercalciuria was equally common in the placebo group. Hypercalciuria and hypercalcemia commonly occur with vitamin D and calcium supplements. Whether hypercalciuria and hypercalcemia are caused by calcium, vitamin D, or both is unclear. These findings may have relevance to the reported increase in kidney stones in the Women's Health Initiative trial. Because calcium 1,200 mg and vitamin D 800 IU/day are widely recommended in postmenopausal women, systematic evaluation of the safety of supplements is warranted in clinical management and in future studies.

Relationship between serum 25-hydroxy vitamin D3 concentration and obesity childhood

Objective To examine the relationship between the concentration of 25-hydroxy vitamin D3[25-(OH)D3] in the serum and the body mass, the severity of obesity, body mass index(BMI), blood lipid, and their predicting role in obesity children. Methods The study recruited 244 subjects, who see the doctor in Wuxi Maternal and Child Health Hospital, Childhood Nutrition Outpatient from Jul.2011 to Feb.2013.The intake dose of vitamin D each day was investigated, and weight, height, BMI, concentration of 25-(OH)D3 in serum, and microelement were also mea-sured.In addition, lipid metabolism of 38 cases with obesity over 3 years old was determined. Results 1.The serum 25-(OH)D3 concentration of obese children was (68.31±23.06) nmol/L.The concentration of 25-(OH)D3 was lowest in the group of obese children over 36 months of age[(55.03±15.18) nmol/L].2.The concentration of 25-(OH)D3 in the group of obese and overweight children was far lower than that of the children in the normal group(F=4.739, P<0.05).3.The concentrations of 25-(OH)D3 in the severely obese children was significantly lower than that of the mild and moderate obesity children(F=9.711, P<0.05).4.There were significantly inverse associations of serum 25-(OH)D3 with weight, weight and height percentage, BMI(r=-0.365, -0.237, -0.175, all P<0.001).5.There were significantly inverse associations between the concentration of 25-(OH)D3 in serum with weight, triglyceride in obese children more than 3 years old(r=0.476, -0.324, all P<0.05). Conclusions The decreasing level of 25-hydroxy vitamin D3 in the serum was associated with obesity.The cause of it might be the increase of the obese adipose tissue, vitamin D getting trapped in fat cells, and all these factors can lead to a less serum vitamin D levels.The vitamin D consumption of obese children is higher than that of normal children, and should supply more vitamin D to reach normal 25-(OH) D3 level. Key words: Serum 25-hydroxy vitamin D3 concentration; Child; Obesity

Role of vitamin D3 in treatment of lumbar disc herniation--pain and sensory aspects: study protocol for a randomized controlled trial.

BackgroundVitamin D receptors have been identified in the spinal cord, nerve roots, dorsal root ganglia and glial cells, and its genetic polymorphism association with the development of lumbar disc degeneration and herniation has been documented. Metabolic effects of active vitamin D metabolites in the nucleus pulposus and annulus fibrosus cells have been studied. Lumbar disc herniation is a process that involves immune and inflammatory cells and processes that are targets for immune regulatory actions of vitamin D as a neurosteroid hormone. In addition to vitamin D’s immune modulatory properties, its receptors have been identified in skeletal muscles. It also affects sensory neurons to modulate pain. In this study, we aim to study the role of vitamin D3 in discogenic pain and related sensory deficits. Additionally, we will address how post-treatment 25-hydroxy vitamin D3 level influences pain and sensory deficits severity. The cut-off value for serum 25-hydroxy vitamin D3 that would be efficacious in improving pain and sensory deficits in lumbar disc herniation will also be studied.Methods/DesignWe will conduct a randomized, placebo-controlled, double-blind clinical trial. Our study population will include 380 cases with one-level and unilateral lumbar disc herniation with duration of discogenic pain less than 8 weeks. Individuals who do not have any contraindications, will be divided into three groups based on serum 25-hydroxy vitamin D3 level, and each group will be randomized to receive either a single-dose 300,000-IU intramuscular injection of vitamin D3 or placebo. All patients will be under conservative treatment. Pre-treatment and post-treatment assessments will be performed with the McGill Pain Questionnaire and a visual analogue scale. For the 15-day duration of this study, questionnaires will be filled out during telephone interviews every 3 days (a total of five times). The initial and final interviews will be scheduled at our clinic. After 15 days, serum 25-hydroxy vitamin D3 levels will be measured for those who have received vitamin D3 (190 individuals).Trial registrationIranian Registry for Clinical Trials ID: IRCT2014050317534N1 (trial registration: 5 June 2014)

Relationship between serum 25-hydroxy vitamin D3 level and carotid atherosclerosis plaque in elderly patients with type 2 diabetes

Objective To explore the relationship between serum 25-hydroxy vitamin D 3 level and carotid atherosclerosis plaque in elderly patients with type 2 diabetes .Methods 308 elderly patients with type 2 diabetes were selected .The carotid artery intimal plaque was measured .According to the characteristics and size of plaque ,they were divided into the medium/big group,small plaque group and no plaque group .Blood pressure,body mass index （BMI）,fasting plasma glucose（FPG）,glycosylated hemoglobin（HbA1c）,blood lipids,c-reactive protein（CRP）and the concentration of serum 25-hydroxy vitamin D 3 were detected .The risk factors forcarotid atherosclerosis plaque were analyzed,exploring the the relationship between serum 25-hydroxy vitamin D3 level and carotid atherosclerosis plaque . Results Age,CRP（4.21 ±1.61） mg/L in the medium/big group was significantly higher than those of the small plaque group（3.41 ±1.92）mg/L and the no plaque group（2.52 ±1.18）mg/L（t=1.96,3.14,all P<0.05）.The level of serum 25-hydroxy vitamin D3 in the medium/big group（15.28 ±5.86）nmol/L was significantly less than that of the small plaque group（24.30 ±7.60）nmol/L and the no plaque group（32.74 ±8.13）nmol/L（t=4.67,3.41,all P<0.01）.The level of serum 25-hydroxy vitamin D3 in the small plaque group was significantly less than that of the no plaque group（t=2.51,P<0.05）.There was positive correlation between carotid atherosclerotic plaques and age , BMI,HbA1c,CRP and LDL-C（ r=0.45,0.38,0.53,0.47,all P<0.05）.There was negtive correlation between carotid atherosclerotic plaques and 25-hydroxy vitamin D3（r=-0.62,P<0.05）.Logstic regression analysis showed that age,BMI,HbA1c,CRP,LDL-C and 25-hydroxy vitamin D3 were independent risk factors for the development of carotid atherosclerotic plaque .Conclusion The risk factors for carotid atherosclerotic plaques in elderly patients with type 2 diabetes are age,BMI,HbA1c,CRP,LDL-C and 25-hydroxy vitamin D3 concentration.25-hydroxy vitamin D3 may be a predictor of carotid atherosclerotic plaques . Key words: Diabetes mellitus, type 2 ; 25-hydroxy vitamin D3 ; Atherosclerosis ; Carotid artery diseases ; Aged