Effect of High-Dose Vitamin D Repletion on Glycemic Control in African-American Males with Prediabetes and Hypovitaminosis D

Objective: This double-blind, randomized, controlled trial evaluated whether 12 months of high-dose vitamin D2 supplementation improved insulin sensitivity and secretion and glycemic status.Methods: African-American males (AAM) with prediabetes (glycosylated hemoglobin [A1C] 5.7-6.4%), hypovitaminosis D (25-hydroxyvitamin D [25OHD] 5-29 ng/mL), and prevalent medical problems were supplemented with vitamin D3 (400 IU/day) and then randomized to weekly placebo or vitamin D2 (50,000 IU). The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from an oral glucose tolerance test [OGTT]) after 12 months of treatment. Secondary outcomes included other glycemic indices, A1C, and incident diabetes.Results: Baseline characteristics were similar in vitamin D-supplemented (n = 87) and placebo (n = 86) subjects completing the trial with average concentrations 14.4 ng/mL, 362 mL × min^-1 × m^-2, and 6.1% for 25OHD, OGIS and A1C, respectively. After 12 months, the vitamin D-supplemented group had a change in serum 25OHD +35 versus +6 ng/mL for placebo, P<.001; OGIS +7.8 versus -16.0 mL × min^-1 × m^-2 for placebo, P = .026; and A1C -0.01 versus +0.01% for placebo, P = .66. Ten percent of subjects in both groups progressed to diabetes. A posthoc analysis of participants with baseline impaired fasting glucose (IFG) showed that more subjects in the vitamin D subgroup (31.6%) than placebo (8.3%) returned to normal glucose tolerance, but the difference did not reach significance (P = .13).Conclusion: The trial does not provide evidence that 12 months of high-dose D2 repletion improves clinically relevant glycemic outcomes in subjects with prediabetes and hypovitaminosis D (NCT01375660).Abbreviations: AAM = African-American males A1C = glycosylated hemoglobin BMI = body mass index D2 = ergocalciferol D3 = cholecalciferol IFG = impaired fasting glucose IGT = impaired glucose tolerance JBVAMC = Jesse Brown VA Medical Center OGIS = oral glucose insulin sensitivity index OGTT = oral glucose tolerance test 25OHD = 25-hydroxyvitamin D VHA = Veterans Health Administration     

A Prospective Study of Commonly Utilized Regimens of Vitamin d Replacement and Maintenance Therapy in Adults

Objective: To determine which vitamin D dose, formulation, and schedule most effectively and safely achieves a 25-hydroxyvitamin D (25&lsqb;OH]D) level of >30 ng/mL (75 nmol/L).Methods: In this prospective study, 100 subjects from the NY Harbor HCS Brooklyn Campus, ages 25 to 85 years, with 25(OH)D <30 ng/mL (<75 nmol/L), were randomized into four groups: cholecalciferol (D3) 2,000 international units (IU) daily; D3 3,000 IU daily; ergocalciferol (D2) 50,000 IU weekly; and D2 50,000 IU twice weekly. All were supplemented with 500 mg calcium carbonate daily. 25(OH)D, parathyroid hormone (PTH), urinary calcium, urinary creatinine, and other variables were measured during 7 visits over 12 months.Results: All groups achieved a mean vitamin D level >30 ng/mL (>75 nmol/L) by visit 4 (5 months). Those receiving 50,000 IU D2 twice weekly displayed the most rapid and robust response, with 25(OH)D reaching >30 ng/mL (>75 nmol/L) after only 1 month and plateauing at 60 ng/mL (150 nmol/L) by 7 months. Although no statistically significant difference was seen in mean 25(OH)D levels between groups 1 through 3, subjects on 50,000 IU D2 weekly more consistently showed higher mean levels than either groups 1 or 2. No episodes of significant hypercalcemia occurred. There was a negative correlation in mean PTH levels and mean vitamin D levels in group 4 and all groups combined.Conclusion: All four schedules of vitamin D replacement were effective in safely achieving and maintaining 25(OH)D >30 ng/mL (>75 nmol/L). D2 50,000 IU twice weekly provided the most rapid attainment and highest mean levels of vitamin D.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; BUN = blood urea nitrogen; Ca/Cr = calcium/creatinine; D2 = ergocalciferol; D3 = cholecalciferol; IU = international units; PTH = parathyroid hormone     

Vitamin D Status and Its Seasonal Variability in Healthy Young Adults in an Asian Indian Urban Population

ObjectiveTo assess the vitamin D status and its seasonal variability in healthy young adults in Chandigarh, a city in northern India.MethodsThe history was elicited and examination was performed pertaining to metabolic bone disease in 329 young adults (18 to 25 years of age) at the end of summer and 237 subjects from the same cohort at the end of winter. The calcium profile, 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone were measured during both the seasons.ResultsAmong the young adults in this study cohort, 25(OH)D sufficiency (≥ 30 ng/mL) was found in 72.5% in summer and in 50.7% in winter. A significantly higher number of men were 25(OH)D sufficient in comparison with women in summer (P = .001). The mean (standard deviation) serum 25(OH)D levels were significantly higher at the end of summer—52.9 (33.7) ng/mL—in comparison with that at the end of winter—31.8 (21.1) ng/mL; P < .001. The intact parathyroid hormone levels were significantly lower in the 25(OH)D-sufficient group (P = .001) and began to increase at 25(OH)D levels below 25 ng/mL. The serum 25(OH)D levels correlated positively with the duration of exposure to sunlight during summer (r = 0.111; P = .05) and also the calcium intake during summer (r = 0.129; P = .03).ConclusionVitamin D sufficiency may be a reality with a combination of young skin, optimal and effective exposure to sunlight, and adequate calcium intake. (Endocr Pract. 2011;17:185-191)     

Low Vitamin D Status Is Associated with Nonalcoholic Fatty Liver Disease Independent of Visceral Obesity in Korean Adults

Objective

To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity in Koreans and to examine whether the associations differ according to the presence of diabetes or insulin resistance.

Research Design and Methods

A total of 1081 adults were enrolled from a population-based cohort in Ansan city. Serum 25(OH)D concentrations were measured in all subjects. Insulin resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Using computed tomography, NAFLD was diagnosed if the liver attenuation index (LAI, the difference between the mean hepatic and splenic attenuation) was <5 Hounsfield Units.

Results

In subjects with diabetes (n = 282), 25(OH)D levels were negatively associated with waist circumference, fasting insulin, HOMA-IR, triglyceride levels, and visceral abdominal fat, and were positively associated with LAI after adjusting for age, sex, season, exercise, and vitamin supplementation. In subjects without diabetes, only triglyceride level was negatively associated with 25(OH)D. The adjusted odds ratio (OR) for NAFLD increased sequentially across decreasing quartiles of 25(OH)D in subjects with diabetes even after adjusting for visceral fat [Q1 vs. Q4; OR for NAFLD 2.5 (95% CI:1.0–6.2)]. In contrast, no significant difference in OR was observed in subjects without diabetes. When we classified non-diabetic subjects by HOMA-IR, an increase in the OR for NAFLD across decreasing quartiles of 25(OH)D was observed in the high HOMA-IR (≥2.5) group [n = 207, Q1 vs. Q4; OR 3.8(1.4–10.3)], but not in the low HOMA-IR (<2.5) group [n = 592, OR 0.8 (0.3–1.9)].

Conclusions

Low vitamin D status is closely associated with NAFLD, independent of visceral obesity in subjects with diabetes or insulin resistance.     

Vitamin D Status and the Risk for Hospital-Acquired Infections in Critically Ill Adults: A Prospective Cohort Study

Introduction

To identify patient characteristics associated with low serum 25-hydroxyvitamin D (25(OH)D) concentrations in the medical intensive care unit (ICU) and examine the relationship between serum 25(OH)D and the risk for hospital-acquired infections.

Methods

This is a prospective observational cohort of adult patients admitted to the medical ICU at an urban safety net teaching hospital in Atlanta, Georgia from November 1, 2011 through October 31, 2012 with an anticipated ICU stay ≥ 1 day. Phlebotomy for serum 25(OH)D measurement was performed on all patients within 5 days of ICU admission. Patients were followed for 30 days or until death or hospital discharge, whichever came first. Hospital-acquired infections were determined using standardized criteria from review of electronic medical record.

Results

Among the 314 patients analyzed, 178 (57%) had a low vitamin D at a serum 25(OH)D concentration < 15 ng/mL. The patient characteristics associated with low vitamin D included admission during winter months (28% vs. 18%, P = 0.04), higher PaO2/FiO2 (275 vs. 226 torr, P = 0.03) and a longer time from ICU admission to study phlebotomy (1.8 vs. 1.5 days, P = 0.02). A total of 36 (11%) patients were adjudicated as having a hospital-acquired infection and in multivariable analysis adjusting for gender, alcohol use, APACHE II score, time to study phlebotomy, ICU length of stay and net fluid balance, serum 25(OH)D levels < 15 ng/mL were not associated with risk for hospital-acquired infections (HR 0.85, 95% CI 0.40-1.80, P = 0.7).

Conclusions

In this prospective, observational cohort of adults admitted to a single-center medical ICU, we did not find a significant association between low 25(OH)D and the risk for hospital-acquired infections.     

The Vitamin D Status in Inflammatory Bowel Disease

Context

There is no consensus on the vitamin D status of children and adolescents with inflammatory bowel disease (IBD).

Aim

To determine the vitamin D status of patients with IBD by comparing their serum 25(OH)D concentration to that of healthy controls.

Hypothesis

Serum 25(OH)D concentration will be lower in patients with IBD compared to controls.

Subjects and Methods

A case-controlled retrospective study of subjects with IBD (n = 58) of 2–20 years (male n = 31, age 16.38±2.21 years; female n = 27, age16.56±2.08 years) and healthy controls (n = 116; male n = 49, age 13.90±4.59 years; female n = 67, age 15.04±4.12years). Study subject inclusion criteria: diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). Vitamin D deficiency was defined as 25(OH)D of (<20 ng/mL) (<50 nmol/L), overweight as BMI of ≥85^th but <95^th percentile, and obesity as BMI ≥95^th percentile. Data were expressed as mean ± SD.

Results

Patients with CD, UC, and their controls had mean serum 25(OH)D concentrations of 61.69±24.43 nmol/L, 53.26±25.51, and 65.32±27.97 respectively (ANOVA, p = 0.196). The overweight/obese controls had significantly lower 25(OH)D concentration compared to the normal-weight controls (p = 0.031); whereas 25(OH)D concentration was similar between the normal-weight and overweight/obese IBD patients (p = 0.883). There was no difference in 25(OH)D between patients with UC and CD, or between subjects with active IBD and controls. However, IBD subjects with elevated ESR had significantly lower 25(OH)D than IBD subjects with normal ESR (p = 0.025), as well as controls (65.3±28.0 nmol/L vs. 49.5±25.23, p = 0.045).

Conclusion

There is no difference in mean serum 25(OH)D concentration between children and adolescents with IBD and controls. However, IBD subjects with elevated ESR have significantly lower 25(OH)D than controls. Therefore, IBD subjects with elevated ESR should be monitored for vitamin D deficiency.     

Preeclampsia and Blood Pressure Trajectory during Pregnancy in Relation to Vitamin D Status

Every tenth pregnancy is affected by hypertension, one of the most common complications and leading causes of maternal death worldwide. Hypertensive disorders in pregnancy include pregnancy-induced hypertension and preeclampsia. The pathophysiology of the development of hypertension in pregnancy is unknown, but studies suggest an association with vitamin D status, measured as 25-hydroxyvitamin D (25(OH)D). The aim of this study was to investigate the association between gestational 25(OH)D concentration and preeclampsia, pregnancy-induced hypertension and blood pressure trajectory. This cohort study included 2000 women. Blood was collected at the first (T1) and third (T3) trimester (mean gestational weeks 10.8 and 33.4). Blood pressure at gestational weeks 10, 25, 32 and 37 as well as symptoms of preeclampsia and pregnancy-induced hypertension were retrieved from medical records. Serum 25(OH)D concentrations (LC-MS/MS) in T1 was not significantly associated with preeclampsia. However, both 25(OH)D in T3 and change in 25(OH)D from T1 to T3 were significantly and negatively associated with preeclampsia. Women with a change in 25(OH)D concentration of ≥30 nmol/L had an odds ratio of 0.22 (p = 0.002) for preeclampsia. T1 25(OH)D was positively related to T1 systolic (β = 0.03, p = 0.022) and T1 diastolic blood pressure (β = 0.02, p = 0.016), and to systolic (β = 0.02, p = 0.02) blood pressure trajectory during pregnancy, in adjusted analyses. There was no association between 25(OH)D and pregnancy-induced hypertension in adjusted analysis. In conclusion, an increase in 25(OH)D concentration during pregnancy of at least 30 nmol/L, regardless of vitamin D status in T1, was associated with a lower odds ratio for preeclampsia. Vitamin D status was significantly and positively associated with T1 blood pressure and gestational systolic blood pressure trajectory but not with pregnancy-induced hypertension.     

Correlating Pre-Operative Vitamin D Status with Post-Thyroidectomy Hypocalcemia

Objective: To examine the relationship between pre-operative vitamin D status and post-thyroidectomy hypocalcemia.Methods: Retrospective study examining 264 total and completion thyroidectomies conducted between 2007 and 2011. Subjects included had a recorded 25-hydroxyvitamin D (25[OH]D) level within 21 days prior to or 1 day following surgery, did not have a primary parathyroid gland disorder, and were not taking 1,25-dihydroxyvitamin D₃ (calcitriol) prior to surgery. Some subjects were repleted with vitamin D pre-operatively if a low 25(OH)D level (typically below 20 ng/mL) was identified. Pre-operative 25(OH)D, concurrent neck dissection, integrity of parathyroid glands, final pathology, postoperative parathyroid hormone (PTH), calcium nadir and repletion, and length of stay were examined.Results: The mean pre-operative 25(OH)D for all subjects was 25 ng/mL, and the overall rate of post-operative hypocalcemia was 37.5%. Lower pre-operative 25(OH)D did not predict postoperative hypocalcemia (P =.96); however, it did predict the need for postoperative 1,25-dihydroxyvitamin D₃ administration (P =.01). Lower postoperative PTH levels (P =.001) were associated with postoperative hypocalcemia.Conclusion: Pre-operative 25(OH)D did not predict a postoperative decrease in serum calcium, although it did predict the need for 1,25-dihydroxyvitamin D₃ therapy in hypocalcemic subjects. We recommend that 25(OH)D be assessed and, if indicated, repleted pre-operatively in patients undergoing total thyroidectomy.Abbreviations: 25(OH)D = 25-hydroxyvitamin D PTH = parathyroid hormone     

Vitamin D Status Predicts 30 Day Mortality in Hospitalised Cats

Vitamin D insufficiency, defined as low serum concentrations of the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with the development of numerous infectious, inflammatory, and neoplastic disorders in humans. In addition, vitamin D insufficiency has been found to be predictive of mortality for many disorders. However, interpretation of human studies is difficult since vitamin D status is influenced by many factors, including diet, season, latitude, and exposure to UV radiation. In contrast, domesticated cats do not produce vitamin D cutaneously, and most cats are fed a commercial diet containing a relatively standard amount of vitamin D. Consequently, domesticated cats are an attractive model system in which to examine the relationship between serum 25(OH)D and health outcomes. The hypothesis of this study was that vitamin D status would predict short term, all-cause mortality in domesticated cats. Serum concentrations of 25(OH)D, together with a wide range of other clinical, hematological, and biochemical parameters, were measured in 99 consecutively hospitalised cats. Cats which died within 30 days of initial assessment had significantly lower serum 25(OH)D concentrations than cats which survived. In a linear regression model including 12 clinical variables, serum 25(OH)D concentration in the lower tertile was significantly predictive of mortality. The odds ratio of mortality within 30 days was 8.27 (95% confidence interval 2.54-31.52) for cats with a serum 25(OH)D concentration in the lower tertile. In conclusion, this study demonstrates that low serum 25(OH)D concentration status is an independent predictor of short term mortality in cats.     

Vitamin D Status and Hypocalcemic Response to Protamine in Exercised and Non-exercised Dairy Cows

Bone resorption was studied in post parturient cows using intravenous injection of protamine. Protamine inhibits bone resorption and the protamine-induced hypocalcemia can be taken as a measure of this process. The studies were performed in a herd where half of the cows had been tied indoors for 21/2 years, the other half had been given daily exercise during the same period. All animals were fed in the same way. The hypocalcémie response to protamine was the same in both groups, which indicates that exercise did not change bone resorption. The serum levels of calcium, inorganic phosphorus and magnesium around parturition did not differ. The daily exposure to daylight increased the serum level of 25-(OH)-chole-calciferol in late summer in the exercised group.     

Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states

The role in skeletal metabolism of the steroid hormone Vitamin D and its nuclear receptor (VDR) is well known. In addition, however, Vitamin D is also involved in a wide variety of other biological processes including modulation of the immune response and regulation of cell proliferation and differentiation. Variations in the Vitamin D endocrine system have thus been linked to several diseases, including osteoarthritis, diabetes, cancer, cardiovascular disease and tuberculosis. Evidence to support this pleiotropic character of Vitamin D has included epidemiological studies on circulating Vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations which occur frequently in the population are referred to as "polymorphisms" and are usually suspected of having only modest and subtle effects. Recent studies have indicated many polymorphisms to exist in the VDR gene, but the influence of VDR gene polymorphisms on VDR protein function are largely unknown. Sofar, three adjacent restriction fragment length polymorphisms (RFLP) for BsmI, ApaI and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied sofar. But because these polymorphisms are probably non-functional, linkage disequilibrium (LD) with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis, and on trying to understand the functional consequences of the variations. Substantial progress has been made including the discovery of novel polymorphisms in the large promoter region of the VDR gene. Eventually, results of this research will deepen our understanding of variability in the Vitamin D endocrine system and might find applications in risk-assessment of disease and in predicting response-to-treatment.     

Maternal Vitamin D Status in Preeclampsia: Seasonal Changes Are Not Influenced by Placental Gene Expression of Vitamin D Metabolizing Enzymes

Preeclampsia, a hypertensive disorder in pregnancy develops in 2–8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.

Objective

To investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.

Methods

25-OH vitamin D and 1,25-(OH)₂ vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.

Results

In patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)₂ vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = −0.81, P<0.0001).

Summary

Patients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia.     

A Meta-Analysis of High Dose,Intermittent Vitamin D Supplementation among Older Adults

Background

The effects of intermittent, high dose vitamin D treatment in older adults have not been documented. We conducted a meta-analysis to provide a quantitative assessment of the efficiency of intermittent, high dose vitamin D treatment on falls, fractures, and mortality among older adults.

Methods

Electronic databases were searched for randomized controlled trials (RCTs) on high dose, intermittent vitamin D supplementation among older adults. Two researchers independently screened the literature according to specified inclusive and exclusive criteria to extract the data. Meta-analysis was performed by using Review Manager 5.1.0 software.

Results

Nine trials were included in this meta-analysis. High dose, intermittent vitamin D therapy did not decrease all-cause mortality among older adults. The risk ratio (95% CI) was 1.04 (0.91–1.17). No benefit was seen in fracture or fall prevention. The risk ratio for hip fractures (95% CI) was 1.17 (0.97–1.41) while for non-vertebral fractures (95% CI) it was 1.06 (0.91–1.22), and the risk ratio for falls (95% CI) was 1.02 (0.96–1.08). Results remained robust after sensitivity analysis.

Conclusion

Supplementation of intermittent, high dose vitamin D may not be effective in preventing overall mortality, fractures, or falls among older adults. The route of administration of vitamin D supplements may well change the physiological effects.     

Calcium and Vitamin D Status in Heart Failure Patients in Isfahan, Iran

Both calcium and vitamin D play important roles in cardiac muscle contraction and performance. In this cross-sectional study, we evaluated the status of serum calcium, PTH and 25(OH)D₃ and their correlation with left ventricular Function and NYHA Functional class in 95 heart failure patients referred to Shahid Chamran Hospital, Isfahan, Iran, by colorimetric, immunoradiometric, and Immunochemiluminescent assays, echocardiography and interview respectively. The study was performed between Oct 2007 and Feb 2008. Twenty eight women and 67 men of functional classes 1, 2, or 3 participated in the study. Mean (SD) of age of the participants was 62(11)?years. Mean (SD) serum calcium and 25(OH)D₃ were 2.41(0.16)?mmol/L and 56.78(51.33)?nmol/L, respectively. The overall prevalence of low vitamin D status was 84.2%. There was no correlation between serum calcium and 25(OH)D₃ with LVEF. Interestingly, patients with hyperparathyroidism (serum PTH>65 ng/L) had lower LVEF (27% versus 32.5% p?=?0.03). NYHA functional class was worse in patients with hyperparathyroidism (p?=?0.08). Hypovitaminosis D is very prevalent in heart failure patients. Hyperparathyroidism in these patients may adversely affect cardiac function. Vitamin D3 might serve as an adjunctive treatment for heart failure patients.     

Determining Vitamin D Status: A Comparison between Commercially Available Assays

Background

Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays.

Methodology/Principal Findings

Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81–89), intermediate for RIA (70 nmol/L, 95% CI 66–74) and lowest with CLIA (60 nmol/L, 95% CI 56–64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D.

Conclusions/Significance

There are substantial inter-assay differences in performance. The most valid method was HPLC-APCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.     

Vitamin D Status and Cause-Specific Mortality: A General Population Study

Background

Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality.

Methods

We included a total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, conducted in 1993–94 and 1999–2001, respectively. Vitamin D status was assessed as serum 25-hydroxyvitamin D. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2009. There were a total of 832 deaths (median follow-up 10.3 years).

Results

Multivariable Cox regression analyses with age as underlying time axis and vitamin D quartiles showed significant associations between vitamin D status and death caused by diseases of the respiratory system, the digestive system, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (p_trend = 0.0042), 0.28 (p_trend = 0.0040), and 0.21 (p_trend = 0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by neoplasms or diseases of the circulatory system.

Conclusion

The associations of vitamin D status and cause-specific mortality suggest that we also look elsewhere (than to cardiovascular disease and cancer) to explain the inverse association between vitamin D status and mortality.     

Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

Background

Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.

Objective

Characterize 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.

Method

We 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).

Findings

Seasonal 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.

Interpretation

25(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.     

Determinants of Vitamin D Status in Fair-Skinned Women of Childbearing Age at Northern Latitudes

Background and Objective

Poor vitamin D status during pregnancy has been associated with unfavorable outcomes for mother and child. Thus, adequate vitamin D status in women of childbearing age may be important. The aim of this study is to investigate the determinants of 25-hydroxyvitamin D (25(OH)D) serum concentrations in women of childbearing age living in Sweden, at latitude 57–58° north.

Method

Eighty four non-pregnant, non-lactating, healthy, fair-skinned women aged between 25–40 years were included. All subjects provided blood samples, four day food records and answered questionnaires about sun exposure and lifestyle. Total serum 25(OH)D was analyzed using Roche Cobas® electrochemoluminiescent immunoassay.

Results

Mean 25(OH)D was 65.8±19.9 nmol/l and 23% of the subjects had concentrations <50 nmol/l. Only 1% had concentrations <25 nmol/l. Determinants of 25(OH)D concentrations were recent sunbed use, recent travel to southern latitude, season, estrogen contraceptive use and use of supplementary vitamin D (R² = 0.27).

Conclusion

Every fifth woman had 25(OH)D concentrations <50 nmol/l. About 30% of the variation in vitamin D status was explained by sun exposure, use of vitamin D supplements and use of estrogen contraceptives. Cutaneous vitamin D synthesis seems to be a major contributor to vitamin D status, even at northern latitudes. Thus, recommendations on safe UV-B exposure could be beneficial for vitamin D status.