Seasonality of UV-radiation and vitamin D status at 69 degrees north.

The main purpose with this study was to assess the seasonal variation in measured UV-radiation and its impact on vitamin D status throughout one year in subjects living at high latitude. Blood samples drawn from 60 volunteers (44 women, 16 men) living at Andenes (69 degrees N), Norway, were collected throughout one year, at two-month intervals. The blood samples were analysed for 25-hydroxy vitamin D [25(OH)D]. Data on dietary intakes of vitamin D, time spent in daylight, use of sun beds and sun seeking holidays were collected by using questionnaires. The ambient vitamin D effective UV-radiation was measured at a site near by Andenes, and the number of hours spent outdoors with sufficient radiation for cutaneous vitamin D production (UV-hours) was estimated for each day. The mean 25(OH)D values were significantly higher at the end of the summer and in December, 2004 and varied from 42.0 nmol L(-1) in October, 2004 and April, 2005 to around 47 nmol L(-1) in December, 2004 and September, 2005. For the whole group, a positive relationship between UV-hours and 25(OH)D was found at UV-hours>or=3.5. However, for subjects with lower 25(OH)D levels i.e. at least one blood measurement with 25(OH)D<37.5 nmol L(-1), the positive relationship were found at around 1.5 UV-hours and more, whereas for the group of subjects that had all their vitamin D values above 37.5 nmol L(-1), positive relationship was found at UV-hours>or=4.0, when adjusting for vitamin D intake, sun bed use and sun seeking holidays. The generally high dietary intakes of vitamin D, especially in winter, mask largely the effect of seasonal variation in UV-exposure, causing an atypical seasonal variation in vitamin D status. The UV-hour variable significantly predicted 25(OH)D levels in blood when adjusted for intakes and artificial UV-radiation exposure and sun holidays abroad.     

Vitamin D and disease prevention with special reference to cardiovascular disease

Circulating 25-hydroxyvitamin D [25(OH)D] is the hallmark for determining vitamin D status. Serum parathyroid hormone [PTH] increases progressively when 25(OH)D falls below 75 nmol/l. Concentrations of 25(OH)D below 50 nmol/l or even below 25 nmol/l are frequently observed in various population groups throughout the world. This paper highlights the relationship of vitamin D insufficiency with cardiovascular disease and non-insulin dependent diabetes mellitus, two diseases that account for up to 50% of all deaths in western countries. There is evidence from patients with end-stage renal disease that high PTH concentrations are causally related to cardiovascular morbidity and mortality. Activated vitamin D is able to increase survival in this patient group significantly. Moreover, already slightly enhanced PTH concentrations are associated with ventricular hypertrophy and coronary heart disease in the general population. Experimental studies have demonstrated that a lack of vitamin D action leads to hypertension in mice. Some intervention trials have also shown that vitamin D can reduce blood pressure in hypertensive patients. In young and elderly adults, serum 25(OH)D is inversely correlated with blood glucose concentrations and insulin resistance. Sun-deprived lifestyle, resulting in low cutaneous vitamin D synthesis, is the major factor for an insufficient vitamin D status. Unfortunately, vitamin D content of most foods is negligible. Moreover, fortified foods and over-the-counter supplements usually contain inadequate amounts of vitamin D to increase serum 25(OH)D to 75 nmol/l. As a consequence, legislation has to be changed to allow higher amounts of vitamin D in fortified foods and supplements.     

Comparison of Venous and Capillary Differential Leukocyte Counts Using a Standard Hematology Analyzer and a Novel Microfluidic Impedance Cytometer

Capillary blood sampling has been identified as a potentially suitable technique for use in diagnostic testing of the full blood count (FBC) at the point-of-care (POC), for which a recent need has been highlighted. In this study we assess the accuracy of capillary blood counts and evaluate the potential of a miniaturized cytometer developed for POC testing. Differential leukocyte counts in the normal clinical range from fingerprick (capillary) and venous blood samples were measured and compared using a standard hematology analyzer. The accuracy of our novel microfluidic impedance cytometer (MIC) was then tested by comparing same-site measurements to those obtained with the standard analyzer. The concordance between measurements of fingerprick and venous blood samples using the standard hematology analyzer was high, with no clinically relevant differences observed between the mean differential leukocyte counts. Concordance data between the MIC and the standard analyzer on same-site measurements presented significantly lower leukocyte counts determined by the MIC. This systematic undercount was consistent across the measured (normal) concentration range, suggesting that an internal correction factor could be applied. Differential leukocyte counts obtained from fingerprick samples accurately reflect those from venous blood, which confirms the potential of capillary blood sampling for POC testing of the FBC. Furthermore, the MIC device demonstrated here presents a realistic technology for the future development of FBC and related tests for use at the site of patient care.     

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     

The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body''s vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets.     

The Vitamin D Dose Response in Obesity

ObjectiveThe prevalence of vitamin D inadequacy is high in obese individuals. Determining the response of serum 25-hydroxyvitamin D (25[OH]D) to vitamin D₃ supplementation in obese and nonobese individuals may lead to concurrent recommendations for optimal vitamin D intake in these populations. The objective of this study was to determine the dose response of vitamin D₃ in subjects with a body mass index ≥ 35 kg/m².MethodsRandomized, double-blind, placebo-controlled study. This study is an extension of our previous study of vitamin D dosing in healthy adults. After an assessment of baseline 25(OH)D levels, participants were randomized to a vitamin D supplementation arm (100 μg daily if baseline 25[OH]D was < 50 nmol/L, or 50 μg daily if baseline 25[OH]D was ≥ 50 nmol/L) or placebo arm. Subjects with baseline 25(OH)D level ≥ 80 nmol/L were excluded from the study. Two months following randomization, a repeat 25(OH)D measurement was done.ResultsFinal analysis included 25 subjects (14 placebo, 11 active). At 2 months, serum 25(OH)D concentration increased to a mean of 75 nmol/L in the active group. Mean slope (i.e., vitamin D₃ response), defined as 25(OH) D change/baseline dose, was 0.398 nmol/L/μg/day.ConclusionThe dose response of vitamin D₃ (slope) in obese subjects was significantly lower (P < .03) at 0.398 nmol/L/μg/day compared to the slope in the previous study of healthy subjects (0.66 nmol/L/μg/day). These results suggest that obese individuals may require 40% higher vitamin D intake than nonobese individuals to attain the same serum 25(OH)D concentration. (Endocr Pract. 2014;20:1258-1264)     

6-Fluoro-vitamin D3: a new antagonist of the biological actions of vitamin D3 and its metabolites which interacts with the intestinal receptor for 1 alpha,25(OH)2-vitamin D3

The biological activity and the binding affinity for the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] intestinal receptor of a new fluorine-containing vitamin D compound, namely 6-fluoro-vitamin D3 (6-F-D3), is reported. A significant interaction of 6-F-D3 with the 1,25(OH)2D3 receptor was found, with a relative competitive index (RCI) of 0.26 +/- 0.04, which is intermediate between 25-hydroxyvitamin D3 (0.14 +/- 0.01) and 1 alpha-hydroxyvitamin D3 (0.46 +/- 0.08), where the RCI of 1,25(OH)2D3 is defined to be 100. In contrast, vitamin D3 was unable to interact with the 1,25(OH)2D3 receptor. Also, the biological activity of 6-F-D3 was assessed in vivo in the vitamin D-deficient chick. 6-F-D3 at doses up to 130 nmol displayed no biological action on either intestinal calcium absorption (ICA) or bone calcium mobilization (BCM) over the time interval of 14-48 h after dosing. However, when 130 nmol 6-F-D3 was given 2 h before and 6 h after vitamin D3 (1.62 nmol), a significant inhibition of vitamin D-mediated ICA was noted. Also, a dose of 130 nmol 6-F-D3 given 2 h before and 6 h after 1,25(OH)2D3 (0.26 nmol) significantly inhibited ICA, as measured at 12 h. 6-F-D3 is the first vitamin D analog found which has an ability to both bind to the 1,25(OH)2D3 receptor and to antagonize the production of biological responses by 1,25(OH)2D3.     

Low Maternal Vitamin D Status during the Second Trimester of Pregnancy: A Cross-Sectional Study in Wuxi,China

BackgroundVitamin D deficiency is common in pregnant women, but an optimal serum vitamin D level during pregnancy has not been determined and remains an area of active research. Vitamin D data from large populations of pregnant Chinese women are still limited.ObjectiveTo evaluate the vitamin D status of women in Eastern China during the second trimester of pregnancy.MethodsA hospital-based, cross-sectional, observational study. Serum 25-hydroxyvitamin D [25(OH)D] concentration was measured in samples from 5823 pregnant women in Wuxi City, China (latitude: 31.5o N), from January 2011 to June 2012.ResultsThe median serum 25(OH)D concentration was 34.0 nmol/L [2.5 nmol/L 25(OH)D = 1 ng/mL 25(OH)D]. Vitamin D deficiency [defined as 25(OH)D < 30 nmol/L according to the Institute of Medicine (National Academy of Sciences, Washington, D.C., USA)] or inadequacy [25(OH)D of 30–49.9 nmol/L] was identified in 40.7% and 38.0% of the women, respectively. Only 0.9% had a 25(OH)D level ≥ 80.0 nmol/L, which is the concentration recommended as adequate by the Endocrine Society (Washington, D.C., USA). Compared with older women, younger women were more likely to be deficient in vitamin D. There were significant differences in the 25(OH)D levels according to season. The 25(OH)D levels reached peak values in September and were correlated with (r = 0.337, P < 0.001), and fluctuated with, average monthly air temperatures.ConclusionsThere is a high prevalence of Vitamin D deficiency among pregnant Chinese women, and 25(OH)D levels varied according to season and air temperature. The results of this study also suggest that currently there is a big gap between the levels of Vitamin D detected in pregnant Chinese women and the levels recommended by the Endocrine Society.     

Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults

The physiologic range for circulating 25-hydroxyvitamin D3 [25(OH)D; the measure of Vitamin D nutrient status] concentration in humans and other primates extends to beyond 200 nmol/L (>80 ng/mL). This biologic "normal" value is greater than current population norms for 25(OH)D. Concentrations of 25(OH)D that correlate with desirable effects extend to at least 70 nmol/L, with no obvious threshold. Randomized clinical trials using 20 mcg (800 IU) per day of Vitamin D show that this suppresses parathyroid hormone, preserves bone mineral density, prevents fractures, lowers blood pressure and improves balance. Calcium absorption from diet correlates with 25(OH)D in the normal range. Health effects of Vitamin D beyond osteoporosis are mostly supported by the circumstantial evidence of epidemiologic studies and laboratory research. These include prevention of cancer and the autoimmune diseases, insulin-dependent diabetes and multiple sclerosis. One mcg per day of Vitamin D(3) (cholecalciferol) increases circulating 25(OH)D by about 1 nmol/L (0.4 ng/mL). A recommended dietary allowance (RDA) is the long-term daily intake level that meets the total requirements for the nutrient by nearly all healthy individuals (it would presume no sunshine). If 70 nmol/L is regarded as a minimum desirable target 25(OH)D concentration, then current recommendations of 15 mcg per day do not meet the criterion of an RDA.     

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.     

Lipid status association with 25-hydroxy vitamin D: Cross sectional study of end stage renal disease patients

BackgroundSome observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients.MethodsWe have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio.ResultsESRD patients with adjusted 25(OH)D concentrations of 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDLC (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L.ConclusionsOur study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients.     

Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status

Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D₃ and its metabolic product—25(OH)D₃ has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6400 IU vitamin D₃/day for 6 months.

Results (1) the relationship between circulating vitamin D₃ and 25(OH)D in both groups was not linear, but appeared saturable and controlled; (2) optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D₃ and 25(OH)D exceeded 0.3; at this point, the V_max of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol.

We hypothesize that as humans live today, the 25-hydroxylase operates well below its V_max because of chronic substrate deficiency, namely vitamin D₃. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be.     

Determination of vitamin D and its metabolites in plasma from normal and anephric man

A multiple assay capable of reliably determining vitamins D(2) and D(3) (ergocalciferol and cholecalciferol), 25(OH)D(2) (25-hydroxyvitamin D(2)) and 25(OH)D(3) (25-hydroxyvitamin D(3)), 24,25(OH)(2)D (24,25-dihydroxyvitamin D), 25,26(OH)(2)D (25,26-dihydroxyvitamin D) and 1,25(OH)(2)D (1,25-dihydroxyvitamin D) in a single 3-5ml sample of human plasma was developed. The procedure involves methanol/methylene chloride extraction of plasma lipids followed by separation of the metabolites and purification from interfering contaminants by batch elution chromatography on Sephadex LH-20 and Lipidex 5000 and by h.p.l.c. (high-pressure liquid chromatography). Vitamins D(2) and D(3) and 25(OH)D(2) and 25(OH)D(3) are quantified by h.p.l.c. by using u.v. detection, comparing their peak heights with those of standards. 24,25(OH)(2)D and 25,26(OH)(2)D are measured by competitive protein-binding assay with diluted plasma from vitamin D-deficient rats. 1,25(OH)(2)D is measured by competitive protein-binding assay with diluted cytosol from vitamin D-deficient chick intestine. Values in normal human plasma samples taken in February are: vitamin D 3.5+/-2.5ng/ml; 25(OH)D 31.6+/-9.3ng/ml; 24,25(OH)(2)D 3.5+/-1.4ng/ml; 25,26(OH)(2)D 0.7+/-0.5ng/ml; 1,25(OH)(2)D 31+/-9pg/ml (means+/-s.d.). Values in two normal human plasma samples taken in February after 1 week of high sun exposure are: vitamin D 27.1+/-7.9ng/ml; 25(OH)D 56.8+/-4.2ng/ml; 24,25(OH)(2)D 4.3+/-1.6ng/ml; 25,26(OH)(2)D 0.5+/-0.2ng/ml. Values in anephric-human plasma are: vitamin D 2.7+/-0.8ng/ml; 25(OH)D 36.4+/-16.5ng/ml; 24,25(OH)(2)D 1.9+/-1.3ng/ml; 25,26(OH)(2)D 0.6+/-0.3ng/ml; 1,25(OH)(2)D was undetectable.     

Increased 25-hydroxyvitamin D levels in portal blood following cholecystokinin injection in the dog

To establish whether an enterohepatic circulation of the metabolites of vitamin D exists, polyethylene catheters were cannulated into the portal vein of dogs. The dogs were then starved for 24 h and injected with cholecystokinin (CCK) to induce gall bladder contraction. At various time intervals thereafter blood samples were collected from the portal and the saphena veins, and sera prepared and analyzed for the metabolites of vitamin D. The serum levels of 25-hydroxyvitamin D [25(OH)D] were found to be significantly higher in the portal blood when compared with levels in peripheral blood following CCK injection. Since portal blood collects nutrients absorbed from the gut and as the dogs were starved for 24 h prior to blood collection, the only source of the increased concentrations of 25(OH)D in portal blood is likely to be bile. These findings support the notion that an enterohepatic circulation of 25(OH)D does exist under normal physiological conditions.     

The solar UV radiation level needed for cutaneous production of vitamin D3 in the face. A study conducted among subjects living at a high latitude (68 degrees N).

Populations at high latitudes experience several winter months with insufficient UV solar radiation to induce a significant cutaneous production of vitamin D. This unique study was designed to pursue an in vivo threshold of UV radiation needed for cutaneous production of vitamin D to take place if only the face was exposed to UV radiation. The vitamin D status were measured by analyzing blood samples weekly from a study group of 15 subjects over a period of 2 months during late winter, when UV radiation can be expected to increase substantially from rising solar elevations. Statistical analysis showed no significant positive association between the mean UV radiation dose and the mean 25(OH)D (25-hydroxy vitamin D) for the group. On an individual basis, however, we found indications that subjects with very low initial concentration of 25(OH)D (<30 nmol l(-1)) seemed to respond to UV radiation as early as in the beginning of March. For other individuals diet seemed to be the dominant controlling factor for 25(OH)D levels.     

1,25-Dihydroxyvitamin D and the Vitamin D Receptor Gene Polymorphism Apa1 Influence Bone Mineral Density in Primary Hyperparathyroidism

Objective

Parathyroid hormone (PTH) and vitamin D are the most important hormones regulating calcium metabolism. In primary hyperparathyroidism (PHPT) excessive amounts of PTH are produced. Bone turnover is enhanced, leading to reduced bone mineral density and elevated levels of serum calcium. The aim of this study was to investigate relations between serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂D) and bone mineral density, as well as known genetic polymorphisms in the vitamin D receptor and enzymes metabolising vitamin D in patients with PHPT.

Design/Subjects

We conducted a cross-sectional study of 52 patients with PHPT.

Results

Mean level of 25(OH)D was 58.2 nmol/L and median 1,25(OH)₂D level was 157 pmol/L. Among our patients with PHPT 36.5% had 25(OH)D levels below 50 nmol/L. Serum 1,25(OH)₂D was inversely correlated to bone mineral density in distal radius (p = 0.002), but not to bone mineral density at lumbar spine or femoral neck. The vitamin D receptor polymorphism Apa1 (rs7975232) was associated with bone mineral density in the lumbar spine.

Conclusions

The results suggest that PHPT patients with high blood concentrations of 1,25(OH)₂D may have the most deleterious skeletal effects. Randomized, prospective studies are necessary to elucidate whether vitamin D supplementation additionally increases serum 1,25(OH)₂D and possibly enhances the adverse effects on the skeleton in patients with PHPT.     

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.     

Development and Validation of a Vitamin D Status Prediction Model in Danish Pregnant Women: A Study of the Danish National Birth Cohort

Vitamin D has been hypothesized to reduce risk of pregnancy complications such as preeclampsia, gestational diabetes mellitus, and preterm delivery. However, many of these outcomes are rare and require a large sample size to study, representing a challenge for cohorts with a limited number of preserved samples. The aims of this study were to (1) identify predictors of serum 25-hydroxy-vitamin D (25(OH)D) among pregnant women in a subsample (N = 1494) of the Danish National Birth Cohort (DNBC) and (2) develop and validate a score predicting 25(OH)D-status in order to explore associations between vitamin D and maternal and offspring health outcomes in the DNBC. In our study sample, 42.3% of the population had deficient levels of vitamin D (<50 nmol/L 25(OH)D) and average levels of 25(OH)D-status were 56.7(s.d. 24.6) nmol/L. A prediction model consisting of intake of vitamin D from diet and supplements, outdoor physical activity, tanning bed use, smoking, and month of blood draw explained 40.1% of the variance in 25(OH)D and mean measured 25(OH)D-level increased linearly by decile of predicted 25(OH)D-score. In total 32.2% of the women were placed in the same quintile by both measured and predicted 25(OH)D-values and 69.9% were placed in the same or adjacent quintile by both methods. Cohen''s weighted kappa coefficient (Κ = 0.3) reflected fair agreement between measured 25(OH)D-levels and predicted 25(OH)D-score. These results are comparable to other settings in which vitamin D scores have shown similar associations with disease outcomes as measured 25(OH)D-levels. Our findings suggest that predicted 25(OH)D-scores may be a useful alternative to measured 25(OH)D for examining associations between vitamin D and disease outcomes in the DNBC cohort, but cannot substitute for measured 25(OH)D-levels for estimates of prevalence.     

Serum 25-hydroxyvitamin D and risk of lung cancer in male smokers: a nested case-control study

Background

A role for vitamin D in cancer risk reduction has been hypothesized, but few data exist for lung cancer. We investigated the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25(OH)D], and lung cancer risk in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers.

Methods

Lung cancer cases (n = 500) were randomly selected based on month of blood collection, and 500 controls were matched to them based on age and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate-adjusted conditional logistic regression. To account for seasonal variation in 25(OH)D concentrations, season-specific and season-standardized quintiles of 25(OH)D were examined, and models were also stratified on season of blood collection (darker season = November–April and sunnier season = May–October). Pre-determined, clinically-defined cutpoints for 25(OH)D and 25(OH)D as a continuous measure were also examined.

Results

Overall, 25(OH)D was not associated with lung cancer. Risks were 1.08 (95% CI 0.67–1.75) and 0.83 (95% CI 0.53–1.31) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.91 (95% CI 0.48–1.72) for the ≥75 vs. <25 nmol/L clinical categories. Inverse associations were, however, suggested for subjects with blood collections from November–April, with ORs of 0.77 (95% CI 0.41–1.45, p-trend = 0.05) and 0.65 (95% CI 0.37–1.14, p-trend = 0.07) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.61 (95% CI 0.24–1.52, p-trend = 0.01) for ≥75 vs. <25 nmol/L. We also found 11% lower risk for a 10 nmol/L increase in 25(OH)D in the darker season based on the continuous measure (OR = 0.89, 95% CI 0.81–0.98, p = 0.02).

Conclusion

In this prospective study of male smokers, circulating 25(OH)D was not associated with lung cancer risk overall, although inverse associations were suggested among those whose blood was drawn during darker months.     

Standardization of Misleading Immunoassay Based 25-Hydroxyvitamin D Levels with Liquid Chromatography Tandem-Mass Spectrometry in a Large Cohort Study

Background

The interest in vitamin D measurement has strongly increased in recent years. The best indicator for circulating vitamin D levels is 25-hydroxy-vitamin D (25(OH)D) which is often measured by different immunoassays. We demonstrate problems in comparability of measures by different immunoassays and the need for standardization in the context of a large population-based cohort study.

Methods

25(OH)D was measured with the immunoassays Diasorin Liaison in 2006 in 5,386 women and in the context of another project with IDS-iSYS in 4,199 men in 2009–2010 (when the Diasorin Liaison was no longer available in the version utilized in 2006). Standardization was performed by re-measuring of 25(OH)D levels in 97 men and 97 women with liquid chromatography tandem-mass spectrometry (LC-MS/MS) to obtain linear regression conversion equations.

Results

Applying a 30 nmol/L cut-off value for vitamin D deficiency would have resulted in 48.3% of women and 12.1% of men with vitamin D deficiency ahead of standardization. The large gender difference was strongly attenuated after standardization of the assays with only 15.7% of women and 14.3% of men with vitamin D deficiency. Standardization on average increased the 25(OH)D levels by 10.3 nmol/L in women and decreased 25(OH)D levels by 2.9 nmol/L in men.

Conclusion

The standardization with LC-MS/MS revealed that much of the observed gender difference was only assay-driven and the extremely high proportion of 48.3% vitamin D deficient women proved to be an exaggeration of the old version of the Diasorin-Liaison immunoassay. Standardization of 25(OH)D immunoassay results by LC-MS/MS is recommended to improve their accuracy and comparability, provided the LC-MS/MS method itself is adequately validated and standardized.