scholarly journals Vitamin D Measurement, the Debates Continue, New Analytes Have Emerged, Developments Have Variable Outcomes

2019 ◽  
Vol 106 (1) ◽  
pp. 3-13 ◽  
Author(s):  
William D. Fraser ◽  
Jonathan C. Y. Tang ◽  
John J. Dutton ◽  
Inez Schoenmakers
Keyword(s):  
Vitamin D ◽  
Quality Assurance ◽  
Measurement Procedure ◽  
Vitamin D Metabolites ◽  
Experimental Conditions ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Target Values ◽  
Analytical Approaches

AbstractThe demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments of immunoassays have changed the landscape. Programmes and materials for assay standardisation, harmonisation and the expansion of the vitamin D external quality assurance scheme (DEQAS) with the provision of target values as measured by a reference measurement procedure have improved standardisation, quality assurance and comparability of measurements. In this article, we describe developments in the measurement of the commonly analysed vitamin D metabolites in clinical and research practice. We describe current analytical approaches, discuss differences between assays, their origin, and how these may be influenced by physiological and experimental conditions. The value of measuring metabolites beyond 25 hydroxyvitamin D (25(OH)D), the marker of vitamin D status, in routine clinical practice is not yet confirmed. Here we provide an overview of the value and application of the measurement of 1,25 dihydroxyvitamin D, 24,25 dihydroxyvitamin D and free 25OHD in the diagnosis of patients with abnormalities in vitamin D metabolism and for research purposes.

scholarly journals Association of Differing Qatari Genotypes with Vitamin D Metabolites

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Youssra Dakroury ◽  
Alexandra E. Butler ◽  
Soha R. Dargham ◽  
Aishah Latif ◽  
Amal Robay ◽  
...  
Keyword(s):  
Vitamin D ◽  
Skin Pigmentation ◽  
Genetic Differences ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Objective. Genetic studies have identified four Qatari genotypes: Q1 Arab, Bedouin; Q2 Asian/Persian; Q3 African; and a fourth admixed group not fitting into the previous 3 groups. This study was undertaken to determine if there was an increased risk of deficiency of vitamin D and its metabolites associated with differing genotypes, perhaps due to genetic differences in skin pigmentation. Methods. 398 Qatari subjects (220 type 2 diabetes and 178 controls) had their genotype determined by Affymetrix 500 k SNP arrays. Total values of 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 25-hydroxy-3epi-vitamin D (3epi-25(OH)D) concentrations were measured by the LC-MS/MS analysis. Results. The distribution was as follows: 164 (41.2%) genotyped Q1, 149 (37.4%) genotyped Q2, 31 (7.8%) genotyped Q3, and 54 (13.6%) genotyped “admixed.” Median levels of 25(OH)D and 3epi-25(OH)D did not differ across Q1, Q2, Q3, and “admixed” genotypes, respectively. 1,25(OH)2D levels were lower (p<0.04) between Q2 and the admixed groups, and 24,25(OH)2D levels were lower (p<0.05) between Q1 and the admixed groups. Vitamin D metabolite levels were lower in females for 25(OH)D, 1,25(OH)2D (p<0.001), and 24,25(OH)2D (p<0.006), but 3epi-25(OH)D did not differ (p<0.26). Diabetes prevalence was not different between genotypes. Total 1,25(OH)2D (p<0.001), total 24,25(OH)2D (p<0.001), and total 3epi-25(OH)D (p<0.005) were all significantly lower in diabetes patients compared to controls whilst the total 25(OH)D was higher in diabetes than controls (p<0.001). Conclusion. Whilst 25(OH)D levels did not differ between genotype groups, 1,25(OH)2D and 24,25(OH)2D were lower in the admixed group, suggesting that there are genetic differences in vitamin D metabolism that may be of importance in a population that may allow a more targeted approach to vitamin D replacement. This may be of specific importance in vitamin D replacement strategies with the Q2 genotype requiring less, and the other genotypes requiring more to increase 1,25(OH)2D. Whilst overall the group was vitamin D deficient, total 25(OH)D was higher in diabetes, but 1,25(OH)2D, 24,25(OH)2D, and 3epi-25(OH)D were lower in diabetes that did not affect the relationship to genotype.

scholarly journals Simple Fast Quantification of Cholecalciferol, 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D in Adipose Tissue Using LC-HRMS/MS

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1977 ◽  
Author(s):  
Laurianne Bonnet ◽  
Marielle Margier ◽  
Ljubica Svilar ◽  
Charlene Couturier ◽  
Emmanuelle Reboul ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Solid Phase ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Relative Standard ◽  
The Impact

Vitamin D metabolism is actively modulated in adipose tissue during obesity. To better investigate this process, we develop a specific LC-HRMS/MS method that can simultaneously quantify three vitamin D metabolites, i.e., cholecalciferol, 25-hydroxyvitamin D3 (25(OH)D3), and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in a complex matrix, such as mouse adipose tissue and plasma. The method uses pretreatment with liquid–liquid or solid–phase extraction followed by derivatization using Amplifex® reagents to improve metabolite stability and ionization efficiency. Here, the method is optimized by co-eluting stable isotope-labelled internal standards to calibrate each analogue and to spike biological samples. Intra-day and inter-day relative standard deviations were 0.8–6.0% and 2.0–14.4%, respectively for the three derivatized metabolites. The limits of quantification (LoQ) achieved with Amplifex® derivatization were 0.02 ng/mL, 0.19 ng/mL, and 0.78 ng/mL for 1,25(OH)2D3, 25(OH)D3 and cholecalciferol, respectively. Now, for the first time, 1,25(OH)2D3 can be co-quantified with cholecalciferol and 25(OH)D3 in mouse adipose tissue. This validated method is successfully applied to study the impact of obesity on vitamin D status in mice.

Vitamin D metabolism in the Damara mole-rat is altered by exposure to sunlight yet mineral metabolism is unaffected

1994 ◽  
Vol 143 (2) ◽  
pp. 367-374 ◽  
Author(s):  
T Pitcher ◽  
I N Sergeev ◽  
R Buffenstein
Keyword(s):  
Vitamin D ◽  
Mineral Metabolism ◽  
Plasma Concentrations ◽  
Sun Exposure ◽  
Inorganic Phosphorus ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Highly Efficient

Abstract Vitamin D may be endogenously synthezised in the skin in the presence of sunlight or, alternatively, acquired from dietary sources. Cryptomys damarensis appear to have a naturally impoverished vitamin D status with low plasma concentrations of both 25-hydroxyvitamin D (25(OH)D; <5 ng/ml) and 1,25-dihydroxyvitamin D (1,25(OH)2D; <20 pg/ml). We attribute this to their underground habitat and herbivorous habits. We questioned whether these subterranean mammals could utilize sunlight-mediated pathways and therefore compared vitamin D metabolism and function when animals were (a) housed naturally (control), (b) given an oral vitamin D3 (D3) supplement (1 IU/g dry matter food eaten per day) and (c) exposed to 10 h of sunlight. Control animals exhibited a highly efficient apparent fractional absorption of both calcium (Ca) and inorganic phosphorus (Pi) (>90%), passive mode of intestinal mineral uptake, yet tightly regulated serum ionized calcium (Ca2+). The ratio of 25(OH)D-1α-hydroxylase (1-OHase) to 25(OH)D-24R-hydroxylase (24-OHase) activity in the kidney, corresponded with a state of vitamin D deficiency. Cryptomys damarensis responded to both oral D3 supplementation and sun exposure by an increase in plasma concentration of 1,25(OH)2D with a commensurate decline (P<0·05) in 1-OHase activity, and a resulting decrease (P<0·05) in the ratio of 1-OHase:24-OHase activity. Despite these changes, the intestinal mode of Ca uptake and plasma total Ca, Ca2+ and Pi remained unchanged with either treatment. Responses to sunlight were less pronounced than that of oral D3 supplementation. These data confirm that naturally vitamin D-deficient mole-rats can convert vitamin D to the active hormone 1,25(OH)2D, and indicate that mole-rats function optimally at the low concentrations of vitamin D metabolites found naturally. Furthermore, these animals exhibit a highly efficient vitamin D-independent mode of intestinal Ca absorption. Journal of Endocrinology (1994) 143, 367–374

Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites

1983 ◽  
Vol 104 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Kinsuke Tsuda ◽  
Jiro Takemura ◽  
Sigeo Nishi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Diabetic Rats ◽  
Plasma Vitamin ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Plasma Urea ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Streptozotocin Induced Diabetes ◽  
25 Hydroxyvitamin D

Abstract. In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-hydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.

scholarly journals Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

2016 ◽  
Vol 37 (5) ◽  
pp. 521-547 ◽  
Author(s):  
Peter J. Tebben ◽  
Ravinder J. Singh ◽  
Rajiv Kumar
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Active Form ◽  
Elevated Serum ◽  
Diagnosis And Treatment ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Stone Formers ◽  
25 Hydroxyvitamin D

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

Vitamin D

2005 ◽  
Vol 289 (1) ◽  
pp. F8-F28 ◽  
Author(s):  
Adriana S. Dusso ◽  
Alex J. Brown ◽  
Eduardo Slatopolsky
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Endocrine System ◽  
Target Cells ◽  
Vitamin D Metabolism ◽  
Diverse Range ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Single Receptor ◽  
Recent Developments

The vitamin D endocrine system plays an essential role in calcium homeostasis and bone metabolism, but research during the past two decades has revealed a diverse range of biological actions that include induction of cell differentiation, inhibition of cell growth, immunomodulation, and control of other hormonal systems. Vitamin D itself is a prohormone that is metabolically converted to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)2D]. This vitamin D hormone activates its cellular receptor (vitamin D receptor or VDR), which alters the transcription rates of target genes responsible for the biological responses. This review focuses on several recent developments that extend our understanding of the complexities of vitamin D metabolism and actions: the final step in the activation of vitamin D, conversion of 25-hydroxyvitamin D to 1,25(OH)2D in renal proximal tubules, is now known to involve facilitated uptake and intracellular delivery of the precursor to 1α-hydroxylase. Emerging evidence using mice lacking the VDR and/or 1α-hydroxylase indicates both 1,25(OH)2D3-dependent and -independent actions of the VDR as well as VDR-dependent and -independent actions of 1,25(OH)2D3. Thus the vitamin D system may involve more than a single receptor and ligand. The presence of 1α-hydroxylase in many target cells indicates autocrine/paracrine functions for 1,25(OH)2D3in the control of cell proliferation and differentiation. This local production of 1,25(OH)2D3is dependent on circulating precursor levels, providing a potential explanation for the association of vitamin D deficiency with various cancers and autoimmune diseases.

Establishing an Accuracy Basis for the Vitamin D External Quality Assessment Scheme (DEQAS)

2017 ◽  
Vol 100 (5) ◽  
pp. 1277-1287 ◽  
Author(s):  
Carolyn Q Burdette ◽  
Johanna E Camara ◽  
Federica Nalin ◽  
Jeanita Pritchett ◽  
Lane C Sander ◽  
...  
Keyword(s):  
Vitamin D ◽  
Quality Assessment ◽  
External Quality Assessment ◽  
Measurement Procedure ◽  
Binding Assays ◽  
External Quality ◽  
External Quality Assessment Scheme ◽  
Hydroxyvitamin D ◽  
Target Values ◽  
High Concentrations

Abstract Until recently, the Vitamin D External Quality Assessment Scheme (DEQAS) assessed the performance of various assays for the determination of serum total 25-hydroxyvitamin D [25(OH)D] by using a consensus mean based on the all-laboratory trimmed mean (ALTM) of the approximately 1000 participants' results. Since October 2012, the National Institute of Standardsand Technology (NIST), as part of the Vitamin D Standardization Program, has participated in DEQAS by analyzing the quarterly serum sample sets using an isotope dilution LC-tandem MS (ID LC-MS/MS) reference measurement procedure to assign an accuracy-based target value for serum total 25(OH)D. NIST has analyzed90 DEQAS samples (18 exercises × 5 samples/exercise) to assign target values. The NIST-assigned values are compared with the ALTM and the biases assessed for various assays used by the participants, e.g., LC-MS/MS, HPLC, and several ligand-binding assays. The NIST-value assignment process and the resultsof the analyses of the 90 DEQAS samples are summarized. The absolute mean bias between the NIST-assignedvalues and the ALTM was 5.6%, with 10% of the samples having biases &gt;10%. Benefits of the accuracy-based target values are presented, including for sample sets with high concentrations of 25(OH)D2 and 3-epi-25(OH)D3.

scholarly journals Vitamin D Metabolism and Profiling in Veterinary Species

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 371 ◽  
Author(s):  
Emma A. Hurst ◽  
Natalie Z. Homer ◽  
Richard J. Mellanby
Keyword(s):  
Vitamin D ◽  
Companion Animals ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Health And Disease ◽  
25 Hydroxyvitamin D

The demand for vitamin D analysis in veterinary species is increasing with the growing knowledge of the extra-skeletal role vitamin D plays in health and disease. The circulating 25-hydroxyvitamin-D (25(OH)D) metabolite is used to assess vitamin D status, and the benefits of analysing other metabolites in the complex vitamin D pathway are being discovered in humans. Profiling of the vitamin D pathway by liquid chromatography tandem mass spectrometry (LC-MS/MS) facilitates simultaneous analysis of multiple metabolites in a single sample and over wide dynamic ranges, and this method is now considered the gold-standard for quantifying vitamin D metabolites. However, very few studies report using LC-MS/MS for the analysis of vitamin D metabolites in veterinary species. Given the complexity of the vitamin D pathway and the similarities in the roles of vitamin D in health and disease between humans and companion animals, there is a clear need to establish a comprehensive, reliable method for veterinary analysis that is comparable to that used in human clinical practice. In this review, we highlight the differences in vitamin D metabolism between veterinary species and the benefits of measuring vitamin D metabolites beyond 25(OH)D. Finally, we discuss the analytical challenges in profiling vitamin D in veterinary species with a focus on LC-MS/MS methods.

Calcium Malabsorption in Elderly Women with Vertebral Fractures: Evidence for Resistance to the Action of Vitamin D Metabolites on the Bowel

1984 ◽  
Vol 66 (1) ◽  
pp. 103-107 ◽  
Author(s):  
R. M. Francis ◽  
M. Peacock ◽  
G. A. Taylor ◽  
J. H. Storer ◽  
B. E. C. Nordin
Keyword(s):  
Vitamin D ◽  
Vertebral Fractures ◽  
Calcium Absorption ◽  
Elderly Women ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Significant Difference ◽  
Before And After ◽  
Calcium Malabsorption

1. Radio-calcium absorption, plasma 25-hydroxyvitamin D [25-(OH)D] and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in 19 elderly women with, and 21 without, vertebral fractures, before and after treatment with 25-hydroxyvitamin D3 [25-(OH)D3], to establish whether malabsorption of calcium in elderly women with vertebral fractures has a cause different from that in elderly women without vertebral fractures. 2. Malabsorption of calcium and low plasma 25-(OH)D and 1,25-(OH)2D concentrations were common in both groups of women but there was no significant difference in these variables between the two groups. 3. After treatment with 40 μg of 25-(OH)D3 daily for 7 days, there was a significant increase in plasma 25-(OH)D and 1,25-(OH)2D in both groups of women, but radio-calcium absorption increased significantly only in the group without vertebral fractures. 4. Elderly women with vertebral fractures have malabsorption of calcium which is resistant to the action of vitamin D metabolites at concentrations which correct calcium malabsorption in elderly women without vertebral fractures.

Vitamin D metabolites regulate osteocalcin synthesis and proliferation of human bone cells in vitro

1985 ◽  
Vol 105 (3) ◽  
pp. 391-396 ◽  
Author(s):  
H. Skjødt ◽  
J. A. Gallagher ◽  
J. N. Beresford ◽  
M. Couch ◽  
J. W. Poser ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Proliferation ◽  
Bone Cells ◽  
Rank Order ◽  
Human Bone ◽  
Dependent Manner ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D

ABSTRACT The effects of six natural vitamin D metabolites of potential biological and therapeutic interest, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), 25-hydroxyvitamin D3 (25-OH-D3), 24R,25-dihydroxyvitamin D3 (24R,25-(OH)2D3), 1,24R,25-trihydroxyvitamin D3 (1,24R,25-(OH)3D3), 25S,26-dihydroxyvitamin D3 (25S,26-(OH)2D3) and 1,25S,26-trihydroxyvitamin D3 (1,25S,26-(OH)3D3) on cell replication and expression of the osteoblastic phenotype in terms of osteocalcin production were examined in cultured human bone cells. At a dose of 5 × 10−12 mol/l, 1,25-(OH)2D3 stimulated cell proliferation, whereas at higher doses (5 × 10−9−5 × 10 −6 mol/l) cell growth was inhibited in a dose-dependent manner. The same pattern of effects was seen for the other metabolites in a rank order of potency: 1,25-(OH)2D3> 1,25S,26-(OH)3D3 = 1,24R,25-(OH)3D3>25S,26-(OH)2D3 = 24R,25-(OH)2D3 = 25-OH-D3. Synthesis of osteocalcin was induced by 1,25-(OH)2D3 in doses similar to those required to inhibit cell proliferation. Biphasic responses were observed for some of the metabolites in terms of osteocalcin synthesis, inhibitory effects becoming apparent at 5 × 10−6 mol/l. The cells did not secrete osteocalcin spontaneously. These results indicate that vitamin D metabolites may regulate growth and expression of differentiated functions of normal human osteoblasts. J. Endocr. (1985) 105, 391–396

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