scholarly journals Controversies in Vitamin D: Summary Statement From an International Conference

2018 ◽  
Vol 104 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Andrea Giustina ◽  
Robert A Adler ◽  
Neil Binkley ◽  
Roger Bouillon ◽  
Peter R Ebeling ◽  
...  
Keyword(s):  
Vitamin D ◽  
Hypovitaminosis D ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
International Conference ◽  
Hydroxyvitamin D ◽  
Disease States ◽  
25 Hydroxyvitamin D ◽  
Total Body ◽  
Definition Of

Abstract Context Vitamin D is classically recognized as a regulator of calcium and phosphorus metabolism. Recent advances in the measurement of vitamin D metabolites, diagnosis of vitamin D deficiency, and clinical observations have led to an appreciation that along with its role in skeletal metabolism, vitamin D may well have an important role in nonclassical settings. Measurement of the circulating form of vitamin D that best describes total body stores, namely 25-hydroxyvitamin D, can be unreliable despite many sophisticated methodologies that have been proposed and implemented. Likewise, evidence from clinical studies showing a beneficial role of vitamin D in different disease states has been controversial and at times speculative. Moreover, the target concentrations of 25-hydroxyvitamin D to address a number of putative links between vitamin D inadequacy and nonskeletal diseases are further areas of uncertainty. Setting To address these issues, an international conference on “Controversies in Vitamin D” was held in Pisa, Italy, in June 2017. Three main topics were addressed: (i) vitamin D assays and the definition of hypovitaminosis D; (ii) skeletal and extraskeletal effects of vitamin D; (iii) therapeutics of vitamin D. Results This report provides a summary of the deliberations of the expert panels of the conference. Conclusions Despite great advances in our appreciation of vitamin D metabolism, measurements, biological actions on classical and nonclassical tissues, and therapeutics, all of which this report summarizes, much more work remains to be done so that our knowledge base can become even more secure.

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.

Familial hypocalciuric hypercalcaemia: observations on vitamin D metabolism and parathyroid function

1983 ◽  
Vol 104 (2) ◽  
pp. 210-215 ◽  
Author(s):  
M. Davies ◽  
P. H. Adams ◽  
J. L. Berry ◽  
G. A. Lumb ◽  
P. S. Klimiuk ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Concentration ◽  
Primary Hyperparathyroidism ◽  
Calcium Excretion ◽  
Renal Tubules ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Renal Tubular

Abstract. Serum vitamin D metabolites, the renal tubular maximum reabsorptive rate for phosphate (TMP/GFR) nephrogenic cyclic AMP (NcAMPI, and CaE (urinary calcium excretion per litre of glomerular filtrate) were measured in 14 adults with familial hypocalciuric hypercalcaemia (FHH). The findings were compared with analyses in 14 patients with surgically proven primary hyperparathyroidism matched for serum calcium, creatinine clearance and vitamin D status (assessed by serum concentrations of 25 hydroxyvitamin D). Vitamin D metabolites were also measured in 16 normocalcaemic relatives of patients with FHH. The serum concentration of 24, 25 dihydroxycholecalciferol was appropriate for the prevailing 25 hydroxyvitamin D and no difference was found between groups. The serum concentration of 1, 25 dihydroxycholecalciferol was significantly greater in primary hyperparathyroidism (P < 0.0005) compared with patients with FHH and their normocalcaemic relatives. TMP/GFR was reduced in both primary hyperparathyroidism (0.53 ± 0.12 mmol/l GF, mean ± sem) and FHH (0.86 ±0.14 mmol/l GF). Patients with primary hyperparathyroidism showed an increase in NcAMP output in the urine (38.5 ± 16 mmol/l GF) which was significantly greater (P < 0.0001) than the normal NcAMP (13.5 ± 9.2 nmol/l GF) found in FHH. CaE was low in FHH indicating increased renal tubular reabsorption of calcium. It is concluded that there is no abnormality of vitamin D metabolism in FHH comparable with the changes observed in primary hyperparathyroidism. It is suggested that the biochemical abnormalities in FHH cannot be explained solely upon an increased sensitivity of the renal tubules to the effects of endogenous parathyroid hormone.

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.

A simplified assay for dihydroxylated vitamin D metabolites in human serum: application to hyper- and hypovitaminosis D.

1980 ◽  
Vol 26 (3) ◽  
pp. 444-450 ◽  
Author(s):  
R S Mason ◽  
D Lissner ◽  
H S Grunstein ◽  
S Posen
Keyword(s):  
Vitamin D ◽  
Human Serum ◽  
Hypovitaminosis D ◽  
Reference Interval ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Vitamin D Intoxication ◽  
25 Hydroxyvitamin D

Abstract We describe a simplified assay for 24,25-and 1.25-dihydroxyvitamin D in human serum. It involves two preparative steps, and normal chick intestine is used in preparing cytosol-binding protein. Our results for 24,25-dihydroxyvitamin D include a reference interval of 2.9—16 nmol/L (1.2—6.7 microgram/L), a mean of 6.7 nmol/L (2.8 microgram/L), an intra-assay CV of 11%, and an interassay CV of 22%. For 1,25-dihydroxyvitamin D, these data were 29—168 pmol/L (12—70 ng/L), 86 pmol/L (36 ng/L), 12%, and 22%, respectively. In hypoparathyroid patients with vitamin D intoxication, mean concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum were significantly above normal; the 1,25-dihydroxyvitamin D concentrations were significantly below normal. Patients with malabsorption and/or post-gastrectomy states had significantly subnormal values for both 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum, and there was a significantly negative correlation between each of these biochemical values and the severity of osteomalacia. We also discuss cost effectiveness of assaying vitamin D metabolites in human serum.

scholarly journals Differential effects of phosphate binders on vitamin D metabolism in chronic kidney disease

2020 ◽  
Vol 35 (4) ◽  
pp. 616-623 ◽  
Author(s):  
Charles Ginsberg ◽  
Leila R Zelnick ◽  
Geoffrey A Block ◽  
Glenn M Chertow ◽  
Michel Chonchol ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Calcium Acetate ◽  
Phosphate Binders ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Sevelamer Carbonate ◽  
25 Hydroxyvitamin D

Abstract Background Phosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown. Methods We performed a secondary analysis of the Phosphate Normalization Trial in which patients with moderate to advanced chronic kidney disease were randomized to receive either placebo, sevelamer carbonate, lanthanum carbonate or calcium acetate for 9 months. We evaluated changes in serum concentrations of vitamin D metabolites including 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the ratio of 24,25(OH)2D3 to 25-hydroxyvitamin D [the vitamin D metabolite ratio (VMR)] and the ratio of serum 1,25(OH)2D to 25-hydroxyvitamin D. Results Compared with placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/mL (95% CI 0.2, 1) and 13.5 pg/ng (95% CI 5.5, 21.5) increase in 24,25(OH)2D and VMR, respectively, and a 5.2 pg/mL (95% CI 1.1, 9.4) reduction in 1,25(OH)2D. Randomization to sevelamer carbonate was associated with a 0.5 ng/mL (95% CI −0.9, −0.1) and 11.8 pg/ng (95% CI −20, −3.5) reduction in 24,25(OH)2D3 and VMR, respectively. There was no association of the sevelamer arm with the change in 1,25(OH)2D3, and randomization to lanthanum carbonate was not associated with a change in any of the vitamin D metabolites. Conclusion Administration of different phosphate binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.

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.

A simplified assay for dihydroxylated vitamin D metabolites in human serum: application to hyper- and hypovitaminosis D.

1980 ◽  
Vol 26 (3) ◽  
pp. 444-450 ◽  
Author(s):  
R S Mason ◽  
D Lissner ◽  
H S Grunstein ◽  
S Posen
Keyword(s):  
Vitamin D ◽  
Human Serum ◽  
Hypovitaminosis D ◽  
Reference Interval ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Vitamin D Intoxication ◽  
25 Hydroxyvitamin D

Abstract We describe a simplified assay for 24,25-and 1.25-dihydroxyvitamin D in human serum. It involves two preparative steps, and normal chick intestine is used in preparing cytosol-binding protein. Our results for 24,25-dihydroxyvitamin D include a reference interval of 2.9—16 nmol/L (1.2—6.7 microgram/L), a mean of 6.7 nmol/L (2.8 microgram/L), an intra-assay CV of 11%, and an interassay CV of 22%. For 1,25-dihydroxyvitamin D, these data were 29—168 pmol/L (12—70 ng/L), 86 pmol/L (36 ng/L), 12%, and 22%, respectively. In hypoparathyroid patients with vitamin D intoxication, mean concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum were significantly above normal; the 1,25-dihydroxyvitamin D concentrations were significantly below normal. Patients with malabsorption and/or post-gastrectomy states had significantly subnormal values for both 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum, and there was a significantly negative correlation between each of these biochemical values and the severity of osteomalacia. We also discuss cost effectiveness of assaying vitamin D metabolites in human serum.

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.

scholarly journals Investigating the Role of Functional Polymorphism of Maternal and Neonatal Vitamin D Binding Protein in the Context of 25-Hydroxyvitamin D Cutoffs as Determinants of Maternal-Neonatal Vitamin D Status Profiles in a Sunny Mediterranean Region

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3082
Author(s):  
Spyridon N. Karras ◽  
Erdinç Dursun ◽  
Merve Alaylıoğlu ◽  
Duygu Gezen-Ak ◽  
Cedric Annweiler ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mediterranean Region ◽  
Binding Protein ◽  
Hypovitaminosis D ◽  
Vitamin D Status ◽  
Vitamin D Binding Protein ◽  
Hydroxyvitamin D ◽  
High Prevalence ◽  
25 Hydroxyvitamin D ◽  
Causative Effect

Recent results indicate that dysregulation of vitamin D-binding protein (VDBP) could be involved in the development of hypovitaminosis D, and it comprises a risk factor for adverse fetal, maternal and neonatal outcomes. Until recently, there was a paucity of results regarding the effect of maternal and neonatal VDBP polymorphisms on vitamin D status during pregnancy in the Mediterranean region, with a high prevalence of hypovitaminosis D. We aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphisms and different maternal and neonatal 25-hydroxyvitamin D (25(OH)D) cut-offs on maternal and neonatal vitamin D profile. Blood samples were obtained from a cohort of 66 mother–child pairs at birth. Our results revealed that: (i) Maternal VDBP polymorphisms do not affect neonatal vitamin D status at birth, in any given internationally adopted maternal or neonatal cut-off for 25(OH)D concentrations; (ii) neonatal VDBP polymorphisms are not implicated in the regulation of neonatal vitamin D status at birth; (iii) comparing the distributions of maternal VDBP polymorphisms and maternal 25(OH)D concentrations, with cut-offs at birth, revealed that mothers with a CC genotype for rs2298850 and a CC genotype for rs4588 tended to demonstrate higher 25(OH)D (≥75 nmol/L) during delivery (p = 0.05 and p = 0.04, respectively), after adjustments for biofactors that affect vitamin D equilibrium, including UVB, BMI and weeks of gestation. In conclusion, this study from Southern Europe indicates that maternal and neonatal VDBP polymorphisms do not affect neonatal vitamin D status at birth, whereas mothers with CC genotype for rs2298850 and CC genotype for rs4588 demonstrate higher 25(OH)D concentrations. Future larger studies are required to establish a causative effect of these specific polymorphisms in the attainment of an adequate (≥75 nmol/L) maternal vitamin D status during pregnancy.

Sign in / Sign up

Export Citation Format

Share Document