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

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.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Azni Lihawa Abdul Wahab ◽  
Hans Gerhard Schneider

Abstract Clinical interest to evaluate serum 25-hydroxyvitamin D[25(OH)D] to assess Vitamin D status in health risks continue to increase exponentially over the last decade. Variability of 25(OH)D measurements remains controversial despite the international initiative Vitamin D Standardization Program (VDSP) to standardise the assays. The aim of the present study was to examine the correlation of 25(OH)D concentrations measured by different assays. We measured 25(OH)D using the new Abbott Alinity and DiaSorin LiaisonXL chemiluminescence immunoassays against the National Institute of Standards and Technology (NIST)-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The immunoassay method were compared with the LC-MS/MS using Passing-Bablok regression and Bland-Altman analysis. Common 25(OH)D cut-point for classification of vitamin D deficiency was used to compare the different assays. 125 adult serum samples were randomly selected and measured 25(OH)D levels ranged between <10 nmol/L to 290 nmol/L as determined by LC-MS/MS. Compared to the LC-MS/MS, both immunoassays demonstrated strong positive relationship based on Passing-Bablok regression analysis. The results were as follows: Abbott Alinity = 0.85x + 1.29nmol/L, 95% CI: -2.39 to 5.03 (r=0.94); DiaSorin LiaisonXL= 0.74x + 2.54nmol/L, 95% CI: -2.53 to 6.18 (r=0.91). Despite apparent good correlation, the overall mean bias was -12.6% for Abbott Alinity and -24.4% for DiaSorin LiaisonXL assays. A higher percentage of patients were classified as vitamin D deficient (25(OH)D <50 nmol/L) using DiaSorin LiaisonXL (53%) followed by Abbott Alinity (49%), when compared with LC-MS/MS (34%). Using 25(OH)D ≥ 50nmol/L as “adequate” determined by LC-MS/MS method, 22% (18/82) and 28% (23/82) of patients were classified as “deficient” when analysed on Abbott Alinity and DiaSorin LiaisonXL respectively. Clinician should be aware of the inter-method variability among different Vitamin D assays despite standardization efforts. These differences could be due to cross-reactivity with 25(OH)D2 and vitamin D metabolites, such as 24,25(OH)2D and epimeric forms. 3-epi-25(OH)D is not separated chromatographically by the LC-MS/MS method used in this study. Therefore, the negative bias observed might be due to interference from the 3-epi-25(OH)D, whereby clinical significance is uncertain. It is present in low concentrations in adult human serum, 1 but seen in significant amounts in neonatal serum.2 It is advisable to monitor serum 25(OH)D level following treatment in the same laboratory. 1. Lensmeyer G, et al. The C-3 epimer of 25-hydroxyvitamin D3 is present in adult serum. JCEM 2012; 97: 163–8. 2. Singh RJ, et al. C-3 epimers can account for a significant portion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status. JCEM 2006; 91: 3055-61.


2018 ◽  
Vol 104 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Andrea Giustina ◽  
Robert A Adler ◽  
Neil Binkley ◽  
Roger Bouillon ◽  
Peter R Ebeling ◽  
...  

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.


2018 ◽  
Vol 56 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Songlin Yu ◽  
Ruiping Zhang ◽  
Weiyan Zhou ◽  
Xinqi Cheng ◽  
Qian Cheng ◽  
...  

Abstract Background: The demand for vitamin D testing is increasing in China. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) immunoassay is specific and accurate but requires expensive equipment, experienced operators, and complicated pretreatment of serum. Automated immunoassays are simple and convenient but only determine total 25-hydroxyvitamin D (25OHD). The objective of this study was to quantify 25OHD2 and 25OHD3 in patients to assist clinical physicians and laboratory directors in choosing the most appropriate method to determine 25OHD. Methods: Vitamin D testing was conducted for 23,695 patients in Peking Union Medical College Hospital from May 2015 to January 2017. Using this large data set, the prevalence and levels of 25OHD2 were analyzed. LC-MS/MS was used to separately determine 25OHD2 and 25OHD3. Results: 25OHD2 (≥2.5 ng/mL) was detected in 16.4% (3877/23,695) of patients. Males had a significantly lower incidence of detectable 25OHD2 (p<0.01); 1077 (13.9%) samples contained detectable 25OHD2 (median: 3.7 ng/mL; 2.5%–97.5%: 2.5–17.2 ng/mL). For females, 2800 (17.5%) samples contained detectable 25OHD2 (median: 4.0 ng/mL; range: 2.5–20.6 ng/mL). Of the 3877 patients with detectable 25OHD2, males had a significantly higher level of 25OHD3 (p<0.01). There was no significant difference in total 25OHD. The proportion of 25OHD2 in total 25OHD was 1.3%–100%; 87.5% (3391/3877) of the samples contained <10 ng/mL 25OHD2. 25OHD2 negatively correlated with 25OHD3 (r=−0.197, p<0.01) and positively correlated with total 25OHD (r=0.217, p<0.01). Conclusions: Prevalence of 25OHD2 in patients tested for vitamin D is relatively high in China. 25OHD2 is significantly negatively correlated with 25OHD3.


1983 ◽  
Vol 104 (2) ◽  
pp. 210-215 ◽  
Author(s):  
M. Davies ◽  
P. H. Adams ◽  
J. L. Berry ◽  
G. A. Lumb ◽  
P. S. Klimiuk ◽  
...  

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.


2019 ◽  
Vol 12 ◽  
pp. 175628481986514 ◽  
Author(s):  
Craig Haifer ◽  
Ian C. Lawrance ◽  
Jacqueline R. Center ◽  
Michael W. Clarke ◽  
Prue H. Hart ◽  
...  

Background: Vitamin D deficiency is associated with active Crohn’s disease (CD). However, it remains unclear if lower 25-hydroxyvitamin D [25(OH)D] concentration is the cause, or consequence, of intestinal inflammation. Existing literature has focused on circulating 25(OH)D rather than the active metabolite 1,25(OH)2D, or its breakdown product, 24,25(OH)2D. We aimed to characterise vitamin D metabolism in a cohort of patients with active and inactive CD. Methods: Fifty-four patients with CD and not on corticosteroids or vitamin D supplements, were enrolled in a 6-month prospective cohort study. Sera were collected on enrolment and at 6 months and tested for 25(OH)D, 1,25(OH)2D, 24,25(OH)2D using liquid chromatography tandem mass spectroscopy as well as vitamin-D-binding protein. Results: There were no differences in 25(OH)D or 1,25(OH)2D levels between participants with active versus inactive disease. Levels of 24,25(OH)2D were significantly lower in those with active compared with inactive disease (mean 3.9 versus 6.0 µmol/l; p = 0.007) and therefore the ratio of 25(OH)D:24,25(OH)2D was higher (mean 17.3 versus 11.1; p = 0.001). In those patients with active disease who achieved remission, there was a mean increase in 25(OH)D of 32.3 nmol/l (i.e. to a level in the sufficient range) and 24,25(OH)2D of 2.1 µmol/l. These increases were not seen in patients with persistently active or inactive disease. Conclusion: Levels of 24,25(OH)2D, but not 25(OH)D, were lower in patients with active CD, and spontaneously increased with resolution of underlying inflammation. The utility of 24,25(OH)2D as a biomarker of disease activity and vitamin D status in CD warrants further exploration.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Youssra Dakroury ◽  
Alexandra E. Butler ◽  
Soha R. Dargham ◽  
Aishah Latif ◽  
Amal Robay ◽  
...  

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.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2539 ◽  
Author(s):  
Vito Francic ◽  
Stan R. Ursem ◽  
Niek F. Dirks ◽  
Martin H. Keppel ◽  
Verena Theiler-Schwetz ◽  
...  

25-hydroxyvitamin D (25(OH)D) is commonly measured to assess vitamin D status. Other vitamin D metabolites such as 24,25-dihydroxyvitamin D (24,25(OH)2D) provide additional insights into vitamin D status or metabolism. Earlier studies suggested that the vitamin D metabolite ratio (VMR), calculated as 24,25(OH)2D/25(OH)D, could predict the 25(OH)D increase after vitamin D supplementation. However, the evidence for this additional value is inconclusive. Therefore, our aim was to assess whether the increase in 25(OH)D after supplementation was predicted by the VMR better than baseline 25(OH)D. Plasma samples of 106 individuals (25(OH)D < 75 nmol/L) with hypertension who completed the Styrian Vitamin D Hypertension Trial (NC.T.02136771) were analyzed. Participants received vitamin D (2800 IU daily) or placebo for 8 weeks. The treatment effect (ANCOVA) for 25(OH)D3, 24,25(OH)2D3 and the VMR was 32 nmol/L, 3.3 nmol/L and 0.015 (all p < 0.001), respectively. Baseline 25(OH)D3 and 24,25(OH)2D3 predicted the change in 25(OH)D3 with comparable strength and magnitude. Correlation and regression analysis showed that the VMR did not predict the change in 25(OH)D3. Therefore, our data do not support routine measurement of 24,25(OH)2D3 in order to individually optimize the dosage of vitamin D supplementation. Our data also suggest that activity of 24-hydroxylase increases after vitamin D supplementation.


2020 ◽  
Vol 35 (4) ◽  
pp. 616-623 ◽  
Author(s):  
Charles Ginsberg ◽  
Leila R Zelnick ◽  
Geoffrey A Block ◽  
Glenn M Chertow ◽  
Michel Chonchol ◽  
...  

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.


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