Circulating vitamin D binding protein levels are not associated with relapses or with vitamin D status in multiple sclerosis

2013 ◽  
Vol 20 (4) ◽  
pp. 433-437 ◽  
Author(s):  
Joost Smolders ◽  
Evelyn Peelen ◽  
Mariëlle Thewissen ◽  
Paul Menheere ◽  
Jan Damoiseaux ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Binding Protein ◽  
High Dose ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Vitamin D Binding Protein ◽  
Vitamin D Metabolism ◽  
Physiological Range ◽  
High Dose Vitamin

Background: A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). Objectives: The purpose of this study was to explore whether there is an association between MS and DBP. Methods: We compared DBP concentrations in blood samples of controls ( n = 30) and subjects with relapsing–remitting MS (RRMS) during remission ( n = 29) and relapse ( n = 15). Furthermore, we explored correlations of DBP with 25- hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D levels (1,25(OH)2D), and the effect of high-dose vitamin D3 supplementation on DBP levels in RRMS patients ( n = 15). Results: DBP-concentration did not differ between the sub-groups measured, and there was no correlation between DBP and vitamin D metabolite concentration within the physiological range. Upon supplementation of high doses vitamin D3, DBP concentration remained unaltered. After supplementation, serum 1,25(OH)2D( R = 0.517, p = 0.049), but not 25(OH)D, correlated positively with DBP. Conclusions: We found no association between DBP, MS, and vitamin D status within the physiological range. After high - dose vitamin D supplementation, DBP concentrations may be relevant for vitamin D metabolism.

scholarly journals Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants

2019 ◽  
Vol 104 (11) ◽  
pp. 5483-5498 ◽  
Author(s):  
Maria Enlund-Cerullo ◽  
Laura Koljonen ◽  
Elisa Holmlund-Suila ◽  
Helena Hauta-alus ◽  
Jenni Rosendahl ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Binding Protein ◽  
Controlled Trial ◽  
Minor Allele ◽  
Analysis Of Covariance ◽  
High Dose ◽  
Vitamin D Status ◽  
Vitamin D Binding Protein ◽  
Term Infants

Abstract Context Single nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding the GC (group component) gene affect 25-hydroxyvitamin D (25OHD) concentrations, but their influence on vitamin D status and response to vitamin D supplementation in infants is unknown. Objective To study GC genotype–related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants. Design In this randomized controlled trial, healthy term infants received vitamin D3 (10 or 30 μg/d) from 2 weeks to 24 months of age. GC SNPs rs2282679, rs4588, rs7041, and rs1155563 were genotyped. rs4588/7041 diplotype and haplotypes of rs2282679, rs4588, and rs7041 (Haplo3SNP) and of all four SNPs (Haplo4SNP) were determined. Main Outcome Measures 25OHD measured in cord blood at birth and at 12 and 24 months during intervention. Results A total of 913 infants were included. Minor allele homozygosity of all studied GC SNPs, their combined haplotypes, and rs4588/rs7041 diplotype 2/2 were associated with lower 25OHD concentrations at all time points in one or both intervention groups [analysis of covariance (ANCOVA) P < 0.043], with the exception of rs7041, which did not affect 25OHD at birth. In the high-dose supplementation group receiving 30 μg/d vitamin D3, but not in those receiving 10 µg/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo3SNP significantly affected intervention response (repeated measurement ANCOVA Pinteraction < 0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increases in 25OHD throughout the intervention. Conclusions In infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.

scholarly journals Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261097
Author(s):  
Max Mimpen ◽  
Linda Rolf ◽  
Geert Poelmans ◽  
Jody van den Ouweland ◽  
Raymond Hupperts ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Risk Allele ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Clinical Consequence ◽  
Serological Response ◽  
Vitamin D Metabolism ◽  
Metabolism Enzymes ◽  
High Dose Vitamin

Introduction A poor 25-hydroxyvitamin D (25(OH)D) status is a much replicated risk factor for developing multiple sclerosis (MS), and several vitamin D-associated single nucleotide polymorphisms (SNPs) have been associated with a higher risk of MS. However, studies on the benefit of vitamin D supplementation in MS show inconclusive results. Here, we explore whether vitamin D-associated SNPs and MS risk alleles confound serological response to vitamin D supplementation. Methods 34 participants from the SOLARIUM study consented to genotyping, of which 26 had vitamin D data available. The SOLARIUM study randomised relapsing-remitting MS patients to placebo or 14,000 IU vitamin D3 for 48 weeks. Participants were categorised as either ‘carriers’ or ‘non-carriers’ of the risk allele for 4 SNPs: two related to D binding protein (DBP) and associated with lower 25(OH)D levels (rs4588 and rs7041), and two related to vitamin D metabolism enzymes CYP27B1 and CYP24A1 and associated with a higher risk of MS (rs12368653; rs2248359, respectively). 25(OH)D levels were determined at baseline and after 48 weeks. Results The DBP-related SNPs showed no difference in 25(OH)D status at baseline, but carriers of the rs7041 risk allele showed lower 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 224.2 vs. 332.0 nmol/L, p = 0.013). For CYP related SNPs, neither showed a difference at baseline, but carriers of the rs12368653 risk allele showed higher 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 304.1 vs. 152.0 nmol/L, p = 0.014). Discussion Vitamin D-related SNPs affect the serological response to high-dose vitamin D supplementation. The effects on more common doses of vitamin D, as well as the clinical consequence of this altered response, need to be investigated further.

Vitamin D metabolism in osteoporotic women during treatment with estrogen, an anabolic steroid, or calcitonin

1990 ◽  
Vol 122 (6) ◽  
pp. 715-721 ◽  
Author(s):  
Dorthe Hartwell ◽  
Christian Hassager ◽  
Kirsten Overgaard ◽  
Bente Juel Riis ◽  
Jan Pødenphant ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Concentration ◽  
Binding Protein ◽  
Total Serum ◽  
Vitamin D Metabolites ◽  
Nandrolone Decanoate ◽  
Vitamin D Binding Protein ◽  
Double Blind ◽  
Vitamin D Metabolism ◽  
Norethisterone Acetate

Abstract. We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.

scholarly journals MON-372 Treatment-Resistant Vitamin D Deficiency: Is It a Vitamin D Binding Protein Issue?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sirisha Thambuluru ◽  
Imran Unal ◽  
Stuart Frank ◽  
Amy Warriner ◽  
Fernando Ovalle ◽  
...  
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Vitamin D Deficiency ◽  
Binding Protein ◽  
High Dose ◽  
Vitamin D Metabolites ◽  
Vitamin D Binding Protein ◽  
Treatment Resistant ◽  
Vitamin D Levels ◽  
25 Oh Vitamin D

Abstract Introduction Vitamin D is present in free and bound forms; the bound form is complexed mainly to vitamin D binding protein (DBP). Vitamin D levels are affected by age, pregnancy, liver disease, obesity, and DBP mutations. We report a patient with treatment-resistant vitamin D deficiency suggestive of a DBP with abnormal vitamin D binding. Clinical Case A 58-year-old Pakistani male with a history of hypertension, sleep apnea and hypogonadism presented to endocrine clinic with symptoms including fatigue, generalized muscle cramps, and joint pain. Evaluation of common causes of fatigue, such as anemia, thyroid dysfunction and adrenal insufficiency were ruled out with CBC, thyroid hormone levels and ACTH stimulation test results all within normal ranges. A 25-OH vitamin D level was profoundly low (4.2 ng/ml; normal 30-100), and a 1,25-OH vitamin D level was undetectable (&lt;8 pg/ml; normal 18-72), leading to a presumptive diagnosis of severe vitamin D deficiency. However, his calcium, phosphorus, alkaline phosphatase and kidney function were in the normal range. Furthermore, the absence of osteoporosis, fracture history, or kidney stones suggested adequate vitamin D action at target tissues; PTH levels were high-normal to minimally elevated, ranging 70-94 pg/ml (12-88pg/mL). Aggressive supplementation with vitamin D3 at 50,000 IU 3 times a week and 5,000 IU daily failed to normalize 25-OH vitamin D (ranged 4.6-10ng/ml; normal 30-100) and 1,25-OH vitamin D levels remained undetectable. Addition of calcitriol resulted in mild hypercalcemia and was discontinued. Malabsorption did not appear to be a contributing factor, as a negative tTG antibody (with normal IgA) excluded celiac disease. Vitamin D metabolites levels measured with mass spectrometry showed undetectable 25-OH vitamin D levels (D2 &lt;4 ng/ml, D3 &lt;2 ng/ml; total &lt;6ng/ml; normal 20-50) and 1,25-OH vitamin D levels (&lt;8 pg/ml). Urine N-telopeptide, 24-hour urine calcium (177mg; 100-240) and bone-specific alkaline phosphatase were all normal. Repeat testing over more than five years showed similar results. DBP levels of 269 ug/ml [104-477] excluded DBP deficiency. Clinical Lesson Vitamin D deficiency is increasingly part of routine testing in internal medicine and endocrinology clinics, as is repletion with high-dose vitamin D. However, in rare cases such as this, relying on 25-OH vitamin D levels can be misleading, and supplementation unnecessary or potentially harmful. Thus, treatment decisions should consider the full clinical context and further evaluation performed when warranted. This patient’s labs are suggestive of an abnormality in the DBP, supporting future examination using molecular testing.

scholarly journals Impact of Etanercept on Vitamin D Status and Vitamin D-binding Protein in Bio-naïve Patients with Psoriasis

2021 ◽  
Author(s):  
Maria Siekkeri Vandikas ◽  
Kerstin Landin-Wilhelmsen ◽  
Sam Polesie ◽  
Martin Gillstedt ◽  
Amra Osmancevic
Keyword(s):  
Vitamin D ◽  
Binding Protein ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Vitamin D Binding Protein ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Highly Sensitive ◽  
Baseline Levels ◽  
The Impact

High levels of serum vitamin D-binding protein have been shown previously in patients with psoriasis compared with healthy controls; a possible role in inflammation is implied. The primary objective of this study was to investigate the impact of 24-week etanercept treatment on vitamin D status and vitamin D-binding protein in patients with psoriasis. The secondary aim was to explore whether pre-treatment vitamin D levels could predict the treatment effect. A prospective observational study was performed, including 20 patients with psoriasis and 15 controls. Serum samples i.a. were analysed for vitamin D metabolites, vitamin D-binding protein and highly sensitive C-reactive protein. Baseline levels of vitamin D-binding protein were higher in patients with self-reported arthropathy than in those without. After 24 weeks’ treatment, an improvement in psoriasis was noted, as was a decrease in highly sensitive C-reactive protein. Vitamin D-binding protein decreased in those with self-reported arthropathy. Higher baseline levels of vitamin D were associated with partly faster and greater improvement in psoriasis. Vitamin D-binding protein may have an inflammatory biomarker role.

scholarly journals Measuring Vitamin D Status in Chronic Inflammatory Disorders: How does Chronic Inflammation Affect the Reliability of Vitamin D Metabolites in Patients with IBD?

2020 ◽  
Vol 9 (2) ◽  
pp. 547 ◽  
Author(s):  
Aysegül Aksan ◽  
Dilem Tugal ◽  
Nathalena Hein ◽  
Katharina Boettger ◽  
Yurani Caicedo-Zea ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Negative Correlation ◽  
Bowel Disease ◽  
Binding Protein ◽  
Fecal Calprotectin ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Vitamin D Binding Protein ◽  
Inflammatory Bowel

Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.

Vitamin D-binding protein and multiple sclerosis: Evidence, controversies, and needs

2018 ◽  
Vol 24 (12) ◽  
pp. 1526-1535 ◽  
Author(s):  
Maria Cristina Gauzzi
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Binding Protein ◽  
Current Evidence ◽  
Vitamin D Metabolites ◽  
Vitamin D Binding Protein ◽  
Multifunctional Protein ◽  
Key Points ◽  
Fluid Body ◽  
And Function

The vitamin D-binding protein (DBP) occupies a key node in the regulation of the vitamin D system. Being the main plasma carrier of vitamin D metabolites, it regulates their stability and bioavailability. However, DBP is also a multifunctional protein with roles in the organism’s actin scavenging system and immunomodulation. All these activities may affect multiple sclerosis (MS) pathophysiology. DBP can be measured in blood and cerebrospinal fluid, body fluids that have been investigated as sources of accessible biomarkers of MS. Yet, available data on DBP expression and function in MS are scattered and somewhat controversial. Aims of this review are to summarize current evidence from studies on DBP in MS patients, to discuss possible shortcomings and to highlight key points that need to be addressed to gain deeper insight into the role of DBP in MS.

Calcium-Regulating Hormones and Minerals From Birth to 18 Months of Age: A Cross-Sectional Study. I. Effects of Sex, Race, Age, Season, and Diet on Vitamin D Status

PEDIATRICS ◽  
1986 ◽  
Vol 77 (6) ◽  
pp. 883-890
Author(s):  
P. Lichtenstein ◽  
B. L. Specker ◽  
R. C. Tsang ◽  
F. Mimouni ◽  
C. Gormley
Keyword(s):  
Vitamin D ◽  
Human Milk ◽  
Binding Protein ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Vitamin D Binding Protein ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

The influence of sex, race, age, season, and diet (cow's milk formula v human milk) on the vitamin D and vitamin D-binding protein status in infants less than 18 months of age was investigated in this crosssectional, prospective study of 198 infants. No differences by sex were observed in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, or vitamin D-binding protein concentrations. By race, black infants had significantly elevated serum 1,25-dihydroxyvitamin D levels relative to white infants. By age, vitamin D-binding protein concentrations increased with increasing age. By season, serum 25-hydroxyvitamin D concentrations were low in winter, whereas 1,25-dihydroxyvitamin D and vitamin D-binding protein were high in winter compared with summer. By diet, formula-fed infants had higher serum concentrations of all measured vitamin D metabolites and vitamin D-binding protein than human milk-fed infants. Thus, race, age, season, and diet exert, individually or in combination, different and significant effects on vitamin D metabolites; these should be considered in assessing infant vitamin D status.

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