Vitamin D: Scientific Studies & News

A forum to discuss the Coimbra Protocol which uses high-dose vitamin D3 to treat multiple sclerosis.

Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Fri Aug 18, 2017 9:59 am



Vitamin D receptor gene polymorphisms and the risk of multiple sclerosis: An updated meta-analysis.



Abstract

BACKGROUND:
The association between vitamin D receptor (VDR) gene polymorphisms and multiple sclerosis (MS) has been extensively studied, but results were controversial.

METHODS:
This meta-analysis aimed to confirm whether VDR gene polymorphisms were associated with MS. Meta-analysis on the association between MS and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allelic contrast, recessive, homozygotes and dominant models. Data were extracted by standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random effects model if the results were heterogeneous. Stratification analysis by the selected study characteristics were performed to detect potential source of heterogeneity.

RESULTS:
A total of 21 relevant studies involving 3593 MS patients and 3917 controls were included in the analysis. The association between TaqI polymorphism and MS risk was significant in the homozygous model (p = 0.006) indicated a significant protective effect of TT TaqI genotype. High latitude (40.1-50°N) was also found markedly influenced TaqI polymorphism and MS risk in the recessive and homozygous models (p = 0.045 and p = 0.015, respectively). Additionally, Asian or low latitude (20.1-30°N) people with ApaI homozygous genotype, '> 2013' publication year people in the allele contrast and dominant models of FokI, '> 40 years' age people with BsmI recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk.

CONCLUSION:
TaqI polymorphism is a significant protective factor for MS. However, the associations between ApaI, FokI and BsmI polymorphisms and MS were found only by study characteristics.



https://www.ncbi.nlm.nih.gov/pubmed/28780323
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Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Sun Aug 27, 2017 9:25 pm



The expression of VDR mRNA but not NF-κB surprisingly decreased after vitamin D treatment in multiple sclerosis patients.



ABSTRACT

BACKGROUND AND PURPOSE:
The aim of this study was to investigate the expression levels of vitamin D receptor (VDR) and NF-κB mRNAs in vitamin D (VD) supplemented multiple sclerosis (MS) patients.

METHODS:
RRMS patients received 50,000 IU vitamin D3/week as an intra-muscular injection for 2 months. Blood samples were obtained from 30 MS patients before and after VD supplementation and 32 healthy individuals, and then VDR and NF-κB mRNA levels were measured by real time PCR method and analyzed with independent and paired t-tests. Moreover, some correlations were performed between the expression levels of selected genes and some clinical features of MS and control groups.

RESULTS:
Surprisingly, the expression level of VDR mRNA significantly decreased after 2 months supplementation with VD in our selected patients and in contrast, the level of serum 25(OH) D increased after supplementation. Although, we didn't find any significant difference in the expression level of NF-κB gene before and after treatment with VD, its expression significantly decreased in untreated MS cases compared with healthy controls.

CONCLUSION:
In conclusion, we found some new evidences from the molecular mechanism of vitamin D effectiveness in MS treatment. Also, we need more functional studies to find the effect of VD on the expression level of VDR mRNA.


https://www.ncbi.nlm.nih.gov/pubmed/28576565
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Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Wed Aug 30, 2017 3:09 pm



Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting



ABSTRACT


Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6–18 months between 2013 and 2015. Participants were supplemented with a wide range of vitamin D doses (1,000 – 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese. Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.




http://www.tandfonline.com/doi/full/10.1080/19381980.2017.1300213?fref=gc&
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Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Fri Sep 08, 2017 9:05 pm



Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis




ABSTRACT


Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (−0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10−88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78–2.78, p = 1.26 × 10−12). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19–1.64, p = 2.63 × 10−5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.




http://www.sciencedirect.com/science/article/pii/S000292971730277X
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Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Tue Sep 12, 2017 4:13 pm



Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment


Background:

Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission.

Case Report:

This is a case report of a patient with severe and refractory myasthenia gravis (MG) who followed a “high-dose vitamin D treatment”, a massive-dose treatment (80 000 to 120 000 IU/day) promoted by a medical center in Brazil (but still not proven), and she had her first complete remission after this type of treatment with increased vitamin D serum levels (400 to 700 ng/mL).

Conclusions:

This case report may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double-blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases.



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734680/
Last edited by AntonioBR on Fri Sep 15, 2017 6:50 am, edited 1 time in total.
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Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Wed Sep 13, 2017 8:40 am



1,25-Dihydroxyvitamin-D3 induces brain proteomic changes in cuprizone mice during remyelination involving calcium proteins.


Abstract
Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis. We recently found that high-dose of the hormonally active 1,25-dihydroxyvitamin-D3 (1,25D) promotes myelin repair in the cuprizone model for de- and remyelination. In the present study, we quantified 5062 proteins, of which 125 were differentially regulated in brain tissue from 1,25D treated mice during remyelination, compared to placebo. Proteins upregulated in the early remyelination phase were involved in calcium binding, e.g. calretinin (>1.3 fold, p < 0.005), S10A5 and secretagogin, and involved in mitochondrial function, e.g. NADH-ubiquinone oxidoreductase chain 3, and acyl-coenzyme A synthetase. Calretinin, S10A5 and secretagogin expression levels were characterized using immunohistochemistry. Calretinin immunoreactivity was significantly increased (>3 fold, p = 0.016) in the medial septal nuclei of 1,25D treated mice in the early remyelination phase. Our results indicate that vitamin D may influence remyelination by mechanisms involving an increase in calretinin expression and potentially other calcium binding proteins.


https://www.ncbi.nlm.nih.gov/pubmed/28818673
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Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Mon Sep 18, 2017 6:16 am



Association of CYP2R1 rs10766197 with MS risk and disease progression.



BACKGROUND:
MS is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Among these, vitamin D and genetic variants associated with vitamin D-metabolism gain great attention. The aim of our study was to assess five SNPs in NADSYN1 and CYP2R1 genes in relation to serum 25-OH-vitamin D3 levels in MS patients and controls.

METHODS:
25-OH-vitamin D3 levels and genotyping of CYP2R1- and NADSYN1-SNPs were investigated both in MS patients and in healthy controls.

RESULTS:
The analysis revealed lower 25-OH-vitamin D3 concentrations in MS patients than in controls and an association of rs10766197 CYP2R1 SNP with MS risk. After stratifying MS patients according to gender, we found that the minor allele A of rs10766197 had a higher frequency in men in comparison to women affected by MS. Additionally, the presence of allele A in men was associated with disease progression, assessed by EDSS and MSSS scores.

CONCLUSION:
The findings of our study open new perspectives for a role of CYP2R1 in both risk and progression of MS, with sex-related differences.


https://www.ncbi.nlm.nih.gov/pubmed/28834557
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Re: Vitamin D: Scientific Studies & News

Postby AntonioBR » Mon Sep 18, 2017 6:18 am



A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis.


Abstract

OBJECTIVE:
Low vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively.

METHODS:
An open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score.

RESULTS:
Forty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls.

CONCLUSIONS:
High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects.



https://www.ncbi.nlm.nih.gov/pubmed/20427749
AntonioBR
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