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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Sun Sep 01, 2013 11:20 am
by MarkW
NZer1 wrote:The jury is still out on Vit D; Nigel
I completely and absolutely disagree with you Nigel. There are a few sceptics (like you) who want absolute evidence for pwMS to increase their vitamin D3 blood level to above 125nmol/L as I suggest. Ed, has knocked down your post, I agree with him.
For a supplement which costs pwMS a few pence/cents a day to take, there is probably never going to be absolute evidence for vitamin D3 in MS as no one is going to fund a population size trial to get absolute proof. The balance of evidence says that spending a few pence/cents a day on vitamin D3 is entirely logical for pwMS. Maybe, you have a better suggestion for pwMS on spending this small amount of money.
MarkW

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Sun Sep 01, 2013 2:03 pm
by NZer1
MarkW wrote:
NZer1 wrote:The jury is still out on Vit D; Nigel
I completely and absolutely disagree with you Nigel. There are a few sceptics (like you) who want absolute evidence for pwMS to increase their vitamin D3 blood level to above 125nmol/L as I suggest. Ed, has knocked down your post, I agree with him.
For a supplement which costs pwMS a few pence/cents a day to take, there is probably never going to be absolute evidence for vitamin D3 in MS as no one is going to fund a population size trial to get absolute proof. The balance of evidence says that spending a few pence/cents a day on vitamin D3 is entirely logical for pwMS. Maybe, you have a better suggestion for pwMS on spending this small amount of money.
MarkW
Hi Mark,
What an interesting reaction you have had to my asking questions and wanting to understand the various role of Vit D in MS especially when these types of questions cannot be answered.

Oh well, takes all kinds to make a World.

I don't have any issue what so ever with maintaining a moderate to hi level of blood tested Vit D, I do hope that people won't assume it is going to make a difference for some reason that we don't understand though.

I would like to learn 'why', as always, there are benefits of direct Sun exposure and why the very activity it requires to have a 'most of body coverage' is very good for anyone, especially if they are lethargic, poor diet or not looking after themselves in general.

I would also like to learn why people have low levels of blood tested Vit D when they have equal of most things such as diet and exposure as their partners for instance who have 'better or higher' levels with the same inputs.
I am also fascinated why PwMS use more Vit D than others who have the same diet, Sun, etc inputs.
To my way of thinking the reason for a PwMS to use more Vit D is very important to learn, rather than supplementing cart blanch, like people did with fluoride for instance!

And Life goes on ;) ,
Nigel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Mon Sep 02, 2013 9:53 am
by Squeakycat
Quite technical article, but the message seems to be that the number of Vitamin D Receptor binding sites is highly correlated with and at a high level of significance with 25(OH)D levels. (r = 0.92, P= 0.0005) Increasing levels above 75 nmol/L (30 ng/ml), increases the number of VDR binding sites.

Perhaps more significantly:
The overlap between genomic regions associated with many autoimmune diseases and VDR binding in primary CD4+ cells strongly suggests a role for vitamin D in many of these diseases, as already seen for MCLs and LCLs [9,10]
Source URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710212/
PMID: 23849224
DOI: 10.1186/1741-7015-11-163
Journal Title: BMC Medicine
Journal Date: 2013
Journal Volume: 11
Journal First Page: 163
Abstract URL: http://www.ncbi.nlm.nih.gov/pmc/article ... t=abstract
Article Title: Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease
Article Authors: Adam E Handel, Geir K Sandve, Giulio Disanto, Antonio J Berlanga-Taylor, Giuseppe Gallone, Heather Hanwell, Finn Drabløs, Gavin Giovannoni, George C Ebers, Sreeram V Ramagopalan

Conclusions

The role of vitamin D in bone health has long been established. The involvement of this vitamin in autoimmune disease is however heavily debated. We provide here an in vivo mechanism as to how vitamin D deficiency may influence autoimmune disease risk, by directly interacting with disease associated genes. Vitamin D sufficiency has been suggested to have a threshold of approximately 75 nmol/L; we provide here biological evidence in support of this, with significant public health implications.

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Mon Sep 02, 2013 10:02 am
by Squeakycat
No association seen between selected vitamin D-related SNPs and MS.
Source URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688728/
PMID: 23840333
DOI: 10.1371/journal.pone.0065487
Journal Title: PLoS ONE
Journal Date: 2013
Journal Issue: 6
Journal Volume: 8
Abstract URL: http://www.ncbi.nlm.nih.gov/pmc/article ... t=abstract
Article Title: Vitamin D3 Receptor (VDR) Gene rs2228570 (Fok1) and rs731236 (Taq1) Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis
Article Authors: Elena García-Martín, José A. G. Agúndez, Carmen Martínez, Julián Benito-León, Jorge Millán-Pascual, Patricia Calleja, María Díaz-Sánchez, Diana Pisa, Laura Turpín-Fenoll, Hortensia Alonso-Navarro, Lucía Ayuso-Peralta, Dolores Torrecillas, José Francisco Plaza-Nieto, Félix Javier Jiménez-Jiménez

PLoS One. 2013; 8(6): e65487.
Published online 2013 June 20. doi: 10.1371/journal.pone.0065487
PMCID: PMC3688728

Vitamin D3 Receptor (VDR) Gene rs2228570 (Fok1) and rs731236 (Taq1) Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis

Elena García-Martín,1 José A. G. Agúndez,2 Carmen Martínez,1 Julián Benito-León,3,4,5 Jorge Millán-Pascual,6 Patricia Calleja,4,5 María Díaz-Sánchez,4,5 Diana Pisa,7 Laura Turpín-Fenoll,6 Hortensia Alonso-Navarro,6,8,9 Lucía Ayuso-Peralta,8 Dolores Torrecillas,8 José Francisco Plaza-Nieto,9 and Félix Javier Jiménez-Jiménez8,9,*
Friedemann Paul, Editor
Author information ► Article notes ► Copyright and License information ►
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Abstract

Background

Some epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the VDR gene and HLADRB1*1501 in the risk for MS.

Objectives

The aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the VDR gene in the risk for MS. A secondary objective was to address the possible interactions between VDR genes and HLADRB1*1501.

Methods

We analyzed the allelic and genotype frequency of VDR rs2228570, rs731236, and HLADRB1*1501 (rs3135388) in 303 patients with MS and 310 healthy controls, using TaqMan Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (http://www.hrc.es/investigacion/metadisc.html; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic.

Results

VDR rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. HLADRB1*1501 showed a high association with the risk of developing MS 4.76(95% C.I. = 3.14–7.27; p<0.0001). The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. HLADRB1*1501 showed lack of interaction with VDR rs2228570 and rs731236 in increasing MS risk.

Conclusions

These results suggest that VDR rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these VDR SNPs and HLADRB1 in the risk for MS.

Possible mechanism for vitamin D in MS

Posted: Mon Sep 02, 2013 10:18 am
by Squeakycat
Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23334593
PMID: 23334593
DOI: http://dx.doi.org/10.1097/NEN.0b013e31827f4fcc
Journal Title: Journal of neuropathology and experimental neurology
Journal Date: Feb 2013
Journal Issue: 2
Journal Volume: 72
Journal First Page: 91-105
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2333 ... t=abstract
Article Title: Expression of vitamin D receptor and metabolizing enzymes in multiple sclerosis-affected brain tissue.
Article Authors: Joost Smolders,Karianne G Schuurman,Miriam E van Strien,Jeroen Melief,Debbie Hendrickx,Elly M Hol,Corbert van Eden,Sabina Luchetti,Inge Huitinga

J Neuropathol Exp Neurol. 2013 Feb;72(2):91-105. doi: 10.1097/NEN.0b013e31827f4fcc.
Expression of vitamin D receptor and metabolizing enzymes in multiple sclerosis-affected brain tissue.

Smolders J, Schuurman KG, van Strien ME, Melief J, Hendrickx D, Hol EM, van Eden C, Luchetti S, Huitinga I.
Source

Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands. smolders@gmail.com

Abstract

Vitamin D deficiency has been implicated as a risk factor for multiple sclerosis (MS), but how vitamin D metabolism affects MS pathophysiology is not understood. We studied the expression of vitamin D receptor (VDR) and related enzymes, including 1,25(OH)(2)D-24-hydroxylase (24-OHase; CYP24A1) and 25(OH)D-1α-hydroxylase (CYP27B1), in CNS tissues of 39 MS patients and 20 controls and in primary human glial cells in vitro. In control and MS normal-appearing white matter (NAWM), nuclear VDR immunostaining was observed in oligodendrocyte-like cells, human leukocyte antigen (HLA)-positive microglia, and glial fibrillary acidic protein-positive astrocytes. There was a 2-fold increase in VDR transcripts in MS NAWM versus control white matter (p = 0.03). In chronic active MS lesions, HLA-positive microglia/macrophages showed nuclear VDR staining; astrocytes showed nuclear and cytoplasmic VDR staining. Staining for 24-OHase was restricted to astrocytes.VDR and CYP27B1 mRNA expressions were increased in active MS lesions versus NAWM (p < 0.01, p = 0.04, respectively). In primary human astrocytes in vitro, the active form of vitamin D, 1,25(OH)(2)D(3), induced upregulation of VDR and CYP24A1. Tumor necrosis factor and interferon-γ upregulated CYP27B1 mRNA in primary human microglia and astrocytes. Increased VDR expression in MS NAWM and inflammatory cytokine-induced amplified expression of VDR and CYP27B1 in chronic active MS lesions suggest increased sensitivity to vitamin D in NAWM and a possible endogenous role for vitamin D metabolism in the suppression of active MS lesions.

Possible role for vitamin D in SPMS

Posted: Mon Sep 02, 2013 10:23 am
by Squeakycat
Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23339019
PMID: 23339019
DOI: http://dx.doi.org/10.1007/s12035-012-8387-1
Journal Title: Molecular neurobiology
Journal Date: Jun 2013
Journal Issue: 3
Journal Volume: 47
Journal First Page: 946-56
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2333 ... t=abstract
Article Title: Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression.
Article Authors: Mingchong Yang,Zhaoyu Qin,Yanyan Zhu,Yun Li,Yanjiang Qin,Yongsheng Jing,Shilian Liu

Mol Neurobiol. 2013 Jun;47(3):946-56. doi: 10.1007/s12035-012-8387-1. Epub 2013 Jan 22.
Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression.

Yang M, Qin Z, Zhu Y, Li Y, Qin Y, Jing Y, Liu S.
Source

Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong 250012, People's Republic of China.

Abstract

Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinal fluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP's role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups' spinal cords could be derived from the disruption of the blood-brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenge system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinal fluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients.

Comprehensive review of vitamin D and autoimmunity

Posted: Mon Sep 02, 2013 10:28 am
by Squeakycat
Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23359064
PMID: 23359064
DOI: http://dx.doi.org/10.1007/s12016-013-8361-3
Journal Title: Clinical reviews in allergy & immunology
Journal Date: 29 Jan 2013
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2335 ... t=abstract
Article Title: The Implication of Vitamin D and Autoimmunity: a Comprehensive Review.
Article Authors: Chen-Yen Yang,Patrick S C Leung,Iannis E Adamopoulos,M Eric Gershwin

Clin Rev Allergy Immunol. 2013 Jan 29. [Epub ahead of print]
The Implication of Vitamin D and Autoimmunity: a Comprehensive Review.

Yang CY, Leung PS, Adamopoulos IE, Gershwin ME.
Source

Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA.

Abstract

Historically, vitamin D has been associated with the regulation of bone metabolism. However, increasing evidence demonstrates a strong association between vitamin D signaling and many biological processes that regulate immune responses. The discovery of the vitamin D receptor in multiple immune cell lineages, such as monocytes, dendritic cells, and activated T cells credits vitamin D with a novel role in modulating immunological functions and its subsequent role in the development or prevention of autoimmune diseases. In this review we, discuss five major areas in vitamin D biology of high immunological significance: (1) the metabolism of vitamin D; (2) the significance of vitamin D receptor polymorphisms in autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; (3) vitamin D receptor transcriptional regulation of immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells; (4) the prevalence of vitamin D insufficiency/deficiency in patients with multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; and finally, (5) the therapeutic effects of vitamin D supplementation on disease severity and progression.

Excellent overview of role of vitamin D in MS

Posted: Mon Sep 02, 2013 10:38 am
by Squeakycat
This study has been mentioned earlier, but in looking at it again, I am struck that it provides an excellent overview of the whole issue of MS and vitamin D, plus makes the recommendation that even before we have a final scientific conclusion, given costs and likely benefits, it simply makes sense to ensure that people with MS have adequate vitamin D levels.
Source URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564873/
PMID: 23356351
DOI: 10.1186/1878-5085-4-4
Journal Title: The EPMA Journal
Journal Date: 2013
Journal Issue: 1
Journal Volume: 4
Journal First Page: 4
Abstract URL: http://www.ncbi.nlm.nih.gov/pmc/article ... t=abstract
Article Title: Can we prevent or treat multiple sclerosis by individualised vitamin D supply?
Article Authors: Jan Dörr, Andrea Döring, Friedemann Paul

Conclusions

In this review article, which follows the recommendations of the “EPMA White Paper” [128], we summarise and discuss available data on the role of VD for the development and disease course of MS. Many lines of evidence, in particular epidemiologic data, preclinical investigations, animal studies, and association studies on VD status and disease activity, suggest that higher serum concentrations of VD are beneficial in terms of the risk to develop MS as well as the further course of the disease in already-established MS. Moreover, VD supplementation is safe, cheap, and convenient to perform. Therefore, it is intriguing to hypothesise that boosting the VD serum levels would be an option to both prevent and treat MS. Despite the inherent methodological drawbacks of epidemiologic studies, existing data on the preventive capacity of higher VD levels are quite compelling. Final proof of this hypothesis would be reached by large-scale prospective epidemiological studies which will probably not be available in the near future, for obvious reasons. With respect to the therapeutic efficacy, an association between higher VD serum concentrations and a favourable disease course has been conclusively shown. Unfortunately, the so-far performed interventional trials, though not negotiating this hypothesis, also do not unambiguously support the idea that raising patients' VD levels would be favourably in terms of disease outcome. Hopefully, ongoing (Table ​(Table2)2) and future trials will shed more light on this aspect.

But, how are we going to deal with this issue in the meantime? From a pragmatical point of view and considering available data on efficacy, safety, tolerability, and last but not least costs, it seems to be reasonable to regularly control 25(OH)VD levels in MS patients, especially during winter months. In patients with inadequate VD, levels should be raised to at least 30–40 ng/ml (75–100 mmol/l), either by appropriate sun exposure and/or adequate VD supplementation. As a rule of thumb, supplementary 1 μg (40 IU) cholecalciferol will increase 25(OH)VD levels by 1 ng/ml (2.5 nmol/l).

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Mon Sep 02, 2013 1:21 pm
by NZer1
Thanks for posting these papers Ed. :)

It seems that there is a stumbling block in the thinking and search by researchers because they 'believe' in the concept that there is something called 'auto-immune disease' that is generated by humans, whether that be genetic or malfunction of our various systems.

If a fresh thinking view happened where they looked at the possibility that technology 'as yet' isn't able to identify the cause of the immune system activation and moved to looking at what could active it that is an external assault of a foreign or non compatible entity that hasn't previously been identified due to either technology or thinking paradigms, then we will be able to move forward.

The study of Stealth Bacteria and Biofilms has a history of rejection for some reason and the medical system seems to prefer to blame the patient as having a defect in their system rather than look at why the immune system has been unable to deal with a more evolved threat than it is designed for.

Microbiologists have shown that bacteria for instance can evolve many times within the hosts life span and that the hosts immune system is unable to evolve in the same way, especially if the bacteria is able to adapt sections of host DNA and also to modify the DNA of it's host so that the bacteria is not treated as a threat.

So the stumbling block in understanding Vit D in diseases like 'MS' and any other 'auto-immune' disease has to move through or around the blockage in thinking of the past.
It appears that Vit D is vital in the processes of the immune system when these types of 'disease' occur but I think that the involvement is secondary, a form of natural increase in the immune system response or reaction requires added Vit D to enhance the immune system.
This is secondary in any 'disease' of the body and 'MS' or auto-immune diseases of any type will experience this. So comparing Vit D levels of 'MS' patients to 'normals' is going to be equal to testing 'auto-immune diseases' to 'normals'.

The activation of the immune system requires more Vit D and when there is more Vit D available it is used in supporting the immune activation and immune cell production.

Increasing the Vit D blood levels and being in Sunlight is a natural 'must do' factor in 'any health status' and more important when there are challenges, imo.

Throw away the sun block, use common sense and eat raw and natural/not processed as much as possible, be Mindfull so that you are not activating the immune system purely by negative thinking, and create as much positivity as possible in everything you do! :)

;)
Nigel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Mon Sep 02, 2013 2:16 pm
by PointsNorth
Hello I thought I'd chirp in. After taking an Organic Acids Test for D levels + much more I found out I was low in vitamin D. I was supplementing 6000iu/day (2 years). I have now increased to 10,000iu/day. I question how much we can take from serum levels. I think that a number of us have malabsorption/transport issues that leave us short of much. I believe I'm deficient in B12 even though I inject constantly and serum levels are sky-high. I think there is more going on here . . .

Working closely with naturopath, MD, Neuro.

PN

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Mon Sep 02, 2013 2:58 pm
by NZer1
Another reason for looking at 'MS' through different eyes;

One for the Americans - CNS Vasodilation - Relief by flush
"CNS vasodilation--a forgotten effective treatment
Central nervous system vasodilation, called "relief by flush," was the treatment of choice for multiple sclerosis in this country in the 1950s (Current Therapy 1950-57, 1962). Between 1946 and 1959, more than 3000 patients with multiple sclerosis and other demyelinating diseases were treated with the CNS vasodilator histamine diphosphate at the Multiple Sclerosis Clinic of St. Joseph Hospital in Tacoma. Most of them improved, some quite dramatically (Jonez 1952). Because the benefit of CNS vasodilation was never proved in controlled trials, its effectiveness has been largely forgotten. Yet histamine vasodilation consistently relieved acute attacks and often the progression of a disease now considered virtually incurable (Good 2002). Brickner (1958) conducted thousands of tests of CNS vasodilators against acute multiple sclerosis symptoms. Every kind of acute symptom could be relieved, Brickner asserted. He pointed out that (a) the transient improvement of vasodilation was easy to overlook; (b) this led physicians to think there was no lasting benefit, but it might only mean long-term vasodilation was necessary; (c) uncertainty due to the possibility of spontaneous remissions could be eliminated by looking for immediate effects; (d) the immediate relief of acute attacks by CNS vasodilators said something crucial about the nature of multiple sclerosis symptoms. Brickner made this last point succinctly:
This must mean that at the moment the drug is used, there is a potential for reversibility of the symptom which is not being realized spontaneously."

More info here: http://www.tldp.com/issue/11_00/ms.htm

It seems the modern equivalent of this therapy is Elaine DeLack and Prokarin. As far as I can tell, only available in America, but it can be obtained with some difficulty (and expense) by PWMS in other countries. Fascinating stuff!


:)
Nigel

High ose vitD3 increases CD4 + TRegs

Posted: Wed Sep 04, 2013 3:46 am
by Squeakycat
The monthly dose equates to a daily dose of 4,666 IU.

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23999998
PMID: 23999998
DOI: http://dx.doi.org/10.1007/s00394-013-0579-6
Journal Title: European journal of nutrition
Journal Date: 3 Sep 2013
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2399 ... t=abstract
Article Title: High-dose cholecalciferol supplementation significantly increases peripheral CD4(+) Tregs in healthy adults without negatively affecting the frequency of other immune cells.
Article Authors: Barbara Prietl,Gerlies Treiber,Julia K Mader,Evelyne Hoeller,Michael Wolf,Stefan Pilz,Winfried B Graninger,Barbara M Obermayer-Pietsch,Thomas R Pieber
Eur J Nutr. 2013 Sep 3. [Epub ahead of print]
High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells.

Prietl B, Treiber G, Mader JK, Hoeller E, Wolf M, Pilz S, Graninger WB, Obermayer-Pietsch BM, Pieber TR.
Source

Department of Endocrinology and Metabolism, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Abstract

BACKGROUND:
Regulatory T cells (Tregs) play a central role in the maintenance of self-tolerance. Animal and in vitro studies suggest that vitamin D is involved in reducing the risk of autoimmunity by modulating Tregs.

METHODS:
In a double-blind, placebo controlled study in 60 healthy volunteers, we assessed the effect of a 12-week high-dose oral cholecalciferol supplementation (140,000 IU/month) on the number and function of CD4posCD25highFoxP3posCD127dim Tregs. We also assessed the clinical safety of the supplementation and the effect on the frequency of other immune cells such as monocytes, dendritic cells, natural killer cells, natural killer T cells, B cells and subgroups of T cells. We also tested the in vitro effect of cholecalciferol on Tregs in human cell cultures.

RESULTS:
By using FACS analysis, ex vivo suppressive co-cultures and apoptosis assays, we were able to show that a cholecalciferol supplementation leads to significantly increased numbers of peripheral Tregs in vivo. Tregs function and the frequency of other immune cells remained unchanged, and no clinically relevant safety concerns were found. The in vitro exposure of human peripheral blood mononuclear cells to cholecalciferol also supported our in vivo findings.

CONCLUSIONS:
Our results indicate a substantial effect of a supplementation with inactive vitamin D on the immune system of healthy humans in vivo and provide a rationale for future studies to investigate the immunomodulatory effects of vitamin D in autoimmune diseases.

Is hypovitaminosis D a consequence rather than cause of dise

Posted: Wed Sep 04, 2013 4:07 am
by Squeakycat
Unfortunately, the answer to this question is behind a paywall. Anyone have access and care to comment?

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23386697
PMID: 23386697
DOI: http://dx.doi.org/10.1136/thoraxjnl-2012-203189
Journal Title: Thorax
Journal Date: Jul 2013
Journal Issue: 7
Journal Volume: 68
Journal First Page: 679
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2338 ... t=abstract
Article Title: Is hypovitaminosis D a consequence rather than cause of disease?
Article Authors: Charles Shee
Thorax. 2013 Jul;68(7):679. doi: 10.1136/thoraxjnl-2012-203189. Epub 2013 Feb 5.
Is hypovitaminosis D a consequence rather than cause of disease?

Shee C.
KEYWORDS:

Bronchiectasis

Comment in

Author response—vitamin D deficiency and systemic inflammation in bronchiectasis. [Thorax. 2013]
Comment on

Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis. [Thorax. 2013]

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Wed Sep 04, 2013 12:55 pm
by NZer1
Thanks Ed,
it appears that the immune system over-activation or 'auto-immune' activation in 'MS' is only a problem when the cytokine numbers are excessive to the task. If the immune system is over active or the volume is in excess the symptom effect is a mirror of 'MS' symptoms. It appears that when Stealth Bacteria have infected and then inflammation occurs they have also modified their DNA and the host cells DNA are modified to avoid detection. So in essence the immune system is flooding the body looking for an inflammation cause or target but unable to identify it.
So this over production of cytokines plus macrophages, monocytes etc are all causing more trouble than the bacteria in regard to symptoms.
Having an over activated immune system due to Vit D supplementation may not be the ideal goal. If there were natural dietary anti-bacterial herbs also used then the die off that the herbs can induce will progressively correct the 'stealth' issues causing the inflammation. To gain a better control of 'Stealth Bacterial' Infections addressing the bio-film protection of the 'bacteria farms' which are 'immune system safe houses' is also necessary.

To address this bacterial problem it has to be a progressive multi-targeted approach that is not seeking a rapid kill because of the added complications of endo-toxin production because as the bacteria die they produce mostly ammonia and then are recycled and detoxed from the body. There is also the added complication of the host cells dying if the bacteria are intracellular.
So this is a confusing situation where Dr's assume that the worsening of the patient is reason to stop treatment when it is more a task of adjusting the treatment to suit the patients coping with the Herx-Hiemer die off, the de-toxing and the secondary Porphyria issues when the mitochondria are not completing their ATP production and that can also produce toxins and side effects.
Reading up on CPn Help/ will give a far more in-depth and accurate understanding and looking at sites on Lyme disease will give the other understanding regarding spirochete bacterial infections and co-infections that accompany Lyme and often worse than Lyme itself!

It appears it is the combination of bacterial types (eg more than one at a time) that is the cause of many assumed 'auto-immune disease' dx's.

;)
Nigel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Posted: Wed Sep 04, 2013 1:10 pm
by NZer1
Some more insights from a 'sceptic' of Vit D supplementing due to knowledge!

The Vitamin-D controversy…
by ADMIN on APRIL 7, 2013


As anyone who has read my regular posts online, you have learned that I am one of few wellness guys who isn’t ga-ga over Vitamin-D. It’s not the 1st time that I’ve cut against the grain in my career, but I want to offer an explanation that will hopefully explain my counter-cultural rationale…

In my humble opinion, Vit-D is the most misunderstood, but over-recommended supplement on the Planet. What is worth noting is that it is, in fact, a Hormone — not a Vitamin, and it is also the FIRST hormone to exist on Planet Earth. Hmmmm. So it’s been around for hundreds of millions of years, we as a species have co-existed with this Hormone for at least 6 million years, and NOW, all of a sudden in the last decade, it has become a crisis of Biblical proportions. Forgive me, but I’m not buying it. Why? Because very few practitioners have taken the time to fully understand exactly HOW this Hormone works or is metabolized in the Human Body.

OK, so let me start with a riddle… We all know that there is a layer of Cholesterol under our skin that when activated by the Sun gets converted into Hormone-D… right? Well, here’s the riddle: How is it that as Americans we have the HIGHEST levels of Cholesterol, and at the same time also have the LOWEST levels of Vit-D on this Planet?!?… Doesn’t make sense, does it? Actually it makes perfect sense, let me explain… (And no, it doesn’t have anything to do with exposure to Sun.)

Let’s go back to that conversion of Cholesterol into Hormone-D’s active form, Calcitriol… there are actually THREE metabolic transactions (under the Skin, in the Liver and in the Kidney) that convert that Cholecalciferol (pre-Hormone-D form) >> Calcidiol (Storage form, aka 25[OH]) >> Calcitriol (Active form, aka 1,25[OH]2). Now here’s where it gets fascinating… ALL of those transactions can ONLY happen when Magnesium is present in proper amounts! Huh? More hmmmm… You mean the Vit-D blood test (aka 25[OH] blood test) is actually a perfect blood test for Mg status? Yup! That’s EXACTLY what I’m saying… And it’s showing that almost everyone in America is woefully short on Maggie!

Given that Vit-D is a Hormone, it’s worth noting that ALL Hormones have a Target Cell and a Target Mission. Vit-D’s Target Cells are the Intestines, and its Target Mission is to have the Intestines ABSORB MORE CALCIUM AND PUT IT INTO THE BLOOD STREAM, AT THE EXPENSE OF MAGNESIUM ABSORPTION… So here’s what that famous blood test is ACTUALLY telling us: the blood test is measuring STORAGE Vit-D (Calcidiol) and it seems that everyone in America is now LOW… Why? Because the body in its innate wisdom KNOWS that there is TOO MUCH CALCIUM in the blood, so it is keeping the Storage Vit-D level low for two reasons: 1) there’s too much Calcium already in the blood; and 2) there’s not enough Magnesium to flip the Storage-D into Active-D. They are flip-sides of the same coin… And how do I know this empirically? I’ve witnessed very same dynamic on hundreds and hundreds of Hair Tissue Mineral Analysis tests on clients.

Right about now, you’re likely getting a headache… forgive me for that. Sometimes, the truth hurts. So when I here about all the wondrous things that “Vit-D” does, I immediately get suspicious. High doses of Vit-D, again — a very strong Hormone, puts significant demands on the Magnesium stores of our body to convert it to its Active status. And like any strong Hormone, it does have an impact, but there is also a heavy price to pay for it. Mildred S. Seelig, MD, one of the world’s greatest authorities on Magnesium, regarded excess Vit-D supplementation as a noted DRAIN on Mg status. And far too many “studies” on Vit-D measure Storage Vit-D levels (Calcidiol), and then in the course of those same “studies,” administer Active Vit-D as a treatment. In the Hospital setting, this is called “clinical science,” at a Carnival it is called “Bait & Switch…”

So what to do, please step back and re-read this post a couple of times until it begins to make more sense to you. What I can add is that there is a very small, growing and stubborn group of health-oriented practitioners that see this as the truth of Vit-D. In fact, every one of the Mg researchers that I’ve had the pleasure of talking with (~a dozen, so far…) does NOT supplement with Vit-D! Why? Because they know the metabolic truth of this very strong chemical, especially inside a Mg deficient body. (Just for the record, there are precious few in America who are NOT in a deficit position as it relates to their Mg status.)

Final comments, what to do? Get more sunshine! Up your Mg supplementation! And should you live near the North Pole or the Upper Midwest), do what your Scandinavian Ancestors did for thousands of years: eat foods that are infused with not just Magnesium, but also Vit-A, and Vit-K which are essential co-factors for the proper metabolism of Vit-D — and how many practitioners have commented on that critical aspect of Vit-D metabolism?!? Aside from Chris Masterjohn, PhD, and Carolyn Dean, MD, ND, the chorus is very, very thin. CAVEAT EATOR!

So, please eat grass-fed Liver, free-range eggs, wild-caught deep-sea fish. These are rich sources of the key nutrients noted above. The last thing I would be putting in my body, or the bodies of my clients, is a synthetically derived “Vitamin” that is made from sheep-skin oil (Lanolin) that is exposed to UV-B light in a factory. It doesn’t sound too natural to me, so I prefer the form that has worked flawlessly on this Planet for thousands of years, and seems to work on most continents outside of North America…

No doubt, this essay will chaff some the wrong way. I regret that, but know that my intent is not to create “Stress!”, but to further enlighten folks to the metabolic truth of how their bodies really work. I welcome any and all comments, and look forward to a greater understanding about this critically important topic, particularly as it relates to our shared commitment to “take Mo’ Maggie!”
http://gotmag.org/the-vitamin-d-controversy/

;)
Nigel