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

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

Postby NZer1 » Tue Jul 30, 2013 1:00 pm

Novel modulating effects of PKC family genes on the relationship between serum vitamin D and relapse in multiple sclerosis

The interplay between genes and environmental factors on multiple sclerosis (MS) clinical course has been little studied.

This study from Australia looks at the interaction between genes and environmental factors on the clinical course of MS. In this case the researchers looked at genes in vitamin D metabolism and vitamin D receptor (VDR)/retinoid X receptor (RXR) transcription factor formation pathway in 141 people with RRMS. Gene-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis.

The researchers found that the relationship between 25-hydoxyvitamin D (25(OH)D) and risk of relapse was significantly different for different alleles of two intronic single nucleotide polymorphism (SNPs) in the protein kinase C (PKC) family genes. These two SNPs were found to significantly modify the association between serum 25(OH)D and hazard of relapse.

The researchers found two other SNPs which were significantly associated with lower levels of 25(OH)D. It is thought that MS may be the result of a misdirected immune response by autoreactive T cells against an unknown CNS antigen. Therefore, the researchers postulate that the abnormalities in PKC activity induced by one or more of these polymorphisms may lead to altered T cell function. In conclusion, this data supports the hypothesis that the interplay between genes and Vitamin D may influence the clinical course of MS as well as the PKC genes involved in the pathogenesis of MS relapse.
http://www.ncbi.nlm.nih.gov/pubmed/23868949
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Tue Aug 06, 2013 4:00 pm

Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risk
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This study from Australia investigated if known MS risk-associated single-nucleotide polymorphisms (SNPs) were associated with clinical course and if these SNPs modified the 25(OH)D-relapse association. The study included a prospective cohort of 141 participants with RRMS.

Results showed that five SNPs were associated with relapse, with significant cumulative genotype risk effects and two demonstrated significant allele dose-response. Two SNPs altered the 25(OH)D-relapse association with significant allele dose-response. Five SNPs changed levels of 25(OH)D, with significant cumulative genotype risk effect. There was no evidence of an association between SNPs and disability. Overall, this study shows an association between known MS risk-associated SNPs and relapse. Therefore, this demonstrates a gene-environment interaction which is likely to influence MS clinical course and supports the role of vitamin D in MS relapse.
CONCLUSIONS:
Our study provides evidence for an association between known MS risk-associated SNPs and relapse. Our findings indicate gene-environment interactions may be an important mechanism on MS clinical course, and provide support for the role of vitamin D in MS relapse.
http://www.ncbi.nlm.nih.gov/pubmed/23886828
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More info on why: Vit D3>125nmol/L min in blood.

Postby MarkW » Sat Aug 17, 2013 4:43 am

The relation between Vitamin D status with fatigue and depressive symptoms of multiple sclerosis.
Ashtari F, Ajalli M, Shaygannejad V, Akbari M, Hovsepian S.
Source
Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

BACKGROUND:
The relation between Vitamin D deficiency with depressive and fatigue symptoms in both Multiple sclerosis (MS) patients and healthy population have been reported. To represent our regional achievement in this field we investigated the relation between Vitamin D status with fatigue and depressive symptoms in MS patients.

MATERIALS AND METHODS:
In two hundred MS patients, depressive symptoms and fatigue were measured using Beck PC (BDI-PC) and FFS scale, respectively. Venous blood sample was obtained from all participants and serum 25-hydroxy Vitamin D was measured by radioimmunoassay (RIA) method. Mean score of FSS, BDI-PC and EDSS were compared in patients with normal and low level of Vitamin D. The relation between FSS, BDI-PC score, EDSS and low Vitamin D status was determined.

RESULTS:
There was a moderate significant correlation between MS disability evaluated by EDSS and fatigue (r = 0.37, P < 0.001) and depression (r = 0.26, P < 0.001). The prevalence of low Vitamin D status was 48.5%. Low Vitamin D status was inversely associated with depressive symptoms of patients with MS (P = 0.02 rs = -0.16), but there was not significant correlation between Vitamin D and fatigue symptoms (P = 0.2).

CONCLUSION:
More interventional studies for determining the role of Vitamin D supplements in this regard is recommended.

KEYWORDS:
Depressive symptom, Vitamin D, fatigue, multiple sclerosis

PMID: 23930114 [PubMed] PMCID: PMC3732898 Free PMC Article
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Why have Vit D3>125nmol/L min in blood.

Postby MarkW » Sat Aug 17, 2013 4:51 am

Int J Prev Med. 2013 May;4(5):585-91.
Vitamin d3 concentration correlates with the severity of multiple sclerosis.
Shahbeigi S, Pakdaman H, Fereshtehnejad SM, Nikravesh E, Mirabi N, Jalilzadeh G.
Source Jondishapour Neurology Clinic, Tehran, Iran.

Abstract
BACKGROUND:
To investigate the possible association between serum 25(OH) vitamin D3 concentration and the severity of disease in Iranian patients with multiple sclerosis (MS) and to compare this concentration with a matched control group.

METHODS:
This was an analytical cross-sectional study performed at Jondishapour Neurology Clinic in Tehran, Iran. Patients with relapsing-remitting MS were categorized by disease severity: mild [0≤ Expanded Disability Status Scale (EDSS) ≤3], moderate (3.5≤EDSS≤5.5), and severe (6≤EDSS). Serum concentrations of 25(OH) vitamin D3, calcium, phosphorus, magnesium, and parathyroid hormone were measured in 98 MS patients and 17 healthy age- and sex-matched controls. Fisher's exact, Kruskal-Wallis, Mann-Whitney U test, and independent t and Spearman rank correlation tests were used.

RESULTS:
Serum 25(OH) vitamin D3 concentration was significantly lower in patients with MS, especially in the severe MS subgroup, compared with healthy controls (P=0.047). There was a statistically significant inverse correlation between 25(OH) vitamin D3 concentration and EDSS score (P=0.049, R=-0.168 by Spearman rank correlation test), which was observed in women only (P=0.044, R=-0.199).

CONCLUSIONS:
Our findings not only further disclose the lower level of vitamin D in MS patients in comparison with healthy controls, but also support the association between vitamin D and disease severity in MS.

KEYWORDS:
25(OH) vitamin D3, disease severity, multiple sclerosis

PMID: 23930170 [PubMed] PMCID: PMC3733190 Free PMC Article
Last edited by MarkW on Sat Aug 17, 2013 5:45 am, edited 1 time in total.
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Abstract mentined by NZ1

Postby MarkW » Sat Aug 17, 2013 5:28 am

Mult Scler. 2013 Jul 25. [Epub ahead of print]
Association between multiple sclerosis risk-associated SNPs and relapse and disability - a prospective cohort study.
Lin R, Taylor BV, Simpson S Jr, Charlesworth J, Ponsonby AL, Pittas F, Dwyer T, van der Mei I.
Source Menzies Research Institute Tasmania, University of Tasmania, Australia.

Abstract

BACKGROUND:
The modulating effects of the multiple sclerosis (MS) risk-associated single-nucleotide polymorphisms (SNPs) on MS clinical course are not well established.

OBJECTIVES:
The objective of this paper is to investigate whether known MS risk-associated SNPs were associated with clinical course, and whether these SNPs modified the 25(OH)D-relapse association.

METHODS:
Using a prospective cohort of 141 participants with relapsing-remitting MS and genotype data followed between 2002 and 2005, genotype-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis, and genetic predictors of 25(OH)D and disability progression were evaluated by multilevel mixed-effects linear regression.

RESULTS:
While no SNP reached statistical significance after multiple testing, five SNPs were associated with relapse, with significant cumulative genotype risk effects and two demonstrated significant allele dose-response. Two SNPs altered the 25(OH)D-relapse association with significant allele dose-response. Five SNPs modified levels of 25(OH)D, with significant cumulative genotype 'risk' effect, and three demonstrated significant allele dose-response. We found no consistent evidence for an association between any SNPs and disability.

CONCLUSIONS:
Our study provides evidence for an association between known MS risk-associated SNPs and relapse. Our findings indicate gene-environment interactions may be an important mechanism on MS clinical course, and provide support for the role of vitamin D in MS relapse.

KEYWORDS:
Genetic, disability, genotype-vitamin D interaction, multiple sclerosis, prospective cohort, relapse

PMID: 23886828 [PubMed - as supplied by publisher]
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Mon Aug 19, 2013 2:00 pm

Vitamin D not the sole cause of high MS rates in northern isles, says scientist
August 18th, 2013 by Malachy Tallack

Vitamin D deficiency is unlikely to be “the single explanatory factor” for the very high rates of multiple sclerosis (MS) in Orkney and Shetland, according to the scientist who has led research into the subject.

Dr Jim Wilson was in Lerwick this week to discuss the initial results of the Northern Isles Vitamin D Study, which tested blood samples from 2,300 people in the islands.

Levels of vitamin D in these samples were measured alongside rates of certain diseases – among them MS, diabetes and heart disease – and this data was compared to 1,000 samples taken in the Central Belt of Scotland.

Given that its principle source is sunshine, Dr Wilson was surprised to find that while levels of vitamin D in the Northern Isles were “terribly low” – around 65 per cent of those sampled were either deficient, severely deficient or at high risk of deficiency – they were in fact marginally higher than those taken from samples in mainland Scotland.

The occupation of those providing samples would have some impact on the results. People with outdoor jobs – of which there are a higher proportion here than in a city – will inevitably get more contact with sunlight than those who work indoors. The results also vary dramatically through the course of a year, with only nine per cent of people found to be deficient in August, compared to 51 per cent in December.

Significantly, the study found no correlation between vitamin D levels in individuals and any of the diseases that were measured. Except, that is, for MS.

In the case of MS, the results were rather less conclusive. Individuals with the disease generally did have very low levels of the vitamin, but it was impossible to say whether this was a cause or a potential effect (the result of spending less time outside, say).

However, the fact that overall levels of vitamin D were not lower here than in the Central Belt suggests that, while it remains an “important” part of the story, and a “risk factor”, it does not provide the long-hoped-for explanation of why Shetland and Orkney have such high rates of multiple sclerosis.

The research into this subject is not at an end, however. Dr Wilson is working together with a newly-formed local group to instigate further study into the incidence of the disease in the islands. Fund-raising for this project is due to commence in earnest soon, with the money going to pay for a PhD student to continue with detailed and focused research on MS.

This will include further investigation into vitamin D deficiency, as well as other potential risk factors.

It will also tie closely into the research already underway in the Viking Health Study, for which Dr Wilson is also responsible.
Five hundred people have already volunteered to take part in that study, based in the former council offices at 4 Market Street, and 200 of those volunteers have been tested.

Over the next two years, a further 1,500 will be involved, making this a hugely significant project, that will provide research material into the health and genetics of Shetlanders.

To take part in the full study, volunteers are required to have two or more Shetland grandparents, and invitations are to be sent out this week to a further 500 people in that category. However, those with just one or no Shetland grandparents can also take part in the health research.

Anyone wishing to get involved in the Viking Health Study should contact Thelma on 0131 651 5141 or 0131 651 5575. To find out more about the Orkney and Shetland MS Research Project contact Tom or Alma Stove.
http://www.shetlandtimes.co.uk/2013/08/ ... -scientist
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Vitamin D + Calcitriol more effective than methylprednisolon

Postby Squeakycat » Sun Aug 25, 2013 1:48 pm

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23968560
PMID: 23968560
DOI: http://dx.doi.org/10.1016/j.jneuroim.2013.07.016
Journal Title: Journal of neuroimmunology
Journal Date: 6 Aug 2013
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2396 ... t=abstract
Article Title: One calcitriol dose transiently increases Helios(+)FoxP3(+) T cells and ameliorates autoimmune demyelinating disease.
Article Authors: Faye E Nashold,Corwin D Nelson,Lauren M Brown,Colleen E Hayes

J Neuroimmunol. 2013 Aug 6. pii: S0165-5728(13)00205-1. doi: 10.1016/j.jneuroim.2013.07.016. [Epub ahead of print]
One calcitriol dose transiently increases Helios+FoxP3+ T cells and ameliorates autoimmune demyelinating disease.

Nashold FE, Nelson CD, Brown LM, Hayes CE.
Source

Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, United States.

Abstract

Multiple sclerosis (MS) is an incurable inflammatory demyelinating disease. We investigated one calcitriol dose plus vitamin D3 (calcitriol/+D) as a demyelinating disease treatment in experimental autoimmune encephalomyelitis (EAE). Evidence that calcitriol-vitamin D receptor pathway deficits may promote MS, and data showing calcitriol enhancement of autoimmune T cell apoptosis provided the rationale. Whereas vitamin D3 alone was ineffective, calcitriol/+D transiently increased central nervous system (CNS) Helios+FoxP3+ T cells and sustainably decreased CNS T cells, pathology, and neurological deficits in mice with EAE. Calcitriol/+D, which was more effective than methylprednisolone, has potential for reversing inflammatory demyelinating disease safely and cost-effectively.

© 2013.

KEYWORDS:

Autoimmunity, Encephalomyelitis, Methylprednisolone, Multiple sclerosis, Vitamin D

PMID:
23968560
[PubMed - as supplied by publisher]


I don't have access to the full article to see what levels of Vitamin D and calcitriol are being used, but assuming that it is in fact "more effective" than methylprednisolone, it would certainly be something that could be safely, easily and inexpensively tested in humans to see if it has similar effect.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby grandsons4 » Sun Aug 25, 2013 2:36 pm

As concerns Squeakycat's post on vitamin D vs. methlyprednisolone, I need help distinguishing the difference between calcitriol and D3, as a search for a definitive answer yielded conflicting information. Is D3 (which I understand to be "cholecalciferol") = 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and calcitriol = 24,25-dihydroxycholecalciferol [24,25(OH)2D3]?
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby jimmylegs » Sun Aug 25, 2013 3:11 pm

there's an excellent article on it all, which I will try to hunt down.

anyway, pro-vitamin d3 is 7-dehydrocholesterol. it is converted by sun exposure at the right wavelength and intensity to pre-vitamin D3 .. cholecalciferol.
(or you can get it by consuming d3, or consuming d2 which the body then converts to d3)
then (primarily) in the liver it is hydroxylated to 25-hydroxycholecalciferol aka 25(OH)vitD3 aka 'calcidiol' ('di' for step two)
after that is hydroxylated once more, (primarily) in the kidneys, to 1,25dihydroxycholecalciferol aka 1,25(OH)2vitD3 aka 'calcitriol' ('tri' for step three), the form that is considered 'active' as a steroid hormone.
the 24,25 form is inactive as a hormone.

http://en.wikipedia.org/wiki/Calcitriol
http://en.wikipedia.org/wiki/24,25-Dihy ... calciferol "It has been proposed that 24,25-dihydroxyvitamin D3 is a metabolite of 25-hydroxyvitamin D3 which is destined for excretion."
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Sun Aug 25, 2013 3:32 pm

grandsons4 wrote:As concerns Squeakycat's post on vitamin D vs. methlyprednisolone, I need help distinguishing the difference between calcitriol and D3, as a search for a definitive answer yielded conflicting information. Is D3 (which I understand to be "cholecalciferol") = 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and calcitriol = 24,25-dihydroxycholecalciferol [24,25(OH)2D3]?

The simple answer is that Vit D3 is one of two commercially available forms of vitamin D available without a prescription, the other being Vit D2.

Calcitriol is a prescription form of vitamin D which is a hormonally bio-active form. It is widely used by people with kidney disease and is currently being tested for a variety of diseases ranging from psoriasis and Crohn's Disease, to a number of cancers as well as MS.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Sun Aug 25, 2013 4:08 pm

The key point would have to be "is there any link what so ever or similarity even between EAE and MS' and if there is can we see references please?

Testing Mice with EAE and Humans with MS appears to be totally unrelated!

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

Postby grandsons4 » Sun Aug 25, 2013 4:15 pm

jimmylegs, hi: Thanks for the "Eins, Zwei, Drei" tip! I get it. D2 (ergocalciferol/plant) and D3 (cholecalciferol/animal) both give rise to the active form (1,25(OH)2D), referred to as calcitriol. Cholecalciferol (AKA calciol) begets Calcifediol (AKA calcidiol), which begets Calcitriol (1,25-dihydroxyvitamin D3) the active form of D3.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Sun Aug 25, 2013 4:25 pm

jimmylegs wrote:there's an excellent article on it all, which I will try to hunt down.

Not sure if this is the "article" you are referring to, but it does have a nice summary showing that it was the combination of calcitriol and Vit D3 which worked while neither worked alone.

Source URL: http://www.jni-journal.com/article/S016 ... 1/abstract
DOI: 10.1016/j.jneuroim.2013.07.016
Journal Title: Journal of Neuroimmunology
Abstract URL: http://www.ncbi.nlm.nih.govhttp://www.j ... 1/abstract
Article Title: One calcitriol dose transiently increases Helios+FoxP3+ T cells and ameliorates autoimmune demyelinating disease

One calcitriol dose transiently increases Helios+FoxP3+ T cells and ameliorates autoimmune demyelinating disease

Faye E. Nashold Corwin D. Nelson Lauren M. Brown Colleen E. Hayes

Received 12 June 2013; received in revised form 24 July 2013; accepted 26 July 2013. published online 21 August 2013.
Abstract

Multiple sclerosis (MS) is an incurable inflammatory demyelinating disease. We investigated one calcitriol dose plus vitamin D3 (calcitriol/+D) as a demyelinating disease treatment in experimental autoimmune encephalomyelitis (EAE). Evidence that calcitriol-vitamin D receptor pathway deficits may promote MS, and data showing calcitriol enhancement of autoimmune T cell apoptosis provided the rationale. Whereas vitamin D3 alone was ineffective, calcitriol/+D transiently increased central nervous system (CNS) Helios+FoxP3+ T cells and sustainably decreased CNS T cells, pathology, and neurological deficits in mice with EAE. Calcitriol/+D, which was more effective than methylprednisolone, has potential for reversing inflammatory demyelinating disease safely and cost-effectively.

Highlights

•Vitamin D supplementation alone does not reverse demyelinating disease in rodents.

•One calcitriol dose induced demyelinating disease remissions, but all animals relapsed.

•One calcitriol dose plus vitamin D sustainably reversed demyelinating disease.

•Calcitriol and vitamin D transiently induced Helios and FoxP3-expressing T cells.

•Calcitriol and vitamin D sustainably depleted T cells from the central nervous system.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby jimmylegs » Sun Aug 25, 2013 4:28 pm

exactly, gs4! :D 25(OH)vitD3 - being the form synthesized by animals, and which can be obtained from sheep's wool when purchased as a supplement, while d2 is synthesized in plants. interestingly you can boost the amount of D2 in mushrooms by 100x (if memory serves) if you put them in the sun for a while before eating.
even so, you'll get a better dose response from dietary or supplemental d3 because it is more absorbable unit for unit than d2, which your body has to convert to d3.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby jimmylegs » Sun Aug 25, 2013 4:30 pm

nope sc the article I was thinking of was an overview of the process of d3 synthesis through its various stages in the liver and kidneys on the way to becoming a steroid hormone. will keep looking :)
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