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

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

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

Postby jimmylegs » Sun Aug 25, 2013 4:33 pm

it's probably a holick article. this seems similar but not quite it. I see I skipped a step in my description of the process above.. oops!
The photobiogenesis and metabolism of vitamin D
http://europepmc.org/abstract/MED/212325
I have definitely seen a PDF before and my current search term choices are not throwing up PDF results. maybe I had full text access last time I was searching...
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby grandsons4 » Sun Aug 25, 2013 4:37 pm

NZer1, hey: I'm not sure there's anything they don't test on mice first, but one particular example of initial testing on mice translating nicely to humans is that of inosine. While I'm aware of the debate surrounding supplementation with inosine (my son believes its lessened both the degree of dizziness he's been having and the amount of tingling in his fingertips), the research I've read on it (and I've read alot) strongly indicates successes in human trials being on par with those of mice.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Mon Aug 26, 2013 5:44 pm

The jury is still out on Vit D;
1. A study out of the Netherlands has identified genetic variants that are associated with both low levels of 25-hydroxyvitamin D and increased longevity. This is the opposite finding of what we might expect from many studies that link higher vitamin D to lower levels of disease. So what to make of it?

2. Paul Albert and Amy Proal discuss why they think vitamin D supplements are mostly harmful in this post. If I correctly understand their main argument, they think that vitamin D may have a short-term palliative effect by suppressing immune response and reducing inflammation, but may have long-term negative health effects by allowing chronic bacterial and viral infections to grow and spread in the body.

3. Todd Becker discusses why he doesn’t take vitamin D supplements in this post. He references Albert and Proal’s research, and suggests that vitamin D sensitivity might be downregulated by excessive supplementation. He notes that the biologically active form of vitamin D (1,25-dihydroxyvitamin D3, or calcitriol) is produced from 25-hydroxyvitamin D by the kidneys, but that most tests only measure 25-hydroxyvitamin D. Some people have low levels of 25-hydroxyvitamin D but adequate or even high levels of calcitriol (the biologically active form of vitamin D).

more detail and data on;
http://jdmoyer.com/2012/11/18/vitamin-d ... #more-5468

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

Postby Squeakycat » Mon Aug 26, 2013 7:22 pm

NZer1 wrote:The jury is still out on Vit D;
:)
Nigel

As you well know, nothing personal. The world needs skeptics and you are the skeptic par excellence!

But, I think for the rest of us, evolutionary biology teaches us that we evolved to make use of sunshine. We are not nocturnal nor do we live under ground out of the sunlight.

We have evolved to make use of things that are abundant in our environment, things like air, water and sunshine.

NZer1 wrote:1. A study out of the Netherlands has identified genetic variants that are associated with both low levels of 25-hydroxyvitamin D and increased longevity. This is the opposite finding of what we might expect from many studies that link higher vitamin D to lower levels of disease. So what to make of it?

Utter nonsense. I won't go into all the reasons this is a stupid study, but refer you to some of the letters that it provoked in the journal.

NZer1 wrote:2. Paul Albert and Amy Proal discuss why they think vitamin D supplements are mostly harmful in this post. If I correctly understand their main argument, they think that vitamin D may have a short-term palliative effect by suppressing immune response and reducing inflammation, but may have long-term negative health effects by allowing chronic bacterial and viral infections to grow and spread in the body.

The fundamental flaw here is that the hormone vitamin D is intimately involved in virtually the entire immune response from activating immune system components to turning them off when the job is done. We evolved in a pretty hostile environment and the immune system frequently over-reacts. Vitamin D turns it on and Vitamin D turns it off. Albert and Proal are looking at the single function and then spinning a hypothesis for which there is simply no evidence. Could be true, but it is certainly not proven by their assertions.

NZer1 wrote:3. Todd Becker discusses why he doesn’t take vitamin D supplements in this post. He references Albert and Proal’s research, and suggests that vitamin D sensitivity might be downregulated by excessive supplementation. He notes that the biologically active form of vitamin D (1,25-dihydroxyvitamin D3, or calcitriol) is produced from 25-hydroxyvitamin D by the kidneys, but that most tests only measure 25-hydroxyvitamin D. Some people have low levels of 25-hydroxyvitamin D but adequate or even high levels of calcitriol (the biologically active form of vitamin D).

Sorry, but again, this is another example of a fundamental misunderstanding of the nature of the different forms of vitamin D in the body by a blogger with a degree in chemistry and philosophy made worse by living in my old home, Northern California. :>)

For now, I'll just say that this is complicated, but would suggest if anyone wants to understand it, they should consult the papers of Dr. Horlick, the discoverer or calcitriol, not a blogger from San Francisco.

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

Postby NZer1 » Mon Aug 26, 2013 10:45 pm

Ed, :)
I believe that the point of the article is as much to show how little we know and how much we assume if we have an opinion.
Vit D on it's own is a bit player in many things and so is oxygen, H2O etc, etc.

Assuming that supplementing a deficit of any of these things is ................ naive.

We humans, as you have said before, are complex and have many support or alternative systems and methods of bypassing problems. With that in mind it gives the thought that we have to have a combination of problems to achieve a disease such as 'MS'.
Topping up with one essential element to Life is .............. naive.

But then again I'm a sceptic, ;)

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

Postby Squeakycat » Mon Aug 26, 2013 11:48 pm

NZer1 wrote:Assuming that supplementing a deficit of any of these things is ................ naive.

I wouldn't be so sure about that. Think oxygen and water. What are your alternatives?
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Tue Aug 27, 2013 12:34 am

Ed, people survive on less than the average PwMS in every respect, and having low measured levels in bloods for instance doesn't mean that there is a shortage of input to the body.
I enjoy the insights that Microbiologists have when they are considering Latitude and Health dysfunctions.
We are made up of more non human life than we are of our own cells. If climate and temperature are suited more to bacteria, such as intracellular or spirochetes, more so than suited to humans the bacteria thrive and adapt the humans to their needs.
Bacteria who adapt and also modify DNA from their host are able to control their hosts internal environment and they have the ability to evolve rapidly and or hibernate when the host conditions are a threat.

We don't know much about bacteria, in fact we have only identified 0.04% of bacteria so we are 'lost' when we consider the involvement of bacteria in chemical theories such as Vit D involvement in Latitude effected diseases. We would also die without bacteria, so what are we and are we in control of our functions and Life?

;)
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Vitamin D and Magnesium

Postby Squeakycat » Wed Aug 28, 2013 4:12 pm

Source URL

Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III

Xinqing Deng, Yiqing Song, JoAnn E Manson, Lisa B Signorello, Shumin M Zhang, Martha J Shrubsole, Reid M Ness, Douglas L Seidner and Qi Dai

BMC Medicine 2013, 11:187 doi:10.1186/1741-7015-11-187

Published: 27 August 2013
Abstract (provisional)

Background

Magnesium plays an essential role in the synthesis and metabolism of vitamin D and magnesium supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. We hypothesized that dietary magnesium alone, particularly its interaction with vitamin D intake, contributes to serum 25-hydroxyvitamin D (25(OH)D) levels, and the associations between serum 25(OH)D and risk of mortality may be modified by magnesium intake level.

Methods

We tested these novel hypotheses utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2006, a population-based cross-sectional study, and the NHANES III cohort, a population-based cohort study. Serum 25(OH)D was used to define vitamin D status. Mortality outcomes in the NHANES III cohort were determined by using probabilistic linkage with the National Death Index (NDI).

Results

High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency. Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin insufficiency. Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median.

Conclusions

Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium. Future studies, including cohort studies and clinical trials, are necessary to confirm the findings.
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Diet, MS and Vitamin D

Postby Squeakycat » Wed Aug 28, 2013 4:29 pm

A second 2012 review of nutritional factors impacting MS found that patients with low blood levels of vitamin D have more brain lesions and signs of a more active disease state. This research suggests a potential link between higher vitamin D levels and lower subsequent disability, but according to the study authors, these observations did not prove a cause-and-effect relationship.5


Source URL: http://www.andjrnl.org/article/S2212-26 ... 1/fulltext
DOI: 10.1016/j.jand.2013.05.010
Journal Title: Journal of the Academy of Nutrition and Dietetics
Journal Date: July 2013
Journal Issue: 7
Journal Volume: 113
Journal First Page: 1004
Article Title: Are There Evidence-Based Dietary Interventions for Multiple Sclerosis?



Journal of the Academy of Nutrition and Dietetics
Volume 113, Issue 7 , Page 1004, July 2013
Are There Evidence-Based Dietary Interventions for Multiple Sclerosis?

Eleese Cunningham, RD

Multiple sclerosis (MS) is a disease whose precise origin is unknown, although it is generally accepted that MS involves an immune-mediated process. The disease is characterized by the destruction of myelin sheath, the protective material that surrounds and protects nerve cells in the brain and spinal cord. The progressive loss and thinning of myelin leads to the formation of scar tissue or plaques. This interferes with the transmission of nerve signals producing symptoms which vary depending on where damage has occurred. Common symptoms of MS include fatigue, pain, numbness, blurred vision, cognitive impairment, and bladder and bowel dysfunction, but the course of MS is unpredictable and varies individually, with some patients experiencing minimal impairment. There is no cure for MS. Medications are used to help control symptoms and slow the progression of the disease.1

A review of complementary and alternative medicine (CAM) use among MS patients indicates that up to 70% of patients with MS try one or more CAM therapies.2 The researchers found most MS patients use both conventional and complementary therapies and perceive both to be beneficial. Dietary supplements commonly used include n-3 fatty acids, lipoic acid, ginkgo biloba, ginseng, green tea polyphenols, and vitamin D. Of these, the supplements identified as warranting further investigation were n-3, lipoic acid, and vitamin D supplementation. A low-fat diet was also identified as a therapy used by many MS patients, with the most popular diet approach being a diet introduced by neurologist Roy Swank over 50 years ago. The Swank diet is characterized by a low amount of saturated fat not to exceed 15 g and supplementation with cod liver oil. Follow-up by Swank reported positive outcomes, but research related to the Swank diet has been criticized for the lack of a control group for comparison for scientific validation.

A 2012 Cochrane review attempted to answer MS patients' questions about safety of dietary regimen and whether these changes could favorably impact the prognosis for people with MS.3 Selection criteria limited participants to adult patients with clinically definitive MS in controlled clinical trials. All controlled trials with advice or instructions on a specific dietary intervention, diet plan, or dietary supplementation (except vitamin D) that were compared to no dietary modification or placebo were eligible. Many dietary interventions have been recommended or studied for managing MS such as allergen-free, gluten-free, and raw food diets, but none were found that met inclusion criteria. The resulting six studies used in the review were all related to polyunsaturated fatty acids. The Swank diet and some of the other dietary intervention studies for MS patients were not included in the review. At the time some of them were published, methodological aspects were not as stringent as they are today, or they were not randomized or had an outcome other than disease progression. The lead researcher of the Cochrane study was quoted as saying that patients with MS should not focus on any particular supplement or dietary approach but adopt healthy eating habits, and also noted a high incidence of malnutrition in patients with MS.4 A second 2012 review of nutritional factors impacting MS found that patients with low blood levels of vitamin D have more brain lesions and signs of a more active disease state. This research suggests a potential link between higher vitamin D levels and lower subsequent disability, but according to the study authors, these observations did not prove a cause-and-effect relationship.5

Considering the wide range in disease course severity and the risk of malnutrition among MS patients, registered dietitians working with MS patients should review the signs and symptoms obtained in the nutrition assessment and diagnose nutrition problems based on these signs and symptoms. Weight and weight history is the first parameter for consideration when malnutrition is suspected. Common problems that may be modified by nutrition care include conditions addressed in the Nutrition Care Manual, such as dysphagia and constipation. Particular attention should be paid to the MS patient's appetite and ability to eat with or without assistance, as well as arrangements regarding food shopping and cooking. RDs need to ascertain the use of dietary supplements given their prevalent use among MS patients. Details on special diets used by MS patients should be reviewed for efficacy and safety. RDs can help consumers critically assess their supplement practices and help them make informed choices. Supportive nutrition education tailored to the individual can help a person with MS meet nutritional needs and regain some feeling of control in his or her life.
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Gene-vitamin D interactions likely to influence pathogenesis

Postby Squeakycat » Wed Aug 28, 2013 4:37 pm

Source URL: http://www.nature.com/nrneurol/journal/ ... 3.160.html
DOI: doi:10.1038/nrneurol.2013.160
Journal Title: Nature Reviews Neurology
Journal Date: 2013-08-13
Article Title: Multiple sclerosis: Gene-vitamin D interactions likely to influence pathogenesis and risk of relapse in multiple sclerosis

Price: $8

Nature Reviews Neurology , | doi:10.1038/nrneurol.2013.16

Bryony Jones

Multiple sclerosis: Gene–vitamin D interactions likely to influence pathogenesis and risk of relapse in multiple sclerosis

Bryony Jones

Abstract

Variants in genes implicated in the vitamin D pathway modify the relationship between levels of the circulating vitamin D metabolite 25(OH)D and risk of relapse in patients with multiple sclerosis (MS), new research shows. Moreover, several single nucleotide polymorphisms (SNPs) are associated with the risk of relapse or with 25(OH)D levels.
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Re: Gene-vitamin D interactions likely to influence pathogen

Postby Anonymoose » Wed Aug 28, 2013 5:15 pm

Squeakycat wrote:Source URL: http://www.nature.com/nrneurol/journal/ ... 3.160.html
DOI: doi:10.1038/nrneurol.2013.160
Journal Title: Nature Reviews Neurology
Journal Date: 2013-08-13
Article Title: Multiple sclerosis: Gene-vitamin D interactions likely to influence pathogenesis and risk of relapse in multiple sclerosis

Price: $8

Nature Reviews Neurology , | doi:10.1038/nrneurol.2013.16

Bryony Jones

Multiple sclerosis: Gene–vitamin D interactions likely to influence pathogenesis and risk of relapse in multiple sclerosis

Bryony Jones

Abstract

Variants in genes implicated in the vitamin D pathway modify the relationship between levels of the circulating vitamin D metabolite 25(OH)D and risk of relapse in patients with multiple sclerosis (MS), new research shows. Moreover, several single nucleotide polymorphisms (SNPs) are associated with the risk of relapse or with 25(OH)D levels.


All I get from that is there is a relationship between vitamin d levels and relapse. Is there a perfect range? Can too high cause relapse? Is the vitamin d level related to fluctuating nature of ms or is ms related to fluctuating nature of vitamin d? Did you buy the paper?
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Wed Aug 28, 2013 5:55 pm

Ed I have seen articles that suggest that Vit D levels are responsible for the triggering of apoptosis and with that in mind these other findings in MS would require very thorough testing for bacterial involvement imo. It could be a classic assumption that Vit D is having an 'MS' effect when it is actually having an effect on a bacterial load instead.
It is also noted that MS is an end result from bacterial involvement (Dr Klinghardt) and that there are stages or other diseases which are sub-groups of the level of infection and time factor of infection plus genetics and geographic location.
So the tiny little minute bit of sceptic in me thinks that the issues of Vit D involvement may be solved when the dx and definition issues are confronted for diseases like MS! :)

;)
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Assumption of primary immunopathogenesis in MS seriously fla

Postby Squeakycat » Fri Aug 30, 2013 3:20 pm

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23982272
PMID: 23982272
DOI: http://dx.doi.org/10.1007/s00702-013-1080-3
Journal Title: Journal of neural transmission (Vienna, Austria : 1996)
Journal Date: 28 Aug 2013
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2398 ... t=abstract
Article Title: Multiple sclerosis is primarily a neurodegenerative disease.
Article Authors: Abhijit Chaudhuri

J Neural Transm. 2013 Aug 28. [Epub ahead of print]
Multiple sclerosis is primarily a neurodegenerative disease.

Chaudhuri A.
Source

Queen's Hospital, Romford, Essex, UK, Chaudhuria@gmail.com.

Abstract

The precise pathogenesis of multiple sclerosis is unknown. The assumption of a primary immunopathogenesis of the disease is seriously flawed and has failed to deliver an effective therapy for most patients. The progressive degeneration of grey and white matter is integral to the natural history of the disease and is reflected in the atrophy of brain and spinal cord. Demyelination is an essential component of this primary neurodegenerative process rather than the target of a systemic immune response. The primary pathology of multiple sclerosis is a process of neurodegeneration based on the integrity of the blood-brain barrier. Primary progressive multiple sclerosis is the prototype neurodegenerative disease, and the relapsing-remitting form in younger population represents the modifying effect of steroids (vitamin D, sex and stress hormones) on metabolic functions of the central nervous system.

PMID:
23982272
[PubMed - as supplied by publisher]
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Fri Aug 30, 2013 3:36 pm

Thanks Ed,
I wonder if the researchers have heard of things like Celiac disease (http://youtu.be/7wYbdcEOVeo) , CCSVI and diseases like Lyme and Cpn infections.
Seems very easy to assume when the blinkers are on, or when the past dialogue is the only source of input to brain storming.
If the original findings of the famous 'Dawson's Fingers' and that central to every lesion is a vein were the basis for any and every discussion of MS causation then I think progress rather than profit could be achieved from PwMS.

:)
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Dose-related effects of vitamin D on immune responses in CIS

Postby Squeakycat » Fri Aug 30, 2013 3:38 pm

While Professor Hutchinson's trial itself may be of interest to some, the background explanation for why Vitamin D may be helpful in CIS is an excellent overview of the subject.

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23981773
PMID: 23981773
DOI: http://dx.doi.org/10.1186/1745-6215-14-272
Journal Title: Trials
Journal Date: 27 Aug 2013
Journal Issue: 1
Journal Volume: 14
Journal First Page: 272
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2398 ... t=abstract
Article Title: Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial.
Article Authors: Karen O Connell,Siobhan Kelly,Katie Kinsella,Sinead Jordan,Orla Kenny,David Murphy,Eric Heffernan,Risteard O Laoide,Donal O Shea,Carmel McKenna,Lorraine Cassidy,Jean Fletcher,Cathal Walsh,Jennifer Brady,Chris McGuigan,Niall Tubridy,Michael Hutchinson

Background

Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, is the most common disabling neurologic disorder of young adults. The causes of MS remain unknown, but it is widely believed that there is interplay between genetic and environmental factors [1]. Evidence for the role of the environment in the development of MS is supported by a strong correlation between MS incidence/prevalence and increased latitude and lower levels of sun exposure, suggesting an association with vitamin D production [2-4]. Individuals who emigrate before the age of 15 years from an area of high MS prevalence to one of low prevalence, acquire the lower risk of MS in their new country of residence.

Migration studies provide perhaps the strongest support for the role of environmental factor(s) in this disease [5,6]. People living at high latitudes are generally deficient in vitamin D, as measured by serum 25- hydroxyvitamin D (25(OH)D) levels [7,8]. In one study, mean winter 25(OH)D levels in healthy control subjects in Ireland were 36.4 nmol/l, and more patients with MS had vitamin D deficiency (serum 25(OH)D levels less than 25 nmol/l) compared with control subjects [9]. Patients have lower serum vitamin D levels during MS relapses, and also have blunted parathyroid hormone responses [10,11]. In 267 Dutch patients with relapsing remitting multiple sclerosis (RRMS), higher vitamin D levels were associated with an increased chance of remaining relapse-free [11]. In 134 North American patients with RRMS or clinically isolated syndrome (CIS) of pediatric onset, the strongest predictor of further relapse was the baseline serum vitamin D level [12]. In a prospective Australian study of 145 patients with RRMS, each increase of 10 nmol/l in baseline serum vitamin D level was associated with a 12% reduction in the risk of a further relapse [13]. Vitamin D deficiency may increase susceptibility to MS even in utero; higher maternal vitamin D intake during pregnancy was associated with a 38% lower risk of MS in offspring [14], and maternal vitamin D levels greater than 75 mmol/l were associated with a 61% reduced risk of MS in children [15]. Month of birth studies showing an increased MS incidence in those with spring versus autumn births also provide evidence of the role of maternal vitamin D [16]. The potential therapeutic effect of vitamin D supplementation was first suggested by Goldberg in 1986 [17]. Dosing studies in healthy volunteers have shown that supplementation with vitamin D 10,000 IU daily results in an increase in serum 25(OH)D levels of 150 nmol/l over a 12 week period [18]. A Canadian phase I/II open-label, placebo=controlled, randomized controlled trial (RCT) of 49 patients with RRMS who were randomized to placebo or escalating doses of vitamin D over a 52 week period showed a trend toward relapse reduction in the actively treated group [19]. This study was primarily aimed at establishing the safety and tolerability of high-dose vitamin D supplementation; the mean vitamin D dose was 14,000 IU per day, and there were no adverse events or hypercalcamia despite maximum mean vitamin D levels of 413 nmol/l being achieved. The results from this phase II trial [19], and from dosing [18] and observational studies [12,13], suggest that pharmacologic doses of vitamin D of up to 10,000 IU/day are safe, and may reduce the risk of relapse by a factor superior to the 30% reduction reported from the pivotal trials of interferons in RRMS [20,21]. Vitamin D modulates both the innate and adaptive immune systems [22]. The active metabolite, 1,25 (OH) vitamin D, primarily mediates its effects through the intracellular vitamin D receptor (VDR) [23], which is present in monocytes, dendritic cells, B-cells, and CD4+ T-cells [11,22]. Activation of VDR alters transcription, proliferation, and differentiation of immune cells [23], and modulates immune response both indirectly, by reducing the activation of pro-inflammatory T-cells by antigen-presenting cells [24], and directly, by inhibiting T-cell and B-cell proliferation [22,25]. This results in a T-helper (Th)2- cell driven anti-inflammatory state [11,22,26].

There is thus accumulating evidence that vitamin D deficiency increases susceptibility to MS, and that vitamin D supplementation reduces disease activity by immunomodulatory mechanisms. It seems probable that serum vitamin D levels of greater than 100 nmol/l are required to produce the immunologic effects of vitamin D and thus, in patients with MS with vitamin D deficiency, doses of 5,000 to 10,000 IU/day are needed to achieve this. Most patients with RRMS, once diagnosed, commence treatment with first-line disease-modifying therapies (DMTs). Several RCTs are underway to examine the effects of vitamin D supplementation in patients with RRMS already receiving first-line DMTs, using clinical and MRI outcomes [27,28]. In the UK and Ireland, patients with CIS are not usually commenced on DMTs until there is clinical or MRI evidence of dissemination in time. These CIS patients, at risk of developing RRMS, may be recruited into trials of potentially therapeutic agents in order to examine the efficacy of specific therapies in preventing the development of clinically definite MS [29]. We have therefore designed this RCT to examine, over a 24 week treatment period the effects on immunologic measures as a primary outcome, both in patients with CIS and in healthy control participants, randomized to either of two doses of vitamin D (5,000 or 10,000 IU) or to placebo. In addition, in the patients with CIS, clinical and MRI efficacy
measures will be assessed as secondary outcomes.
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