all things vitamin D

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Re: Vitamin D And helminth questions!!

Postby jimmylegs » Thu Oct 20, 2011 7:27 pm

i think it's really important to supplement d3 with care. i'd be curious to go back and review the duration of those trials in that meta-analysis.
10,000 IU is a logical upper limit, but in the absence of balanced mineral supplementation i think in time the wheels would come off.
i think i was only taking 4000IU per day when i ran into trouble, but the problems took a long time to manifest.
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Re: Tr1 Regulatory Cells and Vitamin D

Postby CVfactor » Fri Oct 21, 2011 4:01 pm

With the discovery of regulatory T-cells whose function it is to regulate the immune system, it seems that there has been another recent discovery which explains how these regulatory T-cells work:

http://bloodjournal.hematologylibrary.org/content/112/8/3303.abstract

And here is a good graphic from this paper that gives a good description of this recent discovery:

Image

To explain this graphic, the molecule at the left (IgG) represents an immune system antibody. These antibodies contain epitopes from antigens that are derived from pathogens. In laymens terms you can think of an antigen as a key chain and the epitopes as a key on the chain. The epitopes are use to sensitize immune cells to seek out the pathogens within the body once they have be activated by antigen presenting cells (the key has to fit the lock to initiate an immune response).

So anyway, it appears that within these antibodies there has been found Tregitopes that activate regulatory T-cells to shut down the immune response at an appropriate time.

The response to effector epitopes may outnumber the Tregitopes, resulting in an initial inflammatory
response. As antigen is cleared and the ratio of Ig to antigen increases, the balance tips toward tolerance, diminishing immune
response and reducing further tissue damage and adverse systemic effects.


But a key factor in this regulation is that there has to be regulatory T-cells (Tregs), and it appears that people with MS have a deficiency of the number or efficacy of these cells. And from the data I have provided in this post, Vitamin D appears to promote the development of Tregs.
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High dose vitamin D has no impact on MS study suggests

Postby MSUK » Tue Oct 25, 2011 1:24 am

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High dose vitamin D does not appear any better than low doses for people with multiple sclerosis, according to an Australian study.

The preliminary study, which found supplements ineffective at reducing brain lesions, paves the way for a larger trial seeking definitive answers on whether high doses are beneficial, harmful or neutral.

The findings appear today in the journal Neurology....Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1334
MS-UK - http://www.ms-uk.org/
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Re: High dose vitamin D has no impact on MS study suggests

Postby mrbarlow » Tue Oct 25, 2011 4:05 am

small study, short period of time, using D2 supplements (not D3), measure is number of lesions not relapses or changes in EDSS score.

still probably warrants more research.
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Re: High dose vitamin D has no impact on MS study suggests

Postby jimmylegs » Tue Oct 25, 2011 5:17 am

also not in combination with complementary minerals
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Re: High dose vitamin D has no impact on MS study suggests

Postby Dev29 » Tue Oct 25, 2011 6:16 am

Yeah, it probably takes at least a month to start to raise your blood levels if not more. And it may probably take 3 months at target blood levels to begin to have an impact. Also the 6,000 iu compared 1,000 iu is not as big of a difference compared to other small trials which averaged between 10k and 14k per day. And this used D2. Most drugs whether it is Rebif, Copaxone, BG 12, etc take at leat 3 to six months to begin to work. In MS, you really need at least a year long trial, preferably two. This is a good phase I, saftey and tolerability but other than that, we need a large phase II/III trial with probably at the very minimum 60 people in each treatment arm, but preferablly closer to 100 and lasting minimal of a year. And I would use about 10,000iu's per day. No use in doing a trial (other than safety and tolerability) if don't have enough statistical power to answer your question one way or another.
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Re: High dose vitamin D has no impact on MS study suggests

Postby daverestonvirginia » Tue Oct 25, 2011 6:30 am

I agree that the trial was too short, why D2 and not D3? The dosage is not the important part it is the level of vitamin D in ones body that matters. Hate to say it was a bad trial because it did not produce the results we would like, but it just did not seem like a well structured trial.
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Re: High dose vitamin D has no impact on MS study suggests

Postby Dev29 » Tue Oct 25, 2011 7:27 am

Correction, they did use 12,000iu total. And they did measure blood levels. The main criticism of study length and sample size still stands, but a little disappointing. I do know that there is a properly powered trial with vitamin D as an add on to interferon treatment, but because they are doing it right, the results won't be available for a few years.

http://www.medpagetoday.com/clinical-context/MultipleSclerosis/29235
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Re: High dose vitamin D has no impact on MS study suggests

Postby CVfactor » Tue Oct 25, 2011 7:44 am

Does anyone know what the 25(OH)D3 blood levels ranged from in the high dose group? I would like to see a study where they first supplement the study group until they all reach the same serum levels and then start the trial. The amount they supplement with is really irrelevant.
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Re: High dose vitamin D has no impact on MS study suggests

Postby patientx » Tue Oct 25, 2011 8:11 am

The abstract for the study is available here:
http://www.aan.com/go/elibrary/journal

Objective: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS.Methods: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months' double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses.Results: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04).Conclusion: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation.Classification of evidence: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.
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Re: High dose vitamin D has no impact on MS study suggests

Postby CVfactor » Tue Oct 25, 2011 8:55 am

Here is the blood serum levels across the study:

Image
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Re: High dose vitamin D has no impact on MS study suggests

Postby lyndacarol » Tue Oct 25, 2011 6:13 pm

According to the following article:

http://articles.mercola.com/sites/artic ... _DNL_art_1

It is believed that vitamin D3 from oral supplements, which is unsulfated, cannot be converted to D3 sulfate, and may therefore not have the identical health benefits as the vitamin D your skin synthesizes


Perhaps it is the sulfur that makes the difference?

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My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"
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Re: High dose vitamin D has no impact on MS study suggests

Postby mrbarlow » Wed Oct 26, 2011 12:38 am

lyndacarol wrote:According to the following article:

http://articles.mercola.com/sites/artic ... _DNL_art_1

It is believed that vitamin D3 from oral supplements, which is unsulfated, cannot be converted to D3 sulfate, and may therefore not have the identical health benefits as the vitamin D your skin synthesizes


Perhaps it is the sulfur that makes the difference?

__________________________

My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"




Thanks Lynda

I think there was some research that suggested that MS sufferers who sunbathed statistically faired better than those taking supplements of Vitamin D

Of course this maybe statistical bias - ie MS sufferers who happen to sunbath are less affected so able to sunbath etc (association not cause)
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Re: High dose vitamin D has no impact on MS study suggests

Postby lyndacarol » Sun Oct 30, 2011 10:00 am

According to this article, there may be many other reasons to take vitamin D3:

http://articles.mercola.com/sites/artic ... 0_SNL_MS_1

Dental caries has been shown to be inversely related to total sun exposure, with those living in sunnier areas having about half as many cavities as those living in less sunny areas.

Increasing your and your family’s vitamin D levels appears to be a much better option compared to drinking fluoridated water, as there are many additional health benefits of vitamin D, and a number of adverse effects of water fluoridation, including dental fluorosis and potential reduction in IQ.

There are multiple connections between your oral health, heart disease, and vitamin D status, and higher vitamin D levels have been found to prevent health problems related to your mouth, heart, and cardiovascular system.

Vitamin D may also play a crucial role in cancer. Grassroots Health is now implementing the world’s first cancer prevention project and study to evaluate vitamin D as a preventive strategy against breast cancer. Participants are being sought.
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Re: Tr1 Regulatory Cells and Vitamin D

Postby CVfactor » Mon Oct 31, 2011 9:22 am

To review what is now known about regulatory T-cells, there are two basic types: Natural Tregs (nTregs) which are developed in the thymus and induced Tregs (iTregs) which are developed outside of the thymus.

nTregs seem to have the feature of preventing autoimmunity from occuring in the first place.

iTregs seem to migrate to sites of inflamation and shut-down an immune response at the appropriate time (see previous post on how this occurs) to prevent the response from getting out of control which could lead to autoimmunity.

Here is a good overview of the differences from the following paper:

Image
http://www.ncbi.nlm.nih.gov/pubmed/20402669

The important thing to note is that autoimmunity seems to be caused by a defect in nTregs.

How does Vitamin D play a role in this?

It appears that Vitamin D promotes the development of iTregs which can in effect shut-down an autoimmune response at the site of imflamation. In particular, it seems to promote the Tr1 class of regulatory t-cells which produce the anti-inflamitory cytokine (chemical signal) IL-10. Here is a recent high dosage study that demonstrates this:

http://www.ncbi.nlm.nih.gov/pubmed/21179201

Conclusion/Significance: Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and
did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile
supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming
randomized placebo-controlled trials.


Therefore, we speculate that the rise in IL-10+CD4+ T cells might
reflect expansion of inducible regulatory Tr1 cells. The finding of
an altered profile of pro- and anti-inflammatory CD4+ T cells
conforms to observations in experimental studies [5] and further
supports the assessment of vitamin D3 as a natural immune
modulator in MS [3].


To paraphrase, the amount of Tr1 anitinflamitory regulatory t-cells found in the high vitamin D group is nearyly double that of that found in the control group.

Also, recently there was published another high dose Vitamin D paper which I have provided a link here:

http://www.neurology.org/content/77/17/1611

Results: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04).

Conclusion: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation.



However, this study did not evaluate objective parameters such as increases in Tr1 cells but only looked at more subjective measures such as relapse rate.

But it seems to me from everything I have read, Vitamin D will not stop MS. However, one thing it may do is reduce the relapse severity/frequency. This is what I have experienced, but my case is of course anecdotal. I believe the only way to stop MS is by the HSCT protocal which will re-set your immune system back to self tolerance.

One thing that is still not clear though when comparing the different vitamin D trials is the dosage.

The report from the above paper which found no significant benefit of high dose vitamin D maintained a vitamin D level in the range of 130–175 nM 25OHD.

However, the other high dosage study cited above (20,000 IU/day) had a significantly higher serum level without having any ill effects such as hypercalcemia:

Image

This is also the case for the Burton study shown in a previous post with a maximum dose of 40,000 IU/day and average dose of 15,000 IU/day.

Both of these later studies evaluated the T-cell profile and found an anit-inflamitory results.

So, I really don't believe that science yet knows what the optimun levels for vitamin D is in humans. Most of the guidelines are for bone health and the actual amount to maintain a healthy immune system may be much higher. Here is a good desciption of this:

Image
http://www.ncbi.nlm.nih.gov/pubmed/15225842
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