So there's this:
https://chronicillnessrecovery.org/i...article&id=223

I'm wondering what people think of it, and whether anyone knows about this concern. This is the actual study I want to read, but can't find it online: http://www.ncbi.nlm.nih.gov/pubmed/19758226. If anyone has it, I'd appreciate a copy.

Okay, so I have a copy of the article now. It's interesting. And behind it all is this protocol: https://web.archive.org/web/20130622...kb.org/home/mp.

The Marshall Protocol was developed by an Australian engineer with no apparent knowledge of Vitamin D or the VDR. Dr Mercola (whose views I am not always in support of) has discussed it here; http://articles.mercola.com/sites/ar...-protocol.aspx.

The protocol (from https://web.archive.org/web/20130622...kb.org/home/mp) looks very detailed to me - if this was evidence-based science I would have expected to see PubMed accounts of its development and clinical cases notes describing its success. There aren't any.

This link may amuse NT readers but I think that it makes a good point; http://phylogenomics.blogspot.com.au...-marshall.html.

Yes just because there is a paper suggesting they have found all the answers doesn't mean they actually have, especially when it is in a journal with a impact factor of 4. It sounds like a bold claim, I am suspicious of bold claims, if it really were true why has the paper only been cited 30ish times since 2009? There is a paper in some journal on everyone's favourite crackpot theory, but only a extremely small fraction of these will stand the test of time.

The gut microbiome is a hot topic at the moment, but like the author says we have no idea how to safely harness this as a therapy in a clinical environment. There are a lot of theories. The internet is full of snake charmers of people suffering from ill health, I have been victim of a few myself, this is why we have to enquire very deeply into everything, and ask ourselves is this really sensible or am I being misled?

Thanks Kiwi... you beat me to it today.

The MP is still controversial and given all the time that has
elapsed, there are still no real research papers to endorse it.

Dr. Mercola, has in this instance provided a good rebuttal.

I actually went through and I read all the articles and talks they've published and the details of the protocol. Yes, not all journals and articles and studies, etc. are created equal, but I like to know a position before accepting or rejecting it. I'm not really interested in ad hominems or anything dismissive along those lines, though I won't lie, I did have a laugh or two when reading the blog post...

Last night I also came across Mercola's piece, which though it makes some useful points, doesn't address the science behind the model Marshall advances. That's fine, he's not writing in a specialist journal.

A few thoughts:

1. Jumping from computer models to a clinical protocol is problematic in all sorts of obvious ways.

2. There are all sorts of other problems too, e.g., taking antibiotics long term is not prudent for a number of reasons that are apparent to anyone who knows about their side effects.

3. But I'm not really interested in the protocol, but the main claim underlying it all. The meat of the position/model is twofold: (a) vitamin D is an immunosuppressive akin to steroids, and (b) it works by suppressing VDR from functioning.

Firstly, underlying this model is the position that vitamin D deficiency is caused by disease not the other way around. Well, we know that this hasn't been settled. I could say much more here, but it just hasn't been settled either way by studies, so Marshall can't have this one. But for various reasons, my suspicion is that it is (perhaps at least sometimes) caused by disease but that's not based on hard science.

The reason this is important is that it allows Marshall to claim that autoimmunity causes VDR dysfunction and so immune system dysfunction (and it's this that leads to low D levels). Is there evidence for this? If anyone has read his work and his evidence for it, then I'd be curious to know what you think. If I'm not mistaken, the only evidence he has is computer simulation and then just some claims loosely based on some clinical examples, not actual studies, certainly not quality ones. But perhaps I'm wrong. Again, I'm not an expert on this stuff.

Now, let's take (a). This seems to be true and is supportive by all sorts of studies. Here are just two links:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166406/
http://www.readcube.com/articles/10.12659%2FAJCR.894849

What does this all mean though? It's rather complex. What exactly is being suppressed? I'm not an expert so input is appreciated. I don't see enough evidence via Marshall's computer models of (b), namely, that VDR is being suppressed, and that's what's going on, but again perhaps I'm wrong. Kiwi, perhaps you have some thoughts here? It doesn't seem like we can know this.

So, is D suppressing the adaptive immune system in the sense that it's reducing inflammation (by working on the T and B cells), which a number of studies an articles claim, or that it's also reducing the immune systems ability to fight pathogens and to do its work basically? Or do we just not know enough about what or all that it's going? Obviously, key to all this is that it functions like a cortocosteroid. So what exactly does a steroid do to the immune system/mechanism of action, etc.?

I say this because there's also a personal dimension to all this, or personal experience. My levels were low. Then even a 1000 IU a day reduced my symptoms immensely. It very obviously reduced inflammation in my body. But is it also hindering my immune system from fighting off infections and doing whatever else it needs to do? Well, I don't have a baseline, but a few days ago I received my IgG numbers and they're low, not too low, but below normal range, so in the 600s. The rest of the immunoglobulins are fine, it seems. I don't have the IgG subclasses, but soon. I also have mild neutropenia, so I'm just below the normal range. Again, these are the only set of numbers that I have, but they're low. Is the D suppressing production of neutrophils and IgGs? Is this even possible? I just don't know enough about how it all works to say anything here.

Do I think that taking vitamin D or hormone D is suppressing my VDR function? I don't know. Theoretically it's possible, but I don't see the evidence or I don't find it convincing based on what I've read from Marshall and those who argue along the same lines. My guess is no, though it's not impossible, perhaps not even implausible. We know that supplementing hormones can have short term benefits, which I clearly have from D, but that long term is can lead to problems with respect to the body's own natural function.

But at this point I'm more interested in the more supported point, namely, that D is functioning as a corticosteroid. This is a common point, but the studies seem to stop at saying with certainty exactly what's going on. I could say and write more, but I'll leave it at that. I'm not sure if others are as interested in this as I am, but it's clearly a very important issue.

DavidHC, I think that is a great summary of what we know and don't know about the jobs of the VDR - I always find your posts stimulating because they encourage me to try to learn new things. What I have come up with so far is:

A genome-wide screen for genes which may be regulated by the VDR found 229 strong candidates. Of particular interest to the NT community include genes which seem to be involved in Type 1 diabetes, multiple sclerosis, SLE, rheumatoid arthritis. Crohn's disease and a number of cancers. Here is the fairly technical link; http://genome.cshlp.org/content/20/10/1352.long.

Apart from that VDR knockout mice have been made (a knockout mouse is one in which the gene in question has been permanently inactivated). So far it seems that the mice show abnormalities of Ca metabolism (no surprise) - as far as I can see nobody has yet used them to look at other things (autoimmunity, inflammation, etc); http://www.ncbi.nlm.nih.gov/pubmed/22903507.

I will keep digging and report back if I find anything of interest.

Here you go, for the NCBI article. http://www.medicinabiomolecular.com....as/do-1706.pdf

interesting cause of vit deficiency, or its receptor, definitely needs more research

DavidHC, some thoughts:

"It doesn't seem to settle the issue [VDR ablation] either way, almost a technical way of saying we just don't know what's going on, but there's stuff happening. ."

I could not have put it better myself

"B-cells are also affected by 1,25(OH)2D, demonstrating decreased immunoglobulin production, proliferation and differentiation, but increased apoptosis."

I think that this is OK. Most B cells are passive. They only get activated by encountering specific antigens made by pathogens, usually with assistance from helper T cells. Two things happen to activated B cells; they differentiate into passive memory cells which are "ready and waiting" for the next time that their specific pathogenic antigen is present - they then get activated - this is why vaccinations are effective.

Activated B cells also differentiate into plasma cells, which secrete specific antibodies, which deal with the pathogen. If both activated B cells and plasma cells persisted in the absence of their specific antigen there is a risk that they could mutate, leading to an autoimmune disease or a B cell cancer like multiple myeloma. Because of that they "commit suicide" - undergo apoptosis - it seems that Vitamin D/VDR has a role in this.

"Computer simulation is not enough."

Commented on elsewhere.

"this study seems to take it for granted that inhibiting the ongoing proliferation of activated B cells and inducing their apoptosis is beneficial."

See above.

"keeping an eye on my IgG and neutrophils, which I should mention have slightly gone down in the last few months - I have two blood samples over 3 months on that - and the reading was already on the lowest end of the acceptable range."

I don't know enough about the clinical side of things to say much about this - mrsD could well help.

Both D2 and D3 have to be activated by the liver and the kidneys, to work in humans. I personally think it will be many years yet before we know more details about this complex system of D metabolism. Many of the studies so far still use mice or rats.

actually its alot more complicated than that. B-cells have to mature from an immature b-cell, it first has to express, primary igm first, than it switches depending on the situation, to prevent autoimmunity, if the b-cell is autoreactive it is "destroyed" in bone marrow before full maturing, soemtimes it escapes this for unknown reason, and gets into your system, which is where it can get checked, if autoreactive, then it is wiped here as well. If it escapes all of these it can cause autoimmunity, however it should have the genetic changes before hand, for a specific antigen.T-cells is similar as well.
For cancer, it is usually the immature, or stem cell stages that will become myeloma or b-cell cancer, its almost always pre-cursor, cell which are primitive and display self-renewel. fully mature immune cells are less likely to become cancer. Theres also alot of checks and balances that go from immature "precursor to b-cells" which is why autoimmunity is very hard to study sometimes.