Kiwi,

Thank you for the kind words. I'm glad...I can't imagine a life without intellectual stimulation. For my part, I appreciate the responses and engagement form you. Honestly, I'm simply trying to clear some ground in an area in which I'm not a specialist, and to understand how best to proceed with my health.

I appreciate the resources. It seems the VDR is as complex as it gets. I read the technical article and will need to look at it a few more times. So impressive!

I also read through the study to which you linked, with the VDR ablated mice: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511627/. It's interesting. Did you notice this bit?

"The effect of VDR ablation on immune function has been extensively investigated. Although defects in T cell and macrophage function were observed, these were reversed by maintaining normocalcemia in the VDR null mice, suggesting that these abnormalities were secondary to impaired mineral ion homeostasis[28]. However, normocalcemic VDR null mice have decreased IFN production by T helper cells, thought to be secondary to impaired macrophage production of IL-18[29]. VDR null mice exhibit enhanced sensitivity to induction of inflammatory bowel disease[30], but are less susceptible to experimental autoimmune encephalomyelitis[31] and airway inflammation[32], suggesting that the VDR does modulate immune function, but its effects vary depending on the model and perhaps the underlying genetic background of the mice being studied."

It doesn't seem to settle the issue either way, almost a technical way of saying we just don't know what's going on, but there's stuff happening. It is interesting that by establishing mineral homeostasis they seemed to correct some of the issues. The study was clearly not focused on the issue, so perhaps a study focusing on immune system function is needed. You also wonder what would happen long term, or longer term so to speak.

I also read through this: https://www.google.ca/url?sa=t&rct=j...,d.dmo&cad=rja. Note this, especially at the very end:

"Figure 3. The immunomodulatory actions of 1,25(OH)2D. 1,25(OH)2D has diverse and extensive effects on the immune compartment. The innate immune response is affected, with monocytes producing more LL-37 and β-defensin, with increased NOD2 expression and autophagy, while also producing diminished amounts of inflammatory cytokines, with decreased expression of TLR2 and TLR4. Differentiation into macrophages is increased, with macrophages having an increased capacity for phagocytosis and chemotaxis. However, their APC and T-cell stimulatory capacity is decreased. Monocyte and macrophage production of ROS and iNOS is able to both be induced and inhibited, thus regulating their balance. Differentiation into DCs is inhibited, with DCs expressing decreased levels of maturation surface markers. DC production of IL-12 and IL-23 is decreased, while mannose receptor expression and production of IL-10 and CCL22 are increased. When these tolerogenic DCs interact with T-cells, development of Tregs and Th2 cells is increased, with increased production of IL-10, TGF-β, IL-4 and IL-5. The development of Th1 and Th17 cells is inhibited, with decreased production of IL-2, IFN-γ and TNF-α, and attenuation of macrophage activation. B-cells are also affected by 1,25(OH)2D, demonstrating decreased immunoglobulin production, proliferation and differentiation, but increased apoptosis."

I'm still not as well versed in the language to know exactly what's going on, but I can understand "decreased immunoglobulin production, proliferation and differentiation, but increased apoptosis." This can't be good. Though increasing differentiation and inhibition at the same time can explain it's use in cancer treatment, it may not be the best for increasing immunity. This seems to match up with Marshall's claim that D reduces production of antimicrobial peptides (and he refers to the knockout mice study too btw as showing that while 25 is low, biological active and available 1,25 is high). As I mentioned, I had low neutrophils and IgG. This may nothing to do with the D, as there are many other causes, but it might be worth mentioning.

Some further thoughts (even though this is getting too long):

1. I still see no evidence of Marshall's claim that D supplementation blocks VDR function. Computer simulation is not enough.

2. There is plenty of evidence that D works in complex ways and that includes suppressing the innate immune system and its ability for at least B cell proliferation, leading to reduced immunoglobulins and peptides, which may be problematic when trying to fight off a powerful infection. Am I understanding this correctly? There is also this, an older one: http://www.ncbi.nlm.nih.gov/m/pubmed/17641030/. Perhaps I'm misunderstanding this, since this study seems to take it for granted that inhibiting the ongoing proliferation of activated B cells and inducing their apoptosis is beneficial. I'm unclear about this. Is it that they're thinking along the lines of cancer rather than immune issues? This and the study I quote above come to the same conclusion, it seems. I'll think more about this, track it down and read the whole thing.

3. I am willing to believe the hypothesis that microbes can lead to VDR function reduction or dysfunction, given that it's a strategic way to shut off the body's immune system.

4. Despite 3, there's no evidence that the protocol he uses works, in particular there's no study showing that the so called "VDR agonist" olmesartan reactivated VDR function. There is just some computer model, and that's entirely insufficient as evidence for clinical practice. The physician he's working with doesn't even have the best data from his own patients. It seems they really don't know what's going on there, and I'm willing to bet the antibiotics have some benefit and that's what they're often recording.

I'd like to hear more about all this, and to discuss it going forward. Not to mention that I plan to keep reading, including whatever on here that I've yet to read: http://ortho.ucla.edu/body.cfm?id=206. But going forward practically, I'm thinking of just keeping my dose of D low or relatively low, 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'm also going to go ahead with the natural antibiotics, antifungals, etc., which has been the plan for months now. Basically, I don't agree with the Marshall protocol that you have to starve your body of D. That just can't be right, given what we know about human evolution and the importance of sunlight. But even if it is suppressing my immune system, I'll keep an eye on the markers, and will soon be seeing an immunologist anyway. I'll keep an eye on them, getting tested again in a few months, and then also beginning with the herbals to see how that goes. However suppressed my immune system is, the herbals will still do their job. Plus, the numbers show that my immune system is still in decent shape; that is, it's not failing/my numbers aren't dangerously low. And considering the symptom relief I get from such low dose D, and that I don't take a single pharma med, I can give myself at least that little bit.