jimmylegs wrote:I read it as: optimize zinc first, then test to determine if additional d3 or calcitriol are needed.
since zinc corrects overexpression of TNF-alpha and IL-6 as above, AND zinc fosters proper renal hydroxylation of D3 to calcitriol as per the studies above, AND IF vit d3 status is positively correlated with or even dependent on zinc status (a nice specific study would help here), then zinc alone may result in higher levels of endogenous d3 and calcitriol.
I think it more likely that if anything, additional 25(OH)D3 could potentially be needed.. not so much additional supplemental 1,25(OH)2D3.
No! No! NO ! ! !
Not one of these studies suggests that you can halt MS by maintaining adequate levels of zinc. Not a single one.
Or even any of the other diseases where the problem is that 25(OH)D3 is not being converted to 1,25(OH)2D3.
And I think if it were this simple, someone would have stumbled on this besides you, no offense intended.
The problem that is overcome by a single high dose of calctiriol + D3 is that 25(OH)D3 is not being converted to calcitriol in the CNS. You can have perfectly acceptable levels of both 25(OH)D3 and calcitriol in the blood, and adequate levels of 25(OH)D3 in CSF, but still have a problem if the problem is that CYP27B1 conversion is not working.
It is only EAE and mice, but Hayes' series of studies demonstrate that D3 alone will not effect the course of EAE, but calcitriol + D3 will both stop it and keep it in remission. The calcitriol is key to this happening because it makes it directly available to cells bypassing the conversion problem.
I personally would not waste time on zinc since this works in EAE. If it didn't work, zinc might be something to look at.
I've been discussing this offline in the context of active EBV and it will not completely work there because EBV hides in B-cells and blocks the Vitamin D Receptors so making calcitriol available will not have any effect as far as B-cells where there is an active EBV infection.
If calcitriol +D3 doesn't work in MS, then I can see a reason to test zinc in EAE to see if that alone has the same effect as calcitriol + D3.
Again, I'm not disputing that it would make perfect sense to ensure adequate nutritional status before testing calcitriol + D3 in pwMS to eliminate that as a confounding factor in whether it works.
The studies you cite do suggest that it alone could have an effect in MS, but if that is so, why has this not been investigated in MS or at least EAE?
Is there any evidence that people who attain adequate zinc levels after being dx with MS go into remission? Any?
Here is one study of zinc in EAE. It does conclude that there was a reduction in severity, but compare that to a complete remission which was sustained for the duration of the study in 100% of the mice treated with calcitriol +D3:
Source URL: http://www.ncbi.nlm.nih.gov/pubmed/22350510
Journal Title: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
Journal Date: Jun 2012
Journal Issue: 3
Journal Volume: 25
Journal First Page: 529-39
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2235 ... t=abstract
Article Title: Zinc aspartate suppresses T cell activation in vitro and relapsing experimental autoimmune encephalomyelitis in SJL/J mice.
Article Authors: Diana Stoye,Claudia Schubert,Alexander Goihl,Karina Guttek,Annegret Reinhold,Stefan Brocke,Kurt Grüngreiff,Dirk Reinhold
Importantly, administration of a medium range dose of 30 μg/day zinc aspartate [1.5 mg/kg body weight (BW)] in a therapeutic manner led to a significant reduction of the clinical severity of the EAE during the first relapse of the disease. A lower zinc aspartate dose (6 μg/day, 0.3 mg/kg BW) had no significant therapeutic effect on the severity of the EAE, while administration of higher zinc aspartate amounts (120 μg/day, 6 mg/kg BW) led to more severe disease. Taken together, our data suggest that zinc aspartate can modulate activation, proliferation and cytokine production of effector T cells in vitro and in vivo and that activated autoreactive T cells may be potential therapeutic targets of tightly controlled zinc supplementation in autoimmune diseases like MS.
There were four studies in 2001-2003 about Zn-MT-II in EAE that showed effect, but apparently not enough for anyone to follow up on this.
I think you are suggesting that adequate zinc plus a little D3 will have the same effect as calcitriol + D3 in EAE or maybe MS.
I just don't see support for that suggestion. It might work in MS. It might work in EAE. The studies of zinc in EAE suggest that it is helpful, but not a 100% remission and sustained remission in 100% of the the treated mice so I think what we know based on these studies is that it would not be as effective as calcitriol + D3 in EAE. We still, of course, don't know if calcitriol + D3 will work in pwMS.
I have to believe that there would at least be some anecdotal evidence that the combination of zinc and D3 adequacy would stop progression in MS if this were true. I don't see even that evidence and surely, there must be some pwMS who have tried this?