Vit D3>125nmol/L (50ng/ml) in blood. Goal for pwMS

[Anonymoose]

I've been taking 50,000 iu of D3 every 5 days for over a year, no improvements rather a continued steady decline, so I wonder why this isn't working for me Mark!
Nigel

Nigel, three points: 1) It may in fact be working because it is possible that without the vitamin D, things might have been worse, and 2) It isn't the dose that is important. It is the level. Do you know your 25(OH)D levels? 3) I see your situation as one which justifies the cost of testing of co-factors: calcium, copper, zinc and magnesium.

Sweet mother of God!! He's seen the light!! Lol. I was about to sic Jimmylegs on you.
(Psst...Jimmylegs...what do you know about calcitriol and co factors? Should prolly respond on other thread)

[Squeakycat]

The biggest problem for pwMS is low vitamin D3 not magnesium or any another mineral. The scientific evidence shows this

nope and nope.

Assessment of serum magnesium, copper, and zinc levels in multiple sclerosis (MS) patients
http://ijpbs.mazums.ac.ir/browse.php?a_ ... lc_lang=en

Mean serum level of magnesium was 1.87 ± 0.37, copper 110.7 ± 19.5, and zinc 85.4 ± 13.5 in patients (control group), and 2.22 ± 0.24, 133.7 ± 13.4, and 110 ± 8.3 respectively in case group. This difference is statistically significant (P< 0.001).

Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III
http://www.biomedcentral.com/1741-7015/11/187/abstract

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 D 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.

J-legs,
Clearly, co-factors are important, but I don't think we can say at this point whether testing is justified in the absence of evidence that they are an issue. The Iranian study you cite is useful in pointing to a potential problem for pwMS, but N=35 so it is hard to view it as definitive. And while p is given as significant, the difference in the means is only 16% and there is considerable overlap in the 1st standard deviation between pwMS and healthy controls. The study certainly points to an area that should be studied further, but it is hardly proof that there is a problem that suggests that pwMS should rush out to get tested, at least in comparison with the mounting evidence of the association between vitamin D deficiencies and MS.

Given the temperature of the discussion now, let me use a different analogy to illustrate the point I'm making here and I think Mark is making. Some pwMS probably have genetic problems in vitamin D metabolism. Studies so far don't show this to be a widespread problem, but it may certainly be an issue for some people. It would be hard to justify having everyone undergo genetic testing for vitamin D metabolism genetic issues or recommend not supplementing just because some people may have genetic issues, but fully warranted for people who find that their 25(OH)D levels don't rise with either supplementation or sun exposure.

Similarly, there is no question that some pwMS have issues with co-factor deficiencies or will once they start vitamin D supplements and that these will have an impact on the effectiveness of vitamin D supplementation for those with problems.

There is a lot we don't know about all these issues, but it seems to me, and I think this is what Mark is arguing, there is considerably more evidence of a problem with vitamin D deficiencies in pwMS as well as links between MS and vitamin D levels to warrant both level testing and supplementation while there is much less relative weight of evidence of deficiencies in co-factors that would justify the cost of testing absent some evidence of a problem.

Were cost not an issue, I think we would all agree it makes sense to get tested for 25(OH)D levels as well as the main co-factors: calcium, zinc, magnesium and copper.

[Squeakycat]

Sweet mother of God!! He's seen the light!! Lol. I was about to sic Jimmylegs on you.
(Psst...Jimmylegs...what do you know about calcitriol and co factors? Should prolly respond on other thread)

Hard to see the light when you are as blind as I am. :>)

I know you are asking J-legs the question of co-factors and calcitriol levels, but let me provide an answer.

The co-factors relate only to calcitriol because this is the active form of vitamin D. Copper, zinc, magnesium and calcium do not interact with 25(OH)D, the storage form of vitamin D.

As we've discussed elsewhere, the appropriate measure of vitamin D status is 25(OH)D, not 1,25(OH)D, calcitriol. That seems contradictory since calcitriol is the active form of vitamin D. But the reason for measuring 25(OH)D is that it varies considerably with intake of vitamin D while the body goes to great lengths to maintain calcitriol within a very tight range regardless of intake of D3 or calcitriol. In roughly 8 hours, the level of calcitriol will return to the level prior to even a megadose of calcitriol.

Part of the mechanism for maintaining this balance is that when the body expresses CYP27B1, the gene that controls the conversion of 25(OH)D to calcitriol, it also expresses the counterbalancing gene, CPY24A1, which degrades calcitriol to an inactive form which is quickly excreted.

This keeps calcitriol within a very tight range. The more calcitriol produced from 25(OH)D, the more CYP24A1 which degrades any unused calcitriol.

[Anonymoose]

I think the cost to our health and well-being is getting lost here. If you take vitamin d whilst deficient in co factors, the vitamin d isn't going to do you a bit if good...except maybe give you a false sense of security. In light of the overall expense of the drugs we take to alleviate sx that may be caused by nutrient deficiencies and the health we lose, those labs aren't at all expensive and most docs will order them for you so insurance/Medicare will cover the cost.

Re: calcitriol co factors...I haven't a clue what may be involved there. But I assume, like everything else in our bodies, the action of calcitriol uses up micronutrients...which may explain the tapering of high dose calcitriol benefit at six weeks.

[jimmylegs]

Copper, zinc, magnesium and calcium do not interact with 25(OH)D

!?! recall the last few pages of discussion, above.

also:

Magnesium deficit ? overlooked cause of low vitamin D status?
http://www.ncbi.nlm.nih.gov/pubmed/24228832
"Several steps in the vitamin D metabolism, such as vitamin D binding to its transport protein and the conversion of vitamin D into the hormonal form 1,25-dihydroxyvitamin D by hepatic and renal hydroxylation, depend on magnesium as a cofactor."

ie you need magnesium for both hepatic hydroxylation to 25(OH)vitD3 and renal hydroxylation to 1,25(OH)2vitD3

looking forward to seeing these aspects teased out in the near future:
"results should be considered preliminary since biochemical data on individual magnesium status were lacking, confounding cannot be excluded and questions on the dose?response relationship still remain to be answered"

[jimmylegs]

anon, see the vit d thread in natural approach for the last bits of info i found on calcitriol cofactors

[Squeakycat]

I think the cost to our health and well-being is getting lost here. If you take vitamin d whilst deficient in co factors, the vitamin d isn't going to do you a bit if good...except maybe give you a false sense of security. In light of the overall expense of the drugs we take to alleviate sx that may be caused by nutrient deficiencies and the health we lose, those labs aren't at all expensive and most docs will order them for you so insurance/Medicare will cover the cost.

Anon,
Yes and no. If you take D3 and your levels don't increase or things get worse, then I think it makes sense to look into possible co-factor deficiencies. If those are corrected and there are still problems, then genetic testing may be warranted.

And if all the testing is free, sure, go ahead and get tested.

I think what is being debated here is whether you need to do all this testing before taking D3. I don't think that is warranted based on what we know about the associations between MS and vitamin D and the cost of vitamin D3 supplementation compared with what we know about co-factor deficiencies, with the possible exception of magnesium.

[ThisIsMA]

Here is a link to a new Vitamin D study, which measured the affects of Vitamin D on endothelial health in a group of people who were vitamin D deficient with chronic kidney disease.

What interested me is that they used hard science ways to test endothelial function before and after supplementing with D, and they found improvements. Its an open access article (scroll down below the Abstract at the top of the page) in case anyone wants to see the details:

http://www.plosone.org/article/info%3Ad ... ne.0091363

Conclusion

This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.

I wonder if anyone has ever tested vascular endothelial function using the testing methods in this study, in a group of people with MS?

[Squeakycat]

Copper, zinc, magnesium and calcium do not interact with 25(OH)D

!?! recall the last few pages of discussion, above.

J-Legs,
The co-factors cofactor with the bioactive form of vitamin D, calcitriol. That's not to say that they have no role in 25(OH)D levels, only that their molecular and cellular interactions are with the bioactive form, not the storage form, 25(OH)D.

I understood Anon's question to be whether there are different co-factors of interest to calcitriol and 25OH. They are not. The co-factors calcium, zinc, magnesium and copper are co-factors of the bio-active form of vitamin D, calcitriol.

I think a further part of this question is whether to measure 25(OH)D or calcitriol levels. The reason for measuring 25(OH)D is that it changes with food or supplements while calcitriol is maintained by the body in a very tight range. It does vary, but that variation is not as sensitive to intake levels of D3 as 25(OH)D.

I don't think we have different views on this, just differences in the way we are presenting our views.

[Squeakycat]

Here is a link to a new Vitamin D study, which measured the affects of Vitamin D on endothelial health in a group of people who were vitamin D deficient with chronic kidney disease.

What interested me is that they used hard science ways to test endothelial function before and after supplementing with D, and they found improvements. Its an open access article (scroll down below the Abstract at the top of the page) in case anyone wants to see the details:

http://www.plosone.org/article/info%3Ad ... ne.0091363

Conclusion

This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.

I wonder if anyone has ever tested vascular endothelial function using the testing methods in this study, in a group of people with MS?

ThisIsMA,
Not sure that this testing would be particularly useful in pwMS. The vascular problems identified by Zamboni are primarily venous malformations, not arterial restrictions resulting from the formation of plaques which is what they are looking at.

Vitamin D plays a critical role in both because it is the hormone with primary responsibility for the formation of both veins and arteries as well as the ongoing maintenance of endothelial health. It is also critical in hypertension because it is the hormone that controls NO levels which manage vasodilation and contraction.

[Anonymoose]

Copper, zinc, magnesium and calcium do not interact with 25(OH)D

!?! recall the last few pages of discussion, above.

J-Legs,
The co-factors cofactor with the bioactive form of vitamin D, calcitriol. That's not to say that they have no role in 25(OH)D levels, only that their molecular and cellular interactions are with the bioactive form, not the storage form, 25(OH)D.

I understood Anon's question to be whether there are different co-factors of interest to calcitriol and 25OH. They are not. The co-factors calcium, zinc, magnesium and copper are co-factors of the bio-active form of vitamin D, calcitriol.

I think a further part of this question is whether to measure 25(OH)D or calcitriol levels. The reason for measuring 25(OH)D is that it changes with food or supplements while calcitriol is maintained by the body in a very tight range. It does vary, but that variation is not as sensitive to intake levels of D3 as 25(OH)D.

I don't think we have different views on this, just differences in the way we are presenting our views.

Hey squeaky,
You must have found some studies since I first asked about calcitriol co factors. Links?? Are they all ckd sources??

[Squeakycat]

Hey squeaky,
You must have found some studies since I first asked about calcitriol co factors. Links?? Are they all ckd sources??

No. I don't see what there is to find. 25OHD is not bioactive. It is just there to either be converted to calcitriol or degraded.

Meanwhile, calcitriol is interacting with calcium, zinc, magnesium and copper.

[MarkW]

have I mis-understood your position?

you certainly have - willfully, given the entire debate above.. and most succinctly from this page alone:

i think it's fine to recommend d3 supplements to achieve target serum levels - as long as you clearly understand what is going on with cofactors. which have been studied elsewhere, as detailed above.

Playing the fool and deliberately mis-understand people is something I do to extract the views of others. We agree that supplementing Vit D3 is important but you have yet to state if you agree with my target for D3 in blood I think that Ed (Sweakycat) is correct in his view of what to do first.
MarkW

[Anonymoose]

Hey squeaky,
You must have found some studies since I first asked about calcitriol co factors. Links?? Are they all ckd sources??

No. I don't see what there is to find. 25OHD is not bioactive. It is just there to either be converted to calcitriol or degraded.

Meanwhile, calcitriol is interacting with calcium, zinc, magnesium and copper.

Emailing you...

[MarkW]

.......co-factors are important, but I don't think we can say at this point whether testing is justified in the absence of evidence that they are an issue.
Given the temperature of the discussion now, let me use a different analogy to illustrate the point I'm making here and I think Mark is making. Some pwMS probably have genetic problems in vitamin D metabolism. Studies so far don't show this to be a widespread problem, but it may certainly be an issue for some people. It would be hard to justify having everyone undergo genetic testing for vitamin D metabolism genetic issues or recommend not supplementing just because some people may have genetic issues, but fully warranted for people who find that their 25(OH)D levels don't rise with either supplementation or sun exposure.
Similarly, there is no question that some pwMS have issues with co-factor deficiencies or will once they start vitamin D supplements and that these will have an impact on the effectiveness of vitamin D supplementation for those with problems.
There is a lot we don't know about all these issues, but it seems to me, and I think this is what Mark is arguing, there is considerably more evidence of a problem with vitamin D deficiencies in pwMS as well as links between MS and vitamin D levels to warrant both level testing and supplementation while there is much less relative weight of evidence of deficiencies in co-factors that would justify the cost of testing absent some evidence of a problem.
Were cost not an issue, I think we would all agree it makes sense to get tested for 25(OH)D levels as well as the main co-factors: calcium, zinc, magnesium and copper.

Many thanks for your comments Ed. You understand my thinking on D3. Here in the UK, just testing for vit D3 and calcium is cost issue (the cost balance between good D3/calcium levels, (which usually mean good bone density) and cost of fractures from falls is often hard to justify). Testing for the main co-factors is a non starter on NHS.
This subject needs to argued openly, so that pwMS understand vitamin D3 and vitamin D3 hormone. It is a burning issue.
MarkW