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Squeakycat wrote: 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.

Ed,
I think you have uncovered a key point, which is often hidden by terminology and one OH group:

Humans store vitamin D as vitamin D3, which is 25(OH)D or cholecalciferol.

Humans use calcitriol or vitamin D3 hormone, which is 1,25(OH)D.

Hope I have got the names right. I considered adding the structures but it will probably confuse matters.
MarkW

Squeakycat wrote:

NZer1 wrote: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.

Thanks Ed, agreed, that is the crutch of the matter, imo.

If we had calcitriol levels where they ultimately should be for immune system health and function, PLUS all the hundreds of functions that Vit D is believed to do, then what else is there that needs to be be CORRECTED or DISABLED or ERADICATED?

The concept that calcitriol and not Vit D3 supplementation is the vital issue in many or all autoimmune diseases is the secondary issue in my conceptual opinion.

There is very likely another primary factor, 'The Stealth Pathogen Factor', that is present in order that the chain of events occur and the immune system dysfunctions. To look for deficiencies in vitamins and minerals or to look for genes that are functioning against good health is, imo, a dream. The Human mind is looking for things that may work in the simplistic man made scenarios of everyday life, but not in the complex interactions of cellular life.

Vit D supplementing is about closing the gate once the horse has gone. Supplementing would have to have happened in previous generations on the mothers side and in the stages of life up till about teenage years. The research that shows that people who travel before or after age about 15 shows that MS incidence changes by latitude, so where does Vit D fit in that finding? If there is a pathogen or series of pathogens, that are suited to the latitude bracket where MS is most common what would be the outcome? Could this be the cascade of dysfunctions in the immune system that is present in PwMS? The Vit D factor is more likely the forming of the immune system in utero and early life in the same way that infections and ABx modify immune systems in early life.

The Human mind assumes that if you have xyz ill health then something must be missing to cause such a disease of health. Is that ever the case with immune system dysfunction?

Assumptions of the past in general health are being rewritten, the classics are happening as we speak, the fats and sugars in our diets are showing that the thinking has been based on assumptions not science to a point of conclusion.

Another factor in the Vit D dosing debate comes from Terry Wahls amazing new book where she speaks of using diet and sun light rather than supplements 'BECAUSE THAT IS THE WAY THE BODY WILL GENERATE WHAT IT USES AND NEEDS AND WILL ALSO REGULATE THE TOTAL OF THE PRODUCTION OF CALCITRIOL'!
If you supplement with the artificial and synthetic copies of D3 then your body is not able to regulate the total amounts through the natural bodies functions and you are likely to over dose and cause another issue, a side effect of the dosing. Food for thought and food for health. Why dose with synthetics when you can provide the real needs from diet without risk of causing other cascades? Food/diet and sun light or infrared light is not expensive and is what has worked for a few million years!

Look at the chain of events, the cascade effect, and search for the entire picture not the knowledge level of the eyes looking at segments of the picture!
As Sal Sclafani has often said the eyes only see what they want to!

;)
Nigel

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

potentially, for some aspects of this discussion, yes.

we agree that supplementing Vit D3 is important but you have yet to state if you agree with my target for D3 in blood

as always, proposed targets are available here, along with all the other interconnected targets i've hunted down so far via researching levels seen in healthy controls: http://www.thisisms.com/forum/regimens- ... tml#p15460

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.

a few more:
Magnesium concentration in brains from multiple sclerosis patients
http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract
The average Mg content in the CNS tissues, as well as visceral organs except for spleen, of MS patients showed a significantly lower value than that seen in control cases. The most marked reduction of Mg content was observed in CNS white matter including demyelinated plaques of MS samples.

Experimental and clinical studies on dysregulation of magnesium metabolism and the aetiopathogenesis of multiple sclerosis.
http://europepmc.org/abstract/MED/1296766
Magnesium and zinc have been shown to be decreased in central nervous system (CNS) tissues of MS patients, especially tissues such as white matter where pathological changes have been observed.

The effect of magnesium oral therapy on spasticity in a patient with multiple sclerosis
http://www.ncbi.nlm.nih.gov/pubmed/11136367
We found a significant improvement in the spasticity after only 1 week from the onset of the treatment on the modified Ashworth scale, an improvement in the range of motion and in the measures of angles at resting position in lower limbs. No side-effects were reported and there was no weakness in the arms during the treatment.

also, with testing it doesn't really matter what the body of evidence says about magnesium status in ms. you just see how your personal results stack up against healthy controls, and go from there.

I think what is being debated here is whether you need to do all this testing before taking D3.

debate positions in review:

My advice for anyone with MS is to take 5000 IU a day of vitamin D3, all year round. ... some people with MS find it hard to get their level up to 150 nmol/L even if they are taking 10,000 IU dose every day. They may not be absorbing vitamin D well because they don’t have enough of certain minerals and trace elements, sometimes called co-factors. When this happens I suggest taking Lambert’s Mega Mineral Complex (other brands contain similar ingredients).

and this

i consider the passing mention of multimineral use only in the context of those with poor absorption to be irresponsible, especially if people take high doses, absorb it, then experience side effects without understanding possible links to mineral depletion

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.

there is powerful evidence of global problems with suboptimal magnesium and zinc intakes, and some evidence showing that the issue is even worse for ms patients than the rest of the population. so, even if ms patients really are no worse off than average joe, levels should still be optimized prior to high dosing vit d3.

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.

certainly. and where cost of testing is an issue, patients considering high dose d3 still need to understand the importance of daily mineral intake requirements, how their own personal dietary intake stacks up, how to optimize dietary mineral intake, and where necessary, how to appropriately time supplemental mineral intake to minimize potential for side effects from high dose d3.

MarkW wrote:Testing for the main co-factors is a non starter on NHS.
MarkW

Do you know if B12 testing is standard with MS and covered by NHS? If it is, with some further study, it might be possible to make a case to not only allow, but to require co-factor testing in MS.

With a fair wind in terms of financial support to test the Hayes Calcitriol + D3 protocol, I think would could add a substudy to this to look at:

1. The level of co-factors in pwMS, and
2. Whether supplementing to eliminate any deficiencies has a measurable impact on outcomes.

Good to see the research of the past is being used!

Key points that impact this discussion.
1. The Vit D findings where low levels are common in PwMS and that increasing these levels changed the relapse rate are not conclusive that Vit D supplementing was an influencing factor, rather that it was a co-incidence in the study group. MS waxes and wanes especially in RRMS and it has not been identified why, so how can one assume that treatment by Vit D was a factor? The reasons are not provided scientifically that anything related to the processes of Vit D changed with synthetic supplementing in these studies, especially the ANZ Vit D supplementing study in progress down here.

2. The calcitriol involvement in EAE is a finding that is solely dependant on a pathogen being injected into the CNS and rapidly causing an infection of the CNS. The use of calcitriol in a synthetic form by injection into the CNS changed the infection and its symptomatic effects are the study focus. So this is dependant on pathogen involvement rather than the unknown cause of MS!

3. PwMS have no particular event or series of events that combine to create a dx of MS regularly, so how does Vit D supplementing with a non bio available precursor to the hormonal form, calcitriol, change the incidence of MS or the path of progression in MS?

4. Pathogens are known factors in mimic diseases of MS, but MS is impossible to define and identify its origin. When a person with an MS dx is re-dx-ed as having a pathogen infection such as Lyme disease or the many co-infections, the dx of MS is dropped because an improvement in symptoms and progression occurs, but not all people are tested accurately for a definitive pathogen involvement. Once multiple pathogens over time occurs it is almost impossible to dx the symptoms as coming from one source, rather, that the sources have mutated and formed a bio-film of pathogens which are extremely difficult to deplete and regain health of the patient.

5. When Sun Light is limited by latitude, diet is used to provide the precursor to calcitriol in latitudes where there is risk of low Vit D3 levels identified from serum testing. Why isn't MS rampant in these latitudes and covering of the body and a Westernized diet of Islamic cultures in many latitudes is seeing a rise in MS in recent years rather than at a rate of increase since MS was first dx-ed Internationally?

6. The diet of the average PwMS has not been assessed and published for some reason, the history of diet in PwMS has not been assessed and published for some reason, the PwMS such as, Terry Wahls, diet of the past has not been published for some reason? Why would this happen if the changes in diet by people such as Terry Wahls and George Jelinek are showing in their study groups of people on their diets or historically the people following Swank diets and improving their MS not reporting what was and comparing what has made the difference.
If the diet change is making a difference to the disease in general what was the previous diet and what is the learning?

6. Pathogens are known to effect levels or use or require vitamins and minerals such as the ones we have been discussing, such as magnesium which is required/scavenged in abundance by CPn for its cellular processes, yet this isn't factored into the analysis when people are found to have low levels by serum testing and when the magnesium for instance is increased the symptoms of MS change? The bacteria have enough for their needs and the body also has what it needs. The symptoms of many bacterial infections are not caused by the presence of the bacteria as they habit and multiply, rather when the bacteria die they decompose and leave behind endo-toxins that are damaging to the body such as damage to the CNS and waste clearing issues for the immune system and lipid system occur because the immune system is looking for live active pathogens rather than toxins in the CNS.

I'll stop for a sleep now,
Nigel

jimmylegs wrote:

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.

certainly. and where cost of testing is an issue, patients considering high dose d3 still need to understand the importance of daily mineral intake requirements, how their own personal dietary intake stacks up, how to optimize dietary mineral intake, and where necessary, how to appropriately time supplemental mineral intake to minimize potential for side effects from high dose d3.

Agree. Compared with vitamin D, it is relatively easy to attain adequate levels of calcium, zinc, magnesium and copper through diet.

I wouldn't agree that the required vitamin D3 levels are "high," except relative to the low levels recommended by groups such as IOM.

One minute of UV-B exposure provides 1,000 IU of vitamin D. Of course, that's running around with no clothes. The body limits the daily production of vitamin D to 20,000 IU normally, though levels up to 30,000 IU a day can be reached during pregnancy, spurts of bone growth and probably other conditions where the need is higher.

Although I do not have MS, it takes 7,426 IU/day to maintain my 25OHD levels. Below that intake level, my 25OHD level drops. I spend a lot of time in the sun sailing and swimming and eat far more wild salmon than most. Although I have not tested my levels, I do take a combined supplement that provides RDA levels of calcium, magnesium and copper. Haven't found a pill yet that has all of that plus zinc.

i ran into trouble at 4000 IU per day. at one time i wouldn't have called that high either. there's no way i'd need 7400 IU per day to maintain levels.. as i've said elsewhere, i used to be able to expect a 50 nmol/L jump from a short term high dose d3 protocol. after correcting mineral deficits, the same d3 regimen shot my levels from 103 to 271 nmol/L. dose response more than tripled.

what are these rda levels of ca mg and cu, iima? if not using a zinc supplement, how many mgs of elemental zinc are you getting daily from diet? i'm surprised you're supplementing copper and not zinc. pretty counter-intuitive given how often a high copper zinc ratio is problematic, and how rarely the opposite is true.

there are such a diversity dietary and lifestyle routes to similar nutrient problems, that a study of diet alone would be problematic to say the least.

i'd like to be able to compare long term nutritional surveillance data to chronic disease diagnosis stats. like a CHILD study, but tracking nutrient status via blood samples, (since they're using blood samples to look at immune function already) rather than using questionnaires, as well as tracking any diagnosis, not just issues associated with asthma and allergy http://www.canadianchildstudy.ca/

NZer1 wrote:Good to see the research of the past is being used!

Key points that impact this discussion.
1. The Vit D findings where low levels are common in PwMS and that increasing these levels changed the relapse rate are not conclusive that Vit D supplementing was an influencing factor, rather that it was a co-incidence in the study group. MS waxes and wanes especially in RRMS and it has not been identified why, so how can one assume that treatment by Vit D was a factor? The reasons are not provided scientifically that anything related to the processes of Vit D changed with synthetic supplementing in these studies, especially the ANZ Vit D supplementing study in progress down here.

Nigel, I can pull together a series of studies which are placebo controlled which show that the vitamin D group fares better than those on placebo or lower doses. And there are a number of fairly large studies underway currently that should provide more support for this. They do tease out whether the effect is vitamin D, mostly by comparing low doses against higher doses since it is considered unethical to not provide supplements when there is a known deficiency. All these studies could be better and more definitive, but there is little question at this point that D3 supplementation has positive effect in MS.

NZer1 wrote:2. The calcitriol involvement in EAE is a finding that is solely dependant on a pathogen being injected into the CNS and rapidly causing an infection of the CNS. The use of calcitriol in a synthetic form by injection into the CNS changed the infection and its symptomatic effects are the study focus. So this is dependant on pathogen involvement rather than the unknown cause of MS!

First, the calcitriol is not injected into the CNS. It was tested either orally or by various injections and I believe also IV. The cause of EAE and the cause of MS are certainly different, but both are characterized by breaches of the blood brain barrier which is what is done to induce EAE in mice. The CNS is not infected. The infection simply causes a breakdown of the BBB which then allows body-side immune cells to infiltrate into the CNS and at least in Hayes studies, to remain immortal because of a breakdown in the process through which 25(OH)D is converted to calcitriol. We aren't going to know if the Hayes protocol works in pwMS until we test it in pwMS.

NZer1 wrote:3. PwMS have no particular event or series of events that combine to create a dx of MS regularly, so how does Vit D supplementing with a non bio available precursor to the hormonal form, calcitriol, change the incidence of MS or the path of progression in MS?

I'm not sure I fully understand the question, but I think there is a fairly well defined set of initial symptoms that come with MS. Coming up with a clinical diagnosis, as with any diagnosis, requires ruling out all the other things that could cause similar symptoms.

It is increasingly becoming common to test for B-12 and Vitamin D deficiency when MS is suspected.

Correcting any identified vitamin or mineral deficiencies should help to at least slow the onset of clinically definite MS and potentially preventing onset.

The body does not produce calcitriol initially so I'm not sure why you are raising the question of using D3. Dietary forms of vitamin D are either D2 or D3. There is no dietary form of calcitriol.

NZer1 wrote:4. Pathogens are known factors in mimic diseases of MS, but MS is impossible to define and identify its origin. When a person with an MS dx is re-dx-ed as having a pathogen infection such as Lyme disease or the many co-infections, the dx of MS is dropped because an improvement in symptoms and progression occurs, but not all people are tested accurately for a definitive pathogen involvement. Once multiple pathogens over time occurs it is almost impossible to dx the symptoms as coming from one source, rather, that the sources have mutated and formed a bio-film of pathogens which are extremely difficult to deplete and regain health of the patient.

All possibly true. The body's main line of defense against injury and infection is the regulatory hormone vitamin D so whatever the source of the problem, it surely makes sense to ensure that there isn't a deficiency.

NZer1 wrote:5. When Sun Light is limited by latitude, diet is used to provide the precursor to calcitriol in latitudes where there is risk of low Vit D3 levels identified from serum testing. Why isn't MS rampant in these latitudes and covering of the body and a Westernized diet of Islamic cultures in many latitudes is seeing a rise in MS in recent years rather than at a rate of increase since MS was first dx-ed Internationally?

Are you asking why there has been a relatively rapid increase in MS in places such as Kuwait and Iran? I think the answer for women in these places is relatively recent dress restrictions which limit sun exposure, but also in general for men and women, much less time is being outdoors in the past few decades during which increases have been seen in the incidence of MS.

NZer1 wrote:6. The diet of the average PwMS has not been assessed and published for some reason, the history of diet in PwMS has not been assessed and published for some reason, the PwMS such as, Terry Wahls, diet of the past has not been published for some reason? Why would this happen if the changes in diet by people such as Terry Wahls and George Jelinek are showing in their study groups of people on their diets or historically the people following Swank diets and improving their MS not reporting what was and comparing what has made the difference.
If the diet change is making a difference to the disease in general what was the previous diet and what is the learning?

Diet is very hard to study and very hard to change, especially for what I would call extreme diets such as that advocated by Terry Wahls.

At the same time, you hardly need to study that bad diets, lack of exercise and things like smoking and alcohol. People seem to prefer taking a pill to exercising or eating right or limiting smoking and alcohol consumption.

NZer1 wrote:6. Pathogens are known to effect levels or use or require vitamins and minerals such as the ones we have been discussing, such as magnesium which is required/scavenged in abundance by CPn for its cellular processes, yet this isn't factored into the analysis when people are found to have low levels by serum testing and when the magnesium for instance is increased the symptoms of MS change? The bacteria have enough for their needs and the body also has what it needs. The symptoms of many bacterial infections are not caused by the presence of the bacteria as they habit and multiply, rather when the bacteria die they decompose and leave behind endo-toxins that are damaging to the body such as damage to the CNS and waste clearing issues for the immune system and lipid system occur because the immune system is looking for live active pathogens rather than toxins in the CNS.

I'll stop for a sleep now,
Nigel

Just one comment on this. The immune system responds to infection or injury. If a cell is injured by a bacteria, that is enough to provoke an immune response.

jimmylegs wrote:what are these rda levels of ca mg and cu, iima? if not using a zinc supplement, how many mgs of elemental zinc are you getting daily from diet? i'm surprised you're supplementing copper and not zinc. pretty counter-intuitive given how often a high copper zinc ratio is problematic, and how rarely the opposite is true.

The RDA are the USDA RDAs.

My bad. The supplement is calcium, magnesium and zinc, not copper. Each tablet is 33% of the RDA so I take three a day.

all right so for healthy controls probably low on mag and zinc, and the cal mag ratio is probably too high.

jimmylegs wrote:all right so for healthy controls probably low on mag and zinc, and the cal mag ratio is probably too high.

The actual numbers are 333 mg calcium carbonate, 133 mg magnesium oxide, and 5 mg zinc sulfate. There is also some magnesium stearate of an unspecified amount.

which would be in one of the three pills by the looks of it, so all in all it's a 1000-400-15.

ca:mg ratio should be no more than 2:1. and with mag oxide being such a poorly absorbed inorganic insoluble supplemental form, the actual ratio is probably even worse than it looks on the label.

15 mg of zinc is ok for healthy folks (my 3 y-o nephew's gummie multis provide 8mg daily). ms patients need more than a maintenance dose, in order to bump levels up to match healthy control levels.

mag stearate will be a binder or lubricant, something along those lines.

Squeakycat wrote:

MarkW wrote:Testing for the main co-factors is a non starter on NHS.
MarkW

Do you know if B12 testing is standard with MS and covered by NHS? If it is, with some further study, it might be possible to make a case to not only allow, but to require co-factor testing in MS.
With a fair wind in terms of financial support to test the Hayes Calcitriol + D3 protocol, I think would could add a substudy to this to look at:
1. The level of co-factors in pwMS, and
2. Whether supplementing to eliminate any deficiencies has a measurable impact on outcomes.

Hello Ed,
B12 testing is not standard in pwMS under the NHS (National Health Service). The way UK NHS funds GPs pushes them to use as few tests as possible.
I think you could get helpful results from testing co-factors but as a scientist trying to eliminate deficiencies is a uncontrolable step in your study.
MarkW

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

jimmylegs wrote: nope and nope

Squeakycat wrote: 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 ......................

I agree with you Ed and from my analysis the evidence shows our conclusion. However, Jimmylegs disagrees with us.
MarkW

Based on my own Negative experience with Vitamin/Hormone D, and the fact that D uses up magnesium (something that most are low in), It seems inadvisable to recommend taking large amounts (more than 2,000 IU).
A much better solution seems to be to correct levels of cofactors that help to raise D levels, then supplement, if needed, with D.

I think we have to be clear on what our outcome is:
Is it to raise D levels: If so, then raising low levels of cofactors is imperative.
Or, is it to take a specified high amount of D and taking more (and more ?) if the already high intake is not working well enough to raise D levels ?
Maybe we should ask ourselves why we might need to take so much D to get our levels into a particular range.
If D was something that was unrelated to any other nutrients and without risk, then sure take lots of it. However, this is most definitely not the case.
The "you need this one thing to get better" is pharmaceutical approach to health.
The body and nutrition are way more interrelated than that - interrelationships abound and are critically important.