Poll for Vitamin D supplement tolerance and calcitriol levels

[nandixon]

I had high calcitriol when supplementing D. Then I started GcMAF (and stopped supplementing) and both 25 and 1,25 went into the normal zones.

I now take D3 again (2000 iu) as well as GcMAF and calcitriol has remained normal (at last check). I don't notice anything one way or the other from supplementing D 3 though.

Sushi

Thanks @Sushi, I've seen you mention this before and I've wanted to ask you about it.

So, prior to you ever using GcMAF, you had found that your calcitriol levels were going abnormally high when supplementing vitamin D, is that right?

And at that time (still prior to using the GcMAF) when you would supplement the vitamin D you would feel no negative (or positive) effects from it, even though it caused your calcitriol to go high - is that right?

Also, do you or your doctor have any idea what the mechanism would be for the GcMAF being able to lower the calcitriol levels?

Thanks again!

 

[Sushi]

So, prior to you ever using GcMAF, you had found that your calcitriol levels were going abnormally high when supplementing vitamin D, is that right?
And at that time (still prior to using the GcMAF) when you would supplement the vitamin D you would feel no negative (or positive) effects from it, even though it caused your calcitriol to go high - is that right?
Also, do you or your doctor have any idea what the mechanism would be for the GcMAF being able to lower the calcitriol levels?

I didn't know that my calcitriol was high until my doc checked it before prescribing GcMAF. I wasn't aware of negative symptoms from it, but then who knows what causes what symptom!
Yes, my doctor has an idea of the mechanism through which GcMAF normalizes calcitriol levels, but I can't remember what it is! Sorry, some of his other patients might know--KDM.

Sushi

 

[mariovitali]

I don't know what this is. Can someone link me to some background reading?

Hsp70 proteins can act to protect cells from thermal or oxidative stress. These stresses normally act to damage proteins, causing partial unfolding and possible aggregation. By temporarily binding to hydrophobic residues exposed by stress, Hsp70 prevents these partially denatured proteins from aggregating, and allows them to refold. Low ATP is characteristic of heat shock and sustained binding is seen as aggregation suppression, while recovery from heat shock involves substrate binding and nucleotide cycling. In a thermophile anaerobe (Thermotoga maritima) the Hsp70 demonstrates redox sensitive binding to model peptides, suggesting a second mode of binding regulation based on oxidative stress.

http://en.wikipedia.org/wiki/Hsp70#Function_and_regulation

 

[nandixon]

Do you think that the point of up-regulating CBS might be to lower homocysteine levels?

I'd guess that to at least some extent calcitriol participates in helping maintain normal Hcy levels. But I don't know to what extent calcitriol production would actually be increased in order to respond to elevated Hcy, because my understanding is that, normally, calcitriol is maintained in a pretty tight range (tighter than 25-hydroxy D3, which can vary a lot more based on sun exposure and taking vitamin D3/D2 supplements). And, I may have missed it, but I don't recall seeing high calcitriol levels being associated with high Hcy levels.

And do we tend to produce more homocysteine when taking methylation supps? I'm under the impression that my homocysteine-to-methionine conversion is not working well via either pathway.

Taking methylation supplements tends much more to be about recycling the Hcy, versus creating too much Hcy. (I guess the latter might happen if a person also supplemented an excess of methionine, though.)

So Hcy is generally lowered by both methylation (to regenerate methionine) and by the transsulfuration pathway (via CBS). (I haven't looked at issues surrounding Hcy very much, though.)

 

[picante]

Thank you, @mariovitali. I'll need to find some background reading for the background reading . Since this Hsp70 deals with proteins emerging from ribosomes -- then we're talking about transcription? Or translation? Or what?

 

[picante]

And, I may have missed it, but I don't recall seeing high calcitriol levels being associated with high Hcy levels.

This study doesn't say that, but it suggests that 1,25 D gets used for that purpose: http://www.ncbi.nlm.nih.gov/pubmed/21898591

To further explore the potential clinical relevance of our ex vivo findings, human data from the Longitudinal Aging Study Amsterdam suggested a correlation between vitamin D status [25(OH)D(3) levels] and HCY levels. In conclusion, this study showed that cbs is a primary 1,25(OH)(2) D(3) target gene which renders HCY metabolism responsive to 1,25(OH)(2) D(3).

 

[hlahore]

There are many studies which show the need for Magnesium for those with CFS
http://vitamindwiki.com/tiki-index.php?page_id=383

 

[picante]

The text part of this paper is only 5 pages, and relatively easy reading. There's an interesting scatter plot graph on page 4: http://autoimmunityresearch.org/preprints/BlaneyAnnals2009Preprint.pdf

Blaney et al.: Vitamin D metabolites as clinical markers in autoimmune and chronic disease
Annals of the New York Academy of Sciences (PMID: 19758177)
(c) Copyright, 2009, New York Academy of Sciences.

From page 5:

In contrast, 1,25-D appears to be a highly sensitive clinical marker both in diagnosis of autoimmune and associated diseases.It may be fruitful to consider why levels of 1,25-D are elevated in patients with autoimmune diagnoses.One possibility is that the VDR becomes dysregulated when exposed to sufficient quantities of substances created by bacteria that antagonize or otherwise inhibit the VDR. One such substance is the sulfonolipid ligand, Capnine. 48 The protease, caspase-3, which is up-regulated by P. aeruginosa 49 and H. pylori, 50 has a similar effect on the VDR, effectively inactivating it by cleaving it.51 The persistent and difficult-to-culture bacteria that create these substances may play a role in the pathogenesis of autoimmune and related diseases.

As bacterial ligands compromise the activity of the VDR, the receptor is prevented from expressing CYP24, an enzyme that breaks the 1,25-D down into its inactive metabolites.42 This allows 1,25-D levels to rise without a feedback system to keep them in check, resulting in the elevated levels of the hormone as observed in our cohort. Acquired hormone resistance has also been recognized with insulin, thyroid, steroid, and growth hormone releasing hormone. 52, 53

 

[SOC]

The text part of this paper is only 5 pages, and relatively easy reading. There's an interesting scatter plot graph on page 4: http://autoimmunityresearch.org/preprints/BlaneyAnnals2009Preprint.pdf

Blaney et al.: Vitamin D metabolites as clinical markers in autoimmune and chronic disease
Annals of the New York Academy of Sciences (PMID: 19758177)
(c) Copyright, 2009, New York Academy of Sciences.

From page 5:

In contrast, 1,25-D appears to be a highly sensitive clinical marker both in diagnosis of autoimmune and associated diseases.It may be fruitful to consider why levels of 1,25-D are elevated in patients with autoimmune diagnoses.

Interesting. I've been wondering lately if there aren't two clear subsets (entirely different conditions?) under the ME/CFS umbrella -- an autoimmune one and and immune deficient one. We seem to have a substantial group of us that don't catch anything and another substantial group that catches everything. It also looks like we have an elevated vit D group and a recalcitrant low vit D group.

I wonder if those two groups correlate at all -- do the don't catch anything crowd also have elevated vit D (autoimmune subset) while the catch everything folks have low vit D (immune deficient subset). Wouldn't it be crazy if we could identify major subsets with something as simple as a 1,25-D test?

Yeah, it's late, I had a long day, and I'm getting a little punchy.

 

[mariovitali]

Thank you, @mariovitali. I'll need to find some background reading for the background reading . Since this Hsp70 deals with proteins emerging from ribosomes -- then we're talking about transcription? Or translation? Or what?

Proteins have to be properly folded within the Endoplasmic Reticulum (ER) of the Cell. Actually there is a mechanism that oversees whether a protein has been properly been folded or not. If many proteins are unfolded within the ER this generates ER Stress and as a consequence an Unfolded Protein Response (UPR). My theory is that this is the main reason of our problems (i am totally recovered after 7 years of symptoms).

Misfolding and excessive degradation instead of folding and function leads to a number of proteopathy diseases such as antitrypsin-associated emphysema, cystic fibrosis and the lysosomal storage diseases, where loss of function is the origin of the disorder. While protein replacement therapy has historically been used to correct the latter disorders, an emerging approach is to use pharmaceutical chaperones to fold mutated proteins to render them functional.

HSP70 is actually a Chaperone which prevents proteins from misfolding.


Please see here for the mechanism, a regimen that you can try and relevant References.

 

[mariovitali]

There are many studies which show the need for Magnesium for those with CFS
http://vitamindwiki.com/tiki-index.php?page_id=383

Yes that makes sense, since Magnesium aids in proper Calcium Homeostasis within the Endoplasmic Reticulum of the Cell.

Magnesium is an important caution that functions as a cofactor in many enzyme pathways.
Mg modulates and controls cell calcium entry and calcium release from sarcoplasmic and endoplasmic reticular membranes. This calcium transportation control is responsible for its numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow.
The physiological role of Mg is due to its calcium channel blocking properties at smooth muscle, skeletal muscle and conduction system levels. The analgesic properties are due to NMDA receptor blocking action.
Its physiological clinical applications are discussed below.

http://jpma.org.pk/full_article_text.php?article_id=3191

My suggestion for people that have problems with D3 is to also use Magnesium Citrate to prevent Calcium influx within the Endoplasmic Reticulum of the cell.

Please read more here :

 

[nandixon]

Magnesium increases the production of calcitriol. So, in general, a large amount of magnesium is more likely to worsen a high calcitriol situation for people who have that problem, I think. It certainly does for me. (In too high an amount or in the wrong form it increases my fatigue/exhaustion.)

On the other hand, there certainly may be a useful therapeutic window of an amount of magnesium that's helpful, or a particular form of magnesium that's helpful, or a particular time of day that's better to take it at.

I've tried most of the available forms of magnesium over the last 17 years (with the notable exception of magnesium threonate), and magnesium malate is definitely least fatiguing for me, and sometimes even very slightly energizing - at no more than about 100mg (elemental Mg) during the day. I also take ~200 mg at night to help sleep.

As usual, though, everyone is going to be different.

 

[Sidereal]

Interesting. I've been wondering lately if there aren't two clear subsets (entirely different conditions?) under the ME/CFS umbrella -- and autoimmune one and and immune deficient one. We seem to have a substantial group of us that don't catch anything and another substantial group that catches everything. It also looks like we have an elevated vit D group and a recalcitrant low vit D group.

I wonder if those two groups correlate at all -- do the don't catch anything crowd also have elevated vit D (autoimmune subset) while the catch everything folks have low vit D (immune deficient subset). Wouldn't it be crazy if we could identify major subsets with something as simple as a 1,25-D test?

Yeah, it's late, I had a long day, and I'm getting a little punchy.

Interesting idea. I would just add that my own condition morphed from "immune deficient" to "autoimmune" over the course of 20 years. I used to be just like you and some others here - catching every possible infection coming my way, especially respiratory infections. Just as one would start to clear I would catch another one. I lived on antibiotics when I was younger. And so on for about 10-12 years until one day it just stopped and I never caught a normal virus or bacterial infection again. For this reason I believe it is possible that it's one underlying disease with two different expressions, sometimes happening in the same person.

 

[Sidereal]

Magnesium increases the production of calcitriol. So, in general, a large amount of magnesium is more likely to worsen a high calcitriol situation for people who have that problem, I think. It certainly does for me. (In too high an amount or in the wrong form it increases my fatigue/exhaustion.)

Very interesting, I did not know that. Just gonna tag @Rand56 because he has this problem too. Magnesium definitely worsens my condition unless taken in very modest doses transdermally.

 

[mariovitali]

@Sidereal Can you PM me your regimen please?

 

[Sidereal]

@Sidereal Can you PM me your regimen please?

Well, I don't supplement any vitamins if that's what you're asking. They all worsen my condition which is a reasonably common situation in severe ME. I supplement only sodium, potassium and a small bit of transdermal magnesium.

 

[Rand56]

Very interesting, I did not know that. Just gonna tag @Rand56 because he has this problem too. Magnesium definitely worsens my condition unless taken in very modest doses transdermally.

I got on this kick awhile back of slathering a bunch of mag oil on me to try to raise DHEA. The longer I did it, the more I felt like a total slug, and even worsening my depression. I've concluded that I probably get enough of it in my diet, and I'll leave it alone on supplementation. I don't have the high anxiety anyway, so I figured why even bother with it.

Edit: Also, I could have been creating other mineral imbalances from taking it.

 

[Gondwanaland]

I got on this kick awhile back of slathering a bunch of mag oil on me to try to raise DHEA. The longer I did it, the more I felt like a total slug, and even worsening my depression. I've concluded that I probably get enough of it in my diet, and I'll leave it alone on supplementation. I don't have the high anxiety anyway, so I figured why even bother with it.

Edit: Also, I could have been creating other mineral imbalances from taking it.

Magnesium is an iodine antagonist.

 

[Sushi]

Interesting idea. I would just add that my own condition morphed from "immune deficient" to "autoimmune" over the course of 20 years. I used to be just like you and some others here - catching every possible infection coming my way, especially respiratory infections. Just as one would start to clear I would catch another one. I lived on antibiotics when I was younger. And so on for about 10-12 years until one day it just stopped and I never caught a normal virus or bacterial infection again. For this reason I believe it is possible that it's one underlying disease with two different expressions, sometimes happening in the same person.

Ditto!

 

[picante]

Interesting. I've been wondering lately if there aren't two clear subsets (entirely different conditions?) under the ME/CFS umbrella -- and autoimmune one and and immune deficient one. We seem to have a substantial group of us that don't catch anything and another substantial group that catches everything. It also looks like we have an elevated vit D group and a recalcitrant low vit D group.

That looks like the next poll! I've been wondering about these two subsets also. Until I caught an intestinal bug in March, I hadn't had any circulating viruses/infections for 20+ years. Just EBV and shingles, two viruses that were latent and reactivated.

Could you say that the autoimmune group has their immune system in overdrive? That's how I think of mine: thyroid antibodies, EBV antibodies, CMV antibodies. The orthopedic doctor thought I had ankylosing spondylitis or RA, but the tests turned out negative.

And the elevated vit. D -- just to be clear -- is not 25-OH in my case. That one is mid-range.