Poll for Vitamin D supplement tolerance and calcitriol levels

[nandixon]

There's definitely a significant, albeit minority, subset of us with ME/CFS who are intolerant to supplementing vitamin D (either D3 or D2) and who also have associated 1,25-dihydroxyvitamin D3 (i.e., calcitriol) levels that are too high relative to the more commonly measured 25-hydroxyvitamin D3 levels.

The problem seems to be pathological and has, in most cases, nothing to do with a person's intake of any other minerals or vitamins like calcium, magnesium, phosphorus or vitamins A or K, etc. (the usual recommendations from sources like the "Vitamin D Council" are also completely unhelpful).

500 iu is about my limit for the benefits of vitamin D, versus more than that making my "normal" levels of fatigue/exhaustion *much* worse. I have to take it at night, and I can tell that even that amount causes additional next day tiredness, but I seem to end up feeling worse overall with lower amounts.

My calcitriol levels run high, between 75-85 pg/mL (US units; reference10-75), while my "regular" (25-OH) vitamin D levels are low normal.

Assuming those of us with this problem don't all have some occult form of sarcoidosis, which might be responsive to, e.g., prednisone, I really think it could be useful for researchers to look into this because it might lead back to a possible underlying mechanism for some cases of ME/CFS.

I'm guessing the vitamin D/calcitriol problem may affect around 10% of us, but it'll be interesting to see. If you don't know your calcitriol levels please just assume they're normal for purposes of this poll. (You can always come back and change your selection later.) Thanks!

 

[mariovitali]

My belief is that Vitamin D3 is a double-edged sword for CFS, as is Calcium.

Vitamin D3 has the following properties :

a) It induces HSP70 (which is good)
b) It increases Calcium absorption (which cannot be a good thing for some of us)

I would strongly advise those CFS Sufferers that experience worse symptoms when they supplement with D3 to switch to an alternative way for inducing HSP70 (such as Resveratrol or Curcumin) and increase D3 Levels perhaps through the Sun or Special lamps.

Since my theory is that an important element of CFS is Protein Misfolding, Endoplasmic Reticulum Stress and the subsequent Unfolded Protein Response, anything that disrupts Calcium Homeostasis could cause problems.

 

[adreno]

b) It increases Calcium absorption (which cannot be a good thing for some of us)

I thought you were recommending calcium supplements in your other thread?

 

[mariovitali]

This is the exact text (as it stands now) and there is a caution that Calcium for some people may not be a good practice :

-Calcium : Ensure that you have normal calcium levels. Calcium is VERY critical for proper handling of Endoplasmic Reticulum Stress but it can be a double-edged sword if Calcium homeostasis is not functioning properly. In this case, supplementing with Calcium will worsen your symptoms. It is recommended that you first supplement with Magnesium (Calcium Antagonist) and see how you feel.

 

[Sidereal]

Assuming those of us with this problem don't all have some occult form of sarcoidosis, which might be responsive to, e.g., prednisone

I did wonder about that (and hyperparathyroidism) for a while but my symptoms don't fit and I had a fair trial of prednisone (for another dx) which made things worse so I presume this is an ME/CFS subset thing.

 

[nandixon]

Thanks @Sidereal! Did you by any chance have your calcitriol levels checked while you were on the prednisone? I think you've said before that yours runs high.(?)

If I understand correctly, prednisone will suppress the formation of calcitriol that occurs outside the kidneys (like in sarcoidosis but also in other disease states) but not affect the kidneys' normal production of it. So that might at least let us know where it's (not) coming from.

I've wanted to do an experiment and try prednisone just to see how my calcitriol levels react (and maybe feel better in the process, though that wasn't what you found, unfortunately) - assuming my understanding about renal versus non-renal sources of calcitriol is correct.

 

[Sidereal]

Thanks @Sidereal! Did you by any chance have your calcitriol levels checked while you were on the prednisone?

Unfortunately I had no tests while on prednisone. I've only had 1,25 and 25 OH measured once and they were running high and low normal, respectively. Just beware pred can have severe side effects in ME/CFS patients if you decide to try it. If someone feels markedly better on it, personally I would pursue another diagnosis.

 

[Rand56]

I supplemented Vit D quite some time ago. It did raise my levels, but had no impact in how I felt. I do better with sun exposure.

 

[Crux]

Years ago, I was found to be low in vitamin D, started taking it, became mildly hypercalcemic. ( didn't feel mild)

I wasn't taking more than 1000 iu, and when tested, my levels were at 36. ( I had recently stopped it when I figured out that it caused the side effects.)

I haven't had calcitriol measured.

At the time, I was taking the co-factors, A,K2, magnesium. ( not zinc, but it didn't work either)

I've come to suspect that infections may play a part in vitamin D intolerance.

I haven't found much evidence, but here's some.

http://www.ncbi.nlm.nih.gov/pubmed/23979953

http://www.ncbi.nlm.nih.gov/pubmed/11100667

 

[picante]

Thank you for starting this poll, Nan! I've got lots of info to post, and this is the place for it.

I'll start with lab results, and I'm hoping that other people will post theirs:

January 13, 2015 (after a month+ on transdermal B12 oils containing 3000 IU of D3):

• Vit. D 25-Hydroxy: 53.4 ng/mL [range 32-100]
• Calcitriol 1,25 di-OH: 103.1 pg/mL [range 10-75]

March 26 (no D3 -- oral or transdermal -- since January):

• Vit. D 25-Hydroxy: 34.1 ng/mL [range 32-100]
• Calcitriol 1,25 di-OH: 61.2 pg/mL [range 10-75]

I felt noticeably better just after stopping the B12 oils with D3 (extreme brain drag and depression lifted), but no additional improvement in the following weeks. (I did switch back to sublingual B12.)

 

[picante]

Rich VanK once posted a link to this study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222742/

A microarray experiment on MC3T3-E1 murine pre-osteoblasts treated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] revealed a cluster of genes including the cbs gene, of which the transcription was rapidly and strongly induced by 1,25(OH)2D3.

This is in osteoblasts. Can I safely assume that high 1,25 D (calcitriol) might induce more CBS transcription in other tissues?

I don't have a CBS mutation, but I've had increased sensitivities to everything containing sulfite and thiols while on active B12 supps. I stop taking them -- I can eat more high-thiol foods without triggering neck spasms/headaches/nausea.

 

[Gondwanaland]

@picante I wonder if the vitamin D pathway makes any sense to you:

Source

 

[nandixon]

Rich VanK once posted a link to this study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222742/



This is in osteoblasts. Can I safely assume that high 1,25 D (calcitriol) might induce more CBS transcription in other tissues?

I would think so. (Thanks for the link.)

I don't have a CBS mutation, but I've had increased sensitivities to everything containing sulfite and thiols while on active B12 supps. I stop taking them -- I can eat more high-thiol foods without triggering neck spasms/headaches/nausea.

It might be hard to narrow down to a particular gene the specific negative effects that too much calcitriol might be having, though, because it affects the expression of hundreds of different genes. Many of those are up-regulated but some are down-regulated.

 

[Sushi]

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

 

[picante]

@picante I wonder if the vitamin D pathway makes any sense to you:

Yes, it does. I've been trying to understand what happens when there isn't enough calcium in the intestines. I'm confused, though, because you've pointed out that I have some calcium deficiency symptoms, while my blood tests have hovered around (or over) the top of the range since my 30s (I'm 58).

I've been off dairy since last July, though, and now my calcium might be going down, but I'm not sure how to compare ionized calcium (ordered by my ND) to the usual test. Value from Feb. 12th:

Calcium (ionized) 5.1 mg/dL [4.1 - 5.6]
Parathyroid, intact 23 pg/mL [15-65]​

 

[picante]

It might be hard to narrow down to a particular gene the specific negative effects that too much calcitriol might be having, though, because it affects the expression of hundreds of different genes. Many of those are up-regulated but some are down-regulated.

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

 

[picante]

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.

And do you feel better with the lower calcitriol levels? Any specific improvements?

 

[picante]

switch to an alternative way for inducing HSP70 (such as Resveratrol or Curcumin)

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

 

[Sushi]

And do you feel better with the lower calcitriol levels? Any specific improvements?

I feel better with GcMAF but don't think this "feel better effect" (more like more stamina) is related to lower calcitriol.

Sushi

 

[Gondwanaland]

Yes, it does. I've been trying to understand what happens when there isn't enough calcium in the intestines. I'm confused, though, because you've pointed out that I have some calcium deficiency symptoms, while my blood tests have hovered around (or over) the top of the range since my 30s (I'm 58).

I've been off dairy since last July, though, and now my calcium might be going down, but I'm not sure how to compare ionized calcium (ordered by my ND) to the usual test. Value from Feb. 12th:

Calcium (ionized) 5.1 mg/dL [4.1 - 5.6]
Parathyroid, intact 23 pg/mL [15-65]​

In my personal experience high serum minerals = shortage = they are being mobilized from deposits
Unfortunately I don't have knowledge to interpret those results of yours.

Do you eat chia seeds for calcium and phosphorus? K2-MK4? Vit A?

Edit- overactive parathyroid?