Vitamin D sensitivity

nandixon

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According to her sulfated vitamin d behaves somewhat differently from the unsulfated sort, so this might explain why sunlight gives me almost all of the benefits of oral vitamin D without any of the side effects.
@aaron_c Do you have any before and after testing for both 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (aka calcitriol) for when you were taking oral vitamin D supplements versus using sunlight/sunlamps?

If a person has a bad reaction from oral vitamin D and this is due to overly high levels of calcitriol being made, then the same problem should exist with respect to sunlight, assuming approximately equivalent “dosing” of each (the 25-hydroxyvitamin D3 levels should be a good indicator for equivalent dosing).

Or is your bad reaction to oral vitamin D not associated with a high calcitriol level?

What about you @MeSci? Do you have any testing for calcitriol during times when oral vitamin D3 made you feel worse?

If some people feel worse from oral vitamin D but are fine with sunlight that makes me think there may be more than one type of problem going on - one that involves high calcitriol and one that doesn't - because I (and others) feel worse with both oral vitamin D (any kind, D3 and D2) and sunlight, and with each my calcitriol levels are found to be high with testing while 25-hydroxyvitamin D3 is low. (So I only supplement 500 iu of vitamin D3 per day to keep calcitriol in the mid-upper range.)
 

xrayspex

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@aaron_c Do you have any before and after testing for both 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (aka calcitriol) for when you were taking oral vitamin D supplements versus using sunlight/sunlamps?

If a person has a bad reaction from oral vitamin D and this is due to overly high levels of calcitriol being made, then the same problem should exist with respect to sunlight, assuming approximately equivalent “dosing” of each (the 25-hydroxyvitamin D3 levels should be a good indicator for equivalent dosing).

Or is your bad reaction to oral vitamin D not associated with a high calcitriol level?

What about you @MeSci? Do you have any testing for calcitriol during times when oral vitamin D3 made you feel worse?

If some people feel worse from oral vitamin D but are fine with sunlight that makes me think there may be more than one type of problem going on - one that involves high calcitriol and one that doesn't - because I (and others) feel worse with both oral vitamin D (any kind, D3 and D2) and sunlight, and with each my calcitriol levels are found to be high with testing while 25-hydroxyvitamin D3 is low. (So I only supplement 500 iu of vitamin D3 per day to keep calcitriol in the mid-upper range.)
so is calcitriol the first number in my most recent blood test?:
Vitamin D3, 25-Hydroxy 7 ng/mL ng/mL
Vitamin D2, 25-Hydroxy 10 ng/mL ng/mL
Vitamin D, 25-Hydroxy 17 ng/mL 30 - 80 ng/mL

is that what it means? I don't know what the range is for that one. but I know its really low.

so I feel awful in sun and supplement but have low D tests during the times I have tried it.

Nandixon how do you handle feeling bad from the D, or can you take 500 mg and feel alright? I don't feel alright on even just 100mg. I don't know if I would get used to it but can't afford to find out because still work (with accommodations). I would have to be on haldol or something to cope with the side effects.

I like the idea that maybe there is another way or its the lesser of evils, like sure maybe in theory D is good for you, if you don't have ME or an autoimmune problem. I have perused Lupus websites and there is subset of them that feel awful with any form of D. the body has to compromise one thing to save another.

that is interesting that you have delineated two possible types of D problem.
 

nandixon

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so is calcitriol the first number in my most recent blood test?:
Vitamin D3, 25-Hydroxy 7 ng/mL ng/mL
Vitamin D2, 25-Hydroxy 10 ng/mL ng/mL
Vitamin D, 25-Hydroxy 17 ng/mL 30 - 80 ng/mL

is that what it means?
No, none of those values are for calcitriol. It would be labeled something like “Vitamin D3, 1,25-Dihydroxy.”

Nandixon how do you handle feeling bad from the D, or can you take 500 mg and feel alright?
I can take 500 iu and not feel worse provided I'm not also getting sun exposure. If I have to be outside on a given day then I may not take any oral vitamin D the next day or so (but I usually try to cover up pretty well).
 

xrayspex

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No, none of those values are for calcitriol. It would be labeled something like “Vitamin D3, 1,25-Dihydroxy.”


I can take 500 iu and not feel worse provided I'm not also getting sun exposure. If I have to be outside on a given day then I may not take any oral vitamin D the next day or so (but I usually try to cover up pretty well).
thanks, I did not know about this before, you guys are ahead of the game ..............well have you come up with theory why they don't routinely test both types of D? I found this article that explains it a little.....but doesn't address why doctors usually just order the test I listed above.....sounds like it would be a lot more meaningful when compared to 125

http://suzycohen.com/articles/vitamin-d-testing-should-be-more-thorough/
 

nandixon

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have you come up with theory why they don't routinely test both types of D?
In most healthy people, calcitriol production is tightly controlled within a small range and isn’t typically affected much by normal amounts of supplements like oral vitamin D, calcium, magnesium, etc, or even sunbathing. So I think most doctors don't test for it simply because they expect it to always be the same, unlike 25-hydroxyvitamin D3 which can vary quite a bit and which has a much longer half-life than calcitriol and so is a more useful indicator (for healthy people) of vitamin D stores and hence ability to make sufficient calcitriol as needed.
 

aaron_c

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@aaron_c Do you have any before and after testing for both 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (aka calcitriol) for when you were taking oral vitamin D supplements versus using sunlight/sunlamps?
Prior to Supplementing:
Vitamin D, 25-hydroxy: 27.0 ng/mL (reference range 30-100)

After about 7 or 8 months of supplementing:
Vitamin D, 25-Hydroxy: 61.3 ng/mL (reference range 30-100)
Calcitriol (1,25 Di-Hydroxy Vitamin D): 60.5 pg/mL (reference range 19.9-79.3)

I haven't been tested since starting on the UV-B lamp, but I just called my doc and asked if we can test again.

What do you think about the calcitriol?

Another piece of this puzzle might be what happened with boron. Boron can mitigate vitamin d deficiency in rodents and increases serum 25-hydroxy vitamin D. One paper suggests that this might be because it could inhibit 24-hydroxylase, which is the gateway to the major pathway for vitamin D degradation.


(Image borrowed from Pinterest ...and I don't know where they got it from)

So this is what happened with me:

Like I said, I had found a way around the fatigue by taking 3-O-acetyl-11-keto-beta-boswellic acid and extra MK-4, plus sufficient vitamin A. Unfortunately after a few weeks I began to experience insomnia, and eventually I found that it was caused by boron deficiency. And I found that taking boron seemed to increase all of the effects and side-effects of vitamin D even when I hadn't taken vitamin d that day--but one of the side-effects of vitamin D was boron deficiency, and some hours (6-24? hard to remember) after I took the boron I would then get the symptoms of vitamin d deficiency which for me is a fairly specific set of symptoms that I think boils down to BH4 deficiency. So as far as I could tell boron would increase vitamin d, and then the vitamin d would decrease the boron, and then the boron deficiency would increase excretion of vitamin D.

Perhaps there would have been a way to balance the whole equation with enough boron and vitamin D, but the more boron I took the more deficient I became in B2, and there wasn't a way to overcome that (extra B2...caused some problems, maybe a headache?).

My best guess as to what happened was that the extra boron would increase 1,25 dihydroxy vitamin D (because less of it would get broken down and excreted). The extra 1,25 dihydroxy vitamin D, along with vitamin A, would stimulate my body to produce more 24 hydroxylase, blunting the effect of boron. I think this could have depleted boron because boron forms a covalent complex with the product of 24 hydroxylase, meaning that they may have been excreted together in the urine. So while in the short term boron increased levels of 1,25 dihydroxy vitamin d because I was not acutely deficient in vitamin D or because I had too much vitamin A the increased levels of 1,25 dihydroxy vitamin d ended up depleting me of boron.

Interestingly, this is about when I started having severe memory and concentration problems. I now think this is partly due to an overgrowth of candida--and boron is fungicidal, and may play a role in the immune system. Perhaps my boron deficiency allowed for a candida overgrowth? Some of my concentration problems may also have been due to MARCONS, which I tested positive for, and I'm not sure how that would fit into the picture.

I'm feeling too fuzzy today to work out how this might or might not connect with what you were thinking @nandixon . I hope it helps.
 

nandixon

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What do you think about the calcitriol?
It's pretty high but then your (after) 25-hydroxy is pretty high too. I'm guessing that's a fairly normal sort of correlation between the two in terms of their values. (How a person might feel one way or the other at those levels is another matter, of course.)

Another piece of this puzzle might be what happened with boron. Boron can mitigate vitamin d deficiency in rodents and increases serum 25-hydroxy vitamin D. One paper suggests that this might be because it could inhibit 24-hydroxylase, which is the gateway to the major pathway for vitamin D degradation.
That's interesting about the possibility of boron increasing vitamin D levels. I had bought a bottle of 3 mg strength boron a few years ago (I'm not sure why now) and it only took a few tries taking it for it to be clear that it made me feel worse. So if it might have been further increasing my already high calcitriol, that could be the reason.
 

aaron_c

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I have no idea but this is interesting
@aaron_c
From Dr. Carol savage
I didn't realize that vitamin d is thought to directly increase CBS transcription. Although I suppose it could be through the roundabout pathway where vitamin D protects NOS from uncoupling and the increased NO increases CBS somehow (I have yet to see how). That's good info, or a good rumor at any rate.

For now I'm not too concerned about this. She assumes that CBS overactivity is the cause of transsulfuration pathology, and I still think there are other reasons like the oxidation of cysteine that seem more compelling to me.

In a relatively healthy person, of course, increased CBS transcription would just be one more way that vitamin D improves antioxidant capacity.
 

xena

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I didn't realize that vitamin d is thought to directly increase CBS transcription. Although I suppose it could be through the roundabout pathway where vitamin D protects NOS from uncoupling and the increased NO increases CBS somehow (I have yet to see how). That's good info, or a good rumor at any rate.

For now I'm not too concerned about this. She assumes that CBS overactivity is the cause of transsulfuration pathology, and I still think there are other reasons like the oxidation of cysteine that seem more compelling to me.

In a relatively healthy person, of course, increased CBS transcription would just be one more way that vitamin D improves antioxidant capacity.
What do you mean by transulfuration pathology —the overproduction of taurine and sulfites over glutathione? I believe that oxidative stress itself modifies how much cysteine goes to each pathway.

It seems clear that not everyone with a CBS mutation has problems from it yet I think she may be correct about some of it... I tried her CBS rna and immediately my glutathione levels began to go up (at least, I experienced the improvements and symptoms I associate with that). It also helps my ammonia symptoms moderately.

Unfortunately it seems that eating any sulfur foods compromises that glutathione increasing benefit for me. I interpret that as sulfur foods speeding up transsulfuration. I think my health is suffering from the lack of sulfur foods - though I still eat meat - so I'm trying figure out next steps. Any ideas?

I know glutathione production goes up when I use transdermal magnesium or nrf2 boosting agents (both increase the rate of gclc, the enzyme that makes glutathione>. I see some kind of global benefit when I eat celery. I think there is some relation with nitrates or NOS but not sure what it is. I assume that's related to Ammonia detox but maybe also directly affecting glutathione synthesis.

I'm about to experiment with arginine and Citrulline so should be interesting effects Ammonia and nitric oxide wise. I also have about 40 mg of bh4 for experimenting.
 

Gondwanaland

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What anti-glycation supp is that? @Gondwanaland. Also, any suggestion for increasing cold tolerance?
Carcinine. Beta-Alanine and Carnosine do the same thing. They are DAO blockers (so I strongly recommend having histamine-lowering probx on board) thus upregulate other B6 pathways. It tanked my vit D (just tested it today and it went from 35 - 45 ng/mL to 25) and messed up other hormones. It stimulates T4 production. I was taking 1/10 of the lowest recommended dosage, so I recommend caution. It seems to be great for lowering inflammation from insulin resistance.
 

aaron_c

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What do you mean by transulfuration pathology —the overproduction of taurine and sulfites over glutathione? I believe that oxidative stress itself modifies how much cysteine goes to each pathway.
I think that the transulfuration pathology that we see probably occurs because cysteine oxidizes and bonds to another cysteine to form cystine. I am having one heck of a time finding a concise explanation for this... Here is Rich Van Konynenburg:

[Two cysteines] are oxidized to form cystine, pass through hydrogen sulfide, and are eventually converted to thiosulfate and sulfate and are excreted in the urine. This lowers the production of glutathione, which requires cysteine rather than cystine
So increased oxidative stress found in ME/CFS means that more cysteines will be oxidized to form cystine. This can be reversed by a recently studied protein Trp14, but for every cysteine converted to cysteines it needs to be reset by another protein Thioredoxin Reductase (TrxR1), which converts NADPH to NADP+ & H to do so. Low NADPH was at one point suggested as a biomarker for CFS--although the study is still unpublished, so maybe there was a fatal flaw? But assuming low NADPH, Trp14 activity will be slowed.

So if we think of Trp14 as a sort of net that stops cysteine from leaking out a side pathway to become (as we will see) ammonia, pyruvate and sulfite/sulfate, then our situation involves both a higher amount of cysteine trying to leak through (because of increased oxidative stress oxidizing cysteine to cystine) and a less effective net (because there isn't enough NADPH to power TrxR1 effectively). In short: I think it is likely that with our condition, increased amounts of cystine will leak through the side-pathway and both produce more ammonia and more sulfite--just as Yasko fears. I'm just not sure how much heightened CBS activity contributes to the problem.

What happens to cystine if it is not converted back to cysteine? Cystathionine-gamma-lyase (CTH) converts it to pyruvate + ammonia + thiocysteine. Ron Davis has recently spoken about the benefits of adding pyruvate to ME/CFS cell cultures, so perhaps we are deficient in it. In which case CTH might be helping to fill that gap.

"Thiocysteine rapidly decomposes in aqueous solution to form cystine and sulfur" (2 thiocysteine --> cystine + sulfide) [1]. The sulfur (sulfide) quickly combines with water to become bisulfide (HS-) plus hydroxide (OH).

Bisulfide is then combined with Sulfite by Human Sulfide Quinone Oxidoreductase (SQOR) to form thiosulfate. Some of this is excreted in the urine, but some is converted by Glutathione Sulfurtransferase (TST) into sulfite and glutathione persulfide. Glutathione persulfide then further converted to (still) reduced Glutathione plus either sulfite or sulfate, depending on the tissue and the availability of functional sulfite oxidase (SUOX) which requires molybdenum to function. In this way bisulfide is turned into either sulfite or sulfate.

In summary, I think that more cysteine than we would like becomes cystine and then irreversibly is converted to pyruvate, ammonia, and either sulfite or sulfate (sulfite, of course, can later be converted to sulfate by SUOX).

On a separate note, I think it's a stretch to assume that autistic kids, not to mention people with ME, over-produce taurine because Yasko sees high levels in the urine of autistic kids. Candida, zinc deficiency, and other disorders can cause taurine wasting (increased excretion of taurine in the urine). Since candida and zinc deficiency are two problems common to autistic individuals and people with ME, I tend to assume that a high urinary taurine level probably indicates wasting rather than over-production.

I tried her CBS rna and immediately my glutathione levels began to go up (at least, I experienced the improvements and symptoms I associate with that). It also helps my ammonia symptoms moderately.
Interesting.

Unfortunately it seems that eating any sulfur foods compromises that glutathione increasing benefit for me. I interpret that as sulfur foods speeding up transsulfuration. I think my health is suffering from the lack of sulfur foods - though I still eat meat - so I'm trying figure out next steps. Any ideas?
I'm not entirely sure why sulfur foods would compromise glutathione in any major way. They would, of course, increase sulfites, which can have some unpleasant effects.

I have eliminated both sulfite and "ammonia" (aka BH4 deficiency) symptoms in two ways: For sulfites, I take a lot of molybdenum--1500 mcg per day for me. Molybdenum can make people tired at first, I think this is because sulfites can combine with cystine to form s-sulfo-cysteine, a glutamate analog. Molybdenum is necessary to convert sulfites to sulfates, and the reduced sulfite levels can thus make one tired. The effect wears off over some weeks. For "ammonia" or BH4 deficiency I use a UV-B lamp daily, which I believe protects BH4 as outlined here. I also still take malic acid (about 1500 mg per day), which seems to help--possibly because Malate Dehydrogenase regenerates NADPH.

If you have the BH4 I would absolutely experiment with it--and I hope you will report back, er, on some thread I'm a part of.

I think arginine will tend to cause problems with BH4 rather than helping it. I also doubt that citrulline defiency is the problem.

I hope this helps.
 
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Help:
I was on a vitamin D3 protocol for 5 weeks, for ME/CFS, As it has helped some people with this condition.
Meaning taking about 300,000 units of vitamin D in total!
But Unfortunately I reacted very strongly on the protocol, making me bedbound Now in A very short time. :(

Now my specialist/dr. Professor de Mierleir – From Belgium you've heard of him I presume –Says that a subset of his patients reacted very badly to vitamin D. Just As I'm reading in this thread.

No I'm looking for some suggestions to relieve my symptoms..
Any suggestions?
@aaron_c : vitamin A?
 

aaron_c

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I'm looking for some suggestions to relieve my symptoms
Hi Arf

Much of the following I took from my own posts here and here. But I've added a few bits, so it seemed easier to post this as a new post:


Vitamin A, Vitamin K (MK-4) and AKBA Prevented My Vitamin D-Induced Fatigue

Vitamin A helped with fatigue to some degree, but not enough on its own. Vitamin MK-4 (a kind of vitamin K) helped with the fatigue as well and also helped with problems from calcium excess like headaches. The star player ended up being AKBA (3-O-acetyl-11-keto-beta-boswellic acid), a derivative of frankincense, which along with vitamin A and MK-4 removed fatigue as a side-effect of vitamin D.

So why does Vitamin D cause crippling fatigue for some of us and why did Vitamin A, Vitamin K (MK-4) and AKBA successfully relieve those symptoms? I suspect the fatigue results from an interaction between vitamin D and TGF-Beta, which "potently induce 5-lipoxygenase," at least in myeloid cells [1]. Many people with CFS have high TGF-Beta [2].

In case you want to try these things, here are the doses I used:
-1350 mg of Vitacost's 5-LOXIN per day (for the AKBA)
-60 mg per day MK-4
-Vitamin A was all over the place, if I had to do it again I'd be more conservative with that one. Some days I did as much as 10,000 IU of Vitamin A.


Other Side Effects From Oral Vitamin D

Unfortunately, vitamin D also caused huge problems concentrating, which is why I haven't posted much since my vitamin D experiment. Weirdly, stopping vitamin d (it's been a while) hasn't brought my brain back, so my current assumption is that my problems focusing were more of an indirect effect of the vitamin D than a direct effect.

In addition to all this, vitamin d seemed to cause a boron deficiency. Boron increases concentrations of the active form of vitamin D, so perhaps this is part of a feedback mechanism to prevent excessive levels of vitamin D. In any case, it seemed like after a while taking vitamin D would cause symptoms of vitamin d deficiency: what some people refer to as "ammonia" symptoms, in my case diarrhea, a feeling like my blood or lymph was stuck--very uncomfortable--and depression. This would be alleviated by taking boron. Unfortunately, boron depletes riboflavin, and I could never take enough boron to maintain high vitamin d levels without taking so much boron that I had symptoms of riboflavin deficiency. This was why I stopped taking oral vitamin D.


UV-b Lamp Gives Almost All Of The Benefits Of Oral Vitamin D3 But Without Any Side Effects

Using a UV-b lamp for the recommended time every day has provided almost all of the benefits of oral vitamin D without any of the crippling side effects. Specifically, it doesn't make me tired at all, it doesn't seem to deplete boron, and as far as I can tell it hasn't made mental focus any worse than it already is. So far the only explanation for this that I have come across is Stephanie Seneff's word/theory that Vitamin D produced in the skin is in fact vitamin D-sulfate and that the sulfated form of vitamin D has somewhat different properties than the unsulfated form that we get from cod liver oil or just D3 supplements.


  1. Sorg BL, Klan N, Seuter S, Dishart D, Rådmark O, et al.Analysis of the 5-lipoxygenase promoter and characterization of a vitamin D receptor binding site.Biochim Biophys Acta2006;1761: 686–697.[PubMed]
  2. Bennett AL, Chao CC, Hu S, Buchwald D, Fagioli LR, Schur PH. Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.J Clin Immunol.1997;17:160–166. doi: 10.1023/A:1027330616073.[PubMed][Cross Ref]
 
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bspg

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Reading this thread is so strange for me. I experience zero noticeable effects from taking Vitamin D, even if I take a lot. My blood level was borderline low awhile back (I was taking 2000 IU daily) so my Dr. had me take 4000 IU daily for 3 months. After that, my level was good so I've continued on 2000 IU daily since.

All of my healthy friends say it hypes them up, like drinking coffee or something. I wish it had that effect on me! I feel nothing.