Vitamin D sensitivity

aaron_c

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OK, I've been doing a bit of reading on the fat soluble vitamins and how and in what proportion one might take them. I hope yall will forgive some amount of repetition of what I have posted previously in this thread for the sake of putting it all together into one post:

Retinyl and retinol are the same thing.

1. Fat soluble vitamins (FSV) interact with each other for absorption. This study found that:

Significant competitive interactions for uptake were then elucidated among vitamin D, E and K, supporting the hypothesis of common absorption pathways. Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E.​

So D, E and K compete with each other. Vitamin A trumps all of them...probably. Does it depend on the form of vitamin A? See the next section for concerns about the vast majority of vitamin A that we take. [EDIT: Thank you for the article! It seems like they are using retinol, retinyl palmitate and retinyl acetate, all three of which, at least separately, appear to be cause for concern. This article that I am unable to access should explain how they are prepared.]​

2. Vitamin A toxicity might vary widely: This paper that people from the Weston A Price Foundation like to cite found that:

...water-miscible, emulsified, and solid preparations of retinol are approximately 10 times as toxic as are oil-based retinol preparations.
Perhaps this is because the oil-based preparations allow the body to package and regulate the vitamin as it sees fit? Or are some of the naturalish water-miscible and emulsified versions (retinyl-palmitate, for instance) just more potent?
3. Synthetic Vitamin A might be toxic: The Weston A Price Foundation (See the "Vitamin A Knavery section) has an involved rebuttal to a 1995 study that warned pregnant mothers about the dangers of vitamin A. Their conclusion (roughly) was that since people have ingested high doses of vitamin A in the form of animal livers ect for much of human history, seemingly with many benefits and none of the currently described ill effects, perhaps the dangers of vitamin A might be attributed to an ingestion of the single synthetic retinyl form, rather than "Natural vitamin A [which] occurs as a mixture of various isomers, aldehydes, esters, acids and alcohols."

4. An alternate explanation to why synthetic vitamin A might be toxic was given fairly informally by Dave, the owner of Green Pasture (which sells fermented cod liver oil). Obviously, he has a dog in this fight, but the idea is at least interesting to me. He passes on the suggestion of a physician he spoke with that fermentation might be a superior way to extract cod liver oil because enzymatic digestion will always convert organic compounds to the useful isomer, whereas heat or chemical processing will tend to break them down any which way. Perhaps some of the vitamin A toxicity could be from having the wrong isomer interfering with the proper use of vitamin A? Perhaps someone with a better grasp of organic chemistry can add their expertise.

5. Finally I found a little more on how Vitamins A and D work together. Perhaps a little too simply put, vitamin A complexed to its nuclear receptor can form a complex with vitamin d complexed to its nuclear receptor. This (presumably?) activates genes differently than the Vitamin A or D nuclear receptor complexes would activate separately.


So how much of each fat soluable vitamin should we take? I am not sure, but for now I will aim for moderately high doses of high-vitamin foods. I have ordered some fermented cod liver oil/high vitamin butter blend from www.greenpasture.org that is supposed to be something like what Weston A Price would recommend. I will try to remember to post the results, particularly if it seems to work.



 
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aaron_c

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Update on Vitamin A:

It worked!

Since first posting about the possibility of vitamin A helping with "vitamin D fatigue," I have taken vitamin A twice (I think 3000 iu the first time and 4000 the second time.) Both times, separated by about 36 hours, I experienced an almost immediate and fairly profound improvement in my fatigue. Today I went from lying on the bed most of the afternoon with a very limited appetite most of the day to walking around and having conversations in the space of maybe 15-30 minutes. This is similar to what occurred the first time with the exception that my fatigue had not gotten as bad. My appetite also improved somewhat.

I have also tried a moderate increase in cunemuspir (a copper chelate intended for chronic fatigue) and benfotiamine, neither of which appeared to have much of an effect.

The Vitamin A I used was from source naturals, and was derived from fish oil. It is maybe 6-12 months old. Both times I took it with food. The last time the improvement in my symptoms was accompanied by mild nausea--it could have happened the first time, but I am not sure. I don't think that the vitamin A I took was ideal...just what I had on hand.
 

aaron_c

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This website estimates that fermented cod liver oil has about 10,000 IU of vitamin A and about 1,000-2,000 IU vitamin D per teaspoon.

As I mentioned before, different kinds of vitamin A (and I suspect of D) will work in somewhat different ways, so this should be taken very loosely, even ignoring what the owner of greenpastures said in the talk I linked above about the wide variance vitamin quantities labs will find given the same oil. Nonetheless, I thought it was a useful ballpark.
 

alice111

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I can't take vitamin D, but I get a very different reaction: autoimmune flare -joint pain, nosebleeds, and chillblains on my feet.... Very strange. Tried many different brands and forms (liquid, pill, etc) all did the same thing.
Also, strangely I don't get this from the sun!
No one has ever been able to explain this :eek:
 

aaron_c

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@Gondwanaland

You know, I had assumed that because vitamin k doesn't seem to inhibit vitamin A, that a vitamin A deficiency could not cause your bad reaction to vitamin K. I am no longer sure that this assumption is correct. Since vitamin A interacts with the nucleus, it seems entirely possible that a deficiency could cause all sorts of weird complications with other supplements. I don't know enough about what all vitamin A activates, so the only evidence I can offer that this theory might be worth looking into is that in nature, the vitamin k that we get from food often comes alongside vitamin A (in high-vitamin dairy products, goose liver, and eggs). Obviously some (or much?) of our vitamin K comes from fermentation, which doesn't give us vitamin A.

This whole thing is a bit of a shot in the dark, and as such I am not at all sure it would pan out were you to investigate it. Nonetheless, I had the thought, and thought I should pass it on.

On something of a tangent: You mentioned that C. butyricum is causing pain. Are you thinking this is coming from butyrate upregulating vitamin D receptors or is it something else? (The study was on colon cancer cells...not sure if that makes a difference or not).

@alice111: To my ignorant ears, that sure sounds like some kind of immune dysregulation. I know very little about the immune system (@nandixon?), but in the interests of furthering the whole connection-with-vitamin-A thing, I will refer you to this newsletter from the vitamin D council. I actually disagree with them when they warn us off all forms of vitamin a, however one quote might be pertinent:

...A form of vitamin A, retinoic acid, weakly activates the vitamin D response element on the gene and perhaps blocks vitamin D’s more robust activation. In fact, the authors of a 1993 study state “there is a profound inhibition of vitamin D-activated…gene expression by retinoic acid.
Maybe vitamin D without the moderating effects of vitamin A is causing the problem?
 

aaron_c

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Vitamins D, A, Copper and Zinc: More Detail Explaining Vitamin D Sensitivity?

For the past two days I have been taking the Blue Ice brand of fermented cod liver oil. I take 5 ml of 2/3 cod liver oil 1/3 high vitamin butter blend with each meal. Yesterday I experienced fatigue again, so I took vitamin A, however this did not entirely fix the problem. I went looking for more details, and I think I may understand in more detail what is happening:

This study on the interactions of vitamin A, Copper and Zinc has an interesting chart on page 7. In it, you will notice that when vitamin A is supplemented at a very high level (in rats), ceruloplasmin (the major copper-transport protein in the blood) can increase to over twice what it was in rats fed very little vitamin A. This effect is much greater than the effect of copper: Taking ten times more copper appears to increase ceruloplasmin by something like 10%.

As I have stated above, Vitamin D and Vitamin A often appear to work in dynamic concert, which leads me to wonder what effect vitamin D would have on ceruloplasmin levels. Although I wasn't able to find a study looking at this, I did find this website that found 8 instances where Vitamin D was suspected to have lowered ceruloplasmin whereas it found no instances where Vitamin D was thought to have increased ceruloplasmin. Thus, for now I will assume that vitamin D (without sufficient vitamin A) will decrease ceruloplasmin levels, possibly releasing some copper into circulation but ultimately reducing intracellular copper transport. This might decrease the availability of copper to the respiratory chain, thus making one tired.

Although I believe that the above interactions will hold up, I am less sure about the immediate and long-term effects of lowered ceruloplasmin. I will continue taking my fermented fish oil, and if I get strangely fatigued again I will also experiment with taking more copper (in the form of cunemuspir).
 
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Also have problems with D. Feel horrible and every time i take it and my levels are very low below range so doesn't add up. Still trying to understand why but my theory is that it causes more calcium absorption and retention which in turn causes mitochondrial problems, apoptosis, and vasoconstriction. But who knows. I have given up supplementing with it despite the low levels which i am not sure is a good thing, but whats the point if it makes me feel worse.
 

MeSci

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Well - I did it again. I had run out of my omega-3, and decided to risk taking one which contains a modest amount of D3 as the company delivers quickly, as opposed to the other one I use which doesn't have D3 but can take up to 2 weeks to arrive.

Very soon started to feel bad again but didn't make the connection. Nausea, poor appetite, solute diuresis (almost-certainly losing a lot of minerals/electrolytes), weakness, upper-abdominal pain, dizziness, blurred vision (like a mist) and poor focus, lousy sleep, etc. Suddenly realised that it might be the D3 and stopped it yesterday.

Last night I slept really well. :):):) It may have been partly due to the cetirizine, which I took instead of the chlorphenamine I would normally have taken yesterday. I had taken the cetirizine to try to alleviate the nausea which was really getting me down, as I have found that the anticholinergic effects of sedating antihistamines reduce nausea, and I thought that cetirizine might be less sedating than chlorphenamine (I took it in the late afternoon and didn't want sedation so early).

The supplement only contains 200 iu/5 mcg D3, but I think that my D3 stores must have been high due to the previous high-dose D3 and also my exposure to the sun, and I think this supplement must have pushed the level over a threshold. D3 stores can last for months.

Numerous adverse effects with Vitamin D are known, and not at all trivial:

http://www.webmd.com/vitamins-supplements/ingredientmono-929-VITAMIN D.aspx?activeIngredientId=929&activeIngredientName=VITAMIN D#vit_sideeffects
 
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aaron_c

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I should probably mention that my ideas about vitamin A have changed a little. Although I still think that it is essential to take vitamin d with vitamin a (1:10 ratio) and vitamin K, I think taking more vitamin A than this, as I did, may simply be sparing us from bone formation and thus the depletion (from the blood and tissue) of some nutrients that vitamin D would encourage us to put in our bones. Somewhere in the middle of the post I linked to I have a list of various nutrients needed for bone growth and how much they seem to impact my energy.

I imagine further conversations about this should take place on the thread I linked to, for clarity's sake.

@MeSci : When the website is up again (it seems to be down just now) I would suggest checking Chris Masterjohn of the Weston A Price Foundation. He makes what I think is a pretty good case for vitamin A and K deficiencies being the cause of vitamin D toxicity. In particular, he links to studies showing that Vitamin A decreased vitamin D toxicity and vitamin D decreased vitamin A toxicity in rats. I think he also makes a case that the increased calcium from vitamin D can lead to calcification of arteries (one of the more alarming side effects of vitamin D) unless there is sufficient vitamin K.

[Edit: Changed the link--it is now pertinent.]
 
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MeSci

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I should probably mention that my ideas about vitamin A have changed a little. Although I still think that it is essential to take vitamin d with vitamin a (1:10 ratio) and vitamin K, I think taking more vitamin A than this, as I did, may simply be sparing us from bone formation and thus the depletion (from the blood and tissue) of some nutrients that vitamin D would encourage us to put in our bones. Somewhere in the middle of the post I linked to I have a list of various nutrients needed for bone growth and how much they seem to impact my energy.

I imagine further conversations about this should take place on the thread I linked to, for clarity's sake.

@MeSci : When the website is up again (it seems to be down just now) I would suggest checking Chris Masterjohn of the Weston A Price Foundation. He makes what I think is a pretty good case for vitamin A and K deficiencies being the cause of vitamin D toxicity. In particular, he links to studies showing that Vitamin A decreased vitamin D toxicity and vitamin D decreased vitamin A toxicity in rats. I think he also makes a case that the increased calcium from vitamin D can lead to calcification of arteries (one of the more alarming side effects of vitamin D) unless there is sufficient vitamin K.
Thanks, @aaron_c, but I seem to be fine with Vitamin D2, sunlight and UVB lamps - it's just (excessive) oral D3 that messes me up. There is no reason to suppose that non-human studies tell us anything about humans (this is a subject I have studied for many years and worked on in a freelance capacity).

I have occasionally had short-term nausea from sitting in the sun, but this may be nothing to do with Vitamin D, as sunlight has a range of properties. I think I should be getting enough Vit A and K from my diet and supplements.
 

xrayspex

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interesting, I have low NK and intolerant to vit d supp and sun---will have to dig up my lab results, had the immune function test at redlabs/VIP in like 2009

I agree that this is very important and I think has been overlooked for far too long in ME/CFS research. Understanding why a significant subset of ME/CFS people are intolerant to vitamin D supplementation may help give some critical insight into the disease, for everyone. I recently started the vitamin D poll in my signature to try to get some idea how significant the problem may be.

My best guess as to what might be happening is based on the consistent finding in ME/CFS research that a significant number of patients have increased regulatory T cells (Tregs) and correspondingly low natural killer (NK) cell function. (See, e.g.: Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis)

Vitamin D, as calcitriol, significantly induces/helps activate Tregs. This can happen, for example, through increased expression of FOXP3 - a defining Treg attribute. (See also the diagram below for additional immune effects of vitamin D.)

This should mean, I think, that there should be a greater tendency for individuals with high Tregs (and possibly low NK cell function) to be intolerant to vitamin D, while individuals with normal Tregs (and possibly normal NK cell function) should be more likely to tolerate vitamin D.

(Nothing is ever black or white in this disease, of course, and vitamin D affects hundreds of different genes and enzymes.)

View attachment 11231

(Image from: Vitamin effects on the immune system: vitamins A and D take centre stage)
 

xrayspex

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Thanks, @aaron_c, but I seem to be fine with Vitamin D2, sunlight and UVB lamps - it's just (excessive) oral D3 that messes me up. There is no reason to suppose that non-human studies tell us anything about humans (this is a subject I have studied for many years and worked on in a freelance capacity).

I have occasionally had short-term nausea from sitting in the sun, but this may be nothing to do with Vitamin D, as sunlight has a range of properties. I think I should be getting enough Vit A and K from my diet and supplements.
fascinating article/studies related to vitamin D intolerance and suggests calcium supp just as good if goal is to prevent ostepenia etc

https://synergyhn.wordpress.com/lesions/
 

aaron_c

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fascinating article/studies related to vitamin D intolerance and suggests calcium supp just as good if goal is to prevent osteopenia etc
From the link:

This article also discusses the levels of vitamin D and calcium needed to avoid osteoporosis and vascular calcification in the light of new research on blockage of the vitamin D receptor due to bacterial products and elevated 25D.

...

There is another emerging view that centers on the vitamin D receptor (VDR). It is based on the work of Trevor Marshall, Ph.D., who argues that vitamin D receptor (VDR) competence is a crucial, but over looked factor in chronic disease (7, 8). His disease model is based on molecular modeling and clinical research that provides a model of chronic inflammatory disease (7, 8, 9).

Last I checked most of what the Marshal Protocol people put forth is entirely theoretical, based on computer modeling--in silico they call it, as opposed to in vitro or in vivo. Mark London does a pretty evenhanded--although in my opinion somewhat flawed*--takedown of the theories surrounding the Marshal Protocol.

Personally I regard any scientific explanations associated with the Marshal Protocol as highly dubious. Although I do think that their protocol may help some people (and be needlessly dangerous for many more) I don't think it is for the reasons they are suggesting (again, see Mark London). And I think that leads them to some dangerous conclusions about how best to treat a wide variety of conditions.


*Mark London relies on the conventional, high target for vitamin D levels. As Chris Masterjohn explained these numbers are based on Caucasian lifeguards near the equator and probably don't reflect prehistorical norms.
 
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aaron_c

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Thanks, @aaron_c, but I seem to be fine with Vitamin D2, sunlight and UVB lamps - it's just (excessive) oral D3 that messes me up.
I have also found that vitamin D lamps and sunlight are fine for me. So far the best guess I have come up with relies on the controversial Stephanie Seneff, who says that sunlight that reaches our skin produces vitamin D sulfate rather than the unsulfated vitamin d found in D3 supplements. 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

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Once again, my thoughts on Vitamin D have changed over the past year and a half. This is the best I've been able to put them together so far. It includes links to the interview with Dr. Seneff.
 

xrayspex

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I have also found that vitamin D lamps and sunlight are fine for me. So far the best guess I have come up with relies on the controversial Stephanie Seneff, who says that sunlight that reaches our skin produces vitamin D sulfate rather than the unsulfated vitamin d found in D3 supplements. 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.
oh wow I didn't see that other current thread on D....now I don't know where to respond....will just stay here for now

problem is I have ostepenia downward trajectory last 17 years and D is nonexistent on my blood tests practically

but Aaron unlike you here is the rub for me---I cannot go out in the sun except in the winter or late fall.....I have sjogrens but behave more like a lupus person in that regard. It really flares my CFS and pain stuff. Its like I am drunk and feel fluish later....no good. My rheumatologist said if I can't tolerate D3 that I should try D2 and or a tanning bed salon. I just tried D2 and didnt stay on it long, got the excitotoxicity, agitated, hateful, awful feeling. I also suspect it increases inflammation or something, it felt like my neck swelled in the CFS/ME way when in a flare. I didn't try tan bed yet and am not hopeful. But i did try an LED red light rubylux that my friend sent me, and it could have been pure coincidence, I haven't done enough trials yet but timing not good to do more right now, but anyway, after doing it a couple days and increasing the length of it on my face I was awake all night which is not normal for me these days.

I suspect that my body doesn't want it in any form which is why I was intrigued by that Marshall paper I posted above. but i saw on one of these D threads one of yr theories that yr intolerance to D is because of its relationship with calcium which would be a drag if thats the mechanism for me too because thats the alternative mentioned in that paper to combat osteoporosis, calcium vs D. I think my body doesn't want D because I don't tolerate hormones and also because its an immune modulator and its probably killing pathogens in me and causing a herx type situation. I don't know all of the science lingo but I have been reading about this stuff for 25 years and experimenting so I have sort of a feel for what things make sense to me....kind of like someone who can play guitar alright but can't read a note of music. I never wanted to try Marshall Protocol because it seems too out there for me...stay in basement and wear shades all the time (altho that does sound a little bit like what my life has had to turn into lol) but I think he is onto something. And I think Mikovitz was onto something and she had said we don't do well with hormones (before all hell broke loose with her research).

oh and I almost forgot, I found another explanation for why I may not do well--I don't have a gallbladder and a lot of cfs/me folks have trouble with that.That was the beginning of my trouble, messing up my gb and getting it taken out.....so I am sure I have some level of malabsorption and also I have had like genova type tests in the past that say I have a problem with phase 2 of detox....so I probably can't break down the D. My integrative doc said its like chemicals keep circulating in me and make me feel bad. I take charcoal almost every day.

http://www.vitamindwiki.com/Gallbladder removal and vitamin D deficiency