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Vitamin D supplementation causes worsening of symptoms?

pemone

Senior Member
Messages
448
@Sporty
Magnesium is very important for vitamin d3, it seems. I feel worse when taking high doses (>10k) of vitamin d3 but magnesium and k2 make it better. It does activate the immune system and d3's anti-inflammatory effect is very much visible on my skin the very next day! :)

It is important that people understand that inflammation is the result of an activated immune system. You do not take a substance that "activates the immune system" and then have "anti-inflammatory effects".

In fact Vitamin D *may* be immunosuppressive, if you believe the work of Dr Marshall. Your heresay N=1 report would agree with him, because the effect you describe of Vitamin D lowering inflammation would be an immunosuppressive effect.


I am skeptical of the claim that cholecalciferol is structurally similar to calcitriol and therefore can compete with it for VDR binding. I think we could say it therefore might compete, but even then I would guess the chances would be low: I think the body has a vested interest in preventing cholecalciferol from interacting with the receptors that calcitriol does--otherwise what is the point of converting it in the first place?

Also, I looked for where Marshal claimed this and couldn't find it. I asked Joseph about that, so I'll let you know if he says anything.

Here[1] is a study on calcitriol binding to receptors in chick intestines. Among other things, it found that "...removal of hydroxyls at both the ICY and 25 positions (cholecalciferol) completely eliminates the ability to compete [with calcitriol]."

As for the bit about 25(OH)D and calcitriol antagonizing nuclear receptors: I see that he used a computer program to model the interaction of calcitriol with thyroid and other receptors.... Actually, I could see this happening, but I think it is a leap to say that the fix is to cut out vitamin D entirely. As I understand it, upregulation supposedly occurred in response to bacteria blocking the vitamin D receptor. It seems like decreasing vitamin D would be robbing Peter to pay Paul.

You raise great questions regarding Marshall's claim that supplemental Vitamin D is blocking the VDR receptor so that the important form 1,25-dihydroxyvitamin-d cannot fill the receptor to activate it. Marshall has dozens of presentations on Youtube, all of them carefully documented and backed by a lot of cohort research on humans. However, he always gets hit hard by other professionals on this issue of the Vitamin D supplementation blocking 1,25 form and his responses always rely on his computer models. I think this is a weak point in his theory, but please note that he could be wrong on this and his theory would still be incredibly important.

Essentially what Dr Marshall is arguing is that all of the tissues of your body are infected by bacteria. They are pervasive and have evolved over the millions of years apes have been around to target the vitamin D receptor. The vitamin D receptor is what activates the innate immune system that would destroy - or at least greatly limit - those bacteria. Once the vitamin D receptor is deactivated, the bacteria are then free to infect and disable functions of the target tissues. Dr Marshall's claim is that almost all autoimmune diseases are in fact caused by this single unifying idea.

Marshall's protocol relies on a heart disease drug named olmesartan that has an unintended side-effect of activating the VDR receptor. What his cohort trials have shown over the last 10 years is that people who take olmesartan in high doses every four hours get worse for the first year, then sometime in years two to three start to improve, with dramatic improvements appearing after that time. The theory says they feel worse the first year because they are *activating* their innate immune system to fight the bacteria. This is creating inflammation and a worsening of symptoms as the body engages a huge and well-entrenched population of bacteria in the tissues. It takes time to turn the corner.

Here is the report of a cohort of 64 patients with chronic fatigue syndrome who went on Marshall Protocol and showed impressive improvements:

Marshall's claim is that supplemental Vitamin D is immunosuppressive. The reason many people feel better is because they are actually further disabling the VDR receptor - by competing for its use with a non active form of Vitamin D. This lowers inflammation in the short term - in much the way a steroid treatment would - but unfortunately this will make you even more ill in the long term because you are allowing the entrenched infection to become worse.

People who are fighting chronic disease often test with very low levels of vitamin D. Marshall's point is that this is the *result of the disease itself* because the body is actively converting the 25-D form to the 1,25-dihydroxy form. These same people will usually test with very high levels of 1,25-dihydroxy. Why? Because the body converted to the active form but the bacteria disabled the VDR, so the active form could not be used! His point is supplementation in such individuals will further occupy the VDR slots and thus prevent even more of the active form from working.

It's interesting that in my own case I have normal vitamin D levels, but I definitely feel worse taking supplemental vitamin D. I am currently treating my chronic fatigue as the result of biotoxin illness using Shoemaker protocol, and I am remediating my home environment. After I finish with that I may end up putting myself on Marshall protocol not only as further treatent for the CFS but also as a potential prophylaptic for many chronic diseases. His idea is very powerful if even 50% of his ideas are proven correct.
 
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aaron_c

Senior Member
Messages
691
Hi @pemone

I appreciate the opportunity to talk to someone well-versed in the Marshal Protocol.

According to the Mayo Clinic "normal" 25OHD levels are 35-40 ng/mL while "normal" 1,25(OH)2D levels are 24-86 pg/mL. In other words, 25OHD levels are normally about 500-1000 times higher than 1,25(OH)D levels.

I don't know enough about how the body reacts to changes in vitamin D levels, so I suppose it could be possible that doubling normal 25OHD levels would cause a problem...but all the body would have to do to return the hydroxy:dihydroxy vitamin D ratio back to normal would be to convert at the most about 1/250th of the hydroxy to dihydroxy vitamin D.

OK, interesting, this might support his theory...slightly. If we play out a situation where the body doesn't have enough calcium: First, we release parathyroid hormone (PTH). PTH increases calcium in three ways: by increasing bone resorption, by increasing conversion of 25OHD to 1,25(OH)2D, and by increasing urinary loss of phosphate, which would otherwise bind with calcium in the blood. If the "normal" amount of PTH doesn't do the trick, we release more PTH. While this would increase 1,25(OH)2D, it wouldn't increase it back to where the hydroxy:dihydroxy vitamin D ratio is normal, because part of the extra calcium would come from a (pathological) decrease in bone mass and blood phosphate. Presumably, this is all happening at a pretty subtle level, making testing difficult? Or has he tested these things?

The main thing I keep coming back to, though, is that the inhibition of the VDR's by the suspected pathogens seems much more potent than any inhibition perpetrated by somewhat high 25OHD levels. He wants to attribute all sorts of maladies to vitamin D supplementation, but I see much better candidates from the early-mid 1900's--including the advent of antibiotics, which might presumably contribute to the chronic infections he is positing. People have been taking cod liver oil for a long time, and I haven't heard that they suffered high rates of...well any kind of chronic disease, although admittedly I don't know that much about the health of medieval Scandanavians. Please correct me if you have heard differently!

I find the idea of taking olmesartan interesting... And while I could easily avoid taking a vitamin D supplement, I don't like the idea of avoiding sunlight. As Marshal states, "It would seem that activation of the Vitamin D nuclear receptor is achieved by a delicate balance between the concentrations of a number of endogenous hormones." Do you know why he thinks that we need to throw 25OHD levels out of whack? Couldn't one just take olmesartan and leave 25OHD well enough alone?
 

Gondwanaland

Senior Member
Messages
5,094
Please forgive my ignorance, but I will ask the following question based on a recent experience.

I am intolerant to vit D supplementation myself. It gives me symptoms of hypothyroidism and low serotonin, additionally it increases my anti-thyroglobulin antibodies. I tolerate sunlight normally. (I think vit D is needed for T4 synthesis?)

Recently I supplemented with Biotin, which in a few days caused me a strong B6 deficiency - hives, anaphylaxis, sun intolerance.

So I suppelemented with B6 and the anaphylaxis went away, serotonin skyrocketed and I started having serotonin syndrome (migraine, hypersalivation, anorexia, rhabdomyolisis). Then I took B2 and fixed it.

What happened next (after stopping all vitamins) is that I had to drop my 2nd T3 dose of the day. So apparently B6, by increasing serotonin, and/or by promoting T4->T3 conversion, might have been a deficiency I had which prevented me from supplementing with vit D3.

Note: Lymphocyte proliferation is one of the B6 functions, so low B6 can cause immunesuppression, if vit D is high, demanding B6 for other functions (thyroid), it could cause that too little B6 is available for the thymus).

EDIT - not to mention the vit D- B6 interaction on insulin sensitivity
 
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pemone

Senior Member
Messages
448
Hi @pemone

I appreciate the opportunity to talk to someone well-versed in the Marshal Protocol.

According to the Mayo Clinic "normal" 25OHD levels are 35-40 ng/mL while "normal" 1,25(OH)2D levels are 24-86 pg/mL. In other words, 25OHD levels are normally about 500-1000 times higher than 1,25(OH)D levels.

I don't know enough about how the body reacts to changes in vitamin D levels, so I suppose it could be possible that doubling normal 25OHD levels would cause a problem...but all the body would have to do to return the hydroxy:dihydroxy vitamin D ratio back to normal would be to convert at the most about 1/250th of the hydroxy to dihydroxy vitamin D.

OK, interesting, this might support his theory...slightly. If we play out a situation where the body doesn't have enough calcium: First, we release parathyroid hormone (PTH). PTH increases calcium in three ways: by increasing bone resorption, by increasing conversion of 25OHD to 1,25(OH)2D, and by increasing urinary loss of phosphate, which would otherwise bind with calcium in the blood. If the "normal" amount of PTH doesn't do the trick, we release more PTH. While this would increase 1,25(OH)2D, it wouldn't increase it back to where the hydroxy:dihydroxy vitamin D ratio is normal, because part of the extra calcium would come from a (pathological) decrease in bone mass and blood phosphate. Presumably, this is all happening at a pretty subtle level, making testing difficult? Or has he tested these things?

The main thing I keep coming back to, though, is that the inhibition of the VDR's by the suspected pathogens seems much more potent than any inhibition perpetrated by somewhat high 25OHD levels. He wants to attribute all sorts of maladies to vitamin D supplementation, but I see much better candidates from the early-mid 1900's--including the advent of antibiotics, which might presumably contribute to the chronic infections he is positing. People have been taking cod liver oil for a long time, and I haven't heard that they suffered high rates of...well any kind of chronic disease, although admittedly I don't know that much about the health of medieval Scandanavians. Please correct me if you have heard differently!

I find the idea of taking olmesartan interesting... And while I could easily avoid taking a vitamin D supplement, I don't like the idea of avoiding sunlight. As Marshal states, "It would seem that activation of the Vitamin D nuclear receptor is achieved by a delicate balance between the concentrations of a number of endogenous hormones." Do you know why he thinks that we need to throw 25OHD levels out of whack? Couldn't one just take olmesartan and leave 25OHD well enough alone?

Basically, I agree with almost all of this. I think the weakest point in the Marshall Protocol is his claim that 25-D levels should be deliberately reduced down to 12 ng/mL in order to minimize interference with 1,25-dihydroxy form of D. All of this seems to be based on his computer model, which is suggestive but not proof. The fact is that there are many studies showing benefits of D supplementation, so I think he is going to run into a wall of clinicians objecting to his computer model, and he really doesn't need to fight that battle so hard.

For myself, I will stop the Vitamin D supplementation, but I don't think I am going to go out of my way to avoid sunlight and I'm going to trust my body to regulate the 25-D levels. If that slows down his protocol I will live with that. I would have a different point of view if people on the Marshall protocol were making dramatic recoveries within six months. That's not what is happening, and given a three year recovery period I don't see a reason to artificially lower vitamin D to levels that clinically have been shown to create large health risks.

The more interesting idea is that pathogens can disable the VDR and that this results in persistent - sometimes undetectable - infections. The use of olmesartan off-label is also clever, and while I am not familiar with the side effects, it definitely seems to be worth exploring.

Why are modern generations suffering from this condition more broadly? It could be that a combination of high-sugar diets that started in the 1950s (and this would include the reliance in processed foods on wheat and corn starch not just sucrose and high fructose corn syrup) together with lots of vitamin D supplementation has combined to both feed bacterial pathogens with constant high glucose levels in the body, and perhaps the vitamin D supplementation is further downregulating VDR activation. It tooks us millions of years to adapt to our original diets, and it is not crazy to suggest that modern processed foods are pushing us biochemically in directions that our genetics were not designed to deal with very well.

A lot of vitamin D advocates are claiming that Marshall's idea is nonsense, but I haven't seen anyone really disprove his ideas in a compelling way. I think the idea that all autoimmune disease represents different manifestations of the same core idea of bacterial parasitic infection of tissues is powerful and a lot of research effort needs to go into either confirming or refuting that theory.
 

pemone

Senior Member
Messages
448
Please forgive my ignorance, but I will ask the following question based on a recent experience.

I am intolerant to vit D supplementation myself. It gives me symptoms of hypothyroidism and low serotonin, additionally it increases my anti-thyroglobulin antibodies. I tolerate sunlight normally. (I think vit D is needed for T4 synthesis?)

Recently I supplemented with Biotin, which in a few days caused me a strong B6 deficiency - hives, anaphylaxis, sun intolerance.

So I suppelemented with B6 and the anaphylaxis went away, serotonin skyrocketed and I started having serotonin syndrome (migraine, hypersalivation, anorexia, rhabdomyolisis). Then I took B2 and fixed it.

What happened next (after stopping all vitamins) is that I had to drop my 2nd T3 dose of the day. So apparently B6, by increasing serotonin, and/or by promoting T4->T3 conversion, might have been a deficiency I had which prevented me from supplementing with vit D3.

Note: Lymphocyte proliferation is one of the B6 functions, so low B6 can cause immunesuppression, if vit D is high, demanding B6 for other functions (thyroid), it could cause that too little B6 is available for the thymus).

EDIT - not to mention the vit D- B6 interaction on insulin sensitivity

For myself, I have decided that the road to hell is lined with nutritional supplements. B vitamins are powerful mediators of metabolism, and I think the efforts that people go through to balance all of the B vitamins to regulate their metabolisms is dangerous, not efficacious, and simply too complex to test or manage.

I have never been more sick than when I supplemented B vitamins.
 

Art Vandelay

Senior Member
Messages
470
Location
Australia
I have been reading up on the Marshall protocol and its very interesting.

http://mpkb.org/home/pathogenesis/vitamind/metabolism

Is there any current guidance on how best to test for 1,25OHD? In that link it says that whole body serum might be inaccurate.

Testing info is here: http://mpkb.org/home/tests/dtesting

My previous doc (who was quite particular about pathology procedures) used to specify that the blood sample had to be put on ice, but that was the extent of any special instructions.
 

Aerowallah

Senior Member
Messages
131
What about lead toxicity?

After a week supplementing D3 500iu + K2 (I have supplemented magnesium, and am starting calcium) I feel flu-ey and develop insomnia. Sleep is restored after 4 or 5 days off the D3. Like ice to eskimos there are so many ways to feel bad with AF--this way isn't so much fatigue as brain fog, flu aches and pains--and insomnia. Felt the same when I ate too much cilantro three l days running. The insomnia is not anxious but calm and wide awake, with very fractured sleep when it comes. On a neuro test it was accompanied by elevated glutamate. I have high-ish mercury and lead after years of eating sushi and living in lead-lined New York City pre-war apts. I associate these symptoms with metal detox, but never thought I might be running into more with D3...

http://www.ncbi.nlm.nih.gov/pubmed/7531087
http://www.lead.org.au/lanv10n2/lanv10n2-10.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852643/
 
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Aerowallah

Senior Member
Messages
131
Pemone says the road to hell is paved with supplements.

Weird that when I also take B12 (and my best agonizing guess at cofactors), get more insomnia and divide and divide it down to the level of a food dose, and it still gives me insomnia, but the same amount in sardines (with its natural balance of cofactors) is tolerable. Guess with my VDR Taq sardines will be my best option for D, too! Everything we force around here seems to stir up metals, when our individual triggers for AF etc are not well understood. I could take any supplement without side effects before the onset of AF symptoms after a bad flu. I'm closing my drawer of supplements, and going for benign, less targeted improvement, and let sleeping metals lie. The body detoxes what it can when it can--someone told me four years ago--and the optimal balance before forcing more may be a better balanced body. Oh, and CEs take the edge off detox symptoms!

BTW the only supplements that my body loves is Magnesium glycinate and Trace Minerals...and organic food!
 
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uglevod

Senior Member
Messages
220
Who is on Marshall Protocol nowadays? Its main forum is locked(you should apply for membership), the only alternative - chronicillnessrecovery.org - is a pay to access forum.

Besides I've just read that Marshall Protocol is turned into monotherapy effectively becoming an experiment over experiment. So no more ABX, only blood pressure drug(Olmesartan) megadosing. Sign.. it could be turned into something much more significant..
 
Messages
12
Hello,
I resume this topic because I have some problem with vitamin D supplments, both liquid and chewable forms.
I take 1000 u.i. per day to recover low-normal levels, I take in the morning but after 3-4 hours I feel:
-fasciculation
-inner tension
-tachycardia
-insomnia (at night)
-wake up with overactive mind in the night (I feel like I have no more control on my thoughts, I had also a panic attack).

All this symptoms disappear whenever I quit this vitamin.
What's wrong with me?
 

SwanRonson

Senior Member
Messages
300
Location
Alabama
Messages
12
https://drruscio.com/how-to-determine-what-your-optimum-level-of-vitamin-d/

There’s nothing wrong with you most likely. I have this reaction too. Listen to this podcast. The bottom line is you don’t want to supplement vitamin d based solely on a 1,25OHD test. You also need to test parathyroid hormone at the same time. Your body may have equilibrium at your current level and supplementing is messing that up.

My parathormone is normal.
This is my results, seems I have not tested 1,25OHD.

zso5fo.jpg
 

pamojja

Senior Member
Messages
2,393
Location
Austria
1,25(OH)D is the active vitamin D in serum, since it greatly fluctuates it usually isn't used to evaluate stores.
25(OH)D is the storage form of vitamin D in serum, due to it's less fluctuations it's considered more dependable.

Doesn't means that 1,25(OH)D couldn't give additional insight. For example it can be particularly high in states of inflammation.
 

SwanRonson

Senior Member
Messages
300
Location
Alabama
I wrote 1,25OHD meaning total D3. Sorry for the confusion. If parathyroid is within normal range I wouldn't supplement without doing more research. That podcast is a good place to start. You could have hereditary reasons for a lower D3. You really just might not need it.

IMO, supplementing D3 is sort of a brute force tactic. It's not the way your body typically handles that. Sort of like ingesting insulin. It works, but it's going to have side effects.
 

pamojja

Senior Member
Messages
2,393
Location
Austria
Thanks but I also take 100MG per day of magnesium, I don't know if it's enough...

Since you only take 1000 IU ..maybe.

I took about 8000 IUs now for 9 years, and despite getting Magnesium 600 mg from diet and supplementing still much more, I still developed from a subclinical to a very severe Mg-deficiency (very pain-full muscle-cramps). Which I couldn't correct with orally anymore (now on 1.6 g/d of elemental Mg since 9 years). But finally needed Mg-sulfate IVs to correct.

Sort of like ingesting insulin. It works, but it's going to have side effects.

Such side-effects could be prevented though. And the comparison to insulin is very distorting. Insulin only works at increasingly higher doses. With vitamin D once body stores are filled not only less is needed to maintain, but I found the production through sun-light/skin which didn't work for me before, now does what it should. Raising levels.
 

NilaJones

Senior Member
Messages
647
You could try using a special light bulb to produce vitamin D, instead of oral supplements. They market them for lizard owners, because lizards need them. They're pretty cheap. I use one.
The UV light n't good for your eyes, and I find it all so unpleasant for my eyes. The lamp is only warm, not hot, so I just stick it under the blankets next to my bare skin. That way it gets on my skin but not my eyes. The warmth feels good too, in the winter.
My parathormone is normal.
This is my results, seems I have not tested 1,25OHD.

zso5fo.jpg