Poll for Vitamin D supplement tolerance and calcitriol levels

[picante]

I've tried most of the available forms of magnesium over the last 17 years (with the notable exception of magnesium threonate),

I've been taking Mg threonate for a couple of months. It definitely crosses the BBB. If I take it in the evening, I'm awake all night. I've never had anything else make me so thoroughly insomniac -- both times I've made this mistake, I've ended up reading through the wee hours.

 

[Art Vandelay]

Many years ago, my vit.D was quite low (around 30 nmol/L) but my 1,25 dihydroxy calciferol was extremely high (I don't have a copy of the results but my doc said it was triple what it should have been). Supplementing with vit.D always has made me feel awful so I was interested in other explanations as to why this is the case.

Olmesartan has been known to reduce 1,25 D, eg, https://www.chronicillnessrecovery....olmesartan-medoxomil&catid=1:general&Itemid=5

So, on 3 x 40mg of olmsartan per day, my levels dropped to 168 pmol/L. I recently increased my dose to 4 x 40mg per day and my 1,25 D is now 122.

In that time, my vit.D has actually increased to 43 even though I'm avoiding sunlight and dietary and supplemental forms of vit.D.

Since starting on Olmesartan, I've seen improvements in PEM, brain fog and pain in particular but it has made me very light sensitive and does make me Herx a lot.

 

[nandixon]

@Art Vandelay, thanks! Just doing a quick conversion, it looks like:

168 pmol/L = 71 pg/mL
122 pmol/L = 51 pg/mL

so calcitriol is nicely within range now, it seems.

I actually just started with another angiotensin receptor blocker (ARB), losartan, 3 days ago as an initial experiment. I know that olmesartan (Benicar) is the one that Marshall has recommended, but I wanted to see for myself what effect losartan might have.

I've started with just a quarter tablet (i.e., 12.5mg) per day of losartan since my blood pressure tends to run low normal (I take Florinef for low aldosterone) and I'm generally very sensitive to meds. Too early to tell if it's helping yet (no side effects so far).

Note: I was also a little worried about the pseudo-celiac disease problem associated with olmesartan that was discovered in the last few years. See, e.g., Olmesartan and Drug-Induced Enteropathy. Probably pretty low risk, though.

 

[Art Vandelay]

@Art Vandelay, thanks! Just doing a quick conversion, it looks like:

168 pmol/L = 71 pg/mL
122 pmol/L = 51 pg/mL

so calcitriol is nicely within range now, it seems.

I actually just started with another angiotensin receptor blocker (ARB), losartan, 3 days ago as an initial experiment. I know that olmesartan (Benicar) is the one that Marshall has recommended, but I wanted to see for myself what effect losartan might have.

I've started with just a quarter tablet (i.e., 12.5mg) per day of losartan since my blood pressure tends to run low normal (I take Florinef for low aldosterone) and I'm generally very sensitive to meds. Too early to tell if it's helping yet (no side effects so far).

Note: I was also a little worried about the pseudo-celiac disease problem associated with olmesartan that was discovered in the last few years. See, e.g., Olmesartan and Drug-Induced Enteropathy. Probably pretty low risk, though.

Yes, I agree that the risk of that pseudo-celiac problem is extremely low. I haven't come across anyone on the Marshall Protocol who has had that issue. From what I can see, the MP people claim that the celiac problem is actually caused by Herxing while taking too low a dose of olmesartan (they argue that higher doses will protect your organs from the immune activation) although I haven't seen any evidence to back this up.

Interested to hear that you're trialling Iosartan. I actually started the MP on candesartan (2 x 16mg per day from memory) because olmesartan wasn't available in Australia at that time. I got fairly significant Herxing and light sensitivity with it after about two weeks and it wasn't as protective as olmesartan (so the Herxes were quite unpleasant), so I'm really not sure what you can expect. Based on my experience, be cautious!

 

[picante]

Just doing a quick conversion, it looks like

Thanks for the conversion factor, Nandixon. I was looking for that.

 

[picante]

Re 1,25 D and the immune cells:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166406/

As antigen presenting cells (macrophages and dendritic cells), T cells and B cells have the necessary machinery to synthesize and respond to 1,25 D, vitamin D may act in a paracrine or autocrine manner in an immune environment. Moreover, local levels of 1,25 D may differ from systemic, circulating levels as local regulation of the enzymes synthesizing and inactivating vitamin D are different from the controls originating in the kidney. The extrarenal 1-α-hydroxylase enzyme in macrophages differs from the renal hydroxylase as it is not regulated by PTH[5]. Instead, it is dependent upon circulating levels of 25 D or it may be induced by cytokines such as IFN-γ, IL-1 or TNF-α[6]. Furthermore, the macrophage 24 hydroxylase enzyme is a non-functional splice variant, so there is no negative feedback of local 1,25 D production by 1,25 D.

This is slightly over my head (no idea what a non-functional splice variant is). The article is talking about an association between vit. D deficiency and autoimmune disease. That confuses me, because I thought there was a link between high calcitriol and autoimmune disease. Comments?

 

[nandixon]

@picante, thanks for the article. Yes, apparently a deficiency of vitamin D - as measured by 25-hydroxy D levels - might predispose to autoimmune disease. But then once an autoimmune disease is present, it can be associated with high calcitriol (1,25-dihydroxy D) levels.

Unfortunately for us, researchers seem to have been devoting all their energies to showing that vitamin D is good, which it is, of course, but everyone knows this by now. What needs to be studied more are the mechanisms behind why high calcitriol levels develop, which might help us gain better insight into our disease.

 

[alicec]

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 also, though when I was getting all the respiratory infections I was working and exercising and not otherwise sick. I first crashed about 15 years ago and by then the respiratory infections had pretty much disappeared. Since then I simply don't get colds or flus.

I have high 1,25 diOH D, tested for the first time maybe 10 months ago. I had been supplementing vit D3 for several years with no ill-effects based on very low 25 OH D. With the benefit of hindsight I presume the 1,25 diOH D would have been high (and the reason for the low 25 OH D) but I wasn't aware of that issue then and the doctor I was seeing was even more ignorant (recommending high levels of supplementation).

Of my own accord I had the 1,25 diOH D tested and found it was extraordinarily high - almost at toxic levels. I have taken no supplementary D since (and changed my doctor) and have been intending to have another test but haven't got around to it. I will do so soon. I didn't notice that stopping the D supplementation had any effect one way or the other.

With best wishes
Alice

 

[Avalon]

Hi guys,

I'm currently taking Vitamin D3 3000iu + K2 100mcg, its definitely helping with my insomnia although I have aching/buzzy legs on waking in the morning. My main concern is that after my morning dose of Vit D3, I can feel somewhat drugged /sedated for the day and making work difficult.

So I need to look at a number of indicators, does anyone know of labs that do a test bundle of 1,25diOHD, 25 OHD and calcium. What about parathyroid hormone.
I live in the UK, its seems very expensive here and was hoping may be one of the American labs would have an international service.

Thanks again.

 

[nandixon]

@Avalon, I've never seen calcitriol bundled with other tests here in the US. I think doctors would typically only order calcitriol if they'd found high calcium levels. (Calcitriol is a bit expensive as a single test here, too.)

I get identical negative effects, i.e., worsening of my fatigue/exhaustion, from supplementing both vitamin D and omega 3's in the form of fish oils/DHA/EPA. DHA is a natural ligand (activator) of the nuclear receptor called the retinoid X receptor (RXR). And the RXR and the vitamin D receptor (VDR) usually work together as a combined unit to elicit the effects of calcitriol.

So it might be expected that some people will feel bad from both vitamin D and DHA. I'm not sure but that might possibly give you some indirect indication as to your relative calcitriol levels. (And obviously high calcium can indicate a calcitriol problem as well, but my calcium is always mid-range despite high calcitriol and ill effects from supplementing vitamin D.)

 

[aquariusgirl]

Vitamin d Council might do some of those tests ..

 

[out2lunch]

Many years ago, my vit.D was quite low (around 30 nmol/L) but my 1,25 dihydroxy calciferol was extremely high (I don't have a copy of the results but my doc said it was triple what it should have been). Supplementing with vit.D always has made me feel awful so I was interested in other explanations as to why this is the case.

If your calcitriol is high, the feedback mechanism will keep your calciferol low.

Olmesartan has been known to reduce 1,25 D, eg, https://www.chronicillnessrecovery.org/index.php?option=com_content&view=article&id=306:benicarr-olmesartan-medoxomil&catid=1:general&Itemid=5

Thanks for the link. It's been years since I read about the Marshall protocol and the whole vitamin D conundrum.

So, on 3 x 40mg of olmsartan per day, my levels dropped to 168 pmol/L. I recently increased my dose to 4 x 40mg per day and my 1,25 D is now 122.

Whoa! That's a lot of ARB drug! What happened to your blood pressure?

In that time, my vit.D has actually increased to 43 even though I'm avoiding sunlight and dietary and supplemental forms of vit.D.

Again, that's to be expected with calcitriol levels dropping to the normal range as the VDR improves receptivity.

Since starting on Olmesartan, I've seen improvements in PEM, brain fog and pain in particular but it has made me very light sensitive and does make me Herx a lot.

If your immune system is improving, the herx increase would be expected.

Art Vandelay (I love that Seinfeld episode, btw), I have a couple of questions for you and anyone else who knows about or has done this treatment.

The Marshall protocol mainly uses olmesartan as a VDR agonist, which as you described, improved your calcitriol values. But olmesartan also reduces angiotensin II levels, which would be bad if those levels were already low.

Did your doctor test your angiotensin II before starting the olmesartan? And if so, was it elevated?

Here's a page about Benicar from the MP site: https://www.chronicillnessrecovery....olmesartan-medoxomil&catid=1:general&Itemid=5.

This section seems fairly straightforward and validates Art Vandelay's outcomes:

Our observations included:

1. Jarisch-Herxheimer reactions which indicate increased AMP transcription and elimination of intracellular bacteria provided the initial evidence of Benicar®'s agonistic effect on the VDR.

2. Up-regulation of the VDR by Benicar® is evidenced by a reduction in serum calcitriol following administration.

Benicar® is believed to decrease excess 1,25-D by several VDR-mediated effects. The up-regulated VDR:
• transcribes CYP24A1 and CYP3A4 (enzymes which reduce 1,25-D hydroxylation).
• represses CYP27B1 (the enzyme that hydroxylates 25-D to 1,25-D) so less 1,25-D is made.

Consequently, renal control of 1,25-D production is restored and extra-renal production of 1,25-D is reduced.

But this section is making my brain implode:

4. All ARBs block the effects of the pro-inflammatory hormone angiotensin II but Benicar® is the only ARB that reduces the serum level of angiotensin II, which causes inflammation in numerous disease states. Significantly, 1,25-D has a similar effect by repressing renin genetic expression to down-regulate the RAS and reduce angiotensin II.

Am I reading this correctly? Taking Benicar would reduce serum levels of angiotensin II? But it also reduces calcitriol which represses renin expression and reduces angiotensin II production.

In other words, the two counteract each other and blood pressure remains the same?

Is this your experience, Art Vandelay?

This seems so counterintuitive to me.

 

[Art Vandelay]

Whoa! That's a lot of ARB drug! What happened to your blood pressure?

Art Vandelay (I love that Seinfeld episode, btw), I have a couple of questions for you and anyone else who knows about or has done this treatment.

Did your doctor test your angiotensin II before starting the olmesartan? And if so, was it elevated?

In other words, the two counteract each other and blood pressure remains the same?

Hi @out2lunch glad to see a Seinfeld fan! The show has made me laugh through my illness

I'll try and answer your questions as best as I can (I'm not really medically-minded unfortunately). Hopefully someone else can come up with some answers also or you could try the MP forums.

My blood pressure levels did not change much on olmesartan. Prior to starting on the MP, they were probably slightly on the high side (but they jump around a bit). These days they are mostly normal. 4 x 40mg /day is considered a low dose of olmesartan these days. I've spoken to people on 6 x 40mg who haven't had problems and I take 5 x 40mg if I'm having a really tough day. Apparently olmesartan does not reduce blood pressure too much beyond the first 40mg (see the graph here). That being said, I heard of a few people having low blood pressure issues on the MP.

I will have to check with my doctor about my angiotensin II levels. My ACE levels are normal if that helps.

 

[Msinnott]

I didn't really fall into anything on the poll I use to be on high doses vit d made me feel worse the more I upped it. Got my levels checked vit d 25oh was 53 and vit d 1,25 was 147. I started weaning off vit d right away I had to slowly come off of it or my muscles locked up. It took 6 months for my active vit d to drop to 65 and I was feeling much better. then I accidentally took a supp with 4000iui of vit d and it didn't happen right away but I started getting really sick bad moods excessive thirst and urination. Realized it was the supp I was taking and I stopped this caused some major electrolyte imbalances and had to go to the er for dehydration and bp and hr were elevated. I didn't know why I was having such a reaction to a little bit of vit d. I mentioned this on one of my thyroid groups on Facebook they said it might be hyperparathyroid disease. I started getting worked up for it and it took a lot of testing over 5 months but I did have hyperparathyroid disease the vit d had masked it making my levels normal. It wasn't until my active vit d got below 60 that it started showing on my tests my ionized calcium came back high 1.36 (1.1-1.3) each time I tested it it was getting higher as my vit d was coming down. My pth was always normal range of 29 to 49. Same with my vit d it stayed in the low normal range. I finally had my surgery end of May 2015 I had two enlarged parathyroid glands most likely hyperplasia but my surgeon just says they looked normal just they were bigger by about 5 times the normal size. Now my calcium is normal ionized that is serum calcium is low normal and so is phosphate. I have had a bit of mild hungry bone syndrome since my surgery. I now have to take a lot of calcium still can't do too much vit d at the moment because when I do it drops my pth too much and then my calcium goes too low and I get numbness and tingling. Right now I am in the process of trying active vit d calcitriol so far I am not on a high enough dose to keep my calcium up enough. Still so glad I did this surgery I am getting a lot more good days in between the so so ones and I know once my Skelton is done remineralizing I will be doing so much better. I do believe this was what caused a lot of my autoimmune problems and chronic fatigue over the last 10 years.

 

[MeSci]

I don't know what my calcitriol levels are or were at any time, but had to stop taking Vitamin D3 earlier this year due to adverse effects. I recorded my symptoms as:

diarrhoea, burning after defecation, dyspepsia, abdominal pains, ‘adrenaline’ rushes, lower-back pain, polyuria and urinary tract irritation. Also had an alarming episode of unilateral numbness spreading from arm to face and vice versa, plus dizziness and very high blood pressure.

I have some of these symptoms anyway, but they were worse and/or more frequent.

The numbness and dizziness may have been due to a sub-migraine, which I have had a few times, and also had those symptoms with more-obvious migraines. I can't be sure that the symptoms were all due to D3, but they have improved since I stopped taking it.

There is an article here about 'Hypervitaminosis D', but I was only taking about 2250 iu a day in total, which most sources deem to be too low to cause Hypervitaminosis D.

I do think that my kidneys were affected, maybe due to hypercalcaemia.

 

[MeSci]

I don't know what my calcitriol levels are or were at any time, but had to stop taking Vitamin D3 earlier this year due to adverse effects. I recorded my symptoms as:

diarrhoea, burning after defecation, dyspepsia, abdominal pains, ‘adrenaline’ rushes, lower-back pain, polyuria and urinary tract irritation. Also had an alarming episode of unilateral numbness spreading from arm to face and vice versa, plus dizziness and very high blood pressure.

I have some of these symptoms anyway, but they were worse and/or more frequent.

The numbness and dizziness may have been due to a sub-migraine, which I have had a few times, and also had those symptoms with more-obvious migraines. I can't be sure that the symptoms were all due to D3, but they have improved since I stopped taking it.

There is an article here about 'Hypervitaminosis D', but I was only taking about 2250 iu a day in total, which most sources deem to be too low to cause Hypervitaminosis D.

I do think that my kidneys were affected, maybe due to hypercalcaemia.

'Fraid I'm getting some of these symptoms again - and no excessive Vitamin D - so maybe no connection.

 

[J.G]

All of my attempts to supplement Vitamin D ended in immediate failure. My GI tract does not take kindly to fat-solved supplements.

However, I do notice a sizeable positive effect of sun exposure on my energy levels and sense of general well-being/malaise. I haven't figured out exactly why.

One possibility is UV-B induced synthesis of Vitamin D, which has at least two known beneficial effects for PWME:
- Vitamin D [1,25] induces tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of dopamine [link]. The dopamine circuitry is known to be dysregulated in ME/CFS, its levels much below normal.
- As mentioned earlier in this thread: activation of the Vitamin D receptor stimulates enzyme CBS, and thus improves the degradation of Hcy to cysteine, and perhaps synthesis of GSH, via the trans-sulfuration pathway.

We also know that sun and/or light exposure and serotonin synthesis/release are linked, even if we don't understand exactly how. Serotonin levels are low in ME, sometimes (nearly) undetectable. This might be a factor as well.

It would be interesting to know whether PWME who don't tolerate D3 supplementation still benefit from regular sun exposure (or mimicry thereof via specific lamps). If there is indeed such a difference, I wonder what accounts for it.

 

[picante]

However, I do notice a sizeable positive effect of sun exposure on my energy levels and sense of general well-being/malaise. I haven't figured out exactly why.

Sun exposure also releases nitric oxide in the skin.

 

[brenda]

I can't take D because it sets my interstitial cystitis off but a summer of sun seeking has done me good and my OH is 90 whereas this time last year it was 70. I am feeling much better with the extra sun.

 

[J.G]

Sun exposure also releases nitric oxide in the skin.

Interesting. Did not know that. NO is pretty versatile actor, so that's quite a lead to chase down. Thanks