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all things vitamin D

Discuss herbal therapies, vitamins and minerals, bee stings, etc. here

Re: all things vitamin D

Postby Squeakycat » Thu Nov 07, 2013 2:23 pm

ribeye wrote:Hello,
Wondering how the human male dose for calcitriol and d3 regimen can be calculated. 400ng for a mouse would be how much for 100kg man. My GP is interested in this study and is willing to let me try it. He just wants a figure before dosing me.

Having a bit of a flare now and not a huge fan of prednisone.

Thanking all of you for this wonderful forum. Peace to all.


The equivalent human dose of D3 is 4,240 IU/day.

Also, the mice were given a loading dose of D3 aimed at raising their levels to 120 nmol/L (50 ng/ml). The formula for the loading dose is based on your current 25(OH)D3 level.

Loading dose in IU = 40 x (120 nmol - Current 25(OH)D3 level in nmol) x weight in kg

In addition to ascertaining your 25(OH)D3 level, it is important to ensure that kidneys are functioning properly based on BUN and Creatinine levels and that both calcium and phosphorous levels are within normal limits.

The body clears excess calcitriol within 6-8 hours.
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Re: all things vitamin D

Postby ribeye » Sat Nov 16, 2013 11:41 am

Has anyone tried a megadose of calcitriol yet? If I am able to get the go ahead, I will do it. A controlled study would be great but none on my radar so far. Also, what can someone expect to feel when dosed so highly. Is the MTD the absolute limit? Thanks for all of the great info.
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Re: all things vitamin D

Postby Squeakycat » Sat Nov 16, 2013 3:13 pm

ribeye wrote:Has anyone tried a megadose of calcitriol yet? If I am able to get the go ahead, I will do it. A controlled study would be great but none on my radar so far. Also, what can someone expect to feel when dosed so highly. Is the MTD the absolute limit? Thanks for all of the great info.

No one yet, that I know of, but a lot of eager volunteers.

The MTD is far from the absolute limit and it was tested in the context of a weekly dose at this level. In the study, the highest IV dose was 96 mcg, and some testing was done at 168 mcg orally. I'm still looking, but I know that in at least one cancer study, a dose over 300 mcg was tested and that study may have gone as high as 500 mcg.

In the dosing study, as far as I can tell from the study itself, the hypercalcemia was based on lab values, not clinical signs.

The effects of hypercalcemia are generally, nausea, vomiting, diarrhea (and constipation), muscle weakness, excessive thirst, frequent urination, fatigue and lethargy and mental confusion.

Calcitriol should clear the body within 6-8 hours and the standard treatment for hypercalcemia is to withdraw further doses. Since the protocol is a single dose, that is already done. Other treatment for hypercalcemia, usually induced by problems with the parathyroid glands include methylprednisolone, IV fluids, and loop diuretics such as furosemide.

Hoping to have some news on a formal trial soon. The main question is funding.
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Re: all things vitamin D

Postby Andrey » Sun Dec 15, 2013 4:10 pm

Is there any significant risk in trying the one dose of calcitriol and d3 regimen afterwards?

I have been taking d3 for almost a year daily (5.000-10.000 iu in the form of vit. d3 water based drops) having my blood checked for d3 and calcium/creatinin levels every 2-3 months. The d3 levels varied from 80 to 150 nmol... Currently yet I see no reasons change this regimen. So why not try to add one dose of calcitriol?

Theoretically, could I face significant risks if I have a dose of calcitriol and continue my "standard" d3 regimen? Maybe this single calcitriol dose will so much "enchance" current d3 regimen?! (who knows, maybe those mice are not the only lucky ones :) ) Or just don't do anything... Or?

Please share what do you think. What could be this "one dose" of calcitriol for a male of 80 kg? Calcitriol is avaliable here in the form of tablets (0.25 and 0.5 microgramms (one of those tablets come from the copaxone producer Teva :) )

If I understand correctly the worst scenario - is to see signs of hypercalciemia (to check for it I could have a bloodtest every 2 weeks for couple of months) and to quickly react accordingly (stopping d3 and lowering calcium intake), possibly having some positive outcome (like mice?? :) ) So WHY NOT?

Ideas and thoughts would be very helpful!!!

Andrey



P.S.
I perfectly realize that all this (if done) is under my own risk and I would not advise anyone to follow these ideas without a doctor's (at least a GP) instruction as there could be unpredictable adverse effects. These are all just hypothetical ideas.
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Re: all things vitamin D

Postby Squeakycat » Sun Dec 15, 2013 5:26 pm

Andrey wrote:Is there any significant risk in trying the one dose of calcitriol and d3 regimen afterwards?

I have been taking d3 for almost a year daily (5.000-10.000 iu in the form of vit. d3 water based drops) having my blood checked for d3 and calcium/creatinin levels every 2-3 months. The d3 levels varied from 80 to 150 nmol... Currently yet I see no reasons change this regimen. So why not try to add one dose of calcitriol?

Theoretically, could I face significant risks if I have a dose of calcitriol and continue my "standard" d3 regimen? Maybe this single calcitriol dose will so much "enchance" current d3 regimen?! (who knows, maybe those mice are not the only lucky ones :) ) Or just don't do anything... Or?

Please share what do you think. What could be this "one dose" of calcitriol for a male of 80 kg? Calcitriol is avaliable here in the form of tablets (0.25 and 0.5 microgramms (one of those tablets come from the copaxone producer Teva :) )

If I understand correctly the worst scenario - is to see signs of hypercalciemia (to check for it I could have a bloodtest every 2 weeks for couple of months) and to quickly react accordingly (stopping d3 and lowering calcium intake), possibly having some positive outcome (like mice?? :) ) So WHY NOT?

Ideas and thoughts would be very helpful!!!

Andrey



P.S.
I perfectly realize that all this (if done) is under my own risk and I would not advise anyone to follow these ideas without a doctor's (at least a GP) instruction as there could be unpredictable adverse effects. These are all just hypothetical ideas.
The risks associated with calcitriol are minimal and well known, but the issue at the moment is to figure out what dose is needed in humans to have the same effect that it had in mice and then be sure there are no adverse effects of that dose in people with MS.

Calcitriol has a very short half life. It is used or degraded within 6-8 hours so any effect should be transient. But because the goal is to raise CNS levels, a high dose is required, though it may turn out that it isn't all that high compared with some doses that have been tested in people with cancer.

The target 25(OH)D3 level is 125 nmol/L.

Before taking a high dose of calcitriol, it would be important to ascertain that Calcium and Phosphorous levels are normal was well as kidney function (BUN and creatinine).

The risk of raising your 25(OH)D3 levels to one that has "significant" risk of hypercalcemia is minimal.

Without dose escalation testing, there really is no way to know what dose will have the same effect in humans as it did in the EAE mice. Calculations based on weight and surface area for the lowest dose to have effect in mice range from 10 mcg to 120 mcg, but there is simply no way of knowing whether either dose will have the same effect short of testing.

The good news is that because it is possible to measure the effect on immune cells, there is a quite objective way to directly measure the effectiveness within hours of the calcitriol dosing so a small, short dose escalation trial should quickly give us an answer to what dose is needed for effect. That can then be followed up with a larger trial to test the safety of that dose in pwMS. Again, the results will be known in days, not weeks or years.

These trials are currently being planned. As soon as the details are known, a budget will be put together and then we are going to have to raise money to get this testing done. Preliminary estimates are that it could easily be done for less than the cost of three people taking Gilenya, Tecfidera, or Tysabri for a year.
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Re: all things vitamin D

Postby Andrey » Sun Dec 15, 2013 7:07 pm

Maybe we need to ask some MS organization to make and fund such trial as soon as possible (or I hope they are doing that already) ! There should be some possibilites to accelerate this process not to wait years for the results... Doest need FDA approval :)

Even ccsvi was investigated a lot in the past couple of years and that was way more complicated and expensive...

Do you know what calciteiol+d3 regimen trials exist and where do they happen?
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Re: all things vitamin D

Postby Squeakycat » Sun Dec 15, 2013 7:19 pm

Andrey wrote:Maybe we need to ask some MS organization to make and fund such trial as soon as possible (or I hope they are doing that already) ! There should be some possibilites to accelerate this process not to wait years for the results... Doest need FDA approval :)

Even ccsvi was investigated a lot in the past couple of years and that was way more complicated and expensive...

Do you know what calciteiol+d3 regimen trials exist and where do they happen?
A small group of us have committed to fundraising through three existing organizations as soon as the design of a trial is finalized.

This should get us the fastest results. Applying to MS organizations will take a long time and there is no guarantee of getting funding for a trial like this.
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Re: all things vitamin D

Postby Andrey » Sun Dec 15, 2013 7:42 pm

Squeakycat,

It is really exciting to hear that so much is already being done!!! I really hope we'll see the results soon...

Thank you for such useful and informative replies!

Andrey
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D2 vs D3 Re: all things vitamin D

Postby jimmylegs » Sun Mar 02, 2014 10:58 am

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Re: all things vitamin D

Postby Andrey » Mon Apr 21, 2014 3:44 pm

Is there any news on the calcitriol+d3 treatment?

I wonder if anyone tried this "in real life". The first news was quite a while ago and there must be at least someone who tried it...

Instead of steroids at the onset (or together?) would be very interesting.

Or maybe this just did not show any use in humans despite results with mice...

What about trials? If anyone knows some info, would be very interesting to see.

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Re: all things vitamin D

Postby Squeakycat » Mon Apr 21, 2014 6:24 pm

Andrey wrote:Is there any news on the calcitriol+d3 treatment?

I wonder if anyone tried this "in real life". The first news was quite a while ago and there must be at least someone who tried it...

Instead of steroids at the onset (or together?) would be very interesting.

Or maybe this just did not show any use in humans despite results with mice...

What about trials? If anyone knows some info, would be very interesting to see.

Andrey

Plugging away at this. Four people that I know of have been doing empirical testing of the protocol. Here is a recent statement on the efficacy from one of the people who has tried it:
Pre-trial test wrote:The calcitriol absolutely works. And it most definitely should be used by neurologists to treat any MS attack. My personal experience was that for approximately six weeks after taking the calcitriol I had complete elimination of muscle spasticity and complete elimination of clonus. This followed the initial the fact which, to me, was akin to the "steroid high" I experienced from a course of IV Solu-Medrol. The quality of the experience, initially, was different from the anti-inflammatory effect of the steroids, as everything not only felt better, but everything actually worked better. My core control and balance improved dramatically, and my usual "bent-over" posture disappeared. Many many friends spontaneously commented on how much better I was walking. Over the past two weeks to clonus and spasticity are returning. The only side effect I experienced at 37.5 µg was a day of diarrhea.

Everyone who has tried this so far is male and all have progressive MS.

The problem with this testing is that we don't have a way to see if a dose is having the same effect in pwMS as was seen in mice. In the proper clinical trial, there will be several direct measures of that to determine a dose that is both safe and effective.

Professor Hayes has been swamped with teaching duties and unable to devote time to getting a clinical trial underway, but expects to be able to do this as soon as the semester ends.

What can be said so far is that there is clinically obvious effect above a certain dose in males with progressive MS. One person who is RRMS is waiting for a relapse to test the effect at that time in lieu of doing a course of Solu-Medrol.

Another thing that is standing out is that unlike what happens in mice where a single dose of calcitriol followed by daily dosing of Vit D3 was effective, it appears that the dose of calcitriol may have to be repeated periodically at least in male progressives. Since we don't actually know whether the dose level is adequate, this has to be taken for what it is, an observation based on a very small number of tests which are little more than stabbing in the dark to determine a dose.
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Re: all things vitamin D

Postby jimmylegs » Tue Apr 22, 2014 8:33 am

fyi re a familiar cofactor. blame anon for this ;D

fwiw, here are three of the first four google scholar results for a seach on zinc calcitriol:

Zinc modulates mononuclear cellular calcitriol metabolism in peritoneal dialysis patients
http://www.ncbi.nlm.nih.gov/pubmed/8731107
the effect of zinc on mononuclear cellular cytokine and calcitriol production is mediated through different pathways.

Zinc nutritional status modulates the response of 1,25-dihydroxycholecalciferol to calcium depletion in rats
http://europepmc.org/abstract/MED/16194 ... 1Mz4nwo.22
1,25(OH)2D increased in both groups, but was higher in the zinc-replete than the zinc-depleted group at the end of the experiment. ... We conclude zinc depletion diminishes the response of 1,25(OH)2D to calcium depletion in rats.

Zinc nutritional status modulates the 1,25-(OH)2D. Response in uremic rats
http://europepmc.org/abstract/MED/1819762
There was a significant effect of renal function, zinc nutritional status, and the interaction of these factors in accounting for differences in mean 1,25-(OH)2D levels.

not to mention:

Possible alterations of the in vivo 1,25(OH)2D3 synthesis and its tissue distribution in magnesium-deficient rats.
http://europepmc.org/abstract/MED/7669505
We found that magnesium deficiency produced a decrease of both the in vivo synthesis of 3H-1,25(OH)2D3 and the binding of the radioactive hormone to bone tissue.

Hypomagnesemia and the parathyroid hormone-vitamin D endocrine system in children with insulin-dependent diabetes mellitus: Effects of magnesium administration
http://www.sciencedirect.com/science/ar ... 760580486X
All patients were given magnesium orally (6 mg/kg daily of elemental magnesium) for up to 60 days. During treatment, serum magnesium, total and ionized calcium, intact PTH, calcitriol, and osteocalcin concentrations significantly increased, reaching control values. ... These data suggest that magnesium deficiency plays a pivotal role in altering mineral homeostasis in insulin-dependent diabetes mellitus.
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Re: all things vitamin D

Postby Anonymoose » Tue Apr 22, 2014 8:43 am

Hehe. Thanks jimmy. ;)

...and you have to watch competing micronutrients too!!
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Re: all things vitamin D

Postby jimmylegs » Tue Apr 22, 2014 8:50 am

so true!
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Estradiol, testosterone and calcitriol

Postby Squeakycat » Wed Apr 30, 2014 3:35 pm

Posting a link to two recently reported studies of estadiol and testosterone, under vitamin D because like calcitriol, the bioactive form of vitamin D, they are secosteroids and they interact. A complete guess, but I suspect that the benefits of both may well be linked to that interaction with calcitriol.

I posted details here.
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