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!!!
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.