I reported on this study earlier
, but just got around to purchasing the article today as well as stumbled on a press release related to it which has a great summary:
- First, Hayes' team compared the effectiveness of a single dose of calcitriol to that of a comparable dose of a glucocorticoid, a drug now administered to MS patients who experience a bad neurological episode. Calcitriol came out ahead, inducing a nine-day remission in 92 percent of mice on average, versus a six-day remission in 58 percent for mice that received glucocorticoid.
- Next, Hayes' team tried a weekly dose of calcitriol. They found that a weekly dose reversed the disease and sustained remission indefinitely.
- But calcitriol can carry some strong side effects -- it's a "biological sledgehammer" that can raise blood calcium levels in people, Hayes says -- so she tried a third regimen: a single dose of calcitriol, followed by ongoing vitamin D supplements in the diet. This one-two punch "was a runaway success," she says. "One hundred percent of mice responded."
Source URL: http://www.sciencecodex.com/mouse_studi ... _ms-120144
Here is a citation of this study:
Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23968560
Journal Title: Journal of neuroimmunology
Journal Date: 6 Aug 2013
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2396
Article Title: One calcitriol dose transiently increases Helios(+)FoxP3(+) T cells and ameliorates autoimmune demyelinating disease.
Article Authors: Faye E Nashold,Corwin D Nelson,Lauren M Brown,Colleen E Hayes
This is IMPORTANT. Yes, it is a test in EAE and there are other reasons it may not work in humans. But it is the third in a series of studies of calcitriol in EAE and they are all finding the same thing: it reverse the active inflammatory state and puts EAE into remission.
This would be very easy to test in humans and I have been discussing doing a test with five medical professionals who have MS.
Calcitriol is inexpensive and has been in use in human medicine for close to 30 years. Its risks are well known and manageable. It is a prescription drug so it does require a prescription to use.
While it may not have the same effect in humans as it does in mice, I think a good case can be made that because there is an active inflammatory state in EAE, it may well work when there is a relapse in humans.
What I am discussing with the medical professionals is a limited test of calcitriol + vitamin D when there is a flare-up, an active inflammatory state. The protocol is a single, high dose of calcitriol followed by relatively high doses of vitamin D.
At the start of the test, we will look at the 25(OH)D level (plus kidney function and levels of calcium and phosphorus) and provide a single dose of vitamin D3 to increase it to at least 125 nmol/L (50 ng/ml) and then the single dose of calcitriol followed by weekly doses of Vitamin D3, tentatively set at one 50,000 IU dose which is 7,143 IU a day as long as the 25(OH)D level remains above 125 nmol/L. If the 25(OH)D level rises significantly, the dose will be lowered by, for example, only taking one 50,000 IU pill every other week.
Another aspect of a test of this in humans is that in this recent study and the two previous ones in mice, calcium was supplemented in addition to vitamin D3. In one of the studies, it was explicitly stated and tested and found that this ONLY works with calcium. Calcitriol alone was not effective long term without calcium supplementation. The level is somewhere between the 800 mg and 1,200 mg levels that are well under the safe upper limit and low enough to allow for some level of dietary intake of calcium and have frequently been used in test of high levels of vitamin D3.
I have an issue with the statement above that calcitriol "can carry some strong side effects -- it's a "biological sledgehammer" that can raise blood calcium levels in people . . ."
Yes, it can, but this can usually be controlled by administering a single weekly pulse dose, rather than taking it daily. This problem has been managed for at least 20 years by pulse dosing when relatively high doses are involved.
I'm particularly upset that the current Hayes study and several other recent studies on this all cite Wingerchuk as the basis for concluding that there is a grave danger of hypercalcemia with high doses of calcitriol. I have addressed this issue here
before, but because this keeps being thrown up, I want to point out once again that this is NOT what Wingerchuk says:
What the Wingerchuk study they cite actually found was that there was a problem when patients did not follow the study dietary guidelines, PERSISTENTLY failed to follow them!
Results: Two patients [out of 11] withdrew because of symptomatic hypercalcaemia (serum calcium >3.35 mmol/l in each case) resulting from persistent dietary indiscretion. Two diet compliant patients required temporary dose adjustments for mild asymptomatic hypercalcaemia.
Wingerchuk's conclusion is the opposite of what it is being cited as saying:
Oral calcitriol is safe and well tolerated for up to one year by diet compliant relapsing-remitting MS patients.
Source URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739797/
Journal Title: Journal of Neurology, Neurosurgery, and Psychiatry
Journal Date: September 2005
Journal Issue: 9
Journal Volume: 76
Journal First Page: 1294
Abstract URL: http://www.ncbi.nlm.nih.gov/pmc/article
Article Title: A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing–remitting multiple sclerosis
Article Authors: D Wingerchuk, J Lesaux, G Rice, M Kremenchutzky, G Ebers
In fairness to Hayes, the dose of calcitriol if translated into a human dose on the basis of weight is vastly greater than the dose used in Wingerchuk. Sadly, neither Hayes nor Wingerchuk explain how they came up with the doses of calcitriol they used in their studies.
I am hoping that Dr. Hayes will clarify this issue. Meanwhile, it seems appropriate in human testing to use a lower dose than she used in her mice, but one that is higher than the dose used by Wingerchuk and offset this with a higher daily dose of vitamin D3, administered in a weekly pulse dose. The higher vitamin D3 dose is still lower than the upper limit for vitamin D3 and pulsed, should not cause any problems in terms of hypercalcemia.
So, the hope is that we can do a limited test of this at the time of a relapse. We won't need to measure anything other than whether it stops the relapse, something that should be obvious and should happen in days as it does with methylprednisone which was found to be less effective in mice.
Hayes is quoted in the press release saying:
"It's my hope that one day doctors will be able to say, 'We're going to give you an oral calcitriol dose and ramp up the vitamin D in your diet, and then we're going to follow you closely over the next few months. You're just going to have this one neurological episode and that will be the end of it,'" says Hayes. "That's my dream."
We don't really have to wait years for a clinical trial in humans to be organized and funded. Since calcitriol and Vitamin D3 are already available, we can test this today and see whether it works as well in humans as EAE mice.
I am writing up a test protocol with safety procedures, pre-test blood work and proposed doses of calcitriol and vitamin D3. I think we should first test this with medical professionals who are better able to assess the risks involved and then, if we get positive results, provide the test protocol to anyone who thinks they can persuade their primary care physician or neurologist to write a prescription for the testing and calcitriol and monitor ongoing blood tests to ensure that there are no problems with hypercalcemia.