Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Aggressive VitD Level Recommendations

Postby Squeakycat » Thu Sep 05, 2013 6:54 am

Quite aggressive recommendations compared with other standards:

Target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/24002961
PMID: 24002961
Journal Title: Endokrynologia Polska
Journal Date: 2013
Journal Issue: 4
Journal Volume: 64
Journal First Page: 319-27
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2400 ... t=abstract
Article Title: [Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency].
Article Authors: Paweł Płudowski,Elżbieta Karczmarewicz,Milan Bayer,Graham Carter,Danuta Chlebna-Sokół,Justyna Czech-Kowalska,Romuald Dębski,Tamas Decsi,Anna Dobrzańska,Edward Franek,Piotr Głuszko,William B Grant,Michael F Holick,Liudmila Yankovskaya,Jerzy Konstantynowicz,Janusz B Książyk,Krystyna Księżopolska-Orłowska,Andrzej Lewiński,Mieczysław Litwin,Szimonetta Lohner,Roman S Lorenc,Jacek Lukaszkiewicz,Ewa Marcinowska-Suchowierska,Andrzej Milewicz,Waldemar Misiorowski,Michał Nowicki,Vladyslav Povoroznyuk,Piotr Rozentryt,Ema Rudenka,Yehuda Shoenfeld,Piotr Socha,Bogdan Solnica,Mieczysław Szalecki,Marek Tałałaj,Szabolcs Varbiro,Michał A Zmijewski

Endokrynol Pol. 2013;64(4):319-27.
[Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency].

[Article in Polish]
Płudowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sokół D, Czech-Kowalska J, Dębski R, Decsi T, Dobrzańska A, Franek E, Głuszko P, Grant WB, Holick MF, Yankovskaya L, Konstantynowicz J, Książyk JB, Księżopolska-Orłowska K, Lewiński A, Litwin M, Lohner S, Lorenc RS, Lukaszkiewicz J, Marcinowska-Suchowierska E, Milewicz A, Misiorowski W, Nowicki M, Povoroznyuk V, Rozentryt P, Rudenka E, Shoenfeld Y, Socha P, Solnica B, Szalecki M, Tałałaj M, Varbiro S, Zmijewski MA.
Source

p.pludowski@czd.pl.

Abstract

INTRODUCTION:

Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolismas well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activityappear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest thatVitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conferencefocused on overcoming Vitamin D deficiency.

METHODS:
After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses on recommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to Scientific Committee members of the 'Vitamin D - minimum, maximum, optimum' conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting 'Vitamin D - minimum, maximum, optimum' was held on October 19-20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists' voting were reviewed and discussed during eight plenary sessions and two workshops.

RESULTS:
Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges ofserum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20-30 ng/mL(50-75 nmol/L)], and target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]. General practical guidelines regarding supplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, children and adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed.

CONCLUSIONS:
Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementation guidance and population strategies for Vitamin D in Central Europe.

PMID:
24002961
[PubMed - in process]
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Advertisement

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Fri Sep 06, 2013 4:48 pm

The finding that vitamin D3-mediated protection in experimental autoimmune encephalomyelitis (EAE) is estradiol dependent suggests that declining vitamin D3 supplies due to sun avoidance might be contributing to the rapidly increasing female gender bias in MS.

"Estrogen Controls Vitamin D3-Mediated Resistance to Experimental Autoimmune Encephalomyelitis by Controlling Vitamin D3 Metabolism and Receptor Expression1
Faye E. Nashold * , Karen M. Spach † , Justin A. Spanier * and Colleen E. Hayes 2 , *
+ Author Affiliations

*Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI 53706; and
†Department of Immunobiology, College of Medicine, University of Vermont, Burlington, VT 05405


Abstract

Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease with a rapidly increasing female gender bias. MS prevalence decreases with increasing sunlight exposure, supporting our hypothesis that the sunlight-dependent hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is a natural inhibitor of autoimmune T cell responses in MS. We found that vitamin D3 inhibited experimental autoimmune encephalomyelitis (EAE) in intact female mice, but not in ovariectomized females or males. To learn whether 17β-estradiol (E2) is essential for vitamin D3-mediated protection, ovariectomized female mice were given E2 or placebo and evaluated for vitamin D3-mediated EAE resistance. Diestrus-level E2 implants alone provided no benefit, but they restored vitamin D3-mediated EAE resistance in the ovariectomized females. Synergy between E2 and vitamin D3 occurred through vitamin D3-mediated enhancement of E2 synthesis, as well as E2-mediated enhancement of vitamin D receptor expression in the inflamed CNS. In males, E2 implants did not enable vitamin D3 to inhibit EAE. The finding that vitamin D3-mediated protection in EAE is female-specific and E2-dependent suggests that declining vitamin D3 supplies due to sun avoidance might be contributing to the rapidly increasing female gender bias in MS. Moreover, declining E2 synthesis and vitamin D3-mediated protection with increasing age might be contributing to MS disease progression in older women."
http://www.jimmunol.org/content/183/6/3672.long
User avatar
NZer1
Family Elder
 
Posts: 1504
Joined: Thu Feb 18, 2010 4:00 pm
Location: Rotorua New Zealand

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 06, 2013 5:32 pm

NZer1 wrote:Thanks Ed,
it appears that the immune system over-activation or 'auto-immune' activation in 'MS' is only a problem when the cytokine numbers are excessive to the task. If the immune system is over active or the volume is in excess the symptom effect is a mirror of 'MS' symptoms. It appears that when Stealth Bacteria have infected and then inflammation occurs they have also modified their DNA and the host cells DNA are modified to avoid detection. So in essence the immune system is flooding the body looking for an inflammation cause or target but unable to identify it.
So this over production of cytokines plus macrophages, monocytes etc are all causing more trouble than the bacteria in regard to symptoms.
Having an over activated immune system due to Vit D supplementation may not be the ideal goal.
Nigel,
Vit D works both sides of this equation. It stimulates the local immune response, but it also controls it, turns it off when the situation is under control.

The immune system evolved in a hostile environment and as a result, does at time cause more damage than good by "over-reacting" to the problem, causing more damage than whatever provoked the immune system response.

But it is important to understand that vitD both activates and inactivates the immune response.

Further, if "stealth" bacteria are in fact evading the immune system, you still need an immune response, eventually, to clear up things after they die off, what you call "detoxing" is a crucial role of the immune system.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 06, 2013 5:36 pm

NZer1 wrote:To address this bacterial problem it has to be a progressive multi-targeted approach that is not seeking a rapid kill because of the added complications of endo-toxin production because as the bacteria die they produce mostly ammonia and then are recycled and detoxed from the body. There is also the added complication of the host cells dying if the bacteria are intracellular.
So this is a confusing situation where Dr's assume that the worsening of the patient is reason to stop treatment when it is more a task of adjusting the treatment to suit the patients coping with the Herx-Hiemer die off, the de-toxing and the secondary Porphyria issues when the mitochondria are not completing their ATP production and that can also produce toxins and side effects.
Nigel,
Again, it is important to realize that vitD directs the immune response that cleans up all the dead bacteria and cells they have damaged. You need vitD to do that.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 06, 2013 5:41 pm

NZer1 wrote:Some more insights from a 'sceptic' of Vit D supplementing due to knowledge!

OK, so let me start with a riddle… We all know that there is a layer of Cholesterol under our skin that when activated by the Sun gets converted into Hormone-D… right? Well, here’s the riddle: How is it that as Americans we have the HIGHEST levels of Cholesterol, and at the same time also have the LOWEST levels of Vit-D on this Planet?!?… Doesn’t make sense, does it? Actually it makes perfect sense, let me explain… (And no, it doesn’t have anything to do with exposure to Sun.)
Nigel,
Simply not true. VitD levels in the US are NOT the lowest on this planet. I assume the rest of this nonsense is equally well grounded in misinformation.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 06, 2013 5:59 pm

NZer1 wrote:Some more insights from a 'sceptic' of Vit D supplementing due to knowledge!

In my humble opinion, Vit-D is the most misunderstood, but over-recommended supplement on the Planet. What is worth noting is that it is, in fact, a Hormone — not a Vitamin, and it is also the FIRST hormone to exist on Planet Earth. Hmmmm. So it’s been around for hundreds of millions of years, we as a species have co-existed with this Hormone for at least 6 million years, and NOW, all of a sudden in the last decade, it has become a crisis of Biblical proportions. Forgive me, but I’m not buying it. Why? Because very few practitioners have taken the time to fully understand exactly HOW this Hormone works or is metabolized in the Human Body.
Nigel,
It is very true that in the past few years, research on vit D has grown enormously. I get on average alerts on over 20 new papers a day. That wasn't the case even three years ago.

We evolved to take advantage of things that are abundant in our environment: Water, air, sunlight, and minerals such as calcium. If we evolved with dependence on things that were not widely available, we probably would have died out.

We also have a lot of evidence that as human life has changed, we have suffered as a result of the lack of exposure to sunlight. As the industrial revolution took hold, there was an epidemic of rickets because we went from an agrarian environment of ample solar exposure to life in cities where people got much less solar exposure.

I think it can be argued that the advent of TV, video games and computers has probably caused us to have even less solar exposure, especially with dermatologists running around screaming about the dangers of solar exposure. I think it safe to speculate that will probably mean a "new" series of health threats.

What I'm suggesting is that you don't have to know the details of how vit D works to know that a species that evolved with solar exposure that is not getting that exposure is likely to have problems. We didn't evolve living underground or as nocturnal creatures living out of the sun. That tells me that vit D is critical to life whether we know the details of how it works or not.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 06, 2013 6:13 pm

NZer1 wrote:Some more insights from a 'sceptic' of Vit D supplementing due to knowledge!

Given that Vit-D is a Hormone, it’s worth noting that ALL Hormones have a Target Cell and a Target Mission. Vit-D’s Target Cells are the Intestines, and its Target Mission is to have the Intestines ABSORB MORE CALCIUM AND PUT IT INTO THE BLOOD STREAM, AT THE EXPENSE OF MAGNESIUM ABSORPTION… So here’s what that famous blood test is ACTUALLY telling us: the blood test is measuring STORAGE Vit-D (Calcidiol) and it seems that everyone in America is now LOW… Why? Because the body in its innate wisdom KNOWS that there is TOO MUCH CALCIUM in the blood, so it is keeping the Storage Vit-D level low for two reasons: 1) there’s too much Calcium already in the blood; and 2) there’s not enough Magnesium to flip the Storage-D into Active-D. They are flip-sides of the same coin… And how do I know this empirically? I’ve witnessed very same dynamic on hundreds and hundreds of Hair Tissue Mineral Analysis tests on clients.
Nigel,
This utter nonsense. Vit D is in every cell in the body. It controls the adaptive immune response, among other things. The active form can be completely produced (given the raw materials) in a cell that needs vit D without liver or kidney metabolism.

And not everyone in America has low levels of 25(OH)D as is being asserted. The level of bioactive vit D is strictly controlled. It doesn't matter how much sun exposure or Vit D3 you take. The level of calcitriol is strictly regulated to the amount needed by the body, assuming there enough precursors to create it. You can take hundreds of thousands of international units of calcitriol and the level will return to normal, highly regulated levels in a matter of hours.

I don't know where your source here is getting his or her information, but it shows a fundamental lack of knowledge of vit D and if this is what's informing your views on the subject, you need a much more informed source of information.

I would suggest as a starting point, some of Dr. Michael Holick's work including his books aimed at the public.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 06, 2013 6:27 pm

NZer1 wrote:Some more insights from a 'sceptic' of Vit D supplementing due to knowledge!

Right about now, you’re likely getting a headache… forgive me for that. Sometimes, the truth hurts. So when I here about all the wondrous things that “Vit-D” does, I immediately get suspicious. High doses of Vit-D, again — a very strong Hormone, puts significant demands on the Magnesium stores of our body to convert it to its Active status. And like any strong Hormone, it does have an impact, but there is also a heavy price to pay for it. Mildred S. Seelig, MD, one of the world’s greatest authorities on Magnesium, regarded excess Vit-D supplementation as a noted DRAIN on Mg status. And far too many “studies” on Vit-D measure Storage Vit-D levels (Calcidiol), and then in the course of those same “studies,” administer Active Vit-D as a treatment. In the Hospital setting, this is called “clinical science,” at a Carnival it is called “Bait & Switch…”
Nigel,
Right about now I am getting a severe headache. Your source is so misinformed that it hurts.

Calcitriol levels are not a function of the intake of Vit D3. They are a function of the need for calcitriol. Your body will not increase the levels of calcitriol beyond the need regardless of how much time you spend in the sun or how many vit D3 you take. Even if you take calcitriol in huge amounts, it quickly reverts to a normal level based on need.

If you are deficient, levels will increase and that will have an impact on magnesium.

But your body limits the production of active vit D, calcitriol, from sun exposure to the equivalent of 20,000 IU a day (unless you are pregnant or have other needs for vit D) regardless of how much time you spend in the sun. Ditto with vit D supplements.

Enough. I hope I have convinced you that your source of information on vit D is extremely deficient! Read some of Dr. Holick's work. He discovered calcitriol and has studied vit D for 40 years. He actually knows something about the subject, unlike your source.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 06, 2013 6:39 pm

PointsNorth wrote:Hello I thought I'd chirp in. After taking an Organic Acids Test for D levels + much more I found out I was low in vitamin D. I was supplementing 6000iu/day (2 years). I have now increased to 10,000iu/day. I question how much we can take from serum levels. I think that a number of us have malabsorption/transport issues that leave us short of much.
PN,
I think there is considerable evidence that people with disorders such as MS probably do have problems with the absorption and transport of vit D.

There is also the question of whether low levels are the result of the disease process, ie, a higher demand for vit D by the body. This was suggested in one small study which showed that vit D levels decrease as people go from Clinically Isolated Syndrome to clinically diagnosed MS.

The easy way to find out if you have any of the genetic issues that effect how vit D is absorbed, converted or transported is to take adequate levels of vit D and see if this increases your level of 25(OH)D. If it doesn't, then further investigation at a genetic level would be warranted. No point though in doing expensive genetic testing before finding out if there is a problem.

A good guide to what levels of supplementation are needed to achieve different levels of 25(OH)D is provided by the group Grassroots Health. There is a table on their home page.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

New Calcitriol Study ARGH(_)&*&^%*$&^#$

Postby Squeakycat » Wed Sep 18, 2013 8:49 am

New study, Bo, et alia, concludes that calcitriol (1,25(OH)2D3) could be useful in MS, but states that it is "currently avoided to use in patients because the doses needed to achieve therapeutic efficacy is accompanied by hypercalcemia."

Then therapy aimed at reducing TLR8 expression or activation could be developed to treat inflammatory neurological diseases including MS. Regarding the systemic 1,25(OH)2D3 therapy of multiple sclerosis, it is currently avoided to use in patients because the doses needed to achieve therapeutic efficacy is accompanied with hypercalcemia, which is an unacceptable side effect [34].
But that is NOT what the study they cite found. It found there was a problem when patients did not follow the study dietary guidelines, PERSISTENTLY failed to follow them!

Results: Two patients 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.
In fact, the conclusion of the cited study was:
Oral calcitriol is safe and well tolerated for up to one year by diet compliant relapsing-remitting MS patients.
Calcitriol has been in use for over 20 years to manage calcium levels in patients with chronic kidney disease.

A key aspect of high dose calcitriol treatment is to do pulse dosing, that is, instead of giving 1 unit per day, patients take 7 units once a week. (There are variations on the pulsing protocols, but they all come down to avoiding daily dosing.)

This was not done in the pilot study. The patients were given daily doses of calcitriol.
Treatment was initiated with oral calcitriol 0.5 mcg/d and the daily calcium intake limited to 800 mg. The calcitriol dose was increased in 0.5 mcg/d increments every two weeks (if serum calcium and the calcium–phosphorus product remained normal) to the target dose of 2.5 mcg/d.
(Note, 2.5 mcg of calcitriol is the equivalent of a 50,000 IU dose, 2.5 times more than typically used in the management of calcium by patients with kidney disease.)

Source URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597563/
PMID: 23516559
DOI: 10.1371/journal.pone.0058808
Journal Title: PLoS ONE
Journal Date: 2013
Journal Issue: 3
Journal Volume: 8
Abstract URL: http://www.ncbi.nlm.nih.gov/pmc/article ... t=abstract
Article Title: 1,25-Dihydroxyvitamin D3 Suppresses TLR8 Expression and TLR8-Mediated Inflammatory Responses in Monocytes In Vitro and Experimental Autoimmune Encephalomyelitis In Vivo
Article Authors: Bo Li, David J. Baylink, Chandra Deb, Claudia Zannetti, Fatima Rajaallah, Weirong Xing, Michael H. Walter, K.-H. William Lau, Xuezhong Qin

PLoS One. 2013; 8(3): e58808.
Published online 2013 March 14. doi: 10.1371/journal.pone.0058808
PMCID: PMC3597563
1,25-Dihydroxyvitamin D3 Suppresses TLR8 Expression and TLR8-Mediated Inflammatory Responses in Monocytes In Vitro and Experimental Autoimmune Encephalomyelitis In Vivo

Bo Li,1 David J. Baylink,1 Chandra Deb,1 Claudia Zannetti,2 Fatima Rajaallah,1 Weirong Xing,3 Michael H. Walter,1 K.-H. William Lau,1,3 and Xuezhong Qin1,3,*
Serge Nataf, Editor
Author information ► Article notes ► Copyright and License information ►
Go to:
Abstract

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) suppresses autoimmunity and inflammation; however, the mechanism of its action has not been fully understood. We sought in this study to determine whether the anti-immune/anti-inflammatory action of 1,25(OH)2D3 is in part mediated through an interplay between 1,25(OH)2D3 and toll-like receptor (TLR)7/8 signaling. 1,25(OH)2D3 treatment prior to and/or following experimental autoimmune encephalomyelitis (EAE) induction effectively reduced inflammatory cytokine expression in the spinal cord and ameliorated EAE. These effects were accompanied with a reduction in expression of several TLRs with the most profound effect observed for TLR8. The expression of TLR8 adaptor protein MyD88 was also significantly reduced by 1,25(OH)2D3. To determine the molecular mechanism by which 1,25(OH)2D3 suppresses EAE induction of TLR8 and inflammatory cytokine expression, we evaluated whether 1,25(OH)2D3 can directly inhibit TLR8 signaling and the resulting inflammatory responses in human THP-1 monocytes. 1,25(OH)2D3 treatment not only significantly reduced TLR8 expression but also the expression or activity of MyD88, IRF-4, IRF-7 and NF-kB in monocytes challenged with TLR8 ligands. TLR8 promoter-luciferase reporter assays indicated that 1,25(OH)2D3 decreases TLR8 mRNA level in part via inhibiting TLR8 gene transcription activity. As a result of inhibition on TLR8 signaling cascade at various stages, 1,25(OH)2D3 significantly diminished the TLR8 target gene expression (TNF-α and IL-1β). In summary, our novel findings suggest that TLR8 is a new target of 1,25(OH)2D3 and may mediate the anti-inflammatory action of 1,25(OH)2D3. Our findings also point to a destructive role of TLR8 in EAE and shed lights on pathogenesis of multiple sclerosis.


Source URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739797/
PMID: 16107372
DOI: 10.1136/jnnp.2004.056499
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 ... t=abstract
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

J Neurol Neurosurg Psychiatry. 2005 September; 76(9): 1294–1296.
doi: 10.1136/jnnp.2004.056499
PMCID: PMC1739797
A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing–remitting multiple sclerosis

D Wingerchuk, J Lesaux, G Rice, M Kremenchutzky, and G Ebers
Author information ► Copyright and License information ►
This article has been cited by other articles in PMC.
Abstract

Objective: To evaluate the safety and tolerability of oral calcitriol therapy in an open label pilot study.

Methods: 15 ambulatory patients with relapsing–remitting MS and at least one clinical relapse within the previous 12 months received oral calcitriol (target dose: 2.5 µg/d) for 48 weeks. Dietary calcium was restricted to 800 mg/d. Patients were monitored using frequent clinical and laboratory examinations, the expanded disability status scale (EDSS), and brain magnetic resonance imaging (MRI).

Results: Two patients 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. Diet compliant patients experienced mild adverse effects. The on-study exacerbation rate (27%) was less than baseline. Four patients experienced five clinical relapses but only one patient worsened by >1 EDSS point. Brain MRI revealed enhancing lesions in five patients at baseline (33%) and in four (29%) at both 24 and 48 weeks.

Conclusions: Oral calcitriol is safe and well tolerated for up to one year by diet compliant relapsing–remitting MS patients. Further study of vitamin D related mechanisms is warranted in MS.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Wed Sep 18, 2013 12:05 pm

Thanks Ed,
again this highlights the importance of Diet, yet they haven't elaborated!
And in my opinion the way that the study has structured the diet is even more important to the findings. If the researchers have a 'reason' for the diet structure then they have introduced a factor that is just as important as the Vit D3 and it means in my opinion that their conclusions are dubious. The pulsing is not 'mentioned' in the conclusion for some strange reason as well!
But then again I have the quality of Scepticism, and open mindedness when I read these outcomes.

"Conclusions: Oral calcitriol is safe and well tolerated for up to one year by diet compliant relapsing–remitting MS patients. Further study of vitamin D related mechanisms is warranted in MS."
User avatar
NZer1
Family Elder
 
Posts: 1504
Joined: Thu Feb 18, 2010 4:00 pm
Location: Rotorua New Zealand

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Wed Sep 18, 2013 12:48 pm

NZer1 wrote:Thanks Ed,
again this highlights the importance of Diet, yet they haven't elaborated!
And in my opinion the way that the study has structured the diet is even more important to the findings. If the researchers have a 'reason' for the diet structure then they have introduced a factor that is just as important as the Vit D3 and it means in my opinion that their conclusions are dubious.
Nigel,
The diet issue is the consumption of calcium that leads to hypercalcemia.

No effect is seen with dietary intake of up to 800 mg per day of calcium, but at these high doses of calcitriol, it did become a problem in 2 out of 11 cases.

The general proposition that a good diet is good for health is not addressed in this study. They were focused on the problem of hypercalcemia.

As you note, they do not mention pulse dosing at all. This may just be a repeat of what happens when neurologists evaluate veins instead of leaving that to vascular specialists.

They apparently did not talk to the nephrologists who have been using calcitriol for almost 30 years and at high doses, do pulse dosing. Sad.
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Wed Sep 18, 2013 2:05 pm

Squeakycat wrote:
NZer1 wrote:Thanks Ed,
again this highlights the importance of Diet, yet they haven't elaborated!
And in my opinion the way that the study has structured the diet is even more important to the findings. If the researchers have a 'reason' for the diet structure then they have introduced a factor that is just as important as the Vit D3 and it means in my opinion that their conclusions are dubious.
Nigel,
The diet issue is the consumption of calcium that leads to hypercalcemia.

No effect is seen with dietary intake of up to 800 mg per day of calcium, but at these high doses of calcitriol, it did become a problem in 2 out of 11 cases.

The general proposition that a good diet is good for health is not addressed in this study. They were focused on the problem of hypercalcemia.

As you note, they do not mention pulse dosing at all. This may just be a repeat of what happens when neurologists evaluate veins instead of leaving that to vascular specialists.

They apparently did not talk to the nephrologists who have been using calcitriol for almost 30 years and at high doses, do pulse dosing. Sad.


Interesting how these cherry picked changes and standards occur in studies, they don't consider the whole picture and effects such as GI are not considered. The data capture is very blinded!
The 'specialists' that design the study only speak about what they know from their field of interest and when they change factors unknowingly in another aspect by the study, they seem to not notice or acknowledge the effects and outcome.
Purely being in a study has a dramatic effect on the outcomes of the participants partly because they have attention and that extrapolates to how they want to perform.

Not really true science rather a business or marketing model of enquiry!

;)
Nigel
User avatar
NZer1
Family Elder
 
Posts: 1504
Joined: Thu Feb 18, 2010 4:00 pm
Location: Rotorua New Zealand

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Wed Sep 18, 2013 7:14 pm

NZer1 wrote:Interesting how these cherry picked changes and standards occur in studies, they don't consider the whole picture and effects such as GI are not considered. The data capture is very blinded!
The 'specialists' that design the study only speak about what they know from their field of interest and when they change factors unknowingly in another aspect by the study, they seem to not notice or acknowledge the effects and outcome.
Purely being in a study has a dramatic effect on the outcomes of the participants partly because they have attention and that extrapolates to how they want to perform.

Not really true science rather a business or marketing model of enquiry!

;)
Nigel
Bit harsh there, Kiwi Skeptic. :>)

Experiments require that you hold as many things constant as possible and examine the outcome on one or a few things. Each thing you want to measure adds to the cost of the research.

That then tells you whether the thing you are studying is changed.

If you toss everything into the pot, the costs would be unbearable, and you would probably not be able to see whether the change you were expecting occurred or not.

In drug development the hope is that all the external factors that you are unable to examine in the lab can be viewed when you reach the stage of doing clinical trials.

Of course, if you know of a source of unlimited funding for this broad based research that you call true science, I'm sure all the researchers will be happy to spend it. :>)
User avatar
Squeakycat
Family Elder
 
Posts: 375
Joined: Fri Dec 04, 2009 4:00 pm
Location: Yehud, Israel

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Wed Sep 18, 2013 8:41 pm

Reality is sometimes hard to swallow in a pill form Ed!

:
;)
Nigel
User avatar
NZer1
Family Elder
 
Posts: 1504
Joined: Thu Feb 18, 2010 4:00 pm
Location: Rotorua New Zealand

PreviousNext

Return to Chronic Cerebrospinal Venous Insufficiency (CCSVI)

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users