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

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

Postby MarkW » Thu May 08, 2014 12:02 am

Squeakycat wrote:
THX1138 wrote:from minute 41 onward I talk about Vitamin D, and why I don’t like to see blood levels above 40.
- See more at: http://truttmd.com/who-the-heck-is-paul ... R6OZa.dpuf

There are a number of criticisms of the conclusions drawn by IOM from the NHANES all cause mortality data, particularly the emphasis on "increased levels of mortality" above various levels of 25OHD.
The one that I think is most relevant is that these are general population studies in most cases, not pwMS who may in fact require higher 25OHD levels as suggested by a number of studies which show lower rates of relapse from higher levels of 25OHD.....................
There are a number of other issues involved here. You can have high levels of 25OHD, but if conversion of 25OHD is blocked as Hayes has found in her EAE studies, then that level is irrelevant.

Thanks for your comments Ed. I add that THX1138 quotes one doctor from one study. You have the patience to give TiMS readers some of the many papers which show high vit D3 in blood is better for pwMS. This is the balance of probability rather than beyond doubt, which some posters expect.
I advise caution on your comment:
"You can have high levels of 25OHD, but if conversion of 25OHD is blocked as Hayes has found in her EAE studies, then that level is irrelevant". Hayes results did not test high circulating levels of D3 (above 200nmol/L). A biological system (mouse) is unlikely to 'block' the conversion of D3 to D3hormone completely, rather to reduce it. In time, I hope that studies will show that if we humans have vit D3 around 150nmol/L and then pulse with vit D3hormone (calcitriol), normal immune functioning is restored. My advice is to conduct 'proof of concept' trial in women with MS, which is a pharma industry approach. I realise that the Hayes team will take an academic approach as that is their mindset. The advantage of a 'proof of concept' study is that it probably yields quicker results. Speed is money in industry.
Thanks again for your patience on this thread.
MarkW
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Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby muse » Thu May 08, 2014 12:32 am

Mark,

if you would have done your homework properly you wouldn’t recommend supplementing with high dosages of a synthetic Hormone called Vitamin-D without testing for it properly in the first place because it’s DANGEROUS if the cause for someone's D-resistance is Mg-deficiency!
Please remember, more than 80% of the population in the developed world is Mg-deficient, which is a result of modern agriculture/greed/insanity => Mg-depleted soil, water and food but the amount of sunshine is still the same since Mio. of years.

Anyway, I wish you all the best with your human-D-experiment and that you don’t have to learn the truth about BASICS in biochemistry the hard way => totally calcification of your body tissue => developing of more chronic inflammation as you already suffering from => diseases like Alzheimer’s, breast & ovarian cancer in woman/testicle cancer in men, heart attack etc. & death.

And no, I’m not going to run in circles neither with you nor with neurologists, because I don't have time to waste and I want learn about the cause of my disease and how to treat it and not about how to cover up symptoms.
I’m already totally fed up with the “Autoimmune, Calcium & Cholesterol Lie” I don't need another one!!

I wish you all the best, honestly!
Arne

***************************************************************************

Readers of this thread, please ask for these 4 blood tests before you take insanely high dosages of a synthetic hormone called “Vitamin D” (synthetically derived sheep-skin oil exposed to UV-B light) as recommended by Mark.

The 4 basic blood tests are:

1. Magnesium RBC (amount of Mg in red blood cell and NOT in blood serum!)
2. 25(OH)D (Storage form of Hormone-D)
3. 1,25(OH)2D3 (Active form of Hormone-D)
4. "Ionized" Calcium blood test


If test No.1 is 6.0mg/dL (this is a sufficient amount of Mg in the body tissue needed for the production of "Vit.-D" because Mg-deficiency causes Vit.-D resistance/deficiency!) and test No.3 is low, and test No.4 is low too then and only then taking supplemental "D" (e.g cod-liver oil) would be advised.

Test No.2 it's essentially a distortion of reality because low "Calcidol" (storage form) is caused by to much Calcium in the blood, which means there is too little Mg in the blood. Much better to know is the true status of your active hormone and its mineral focus Calcium. Excess Calcium is the precursor to inflammation and more excess Calcium to Magnesium is the cause of hormonal imbalances, disease & death.


More about (Vitamin) Hormone D, Cholesterol, Calcium & Magnesium Connection
https://www.facebook.com/notes/arne-kaminsky/the-vitamin-hormone-d-cholesterol-calcium-magnesium-connection/10151844911511987.
"MS" doesn't exist! - CCSVI dx Nov.2009, 1. angio LVJ & RVJ June 2010, 2. angio RVJ April 2011, January 2012 2. restenosis, reversed after ~1 year intake of high dosage Magnesium only. ThisIsCCSVIinMS: http://tinyurl.com/nwy5x58
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby jimmylegs » Thu May 08, 2014 2:26 am

note from the above, the utility of serum mag as an indicator - even though both values are normal (and i would argue both are suboptimal at a minimum, and more accurately outright deficient as long as we disregard faulty normal ranges).
Determinants of vitamin D status in patients with hip fracture and in elderly control subjects13
http://ajcn.nutrition.org/content/46/6/1005.full.pdf
Sunshine score and dietary and biochemical data from 125 patients with hip fracture and from 74 elderly control subjects
............................................control subjects...........patients
Vitamin D intake (IU/d).....................114 ± 44...........116 ± 63
Magnesium (mmol/L).......................0.82 ± 0.07........0.76 ± 0. 12
25-hydroxyvitamin D (nmol/L)...........32.9 ± 13.6........18.5 ± 10.6
l,25-dihydroxyvitamin D (pmal/L)........105 ± 31..............79 ± 46

teasing out the 'sunshine score' element of this article, i note the following with interest:

control subjects with low sunshine scores have serum 25(OH)vitd3 levels averaging 24.3 ± 9.1 nmol/L, while patients with similarly low sunshine scores have MUCH lower serum 25(OH)vitD3 levels, averaging 13.3 ± 5.7 nmol/L... this despite the patients having slightly higher average vit d3 intake overall. the dynamic is repeated when you compare patients and controls with intermediate and high sunshine scores.

re cost concerns, comparison info:
http://www.lef.org/Vitamins-Supplements ... -Test.html just under $120
http://www.lef.org/Vitamins-Supplements ... -Test.html less than $20
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Thu May 08, 2014 3:45 am

MarkW wrote:My advice is to conduct 'proof of concept' trial in women with MS, which is a pharma industry approach. I realise that the Hayes team will take an academic approach as that is their mindset. The advantage of a 'proof of concept' study is that it probably yields quicker results. Speed is money in industry.
Thanks again for your patience on this thread.
MarkW

So far a handful of people have tested various doses of calcitriol. All are males with a progressive form of MS. All have seen positive changes which hold for approximately 3 months at which point they have taken a repeat dose of calcitriol.

Because these tests have been informal, we don't know whether they have effected the changes in the immune system that Hayes saw in her EAE mice.

Prof Hayes has been swamped with teaching duties and unable to put together a scientific panel to guide the clinical trials, but the aim is to do testing that provides quick results in terms of the required dose and then to look at efficacy over a longer timeframe. It is our hope that all the co-factors about which Muse and Jimmylegs have raised questions will be tested so that we have a basis for judging efficacy.
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Proof of Concept - Calcitriol Pulse

Postby MarkW » Tue May 13, 2014 4:16 am

Squeakycat wrote:
MarkW wrote:My advice is to conduct 'proof of concept' trial in women with MS, which is a pharma industry approach. MarkW

So far a handful of people have tested various doses of calcitriol. All are males with a progressive form of MS. All have seen positive changes which hold for approximately 3 months at which point they have taken a repeat dose of calcitriol.
Because these tests have been informal, we don't know whether they have effected the changes in the immune system that Hayes saw in her EAE mice.

Hello Ed,
There are two reasons for starting with females:
1-Ratio of pwMS is approx 3female:1male. So test in larger group.
2-Dosage of calcitriol in female mice was approx half that of males (Hayes study). Using females enables study to give a higher (more effective?) dose.

A proof of concept study must not vary the dose of calcitriol. Simply changing dose adds variables to your study. I suggest that subjects take 5000IU/day D3 as a start. Get their D3 levels, D3H and immune indicator levels measured weekly over several weeks, once stable, pulse with highest dose allowed of calcitriol (everyone gets same dose per kg). Then continue to measure D3/D3H/indicator as before. Report if any difference in D3/D3H/indicator level after pulse. Remember you are NOT concerned with symptoms of MS rather answer "does the xx/kg calcitriol pulse change the D3H/indicator level measured."
This is how basic a proof of concept study needs to be. I fear your study has too many variables. You have one big variable already - humans. If advising on this study I would exclude people with insufficient levels of co-factors from the study. Trying to supplement for any shortage just adds to your variables.
The proof of concept study (in pharma) addresses the question 'is this product viable???'. I realise this is not in the thinking of academics but needs to addressed. Otherwise you will spend many years trying to get meaningful results.
As an aside - CCSVI could be accepted as a method for increasing CSF flow by now. Rather than endless arguments about the cause of MS.
Sounds like you have uncovered a dosing interval for pulses by accident. I suggest pulses of calcitriol every 2 months to keep the beneficial effect in progressive MS.
Good luck with the study.
Kind regards,
Mark.
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Proof of Concept - Calcitriol Pulse

Postby Squeakycat » Tue May 13, 2014 5:00 am

MarkW wrote:Hello Ed,
There are two reasons for starting with females:
1-Ratio of pwMS is approx 3female:1male. So test in larger group.
2-Dosage of calcitriol in female mice was approx half that of males (Hayes study). Using females enables study to give a higher (more effective?) dose.

A proof of concept study must not vary the dose of calcitriol. Simply changing dose adds variables to your study. I suggest that subjects take 5000IU/day D3 as a start. Get their D3 levels, D3H and immune indicator levels measured weekly over several weeks, once stable, pulse with highest dose allowed of calcitriol (everyone gets same dose per kg). Then continue to measure D3/D3H/indicator as before. Report if any difference in D3/D3H/indicator level after pulse. Remember you are NOT concerned with symptoms of MS rather answer "does the xx/kg calcitriol pulse change the D3H/indicator level measured."
This is how basic a proof of concept study needs to be. I fear your study has too many variables. You have one big variable already - humans. If advising on this study I would exclude people with insufficient levels of co-factors from the study. Trying to supplement for any shortage just adds to your variables.
The proof of concept study (in pharma) addresses the question 'is this product viable???'. I realise this is not in the thinking of academics but needs to addressed. Otherwise you will spend many years trying to get meaningful results.
As an aside - CCSVI could be accepted as a method for increasing CSF flow by now. Rather than endless arguments about the cause of MS.
Sounds like you have uncovered a dosing interval for pulses by accident. I suggest pulses of calcitriol every 2 months to keep the beneficial effect in progressive MS.
Good luck with the study.
Kind regards,
Mark.

I won't be deciding what the scientists conducting these studies decide is the right approach.

But the initial goal is to find the dose that has the same effect on the immune system as calcitriol does in EAE. We can be fairly certain that this dose will vary between males and females and there may also be other relatively easily defined groups such as relapsing versus progressive or active flare up versus remission.

Since the goal is finding the right dose, the normal approach would be dose escalation (or de-escalation) to see what dose has effect.

One of the frustrations I have with a lot of the vitamin D studies is that you don't know what the 25OHD levels are at the start and to the extent that they vary greatly, a lot of the vitamin D in the trial simply goes toward attaining an effective level. It has always seemed to me that if you want to see effect, then everyone should be at roughly the same starting level of 25OHD and that those who fall below a presumed effective level (say 125 nmol/L) should be brought up to that level with a loading dose right at the beginning.

I also lament the focus on dose not level of so many studies. Surely it is the level that counts, not the amount each person needs to attain a level that has effect.

So it seems to me that the first goal is to find what dose of calcitriol has the desired effect on the immune profile, including whether that dose varies by sex or other well defined categorizations.

The second goal and likely a separate study is to find what level of vitamin D3 is necessary to maintain remission brought on by calcitriol as well as the question of whether it is necessary to repeat the calcitriol dose if D3 alone is insufficient to maintain remission.

Then, having determined what doses or levels of 25OHD are required, we do need to look at efficacy. Do the changes in the immune profile allow recovery of lost function? Over what time period? Which functions? It is one thing to see a change in the immune profile and something else entirely to see whether that has clinically beneficial effects in the treatment or management of MS. This study also necessarily has to run at least several years because changes will take time, not happen instantly.

We may be looking at this from slightly different perspectives. I agree completely that simplifying things is key to understanding how the independent variable (calcitriol and D3 doses) effect the dependent variable (change in immune profile). I think that correcting co-factor deficiencies eliminates them as variables and you seem to be saying that dealing with them complicates the study. The good news is that real expert scientists who have done lots of clinical trials of MS and vitamin D will decide that, not you or me. :lol:
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Re: Proof of Concept - Calcitriol Pulse

Postby MarkW » Tue May 13, 2014 8:33 am

Squeakycat wrote:I won't be deciding what the scientists conducting these studies decide is the right approach.............We may be looking at this from slightly different perspectives. I agree completely that simplifying things is key to understanding how the independent variable (calcitriol and D3 doses) effect the dependent variable (change in immune profile)...... The good news is that real expert scientists who have done lots of clinical trials of MS and vitamin D will decide that, not you or me. :lol:

I do not have the same confidence as you in the abilities of academics to design clinical trials which get us to a marketable solution, quickly. There is a significant difference between the approach that industry takes to clinical trials compared to academic research. I suggest that you only measure one variable (change in immune profile) and remove all other variables. This could done by giving all subjects a single dosage level of D3 (5000iu/day) but only using those subjects who have D3 above 125nmol/L and adequate co-factors after a period at this dosage. A single dose pulse (xx/kg) should be used, which could be reduced (de-escalated) in follow up trials. The time between pulses is set at a low period (maybe every month) so that this variable is eliminated.
I hope the academics designing the trial will seek advice from pharma. I have seen industrial pharma trial design, it gets you to a decision point more quickly than any academic approach. Hence I suggest the people spending money on this trial seek industrial pharma advice. It will be money well spent.
We will probably only get one shot at such a trial. Please ask the academic trial designers to use it carefully. :roll:
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby jimmylegs » Wed May 14, 2014 2:46 am

I think that correcting co-factor deficiencies eliminates them as variables and you seem to be saying that dealing with them complicates the study.
agree on both points. the thing with eliminating deficiencies is that it means your trial conditions are not representative of the average patient. ideally, you'd want to study real patients as well as identify optimal conditions. so, you could add a few nuances (read: time and money) to your study design.

using mag for a cofactor example, perhaps you'd obtain serum magnesium level before and after running d3 supplementation tests, and perhaps you would have a magnesium supplement group and a placebo group. then you could look at response to d3 doses and or combos across an array of serum mag ranges (using perhaps 2.2-2.3 mg/dL as a lower cutoff for mag sufficiency).
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Vit D in a sunny climate

Postby MarkW » Mon May 19, 2014 4:47 am

Happy reading.......................MarkW

Arq. Neuro-Psiquiatr. vol.72 no.2 São Paulo Feb. 2014
http://dx.doi.org/10.1590/0004-282X20130252

http://www.scielo.br/scielo.php?script= ... so&tlng=en

Guidelines
Supplementation and therapeutic use of vitamin D in patients with multiple sclerosis: Consensus of the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology

Doralina Guimarães Brum 1 , Elizabeth Regina Comini-Frota 2 , Claúdia Cristina F. Vasconcelos 3 , Elza Dias-Tosta 4
1Departamento de Neurologia, Psicologia e Psiquiatria, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu SP, Brazil;
2Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte MG, Brazil;
3Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ, Brazil;
4Hospital de Base do Distrito Federal, Brasília DF, Brazil.

ABSTRACT
Multiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating, and degenerative central nervous system disease. Even though the etiology of MS has not yet been fully elucidated, there is evidence that genetic and environmental factors interact to cause the disease. Among the main environmental factors studied, those more likely associated with MS include certain viruses, smoking, and hypovitaminosis D. This review aimed to determine whether there is evidence to recommend the use of vitamin D as monotherapy or as adjunct therapy in patients with MS. We searched PUBMED, EMBASE, COCHRANNE, and LILACS databases for studies published until September 9 th , 2013, using the keywords “multiple sclerosis”, “vitamin D”, and “clinical trial”. There is no scientific evidence up to the production of this consensus for the use of vitamin D as monotherapy for MS in clinical practice.

Key words: vitamin D; multiple sclerosis; experimental autoimmune encephalitis

The therapeutic use of vitamin D for treating multiple sclerosis (MS) is a controversial issue that is of interest to physicians, researchers, and patients. The Scientific Department of Neuroimmunology (DCNI) of the Brazilian Academy of Neurology (ABN) organized a meeting on September 12, 2013, to discuss the basic aspects of vitamin D metabolism, results of in vitro and experimental studies on experimental autoimmune encephalomyelitis (EAE), and controlled clinical trials of vitamin D in MS. Neurologists and researchers participating in the meeting approved a guideline consensus to guide Brazilian neurologists in the care of patients with MS.

VITAMIN D, MS, AND EAE
Vitamin D is an important hormone for calcium homeostasis and bone metabolism 1 . Besides its action in bone tissue, vitamin D has a role in cell differentiation, cell growth inhibition, and immune system modulation 2 . The main source of vitamin D is ultraviolet-B radiation (95%). However, no consensus has been reached on optimal serum vitamin D levels for human metabolic needs 3 , 4 . The association between vitamin D and autoimmune diseases and neoplasms has been established in recent years 5 , but this relationship has not yet been fully elucidated.
Multiple sclerosis is an inflammatory, autoimmune, demyelinating, and degenerative central nervous system (CNS) disease, whose geographic and ethnic distribution is characterized by a higher prevalence in northern hemisphere countries, particularly in populations of Caucasian origin 6 .
The predominantly temperate climate in the northern hemisphere with long periods of low solar radiation and the relatively high prevalence of hypovitaminosis D observed in population studies 7 have led to the hypothesis that this deficiency may explain the geographical distribution of MS. Moreover, it has been suggested that adequate serum levels of vitamin D could help reduce the risk of developing MS 8 , 9 .
Even though the etiology of MS has not yet been fully elucidated, there is evidence that genetic 10 , 11 and environmental 12 factors interact to cause the disease. Among the main environmental factors studied, those more likely associated with MS include certain viruses 13 , smoking 14 , and hypovitaminosis D 15 , 16 . The latter is particularly important in the northern hemisphere, where the seasonal variation and subsequent reduction in ultraviolet-B radiation in winter may lead to a higher prevalence of hypovitaminosis D. Some conditions represent risk of hypovitaminosis D in the general population such as long stay indoors, use of sunscreen, and skin pigmentation 17 , 18 . Motor limitations associated with later stages of MS may contribute to the occurrence of hypovitaminosis D in this group of patients 19 .
Unlike northern hemisphere countries, solar radiation in Brazil is believed to be plentiful in all seasons and regions to prevent hypovitaminosis D. Thus, the amount of sunlight one is exposed in Brazil should be enough to avoid hypovitaminosis D in healthy individuals when exposed to sunlight even for short periods. Nevertheless, no studies have compared serum vitamin D levels among Brazilian regions, whereas few studies have analyzed serum vitamin D levels in a selected risk group 20 .
Preliminary experimental studies have demonstrated an immunomodulatory role of vitamin D on human immune cells in vitro 21 , 22 and in an experimental animal model (EAE) 23 , 24 . An in vitro study with peripheral blood cells of patients on vitamin D therapy showed that serum levels above 40 ng/ml may exert modulatory action on immune cells 20 . Additional studies are underway to better understand this immunomodulatory effect on autoimmune diseases.
This review aimed to determine whether there is evidence to recommend the use of vitamin D as monotherapy or as adjunct therapy in patients with MS. We searched PUBMED, EMBASE, COCHRANNE, and LILACS databases for studies published until September 9 th , 2013, using the keywords “multiple sclerosis”, “vitamin D”, and “clinical trial”. Randomized controlled clinical trials with vitamin D in patients with MS were included in the analysis.

RANDOMIZED AND CONTROLLED CLINICAL TRIALS WITH VITAMIN D IN THE TREATMENT OF MS
To evaluate the therapeutic response of vitamin D in MS patients, we selected double-blind, randomized, controlled clinical trials from the literature 25 , 26 - 28 . These studies are still scarce and most were not designed to evaluate therapeutic response to vitamin D. Next, we discuss the most relevant studies.
A clinical study conducted in Finland 25 in 66 patients with relapsing-remitting multiple sclerosis (RRMS) compared a group with 34 patients using 20,000 IU/week of vitamin D and interferon beta-1b (IFNβ-1b) to another group with 32 patients using IFNβ-1b only. In that study, primary outcomes included tolerability and safety aspects, and number of new lesions and gadolinium enhancing lesions on MRI scans. Secondary outcomes included clinical parameters such as annual relapse rate and changes in the Expanded Disability Scale Score (EDSS), in addition to other imaging parameters. The authors observed that the treated group showed fewer new T2 lesions, but there were no significant differences in clinical parameters between the two groups after 12 months. However, there was a significant reduction in the number of gadolinium enhancing lesions in the vitamin D group.
Another study, conducted in Norway 26 , compared bone mineral density, relapse frequency, disease progression, and motor function measures between 35 patients with MS using 20,000 IU of cholecalciferol per week associated with 500 mg/day of calcium and a control group of 33 patients with MS using 500 mg/day of calcium only for two years 26 . Patients in both groups had been previously using immunomodulatory drugs (interferon beta or glatiramer acetate) for a similar period of time. No differences in annual relapse rate and changes in functional capacity measured by EDSS were observed between the two groups, even though vitamin D levels ranged from 24.72 ng/ml in the placebo group to 49.26 ng/ml in the vitamin D group. The study was not powered to address clinical outcomes 12 .
A phase II study developed in Iran 27 compared 25 patients with RRMS receiving the active form of vitamin D (calcitriol) at a dose of 0.25 µg/day with patients receiving placebo 27 . Both groups used conventional immunomodulators. There was no difference in the EDSS between the calcitriol and placebo groups after 12 months followup 13 . It should be noted in that study the small sample size and inclusion criterion of serum 25-hydroxyvitamin D level >40 ng/ml.
A randomized study in Australia 28 compared 11 patients with RRMS treated with vitamin D2 in a dose of 6,000 IU twice daily in addition to a daily low-dose (1,000 IU) with 12 patients receiving the 1,000 IU/day dose only 28 . The neuraxial index of inflammatory activity on MRI was compared between the high-dose and low-dose groups. No significant differences between the groups were detected.
A meta-analysis of the studies cited above detected no difference in the number of relapses between the groups 29 . The number of new lesions and gadolinium enhancing lesions were compared to serum vitamin D levels in other two studies and the findings were conflicting 26 , 30 . Limitations of the studies include different dosages and forms of vitamin D administered.
In contrast to epidemiological and experimental studies, randomized trials on the use of vitamin D in MS showed no significant differences in the parameters of disease activity – relapse rate, EDSS progression, and new or gadolinium enhancing lesions on MRI – between the group receiving vitamin D and groups receiving placebo or a smaller dose of vitamin D. These differences and other contradictions indicate the need to conduct double-blind, randomized, controlled trials in large groups of patients, considering the differences between clinical, neuroimaging, biological, and immunological variables, and powered to accurately estimate the therapeutic efficacy and possible side effects of vitamin D in MS.

VITAMIN D AND OTHER ISSUES
Normal range
The Institute of Medicine (IOM) and the American Society for Endocrinology advocate different levels of vitamin D to maintain bone health: ≥20 ng/ml and ≥30ng/ml, respectively 3 , 4 . There is no consensus on whether bone cells and immune cells require different levels of vitamin D. In addition to the lack of consensus on the normal range values for vitamin D, the toxic serum concentration and the concentration leading up to this condition are also controversial. In adults, doses greater than or equal to 10,000 IU/day are associated with hypercalcemia 31 , 32 .
High performance liquid chromatography (HPLC) followed by mass spectrometry is considered the gold standard for analysis of serum 25-OH vitamin D levels. However, the technique is laborious, expensive, and is not available in most Brazilian laboratories. Other methods such as chemiluminescence, enzyme immunoassay, and radioimmunoassay are also used. Thus, variability in results can occur depending on the assay used 33 . In Brazil, there is no efficient inter-laboratory validation system, which can also result in great variability in results. Moreover, certain medications such as anticonvulsants and corticosteroids may have a role in reducing serum levels of vitamin D.

SAFETY PROFILE
The safety profile of different serum vitamin D levels has been evaluated in an open, randomized study conducted in Canada 31 . In that study, a group of 25 patients with MS used escalating cholecalciferol (vitamin D3) doses up to 40,000 IU/day, whereas a second group of 24 patients used 4,000 IU/day. Patients in both groups used immunomodulators (interferon beta and glatiramer acetate) in combination with cholecalciferol. The maximum 40,000 IU/day dose was used for up to six months, followed by 10,000 IU/day for three months and gradual suspension over three months. Both groups received calcium (1,200 mg/day) throughout the trial, and serum calcium was determined. Serum 25-hydroxivitamin D (25-OH-vitamin D) reached a maximum mean above 250 nmol/l (100ng/ml) during the 40,000 IU/day dosing period. No hypercalcemia was detected during the 10,000 IU/day dosing period, even with serum levels ≥ 100 ng/ml, suggesting that that dose is safe (Class level II evidence). In addition, neither serum calcium nor parathormone urinary levels were altered, even when serum concentrations were higher. Further studies are needed to confirm these findings.

VITAMIN D – SIDE EFFECTS
Clinical picture of vitamin D intoxication may include signs and symptoms originating in different systems: nausea and vomiting, anorexia, abdominal pain, constipation; polydipsia, polyuria, dehydration, nephrolithiasis, nephrocalcinosis, nephrogenic diabetes insipidus, chronic interstitial nephritis, acute and chronic renal failure; hypotonia, paresthesia, confusion, seizures, apathy, coma; arrhythmia, bradycardia, hypertension, cardiomyopathy; muscle weakness, calcification, osteoporosis; and conjunctival calcification 34 - 36 . Hypercalcemia is the most important side effect, and when observed in the laboratory is suggestive of intoxication 37 .
During use of vitamin D, in addition to serum calcium, urinary calcium should be assayed periodically. Serum concentration of parathyroid hormone (PTH) should also be determined and must not exceed the lower reference values of normality indicative of suppression, which is a non-recommended condition 35 .

FINAL CONSIDERATIONS
Considering the body of information presented here, the DCNI/ABN defines the consensus that:
1. It is recommended to dose vitamin D in patients with clinically isolated syndrome and MS, regardless of the stage of disease, particularly those making frequent use of corticosteroids or anticonvulsivants.
2. Peripheral blood levels of vitamin D lower than 30ng/ml should be corrected in patients with MS, at any stage, or in patients with demyelinating isolated syndrome (grade D recommendation).
3. Peripheral blood levels of vitamin D higher than 100 ng/ml should be avoided until new guidelines are established (grade D recommendation).
4. There is no scientific evidence up to the production of this consensus for the use of vitamin D as monotherapy for MS in clinical practice . Therefore, currently, vitamin D monotherapy for MS is considered experimental. For its use in clinical trials, these must be approved by the Human Research Ethics Committee, regulated by the National Commission for Ethics in Research (CONEP), approved by the Regional Medical Board, and informed consent should be provided by patients.
5. According to data from in vitro studies with peripheral blood cells of patients using vitamin D, serum levels above 40 ng/ml are likely to cause modulating action on immune cells 17 . Based on that evidence, vitamin D supplementation at doses that maintain serum levels of patients between 40 ng/ml and 100 ng/ml may be recommended, as these are safe levels (grade D recommendation).
6. Considering the individual differences in replacement needs and serum levels of vitamin D, that a study in healthy subjects showed that 5,000 IU/day of vitamin D for 15 weeks increased serum levels up to 60ng/ml, and that doses up to 10,000 IU/day were considered safe, we recommend individualized doses until reaching serum levels between 40 ng/ml and 100 ng/ml (grade D recommendation).
7. Considering that low vitamin D serum levels in patients with isolated demyelinating syndrome could affect the relative risk of conversion to MS 16 , we recommend the analysis of serum vitamin D levels in those patients and that a correction is made whenever necessary (grade D recommendation).
8. Because vitamin D3 is a secosteroid hormone, its use should be escalated. Moreover, monitoring serum 25-hydroxivitamin D would be extremely important before increasing dosage to determine whether supplementation is actually effective (grade D recommendation).

We thank the contributors who performed critical review of the manuscript: Amilton Antunes Barreira, Danilo Lima Varela, Denis B. Bichuetti, Felipe von Glehn, Eduardo Antônio Donadi, Gutemberg Augusto Cruz dos Santos, Marcos Papais-Alvarenga, Maria Fernanda Mendes, Maria Cecilia Vecino, Maria Lúcia Vellutini, Paulo Pereira Christo, Thiago Faria Junqueira, Soniza Vieira Alvez Leon, and Yara Dadalti Fragoso (Fragoso, YD). We also thank the invaluable expert assistance of Paulo S. Moraes Júnior in using Microsoft Lync for support in the online meeting.

This manuscript was reviewed by a professional science editor and by a native English-speaking copy editor to improve readability.

References
1. . Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev 2005;10:94-111. [ Links ]
2. . Bikle DD. Vitamin D regulation of immune function. Vitam Horm 2011;86:1-21. [ Links ]
3. . Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metabl 2011;96:1911-1930. [ Links ]
4. . Rosen CJ, Abrams SA, Aloia JF, et al. IOM committee members respond to Endocrine Society vitamin D guideline. J Clin Endocrinol Metab 2012;97:1146-1152. [ Links ]
5. . Holick MF. Vitamin D: important for prevention of osteoporosis, cardiovascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers. South Med J 2005;98:1024-1027. [ Links ]
6. . Kurtzke J. A reassessment of the distribution of multiple sclerosis. Acta Neurol Scand 1975;51:137-157. [ Links ]
7. . Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc 2013;88:720-755. [ Links ]
8. . Goldberg P, Fleming MC, Picard EH. Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 1986;21:193-200. [ Links ]
9. . Martinelli V, Dalla Costa G, Colombo B, et al. Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Mult Scler 2013, Epub Ahead of Print [ Links ]
10. . Ebers GC, Bulman DE, Sadovnick AD, et al. A population-based study of multiple sclerosis in twins. N Engl J Med 1986;315:1638-1642. [ Links ]
11. . Sawcer S, Hellenthal G, Pirinen M, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476:214-219. [ Links ]
12. . Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood) 2004;229:1136-1142. [ Links ]
13. . Lucas RM, Ponsonby AL, Dear K, et al. Current and past Epstein-Barr virus infection in risk of initial CNS demyelination. Neurology 2011;77:371-379. [ Links ]
14. . Hedström AK, Sundqvist E, Bäärnhielm M, et al. Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis. Brain 2011;134:653-664. [ Links ]
15. . Ascherio A, Munger K. Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol 2008;28:17-28. [ Links ]
16. . Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832-2838. [ Links ]
17. . Maeda SS, Saraiva GL, Kunii IS, et al. Factors affecting vitamin D status in different populations in the city of Sao Paulo, Brazil: the Sao PAulo vitamin D Evaluation Study (SPADES). BMC Endocr Disord 2013;13:14. [ Links ]
18. . Libon F, Cavalier E, Nikkels AF. Skin color is relevant to vitamin D synthesis. Dermatology 2013;227:250-254. [ Links ]
19. . Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 2008;14:1220-1224. [ Links ]
20. . Arantes HP, Kulak CA, Fernandes CE, et al. Erratum to: correlation between 25-hydroxyvitamin D levels and latitude in Brazilian postmenopausal women: from the Arzoxifene Generations Trial. Osteoporos Int 2013;24:2899-2900. [ Links ]
21. . Kimball S, Vieth R, Dosch HM, et al. Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J Clin Endocrinol Metab 2011;96:2826-2834. [ Links ]
22. . Allen AC, Kelly S, Basdeo SA, et al. A pilot study of the immunological effects of high-dose vitamin D in healthy volunteers. Mult Scler 2012;18:1797-1800. [ Links ]
23. . Farias AS, Spagnol GS, Bordeaux-Rego P, et al. Vitamin D3 induces IDO(+) tolerogenic DCs and enhances Treg, reducing the severity of EAE. CNS Neurosci Ther 2013;19:269-277. [ Links ]
24. . Correale J, Ysrraelit MC, Gaitán MI. Vitamin D-mediated immune regulation in multiple sclerosis. J Neurol Sci 2011;311:23-31. [ Links ]
25. . Soilu-Hänninen M, Aivo J, Lindström BM, et al. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2012;83:565-571. [ Links ]
26. . Kampman MT, Steffensen LH, Mellgren SI, Jørgensen L. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Sclerg 2012;18:1144-1151. [ Links ]
27. . Shaygannejad V, Janghorbani M, Ashtari F, Dehghan H. Effects of adjunct low-dose vitamin d on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial. Mult Scler Int 2012;2012:452-541. [ Links ]
28. . Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology 2011;77:1611-1618. [ Links ]
29. . James E, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan SV. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Mult Scler 2013;19:1571-1579. [ Links ]
30. . Mowry EM, Waubant E, McCulloch CE, et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 2012;72:234-240. [ Links ]
31. . Gallo S, Comeau K, Vanstone C, et al. Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: a randomized trial. JAMA 2013;309:1785-1792. [ Links ]
32. . Burton JM, Kimball S, Vieth R, et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010;74:1852-1859. [ Links ]
33. . Roth HJ, Schmidt-Gayk H, Weber H, Niederau C. Accuracy and clinical implications of seven 25-hydroxyvitamin D methods compared with liquid chromatography-tandem mass spectrometry as a reference. Ann Clin Biochem 2008;45:153-159. [ Links ]
34. . Koul PA, Ahmad SH, Ahmad F, Jan RA, Shah SU, Khan UH. Vitamin d toxicity in adults: a case series from an area with endemic hypovitaminosis d. Oman Med J 2011;26:201-204. [ Links ]
35. . Zittermann A, Prokop S, Gummert JF, Börgermann J. Safety issues of vitamin D supplementation. Anticancer Agents Med Chem 2013;13:4-10. [ Links ]
36. . Ashizawa N, Arakawa S, Koide Y, Toda G, Seto S, Yano K. Hypercalcemia due to vitamin D intoxication with clinical features mimicking acute myocardial infarction. Intern Med 2003;42:340-344. [ Links ]
37. . Bell DA, Crooke MJ, Hay N, Glendenning P. Prolonged vitamin D intoxication: presentation, pathogenesis and progress. Intern Med J 2013;43:1148-1150. [ Links ]
================================================
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby jimmylegs » Mon Jun 02, 2014 4:54 am

got the blinders thoroughly on, don't they? not one mention of magnesium in the main text, and only one single reference with magnesium in the title?

time will tell

Correlation of serum magnesium with serum levels of 25-hydroxyvitamin D in hemodialysis patients (2014)
http://www.nikanrescorp.com/index.php/N ... e/view/9/9
Impaired absorption of magnesium appears to be related to deficient synthesis of the active metabolite of vitamin D by the nonfunctioning kidneys (12-17).

Relationship of Serum Magnesium and Vitamin D Levels in a Nationally‑Representative Sample of Iranian Adolescents: The CASPIAN‑III Study (2013)
http://ijpm.mui.ac.ir/index.php/ijpm/ar ... /1269/1344
Methods: The study participants consisted of 330 students, aged range from 10 to 18 years, consisting of an equal number of individuals with and without hypovitaminosis D. The correlation between serum 25 hydroxy vitamin D (25(OH) D) and magnesium (Mg) concentrations was determined.
Results: The mean age of participants was 14.74 ± 2.587 years, without significant difference between those with hypovitaminosis D and those without it. The mean 25(OH) D level was 6.34 ± 1.47 ng/ml in the group with hypovitaminosis D and 39.27 ± 6.42 ng/ml in the group without it. The mean Mg level was 0.80 ± 0.23 mg/dl with lower level in the group with hypovitaminosis D than in others (0.73 ± 0.22 mg/dl vs. 0.87 ± 0.22 mg/dl, respectively) and according to t‑test analysis, significant lower levels in the deficient group was observed (P = 0.0001). The linear regression analysis showed the meaningful relationship between Mg and 25(OH) D serum levels (P = 0.0001).
Conclusions: Our study revealed significant associations between serum Mg and 25(OH) D levels. This finding may be of use for further studies on the prevention and management of hypovitaminosis D in children and adolescents. Further longitudinal studies shall evaluate the underlying mechanisms and the clinical significance of the current findings.

look at that, serum magnesium being all informative and such!!

really good graphic here:

Evaluation of 25(OH) Vitamin D3 with Reference to Magnesium Status and Insulin Resistance in T2DM (2013)
http://www.ncbi.nlm.nih.gov/pmc/article ... figure/F1/
Figure 1 - Comparison of Vitamin D, Calcium and magnesium levels in T2DM cases
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New Study: Protective Role of Vitamin D in Neurodegenerative

Postby ThisIsMA » Tue Jun 24, 2014 11:44 am

Recently published study:

http://iospress.metapress.com/content/n22q7774r7n85287/

Additional Clues for a Protective Role of Vitamin D in Neurodegenerative Diseases: 1,25-Dihydroxyvitamin D3 Triggers an Anti-Inflammatory Response in Brain Pericyte
Journal Journal of Alzheimer's Disease ...Online Date Monday, June 16, 2014


Abstract

Epidemiological and experimental studies suggest that 1,25-dihydroxyvitamin D3 (1,25D) plays a neuroprotective role in neurodegenerative diseases including Alzheimer's disease. Most of the experimental data regarding the genes regulated by this hormone in brain cells have been obtained with neuron and glial cells. Pericytes play a critical role in brain function that encompasses their classical function in blood-brain barrier control and maintenance. However, the gene response of brain pericyte to 1,25D remains to be investigated. Analyses of the transcriptomic response of human brain pericytes to 1,25D demonstrate that human brain pericytes in culture respond to 1,25D by regulating genes involved in the control of neuroinflammation. In addition, pericytes respond to the pro-inflammatory cytokines tumor necrosis factor-α and Interferon-γ by inducing the expression of the CYP27B1 gene which is involved in 1,25D synthesis. Taken together, these results suggest that neuroinflammation could trigger the synthesis of 1,25D by brain pericytes, which in turn respond to the hormone by a global anti-inflammatory response. These findings identify brain pericyte as a novel 1,25D-responsive cell type and provide additional evidence for the potential value of vitamin D in the prevention or therapy of Alzheimer's disease and other neurodegenerative/neuropsychiatric diseases associated with an inflammatory component.
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Vit D3 and Cholesterol

Postby MarkW » Wed Jun 25, 2014 3:31 am

Interesting finding from the folks at Buffalo..............MarkW

J Steroid Biochem Mol Biol. 2014 Jun 17. pii: S0960-0760(14)00121-6. doi: 10.1016/j.jsbmb.2014.06.007. [Epub ahead of print]
Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes: Results from a multi-center study.
Browne RW1, Weinstock-Guttman B2, Zivadinov R3, Horakova D4, Bodziak ML1, Tamaño-Blanco M5, Badgett D5, Tyblova M4, Vaneckova M6, Seidl Z6, Krasensky J6, Bergsland N7, Ramasamy DP7, Hagemeier J7, Qu J5, Havrdova E4, Ramanathan M8.

Abstract
CONTEXT:
High serum cholesterol is adversely associated with clinical and imaging disease progression outcomes in multiple sclerosis (MS) and in clinically isolated syndrome (CIS), the earliest stage of MS. Low vitamin D levels are associated with an increased risk of disease progression.

OBJECTIVES:
To investigate the mechanisms mediating the adverse effects of cholesterol in CIS and to determine the role of the nexus between the vitamin D3 (D3) and cholesterol pathways.

DESIGN:
Multi-center, prospective, longitudinal prospective study.

SETTING:
University hospital multiple sclerosis centers.

INTERVENTION:
Serum samples were obtained prior to any treatment from study subjects.

METHODS:
Serum obtained prior to any treatment from 172 CIS patients enrolled in a multi-center, prospective, longitudinal study (119 females: 53 males, age: 28.1±SD 8.1 years) were analyzed for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), ApoAII, ApoB, ApoE, and lipoprotein-a. Levels of 25-hydroxy D3 (25(OH)D3), 1,25-dihydroxy D3, and 24,25-dihydroxy D3 were measured using liquid chromatography-mass spectrometry.

RESULTS:
Greater levels of HDL-C biomarkers (e.g., HDL-C itself, ApoAI, ApoAII and paroxonase arylesterase activity) and LDL-C biomarkers (e.g., LDL-C itself, Apo B) were associated with greater 25(OH)D3. The effects of HDL-C biomarkers were stronger than those of LDL-C. Free cholesterol and cholesteryl ester levels were positively associated with higher 25(OH)D3 levels. Cholesterol palmitate was particularly potent. The nexus between the D3 and cholesterol pathways was proximal to, or in linkage disequilibrium with, 7-dehydrocholesterol reductase DHCR7 rs1790349, endothelial lipase LIPG rs4939883 and proprotein convertase subtilisin/kexin type 9 PCSK9 rs11206510.

CONCLUSIONS:
The associations between cholesterol biomarkers and vitamin D metabolite levels in CIS are consistent with the biochemical inter-dependence between the two pathways. Cholesterol biomarkers should be considered for inclusion as covariates when assessing vitamin D levels in CIS.

KEYWORDS:
Cholesterol; Clinically isolated syndromes; Environmental factor; Interactions; Lipid; Multiple sclerosis; Vitamin D

PMID: 24950029 [PubMed - as supplied by publisher]
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Vit D3 and vascular regeneration

Postby MarkW » Thu Aug 14, 2014 4:47 am


Interesting find PointsNorth. Raises the question if this works for pwMS.
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Vitamin D Promotes Vascular Regeneration.

Postby MarkW » Thu Aug 14, 2014 5:22 am

Circulation. 2014 Jul 11. pii: CIRCULATIONAHA.114.010650. [Epub ahead of print]

Vitamin D Promotes Vascular Regeneration.
Wong MS1, Leisegang MS2, Kruse C2, Vogel J1, Schürmann C2, Dehne N1, Weigert A1, Herrmann E2, Brüne B1, Shah AM3, Steinhilber D1, Offermanns S4, Carmeliet G5, Badenhoop K6, Schröder K2, Brandes RP7.

Abstract
BACKGROUND:
-Vitamin D deficiency in humans is frequent and has been associated with inflammation. The role of the active hormone, 1,25-dihydroxy-vitamin D3 (1,25-VitD3) in the cardiovascular system is controversial. High doses induce vascular calcification; vitamin D3 deficiency, however, has been linked to cardiovascular disease as the hormone has anti-inflammatory properties. We therefore hypothesized that 1,25-VitD3 promotes regeneration after vascular injury.
METHODS AND RESULTS:
-In healthy volunteers supplementation of VitD3 (4000 I.E. cholecalciferol/day) increased the number of circulating CD45-CD117+Sca1+Flk1+ angiogenic myeloid cells (AMC), which are thought to promote vascular regeneration. Similarly, in mice 1,25-VitD3 (100ng/kg/d) increased the number of AMCs and promoted re-endothelialization in the carotid artery injury model. In streptozotocin-diabetic mice, 1,25-VitD3 also promoted reendothelialization and restored the impaired angiogenesis in the femoral artery ligation model. AMCs home through the stromal cell-derived factor 1 (SDF1) receptor CXCR4. Inhibition of CXCR4 blocked 1,25-VitD3-stimulated healing pointing to a role of SDF1. The combination of injury and 1,25-VitD3 increased SDF1 in vessels. Conditioned medium from injured, 1,25-VitD3 treated arteries elicited a chemotactic effect on AMCs, which was blocked by SDF1-neutralizing antibodies. Conditional knockout of the vitamin D receptor (VDR) in myeloid cells but not the endothelium or smooth muscle cells blocked the effects of 1,25-VitD3 on healing and prevented SDF1 formation. Mechanistically, 1,25-VitD3 increased Hif1α through binding to its promoter. Increased HIF signaling subsequently promoted SDF1 expression as revealed by reporter assays and knockout and inhibitory strategies of HIF1α.
CONCLUSIONS:
-By inducing SDF1, VitD3 is a novel approach to promote vascular repair.
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Source of Vit D3

Postby MarkW » Mon Sep 15, 2014 5:17 am

I recently was asked about D3 for vegans who do not take lanolin derived D3. Some manufacturers use fish body oil or krill oil so those could meet some needs but not vegan requirements. My usual word of caution on using Cod Liver Oil at high
doses, always calculate the dose of Vitamin A being taken as that is toxic at high levels.
Doing some self education on vegan D3 and I found a product:
MRM Vegan Vitamin D3 5,000 IU 60 Vegan Capsules
Has anyone used this product?
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
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