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.

Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby NZer1 » Mon Jan 14, 2013 11:49 am

Another insight for Mark and your approach to VitD supplementing.

In NZ we can only get Vit D3 in 50,000 ui form, and we cannot import it from suppliers such as IHerb or Vitacost, they won't supply due to regulations.

So pulse is the standard way to supplement in NZ.

R,
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby MarkW » Thu Jan 17, 2013 3:36 am

NZer1 wrote:In NZ we can only get Vit D3 in 50,000 ui form, and we cannot import it from suppliers such as IHerb or Vitacost, they won't supply due to regulations.
So pulse is the standard way to supplement in NZ.

Hello Nigel,
I am not aware of the NZ regs but they are usually similar to UK. A doctor and pharmacist (with an import licence) can usually import most legal drugs in UK/EU, if they work together. Is vit D3 5000iu a POM in NZ?
50,000iu as a pulse dose carries more risks than 5000iu daily. I only recommend such a dose of 50,000 iu under medical supervision. I am happy to recommend 5000 iu/day as a first step to pwMS on their own.
The important point is the blood D3 level (above 125mmol/L) achieved in the person and I trust you are having yours (and essential minerals) checked.
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: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby jimmylegs » Thu Jan 17, 2013 6:04 am

from the first post of my 'regimen' thread, back in the days when it was called 'vitamin d3 megadose' or something like that. mostly posted as a cautionary tale about 50,000iu/d. has some other tidbits. as you read through, there's an interesting aside re zinc and uric acid.

regimens-f22/topic2489.html#p15460

this is from the 'back to the beginning' section at the end of the summary points in the first post, june 2006

BACK TO THE BEGINNING...

* * *

In my continuing spirit of self-guinea-pigdom, I am trying a short burst of big time vitamin D3. This is in order to boost my serum levels up to around 125-150 nmol/l (the level recommended by one of my doctors, who also has MS).

I figured out from the literature, that it was going to take 5 months to get where I am supposed to be, if I stayed on my recent average 4400IU daily.

So, I found out from the drug info centre, how much to take to get a quick jump up about 50 nmol/l. They said they do 50,000IU per day for 10 days, but would usually use that on people that were seriously deficient.

My last level was 72 nmol/l which is only a little bit under the good zone for bone health. Some would argue it is way low for immune system health. So, I am not worried by jumping up another 50 nmol by next week.

I went to my family doc and asked for a prescription for 50000iu for 10 days and 4000 iu per day daily maintenance thereafter.

She said okay but also gave me a lab requisition for baseline testing prior to starting the big dose, another lab req for right after the big doses are over, and a third req for 2 weeks after to see if we're on the right track re: maintenance at 4000 IU/d.

My lab's computer system says that serum D3 levels over 250 are toxic but I relayed the story about the south indian workers with unsupplemented natural levels over 450 [edit: i'm okay with 250 being a safe upper end of the range, and anyway i was not and am not going for over 250!]. I also mentioned that I had a reference from my dietitian that listed a study where 50000IU taken daily for a month resulted in serum levels of 320, so 10 days should be safe in my case, and won't even get near her 250 limit anyway.

So the pharmacy i went to has a compounding license and he had ordered me the smoking highly concentrated D3 after a discussion we had last week. It's 1,000,000IU/gm. So I take 1/20th of a gm per day for 10 days. Instead of having to take 50 d3 pills each day for 10 days, I get to have about 2 drops of this liquid from a graduated oral syringe. SA-WEEEET! so much better than pills!

so, i get the baseline D result back probably on Monday, and will keep u all posted as to the improvement in my levels, and hopefully general condition and symptoms.

ttfn!

now from my first zinc test (jan 2008 only took me 2+ years from first musing about the zinc aspect while overseas, to actually getting some data :S ) note the aside re uric acid
regimens-f22/topic2489-75.html#p34864

it's about time to get back on the supplement regimen again, as the legs have started to go jimmy again and everything.

the following list of results displays
test item;...result; (lab reference range); "lab comment"

serum ferritin;...............82; (51 - 140); "probably not iron deficient"
...
Uric Acid;.....................194; (150 - 350)
25-OH vitamin d3;..........74; (22.5 - 94.3)
zinc;...............................8.6; (11.5 - 18.5)
...
uric acid: BOO! stupid ms average, on the dot, AGAIN. food is not doing the trick, apparently.

d3: 22.5 - in the normal range?? that is so not healthy. 74 - BOOOO! i'm going to do that 50,000IU per day for 10 days thing again and kick it up to 150

zinc: interesting. i had not looked carefully through my posts once my legs went squirrelly during this last long layoff from the supplements. i kept having good intentions and then slacking.
the legs started to jimmy out on me again. i remembered an iron connection. i have purchased some within the last week and it worked somewhat. now my bloodwork shows low zinc. i just re-read my posts more thoroughly to note how while in australia i had connected the remaining jimmylegs issues to zinc, to resolve it the rest of the way.
so, i'll take zinc with meals, iron in between, and let you know if the jimmy thing backs off again.

lol i was such a dummy. the iron was pretty decent, if this set of results cropped up now, i would only worry about the zinc. i can't even take iron supplements any more. levels get too high.

and this is from 2009 after fixing zinc deficiency (skippped posting any musings about the zinc/ua connection but you can see the rest of the tale in there too.. it shows a clear link and a plausible leap to zinc potentially influencing d3 status. wasn't clear enough on zinc finger proteins and VDR stuff back then, to make any kind of solid assertion about why)

regimens-f22/topic2489-150.html#p59321

d3 is in. 103 nmol/L.
aiming for 50 higher than that.
therefore am once again on 50,000IU/d for 10d. today is day 5.

as of today have another lab req for zinc, uric acid, copper.
also selenium.
d3, e, and a down the road a bit.

regimens-f22/topic2489-150.html#p61318

jun 19 labwork is starting to come in.

i actually overdid it with the D3!?!
instead of getting it up to 150 like the first time, this time around it went from 103 to 271 nmol/L!!!
i think this might be because of fixing the zinc deficiency, but i'm not clear on exactly how yet.

more good news re: zinc and uric acid. i'm up to 16.1 with the zinc, and the uric acid has jumped again, right in synch - it's at 278 now!!! only 12 more to go.
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby Squeakycat » Thu Jan 17, 2013 6:32 am

MarkW wrote:50,000iu as a pulse dose carries more risks than 5000iu daily. I only recommend such a dose of 50,000 iu under medical supervision. I am happy to recommend 5000 iu/day as a first step to pwMS on their own.

Mark,
My understanding of this issue is that you might have more problems with hypercalcemia by daily dosing than pulse dosing which would make high daily doses more of a risk than a pulse dose.

The reason is that vitamin D promotes calcium absorption which would increase with a daily dose. But a large pulse dose drives down parathyroid hormone which is the key signaling to the kidneys to retain calcium and increase both absorption from the intestines and resorption from bones. By lowering PTH, a pulse dose makes hypercalcemia much less likely.

Have I gotten this wrong?

Ed
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby jimmylegs » Thu Jan 17, 2013 6:45 am

my understanding is that serum d3 levels are inversely correlated with PTH. i haven't been nose to the grindstone with vit de research over the last few yrs but i would think that correlation would be independent of pulse vs daily doses.

can anyone link to a study examining d3 interrelationships with PTH under different rates of exposure/intake and/or supplementation?

i have learned not to take calcium any more, now that my zinc and d3 levels are good. if i take calcium, i get muscle spasticity. if i stick with d3 mag and zinc (and a few other things of course, but not specifically relevant here), all good.
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby NZer1 » Fri Jan 18, 2013 3:33 pm

Waiting on Bloods results, btw.

This is interesting when you think rather than listen to the angle of the reader, Prof Taylor.
The genome link found; " This GWAS discovered 2 new genetic regions involved in MS. These 2 regions were of great interest as the strongest association was for a SNP in the region of a gene known as CYP27B1 which is the gene that converts the inactive form of vitamin D into the active form of vitamin D. The second area was in a gene known as CD40, this gene has been implicated in the development of rheumatoid arthritis but the effect in MS was in the opposite direction where the risk for MS was not the same as the risk for RA." this could actually be a link in a different manor than assumed by Prof Taylor. CPn infections are linked to Vit D suppression which changes the apoptosis of the hosts cells and enables CPn bacteria to use the host cells as their life support by using the host cells energy source to multiply and survive whilst hiding from the hosts immune system. The link to RA is also known with CPn infections and for both MS and RA to be associated is 'uncanny'!
It would be a paradigm shifter to get this info in front of Prof Taylor to enable a boarder search and linking of Scientific Minds. Hopefully Dr Paul Thibault can assist!
The Australian and NZ Vit D test program would also benefit from some insights about the links to CPn and it's ability to alter the Immune System by adapting immune cell DNA to it's own to avoid detection, as well as altering other Vit D functions in the body of which there are Hundreds to consider.

Quote;
To all participants in the genetic portion of the New Zealand MS Prevalence Study
Many of you will remember spitting into a little bottle and mailing it back to Christchurch in 2007 and 2008 and may have wondered “what ever happened to it”. Well those samples have been involved in a significant amount of ground breaking research into the genetic basis of MS.
As many of you will be aware MS is more common in relatives of people with MS and the risk of MS increases with the degree of relatedness. For example, if you take identical twins where one twin develops MS the risk of the other twin getting MS is around 25%, indicating that there is around a 25% contribution from genes to the risk of MS. If you have a brother or sister with MS your risk of MS is increased by around 5%. This familial clustering of MS has intrigued researchers for many years and in the 1970’s the first area in the genome associated with MS was discovered. This area referred to as the HLA region on chromosome 6 is a group of genes that are critically important in how our immune system works. Particularly in relation to how we identify foreign cells or bacteria. Having a particular genetic makeup in this region referred to as HLA DRB!*15:01 increases a person’s risk of getting MS three fold. However, whilst 60 – 70 per cent of people with MS carry this gene so too do 30-40% of the population without MS. Therefore it is not a useful marker that we can use to diagnose MS. It took till 2007 to find the next genes that were associated with MS; these genes were found using a new and powerful genetic technique known as Genome Wide Association Studies or GWAS.
Essentially a GWAS study compares the common normal variations across the genome known as single nucleotide polymorphisms (SNPs) between thousands of cases and controls. We collected the saliva samples from people in NZ to undertake what in 2007 was the largest GWAS of MS cases. NZ cases contributed around 30% of the 1600 cases of MS studied from throughout Australia and New Zealand as part of the Australian & New Zealand MS genetics consortium (ANZGENE). This GWAS discovered 2 new genetic regions involved in MS. These 2 regions were of great interest as the strongest association was for a SNP in the region of a gene known as CYP27B1 which is the gene that converts the inactive form of vitamin D into the active form of vitamin D. The second area was in a gene known as CD40, this gene has been implicated in the development of rheumatoid arthritis but the effect in MS was in the opposite direction where the risk for MS was not the same as the risk for RA. These results were published in the highly regarded journal Nature Genetics in 2009. Subsequently ANZGENE combined with researchers from many other countries to do an even larger GWAS including nearly 10,000 MS cases from 15 countries including 400 cases from NZ. This much larger study was able to find another 25 areas on the genome that were associated with MS. These genes were interesting as they confirmed that many of the risk genes were involved in immune function. This paper was published in the Journal Nature in 2011. Subsequently, with our colleagues in the US, we have combined data from several other GWAS studies and have pushed the number of genes associated with MS to nearly 60.
The major effort now is to try and work out how and why these genetic markers influence the risk of MS. We are continuing to work on this with our international colleagues to develop a major project to fine map the changes in MS genes using Immunochip. This project has recruited 20,000 MS cases and is nearly complete. This will provide researchers with a much better map of the genes that are associated and may help explain the genetics of MS in much more detail.
Consequently NZ MS DNA has been critically involved in some of the largest DNA experiments ever undertaken. The results of these experiments have greatly improved our understanding of MS genetics but there is still a long way to go. Many people on hearing of these discoveries immediately think that we can now perform a genetic test to diagnose MS. Unfortunately this is not the case, all the genes described so far, apart from the HLA gene found in the 1970s, only have a modest effect on the risk of MS increasing the risk by 10 – 30 %. In a rare disease such as MS where the risk is around 1;1000 for NZ women this increases the risk to 1.2 or so per 1000. Consequently from the diagnostic point of view they are not useful at all. However what they do provide is an insight into the complex manner by which MS occurs and the central role of the immune system.

We are continuing to work hard to unravel the course of MS and the samples that were contributed by you have been immensely valuable and may well translate into even greater discoveries over the next few years. We will keep you informed of the continuing progress of your extremely valuable sample.
We once again thank you for your participation in this study.

Regards
Prof Bruce Taylor
For the New Zealand MS Prevalence Study
http://msnz.org.nz/Page.aspx?pid=284
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby jimmylegs » Fri Jan 18, 2013 3:51 pm

just d3 levels, nz? did you get any related tests done?
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby Squeakycat » Fri Jan 18, 2013 4:37 pm

jimmylegs wrote:my understanding is that serum d3 levels are inversely correlated with PTH. i haven't been nose to the grindstone with vit de research over the last few yrs but i would think that correlation would be independent of pulse vs daily doses.

can anyone link to a study examining d3 interrelationships with PTH under different rates of exposure/intake and/or supplementation?

There are literally hundreds of studies of this question, though few that directly address it. :>)

Here's a typical quote:
Subjects were randomized to receive oral cholecalciferol, as a single dose of 300 000 IU (group 1) or 800 IU (group 2) daily for 9 months. Both groups received 1250 mg calcium carbonate per day. Serum 25(OH)D and PTH levels were measured at baseline and after 1, 2, 3, 6, and 9 months. Serum 25(OH)D levels in group 1 were significantly higher than in group 2 during the study (P < 0.001). After 1 (P < 0.001) and 2 (P < 0.04) months of treatment, mean serum 25(OH)D levels were higher in group 1. The number of subjects who reached serum 25(OH)D levels >/=20 ng/dl was higher in group 1, after the first (P < 0.001) and third (P = 0.008) months. In the short term, a single 300 000 IU oral dose of vitamin D(3) was more effective than 800 IU per day to increase serum 25(OH)D levels in elderly persons, living in a low-income housing unit, who were taking 500 mg elementary calcium supplement per day.

http://www.ncbi.nlm.nih.gov/pubmed/18979160


The main problem with the studies in answering the question is that most deal with special populations such as people with kidney failure, elderly with hip fractures and so on or addressed multiple issues such as whether D2 is more effective than D3. I can't find anything that specifically looks at the impact of vitamin D dose on PTH.

Another issue is the form of vitamin D being used. There are many studies of the impact of high dose calcitriol versus daily dosing. And a lot depends on baseline PTH and 25(OH)D levels.

For the past 21 cat years, I have pulse dosed calcitriol in my kitties with renal failure because they inevitably become hypercalcemic when the dose is administered daily. I first looked this up over 12 years ago and saw that this was common practice in the treatment of hyperparathyroidism in people with kidney disease.

My understanding of the underlying mechanism is that a high dose is more effective in driving down PTH than daily dosing.

I'll keep looking. I have a series of studies involving high dose calcitriol as a treatment for cancer that I know addressed this, they just aren't showing up when I do a PubMed search at the moment.
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby NZer1 » Fri Jan 18, 2013 4:50 pm

Ms jimmy I got several from you list and I can't find my list at the moment, all will be revealed early next week!

Ed it will be interesting to find some insights to Vit D and genetic influences and also the absorption when under stress from various illnesses.
It appears that there is a difference with things like infection versus psychological and versus injury.
I am unable to help with any links at the moment, I remember seeing something when I was looking through Strattons work and will have another look.

Regards,
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby NZer1 » Sat Jan 19, 2013 4:54 pm

Left field insight to Vit D, There are comments on the effects of Vit D metabolism;
http://buhnerhealinglyme.com/miscellane ... -protocol/
"Nevertheless, his finding still stands true – there are people, myself included – whoi do not metabolize vitamin D in the normal way and thus these people should never be given vitamin D supplements as this will create a huge problem for their immune system."

and
http://www.natmedtalk.com/f50/1643-mars ... y-one.html
"The Marshall Protocol was developed by Trevor Marshall, PhD, in 2002 to treat certain diseases that involve Th1 immune system dysfunction.

Dr. Marshall's papers describe how numerous Th1 diseases such as sarcoidosis, Lyme disease, chronic fatigue syndrome, fibromyalgia, lupus and rheumatoid arthritis (among others) are caused by Cell Wall Deficient (CWD) bacteria of various species......

An essential part of the Marshall Protocol is avoidance foods and vitamin supplements containing vitamin D to reduce the level of this hormone which suppresses the immune system......

and
The protocol also includes the introduction of carefully, selected low dose antibiotics in a pulsed schedule"......

http://www.marshallprotocol.com/forum2/364.html

"Ingested Vitamin D is an immune-suppressant, similar to the function that prednisone performs. Ingested Vitamin D suppresses the action of the VDR (Vitamin D Receptor) and thus turns-off the immune system's Th1 response so it cannot fight the intra-phagocytic bacteria. People feel better in the short-term, but will succumb to the infection more rapidly in the long-run"......

http://www.marshallprotocol.com/forum2/4062.html

"The MP coordinates the use of Benicar (Olmesartan medoxomil), and specific, pulsed, low-dose, bacteriostatic, oral antibiotics to enable the immune system to destroy the persistent bacteria [5]. Correctly dosed, Benicar reduces inflammatory cytokine production by blocking the angiotensin II, type I receptors to inhibit, inter alia, the release of tumor necrosis factor-alpha during the Th1 immune reaction"......

http://autoimmunityresearch.org/phase1.pdf

and
http://www.prweb.com/releases/2008/1/prweb639651.htm
New Research Challenges Concept of Vitamin D Deficiency
The vitamin D deficiency long interpreted as a cause of disease is more likely the result of the disease process and increasing intake of vitamin D often makes the disease worse.
Email PDF Print
Thousand Oaks, CA (PRWEB) January 21, 2008

Low blood levels of vitamin D have long been associated with disease, and the assumption has been made that vitamin D supplements may protect against disease. In the light of new knowledge that hundreds of genes are dependent on vitamin D, this assumption needs to be reconsidered.
In a report published in the current issue of the journal BioEssays(1), Trevor Marshall, Ph.D., professor at Australia's Murdoch University School of Biological Medicine and Biotechnology, explains how increased vitamin D intake affects much more than just nutrition or bone health. The paper explains how the Vitamin D Nuclear Receptor (VDR) acts in the repression or transcription of hundreds of genes, including genes associated with diseases ranging from cancers to multiple sclerosis.
"The VDR is at the heart of innate immunity, being responsible for expression of most of the antimicrobial peptides, which are the body's ultimate response to infection," Marshall said. "Molecular biology is now forcing us to re-think the idea that a low measured value of vitamin D means we simply must add more to our diet. Supplemental vitamin D has been used for decades, and yet the epidemics of chronic disease, such as heart disease and obesity, are just getting worse."
"Our disease model has shown us why low levels of vitamin D are observed in association with major and chronic illness," Marshall added. "Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune system so that the body cannot fight disease and infection effectively."
Marshall's research has demonstrated how ingested vitamin D can actually block VDR activation, the opposite effect to that of Sunshine. Instead of a positive effect on gene expression, Marshall reported that his own work, as well as the work of others, shows that quite nominal doses of ingested vitamin D can suppress the proper operation of the immune system. It is a different metabolite, a secosteroid hormone called 1,25-dihydroxyvitamin D, which activates the VDR to regulate the expression of the genes. Under conditions that exist in infection or inflammation, the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status.
Vitamin D deficiency, long interpreted as a cause of disease, is more likely the result of the disease process, and increasing intake of vitamin D often makes the disease worse. "Dysregulation of vitamin D has been observed in many chronic diseases, including many thought to be autoimmune," said J.C. Waterhouse, Ph.D., lead author of a book chapter on vitamin D and chronic disease (2). "We have found that vitamin D supplementation, even at levels many consider desirable, interferes with recovery in these patients."
"We need to discard the notion that vitamin D affects a disease state in a simple way," Marshall said. "Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease. The comprehensive studies are just not showing that supplementary vitamin D makes people healthier."

and
http://trevormarshall.com/BioEssays-Feb ... eprint.pdf
Conclusion
This BioEssay has examined a number of ways in which,
while the widespread use of Vitamin D as a food supplement
may be providing short term benefits to a subset of the
population, epidemic expansion of obesity and chronic
disease are quite possibly the legacies to be bestowed upon
future generations.
This BioEssay has examined a number of ways in which,
while the widespread use of Vitamin D as a food supplement
may be providing short term benefits to a subset of the
population, epidemic expansion of obesity and chronic
disease are quite possibly the legacies to be bestowed upon
future generations.
The concept that “The Sunshine Vitamin” really is just a
vitamin, with the consequent implication of a linear ‘vitamin
in, benefit out’ model, is clearly no longer tenable. At any
level of molecular analysis, the Vitamin D metabolites are
part of the delicate homeostasis which allows our bodies to
express genes, and to express them when the need arises.
The concept that “The Sunshine Vitamin” really is just a
vitamin, with the consequent implication of a linear ‘vitamin
in, benefit out’ model, is clearly no longer tenable. At any
level of molecular analysis, the Vitamin D metabolites are
part of the delicate homeostasis which allows our bodies to
express genes, and to express them when the need arises.
The conviction that one can, with impunity, continue to add
higher and higher concentrations of this secosteroid to the
food chain is still firmly held by many of our clinical
colleagues. This is a recipe which could easily lead to a
public health disaster. Yet the ‘vitamin’ model has a
seductive simplicity, a simplicity which offers a welcome
escape from the complex world of modern molecular
medicine.
The conviction that one can, with impunity, continue to add
higher and higher concentrations of this secosteroid to the
food chain is still firmly held by many of our clinical
colleagues. This is a recipe which could easily lead to a
public health disaster. Yet the ‘vitamin’ model has a
seductive simplicity, a simplicity which offers a welcome
escape from the complex world of modern molecular
medicine.
Molecular biologists have a duty to share their new-found
genomic knowledge with their clinical colleagues. They
need to help them understand the steroidal nature of Vitamin
D. To help them understand that this substance is intimately
involved in the transcription of hundreds, probably
thousands, of genes. Genes which determine the course of
immune disease, and cancers. At the very least, we must
ensure that every researcher understands the importance of
measuring the concentration of the actual transcriptional
activator, 1,25-dihydroxy-vitamin-D.
Molecular biologists have a duty to share their new-found
genomic knowledge with their clinical colleagues. They
need to help them understand the steroidal nature of Vitamin
D. To help them understand that this substance is intimately
involved in the transcription of hundreds, probably
thousands, of genes. Genes which determine the course of
immune disease, and cancers. At the very least, we must
ensure that every researcher understands the importance of
measuring the concentration of the actual transcriptional
activator, 1,25-dihydroxy-vitamin-D.
Biologists need to raise their voices and help Federal
regulators understand what is being discovered about the
wonderful genetic tapestry which has historically allowed
Homo sapiens to thrive, and to control its environment.
Biologists need to raise their voices and help Federal
regulators understand what is being discovered about the
wonderful genetic tapestry which has historically allowed
Homo sapiens to thrive, and to control its environment.
While it is true that molecular biology can still only precisely
describe a very small fraction of the human experience,
what it can describe it does so in exquisite detail. It is critical
that Medicine revisits the role which has been assigned to
"The Sunshine Vitamin," properly recognizing its function as
a secosteroid, a transcriptional activator, key to the proper
operation of the innate immune system.

and
http://mpkb.org/home/pathogenesis/vitamind
Science behind vitamin D
A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin D (25-D) and that consuming greater quantities of vitamin D, which further elevates 25-D levels, alleviates disease symptoms.

Some years ago, molecular biology identified 25-D as a secosteroid. Secosteroids would typically be expected to depress inflammation, which is in line with the reports of short-term symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies is now giving way to a more complex description of action.

When active, the Vitamin D nuclear receptor (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides. Additionally, recent research on the Human Microbiome shows that bacteria are far more pervasive than previously thought, dramatically increasing the possibility that the spectrum of chronic diseases is bacterial in origin.

Emerging molecular evidence suggests that symptomatic improvements among those administered vitamin D is the result of 25-D’s ability to temper bacterial-induced inflammation by slowing VDR activity. While this results in short-term palliation, persistent pathogens that influence disease progression proliferate over the long-term.....................
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby Squeakycat » Sat Jan 19, 2013 10:14 pm

Nigel,

All of this makes perfect sense if you believe that night is day and north is south and you toss out 30 years worth of research on vitamin D. :roll:

Science. 2006 Mar 24;311(5768):1770-3. Epub 2006 Feb 23.
Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL.
Source
Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Abstract
In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.


Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22593-8. doi: 10.1073/pnas.1011624108. Epub 2010 Dec 13.
T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism.
Edfeldt K, Liu PT, Chun R, Fabri M, Schenk M, Wheelwright M, Keegan C, Krutzik SR, Adams JS, Hewison M, Modlin RL.
Source
Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
Abstract
We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-γ, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-γ up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1α-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D(3) (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.

Full text


PLoS One. 2009 Jun 5;4(6):e5810. doi: 10.1371/journal.pone.0005810.
Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses.
Liu PT, Schenk M, Walker VP, Dempsey PW, Kanchanapoomi M, Wheelwright M, Vazirnia A, Zhang X, Steinmeyer A, Zügel U, Hollis BW, Cheng G, Modlin RL.
Source
Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America. philip@bruinphd.com
Abstract
Antimicrobial effector mechanisms are central to the function of the innate immune response in host defense against microbial pathogens. In humans, activation of Toll-like receptor 2/1 (TLR2/1) on monocytes induces a vitamin D dependent antimicrobial activity against intracellular mycobacteria. Here, we report that TLR activation of monocytes triggers induction of the defensin beta 4 gene (DEFB4), requiring convergence of the IL-1beta and vitamin D receptor (VDR) pathways. TLR2/1 activation triggered IL-1beta activity, involving the upregulation of both IL-1beta and IL-1 receptor, and downregulation of the IL-1 receptor antagonist. TLR2/1L induction of IL-1beta was required for upregulation of DEFB4, but not cathelicidin, whereas VDR activation was required for expression of both antimicrobial genes. The differential requirements for induction of DEFB4 and cathelicidin were reflected by differences in their respective promoter regions; the DEFB4 promoter had one vitamin D response element (VDRE) and two NF-kappaB sites, whereas the cathelicidin promoter had three VDREs and no NF-kappaB sites. Transfection of NF-kappaB into primary monocytes synergized with 1,25D3 in the induction of DEFB4 expression. Knockdown of either DEFB4 or cathelicidin in primary monocytes resulted in the loss of TLR2/1-mediated antimicrobial activity against intracellular mycobacteria. Therefore, these data identify a novel mechanism of host defense requiring the induction of IL-1beta in synergy with vitamin D activation, for the TLR-induced antimicrobial pathway against an intracellular pathogen.

Full text

And just one more of many, many studies on the role that Vitamin D plays in activating the innate immune system in response to pathogens.

Cell Microbiol. 2010 Aug;12(8):1026-35. doi: 10.1111/j.1462-5822.2010.01491.x. Epub 2010 Jun 14.
Innate immunity to mycobacteria: vitamin D and autophagy.
Jo EK.
Source
Department of Microbiology, Chungnam National University School of Medicine, Jungku, Daejeon, Korea. hayoungj@cnu.ac.kr
Abstract
Autophagy is an ancient mechanism of protein degradation and a novel antimicrobial strategy. With respect to host defences against mycobacteria, autophagy plays a crucial role in antimycobacterial resistance, and contributes to immune surveillance of intracellular pathogens and vaccine efficacy. Vitamin D3 contributes to host immune responses against Mycobacterium tuberculosis through LL-37/hCAP-18, which is the only cathelicidin identified to date in humans. In this review, we discuss recent advances in our understanding of host immune strategies against mycobacteria, including vitamin D-mediated innate immunity and autophagy activation. This review also addresses our current understanding regarding the autophagy connection to principal innate machinery, such as ubiquitin- or inflammasome-involved pathways. Integrated dialog between autophagy and innate immunity may contribute to adequate host immune defences against mycobacterial infection.

Full text.

It is complete utter nonsense to suggest that vitamin D acts like a steroid to suppress the immune system. Those proinflamatory cytokines are in fact activated and controlled by vitamin D when there is injury to a cell.

I'm not saying that supplements are superior to sunshine. Nor am I saying that there aren't people with special conditions such as sarcodosis in which vitamin D can be harmful.

But vitamin D is so vital to so much of the immune system response to pathogens and injuries, it is just upside down to suggest otherwise, absent actual proof. Bold assertions are not proof, imo.
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby NZer1 » Sat Jan 19, 2013 10:41 pm

Ed the studies and theories that you listed are not supported by the next step, to supplement and test the long term benefits, and long term is 5-10 years!

The point I see is that there is a 'likelihood" that a pathogen eg Lyme of CPn can modify the VDR system and through modifying macrophages etc and altering itself by adapting immune system DNA to avoid detection. So supplementing will become a negative as you have said earlier.

The studies need to consider the spectrum of subjects they use in a different mind set, and over time to understand what is truly happening with pathogen infections and Vit D levels.

Sorry to shattered to reply intelligently talk tomorrow,

N
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby MarkW » Sun Jan 20, 2013 6:18 am

Hello Nigel and Ed,
i love the research you are posting. I do not understand how all this science fits into actual human biology. Added to this pwMS do not behave (in biological terms) like most human beings. I am not going to cite papers as it is the unexpected results in clinical studies which have led me to this thinking. Blood levels of D3 are very important to pwMS but as a scientist I cannot exactly say why. My latest thinking is that vit D3 acts like a regulatory hormone on immune genes which have been turned up/on in an epigenetic manner by EBV/CPn and other things. If D3 is not present at higher blood levels the epigenetic up/on immune switches are not controlled. I also think that BBB porosity is regulated by epigenetics, otherwise why would it change in the relapsing-remitting stages of MS?
I am leading a seminar for Oxford Uni medical students on MS this week and will introduce the subject "MS is an epigenetic disease?" as the final topic. I hope to make the students think about the orthodoxy that "MS is an autoimmume disease". My thinking is not on ThisISMS for this week.
My recommendation = FIRST STEP - take 5000iu of D3 in oily form every day. STEP TWO (if possible) - have D3 blood levels measured with Zn, Ca, Mg and Se. Adjust/add diet/doses of D3 and minerals so that blood D3 is 125mmol/L (50ng/ml) minimum and minerals are 'normal', under medical supervision. From the data I have studied this makes excellent business/economic sense but the scientific data is not available to answer why.
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: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby 1eye » Sun Jan 20, 2013 11:09 am

At the very least, we must ensure that every researcher understands the importance of measuring the concentration of the actual transcriptional activator, 1,25 dihydroxy-vitamin-D.


Always good to measure. Always. Not just for every researcher, but for everybody.

A couple of facts may be related.

1. Atherosclerosis is associated with CPn.

2. CPn is thought to inhabit immune cells (macrophages).

3. Valves in veins are there for one reason, to prevent reflux, or reverse flow. Reverse flow probably damages capillaries, which contain the highest surface area of the endothelium, and are coincidentally where much oxygen and sugar is transferred to tissues.

4. In valve pathologies, immune cells congregate at the valve site.

Perhaps CPn is infecting valves, in the form of an accumulation of immune cells at valve sites. Then when reverse flow occurs (whether it is successfully stopped by a competent valve, or allowed through by an incompetent one, some of these CPn infected macrophages are starved of oxygen. But when apoptosis happens, infection becomes visible to the immune system, attracting attention of the whole immune system. Some collateral damage may be to nerve cells, or myelin.

BTW how does the Blood Brain Barrier figure into this? My understanding is that T cells use blood vessel walls as a highway. Do they travel independent of the direction of blood flow? When they are between vessels, yes. Otherwise, I don't know. From what it looks like, they spend most of their time on the outside of the circulatory system, traveling on the outside, and pop in and out of the bloodstream on signal. Probably there are many molecular signals we can't see (pathways). When the BBB becomes more porous, perhaps signalling (is vitamin D part of immune signaling?) becomes disrupted because more immune cells than are warranted or signaled for, now easily and more frequently traverse the BBB.

My latest thinking is that vit D3 acts like a regulatory hormone on immune genes which have been turned up/on in an epigenetic manner by EBV/CPn and other things. If D3 is not present at higher blood levels the epigenetic up/on immune switches are not controlled. I also think that BBB porosity is regulated by epigenetics, otherwise why would it change in the relapsing-remitting stages of MS?

Does it change then? I thought it preceded the disease itself.

I think BBB permeability is vulnerable to probably a number of thing, epigenetics maybe among the things that determine its vulnerability.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
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Re: FIRST STEP-Take Vitamin D3 Before & After De-Stenosis.

Postby jimmylegs » Sun Jan 20, 2013 5:59 pm

i confess i'm not reading in great detail, but just to clarify re vit d3, my understanding is not that it acts like a steroid, or acts like a hormone, but that it *is* a steroid (sterol subclass) hormone.

in 2006 i remember finding a study that specified immune system action of interferon beta, and that 1,25dihydroxyvitamind3 was found to have the same action on the immune system. i've tried looking for it a few times since with no success. would love to track that sucker down and have another look!

nigel, looking forward to seeing your results :D
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