Abstract Recent attempts to increase vitamin D supplementation to prevent and treat chronic disease have arisen primarily out of observations of low vitamin D levels (25-D) being associated with a variety of diseases. However, new research indicates that these low vitamin D levels are often the result rather than the cause of the disease process, just as in the autoimmune disease, sarcoidosis. Trevor Marshall, PhD, recently summarized this alternative perspective on vitamin D, in a session he co-chaired at the 6th International Congress on Autoimmunity. He and his colleagues presented in silico* and clinical data from the last eight years, indicating that intraphagocytic bacteria are able to block the vitamin D receptor (VDR), and this leads to abnormally low measured vitamin D levels. A second consequence of the bacteria-induced VDR blockage is inhibition of innate immunity. By blocking the VDR, bacteria are able to cause persistent infection and inflammation and thus cause many chronic diseases. Short-term symptom reduction observed from vitamin D supplementation appears to be due to immune suppression by precursor forms of vitamin D that add to the bacterial blockage of the VDR. In silico data also indicates that high levels of vitamin D metabolites suppress antimicrobial peptide production by binding to other nuclear receptors (e.g., thyroid-alpha-1, glucocorticoid). Increasingly, epidemiological, geographical and clinical data are lending support to this model of disease. Studies using more advanced cell culture and molecular techniques are confirming the presence of previously undetected bacteria, including biofilm and cell wall deficient bacteria, as well as "persisters." A greater understanding of how bacteria resist standard antibiotic approaches is also being gained. A protocol has been developed that is successfully restoring VDR and innate immune function with a VDR agonist and eliminating pathogens with low-dose, pulsed combinations of antibiotics. Immunopathological reactions (a.k.a., Jarisch-Herxheimer reactions) occur due to increased pro-inflammatory cytokines resulting from bacterial killing. The result is an exacerbation of symptoms with each dose of antibiotic, but improvement occurs over the long-term. Remission is being achieved in numerous chronic conditions, including many autoimmune diseases and fibromyalgia, as well as many diseases of aging. Although vitamin D ingestion is avoided as part of this protocol, the evidence indicates that the net result of the protocol is improved vitamin D receptor activation.
Posts: 246 | From Grass Valley, CA | Registered: Jun 2007
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posted
Almost all of the references for that paper are presentations by Trevor Marshall at various gatherings, or the author himself, if you are wondering about the quality of evidence and potential bias.
Posts: 195 | From Manchester, CT | Registered: Jun 2008
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posted
"However, new research indicates that these low vitamin D levels are often the result rather than the cause of the disease process, just as in the autoimmune disease, sarcoidosis."
Ummm, what *research* would that be, exactly?
Posts: 845 | From Eastern USA | Registered: Jul 2006
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bejoy
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posted
Interesting, as there is research that Vit D results in improvements for MS patients. MS is often linked to lyme disease.
-------------------- bejoy!
"Do not go where the path may lead; go instead where there is no path and leave a trail." -Ralph Waldo Emerson Posts: 1918 | From Alive and Well! | Registered: Feb 2007
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When someone has a low vitamin D level, an attempt to determine if they improve or worsen with vitamin D should be made, this is as simple as walking outdoors for 5 minutes on a sunny day. If you feel terrible in the sun, the 1,25 di hydroxy should be tested. If it is high, MP can be should be entertained. Marshall makes assumptions in his theory that may not be well supported, I would like to see absolute proof that bacteria adhere to and inactivate the VDR before I would try to avoid something that has been an important part of our metabolism since the dawn of time. MP works for some, not all, just like anything else.
Posts: 442 | From Biddeford, ME | Registered: Nov 2007
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posted
I have a feeling that some people will do better without D supplementation and some need it. Would be nice if they could figure out which is which.
It does seem possible that pathogens could interfere with this system for some reasons that benefit them. What to do about it though is not clear.
Not sure I entirely trust in silico results.
Why would immune suppression make people feel better temporarily? Because there aren't herxheimer reactions from abx? Because cytokines causing inflammation are suppressed?
Posts: 8430 | From Not available | Registered: Oct 2000
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oxygenbabe
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Science News writeup of new study
Molecular link between vitamin D deficiency and MS The vitamin may interact with a gene associated with multiple sclerosis By Tina Hesman Saey Web edition : Thursday, February 5th, 2009 font_down font_up Text Size
Scientists are shining some sunlight on the molecular connection between vitamin D deficiency and multiple sclerosis.
A form of vitamin D triggers activity of an immune system gene linked to the disease, researchers from the University of Oxford and the University of British Columbia report in a study published online February 6 in PLoS Genetics.
Epidemiology reports have previously found that the farther people live from the equator, the more likely they are to develop multiple sclerosis. MS is an auto-immune disease in which the body attacks the myelin sheath that protects nerve cells. More than 2.5 million people worldwide have the disease.
People who have multiple sclerosis often have low levels of the vitamin in their blood. But scientists did not know how vitamin D works in the immune system, or how deficiency of the vitamin is connected to the disease. The new study is the first to establish a genetic link between MS and vitamin D.
``It's certainly teasing away at understanding why someone develops MS to begin with,'' says Patricia O'Looney, vice president of biomedical research at the U.S. National Multiple Sclerosis Society in New York City.
Previous genetic studies have shown that people with one variety, or allele, of the HLA-DRB1 gene have a greater chance of getting MS. The gene is located in the major histocompatibility complex on chromosome 6, one of the most variable regions in the human genome. HLA-DRB1 comes in 400 varieties. One of those alleles, designated HLA-DRB1*1501, is the most common variant in Northern Europeans and those who carry the allele have a three times greater risk of developing MS...
More on the Miracle of Vitamin D - Part Two (of Three) Last month we began a discussion of vitamin D. As you may recall from my article and my book, The Lyme Disease Solution, I am a major supporter of blood testing for vitamin D levels and of treating vitamin D deficiency aggressively using "vitamin D3". As I expected, I received several responses from readers challenging the notion that vitamin D was, in fact, beneficial in the chronic Lyme disease setting. Therefore, in this article I wish to first of all deal with the idea that vitamin D is harmful to Lyme patients.
Several years ago I became aware of something that many of you know called the "Marshall Protocol" (MP). Originally developed to help patients with sarcoidosis by Trevor Marshall, Ph.D., his theories led him to recommend his protocol for the treatment of patients with other chronic inflammatory conditions such as chronic fatigue, fibromyalgia, and chronic Lyme.
Basically, the protocol consists of 3 components: (1) low dose antibiotics (primarily minocycline), (2) use of an oral antihypertensive (in the ARB class) called Benicar, and (3) severe restriction of vitamin D both via dietary restriction and reduction of sunlight exposure. This protocol got my attention primarily because it was being recommended by an LLMD whom I respect, Dietrich Klinghardt, M.D., Ph.D. (Interestingly, Dr. Klinghardt has subsequently stated on a DVD in 2006 that his MP results had been disappointing.)
A thorough review of the MP is much too large a subject to attempt to tackle in this Newsletter. In short, I do not believe that the preponderance of evidence shows that vitamin D (in either the 25-OH or 1,25-OH form) clinically acts as an immunosuppressive steroid, as alleged by the MP. Rather, I see vitamin D as being a very important immune-modulating substance that ramps up "Th1" when needed and cools down "Th1" when not needed. I refer you a very scholarly webpage that discusses the controversy related to the MP in great depth. Please see the following excellent site that covers the topic very well: http://stuff.mit.edu/people/london/universe.htm
Meanwhile, if your LLMD is using the MP and you are doing well, I do not recommend that you make any major changes based on this Newsletter alone. However, if you are improving, the truth is that it could very well be due to the low dose antibiotics being used on the MP. I doubt vitamin D deprivation has much to do with any benefit you are gaining. My experience would say that there is not nearly enough evidence to justify restriction of such an important thing as vitamin D.
The next topic I wish to cover transitions nicely from the previous discussion. Did you know that vitamin D has important antibiotic properties? The story of tuberculosis (TB) illustrates this well. Before the advent of antibiotics against TB in the 1950's and 1960's, the treatment for TB was a three step program: get several months of rest (for instance at a "sanitorium"), drink one quart of milk daily, and get several hours of sunlight exposure daily. It turns out that this treatment protocol helped many people recover from TB. The secret to its success was, in great part, due to the effect of sunlight in increasing levels of vitamin D in the body. Vitamin D was instrumental not only in improving immune function, but also in the production of a substance called "cathelicidin". Cathelicidin is produced by the white blood cells and is active against viruses (ex. influenza and cold viruses), tuberculosis, and fungi.
Could it also have effects against Lyme bacteria? If so, is this why Lyme patients generally feel much better in the summer when sunlight exposure raises vitamin D (and cathelicidin) levels in the body? No one knows for sure, but I suspect that trio of sunlight, vitamin D, and cathelicidin is very helpful for both its immune supporting properties and its possible antibiotic effects against Lyme.
What about testing for vitamin D? The consensus among experts is that the best blood test to do is the "25-OH vitamin D" level. It is the form of vitamin D that is made by the liver and is a true indicator of the vitamin D status of the body. It is then activated by the kidneys and at the local tissue level to the active form called "1,25-OH vitamin D". While the MP recommends testing 25-OH and 1,25-OH, I would disagree with the need to test 1,25-OH. And I recommend reading the above mentioned webpage in order to understand all the reasons for omitting the test for 1,25-OH.
Are all labs able to do accurate vitamin D testing? The major commercial labs are Labcorp and Quest. Both do vitamin D 25-OH levels. However, there is a fundamental difference in the methodology used by each lab. Quest uses the LC-MS/MS (liquid chromotatography-mass spectrometry) method. Labcorp uses the more reliable Liaison (DiaSorin) method. My understanding is that the Labcorp methodology is the preferred method and, therefore, this is the lab you should request for having your vitamin D assay done if at all possible.
What are the normal and optimal levels for 25-OH vitamin D? You will find vitamin D levels measured using 2 different types of units: (1) ng/ml and (2) nmol/l. The most common way of reporting vitamin D levels is in the "ng/ml" format (used by the commercial labs) and that is the one we will use in the Newsletter. Here is what we consider to be "normal" and "optimal" levels of vitamin D.
Normal levels: 20-56 ng/ml Optimal levels: 45-65 ng/ml (and should never fall below 30 ng/ml)
How often should a vitamin D level be checked? In general, I recommend checking vitamin D 25-OH levels two to three times a year - in the fall, the mid winter, and perhaps sometime in the summer (to see if supplementation is necessary when sun exposure is at its greatest).
Next month I will discuss in the Newsletter the best ways to achieve an optimal level of vitamin D. We'll look at sunlight exposure and sunscreens. We'll look oral supplementation - vitamin D2 vs. D3. We'll answer the question of how much to take in order to predictably raise your levels. And more.
Posts: 1155 | From Southeast | Registered: Oct 2005
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posted
I had forgotten to mention that MIT website Singleton references. That page is truly a gem. Someone debunked the living bejesus out of the marshall protocol, and while it will take a couple hours to read, its definitely worth your time.
Posts: 195 | From Manchester, CT | Registered: Jun 2008
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METALLlC BLUE
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Member # 6628
posted
When I asked my physician in NY about Vitamin D and the Marshall Protocol yesterday I was told and I quote "Avoiding sunlight, and allowing vitamin D levels to drop to near zero by avoiding not only sun, but all varieties of vitamin D in foods as well, is extremely unhealthy and will lead to serious problems eventually, I do not advocate for the Marshall Protocol, and feel it should be avoided. We have seen hundreds of patients through our practice who have tried to use the protocol as directed by Dr. Marshall only to see them return years later much sicker than they previously were. Some occasionally improved-- only to relapse later --, but I'd say 99% did not based on our observation and testing."
It's one opinion, not a fact, but I asked because I had been following these threads on Vitamin D.
-------------------- I am not a physician, so do your own research to confirm any ideas given and then speak with a health care provider you trust.
oxygenbabe
Frequent Contributor (1K+ posts)
Member # 5831
posted
METALLIC...In NY we only get Vitamin D from our sun from March thru October. Nov-Feb the angle of the sun is such we can't make Vitamin D--and Mass. may be worse...so stock up on your sun in the summer so it carries you thru the winter.
I can't wait for March...I take my daily walks, I am going to sunbathe!
Posts: 2276 | From united states | Registered: Jun 2004
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posted
I did the MP for 6 months... It made me so sick we didn't know what would happen to me. I could not lift my head, speak, walk, or get out of bed... I was even too sick to leave the house to get to a doctor. It took me MONTHS to recover from what the MP did to me, and I think I may still be recovering from effects of it.
My Vit D level was 4 on the MP. My 1,25 D was NEVER elevated yet I was told I was a candidate for the MP... It works for some, but NOT everyone...
If there was no sun, there would be no life.
-------------------- "You'll be surprised to know how far you can go from the point you thought it was the end" Posts: 946 | From Massachusetts | Registered: Apr 2008
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METALLlC BLUE
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Member # 6628
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OB, that's exactly what my LLMD said to me yesterday. About the angle, sunlight from Nov, March etc. Funny you mention it.
-- Mike
-------------------- I am not a physician, so do your own research to confirm any ideas given and then speak with a health care provider you trust.
map1131
Frequent Contributor (5K+ posts)
Member # 2022
posted
In my experience, which is all I know for sure, my situation...Vit D3 helps me. I've recently been blood tested for this.
I don't have the results yet. I've just never bougth into the Marshall protocol. But that again is based on what has happened to me the last 10 yrs.
Many over the years have complained about the sun making them feel more ill. Many of us have said the sun actually makes us feel better. This must be based on individual needs or illnesses.
Since all of us do not present with the exact same bacteria, virus or parasite illness, or the same difiencies????
If the Marshall protocol is helping you to wellness, that's great. But I know without a doubt, if I had no sun, I might as well be dead.
Sunshine is one of my favorite pleasures.
Pam
-------------------- "Never, never, never, never, never give up" Winston Churchill Posts: 6478 | From Louisville, Ky | Registered: Jan 2002
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METALLlC BLUE
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Member # 6628
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Yeah, I don't discount it entirely. I've heard of success stories directly from people who I know. They are far and few however, so I'm not sure.
-------------------- I am not a physician, so do your own research to confirm any ideas given and then speak with a health care provider you trust.
lymeHerx001
Frequent Contributor (1K+ posts)
Member # 6215
posted
Im bumping this instead. And Im reading it.
Is marshal an oddball or what? Maybee he is groundbreaking. What camp do I follow. I want to get better dammit!
Posts: 2905 | From New England | Registered: Sep 2004
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
MS has been linked to reactivated HHV6. Oct, 2008
Vitamin D - prolactin (Prolactin given to mice spontaneously restored the myelin sheath.):
"Synergistic Activation of the Prolactin Promoter by Vitamin D Receptor and GHF-1: Role of the Coactivators, CREB-Binding Protein and Steroid Hormone Receptor Coactivator-1 (SRC-1)"
Overexpression of IL 6 looks to be harmful to the cells that make the myelin sheath:
"One of the cell types injured by high levels of IL-6 includes oligodendrocytes, which help produce the protective myelin sheath coating around nerve cells."
However,
"sIL-6R/IL-6 complex can stimulate neurites outgrowth promote survival of neurons, hence may be important in nerve regeneration through remyelination."
Okay...so is a pathogen, a virus, locking onto the IL-6 receptor preventing IL-6 from working?
Hepatitis B?
"Possible role of human interleukin-6 and soluble interleukin-6 receptor in hepatitis B virus infection"
Vitamin D and IL6:
"Inhibition of p38 by Vitamin D Reduces Interleukin-6 Production in Normal Prostate Cells via Mitogen-Activated Protein Kinase Phosphatase 5: Implications for Prostate Cancer Prevention by Vitamin D"
Stress makes MS worse.
" Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis."
When estrogen drops = more pains, gals.
Townsendletters lost me as a reader in Dec., 2008 when they published an article by Dr. S.
[ 02-20-2009, 02:15 AM: Message edited by: Marnie ]
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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posted
D is question we all have to answer for ourselves. For me, I eat well and I supplemented D and Fish oil well before all hell (Lyme and co.) broke loose. So diet was not an issue. And though I have a desk job, I walk the dog, run and ride the bike year round, so sun exposure was not an issue either. But the D 25 came in low, and the 1,25 a little elevated.
So Marshall made sense to me. After six months of treatment, it seemed like Lyme and co. was winning, so the tx was altered; Benicar was added to a Marshall-similar (more and more often) quiver of pulsed abx.
I do not avoid D, nor do I add it. Same with sunshine. I am looking forward to the most recent D 25 and D 1,25 lab findings. I will then re-evaluate supplements/restrictions.
But in the meantime I feel better. I felt better the week I started the Benicar. It has been a slow-go since (2.5 months) but I have been strong enough to do a snowboard vacation, and sign up for a mountain bike race.
I do not know the reason for the improvement, or if it will continue. I just wanted to add to the conversation -- from somewhere in the middle of the "to D or not to D" world...
-------------------- enjoy the day.
-jmb Posts: 208 | From Maryland | Registered: Dec 2008
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lymeHerx001
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posted
jmb, did you notice anything with your blood pressure after starting benicar?
Posts: 2905 | From New England | Registered: Sep 2004
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posted
I watched the BP rise, from a baseline of 115/75 to 150/90, over six months. So I welcomed the Benicar if only to lower the pressure. I started with a low dose, and upped it to the minimum Marshall-specified dose of 40 every eight hours.
The MP folks will tell you that Benicar is not a very good blood pressure med; I think they quote studies showing 12 mm is the max reduction. I picked up a portable blood pressure monitor when I began the Benicar, and still keep a log. I have seen it as low as 95/60 but in general I see 110/70.
I can tell you that once in a while I will "stand up too fast" (but have never fallen down.) I am an over-analyzer so I will note that in general I have noticed a slight decrease in aerobic capabilities since I started Benicar, but I am not sure I can blame the medication -- as winter weight is the (figurative) elephant in the room. I will continue to monitor as springtime and summer roll around.
Also since I started the Benicar I have not had a ``head-splitter'' headache, which I endured like clockwork every 12 days from the onset of sickness, and like I said I do feel like I am small-stepping to feeling well. Executive function is still a bit of a weakness.
So if you see some on the street or at the market, please send it to me...
-------------------- enjoy the day.
-jmb Posts: 208 | From Maryland | Registered: Dec 2008
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Bugg
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Member # 8095
posted
JMB--
I'm so pleased to read about your progress....Please keep us posted on what works for you...I think it's so wonderful that you're winning the battle against this disease...
Posts: 1155 | From Southeast | Registered: Oct 2005
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posted
hey jmb - like many others here, i'm so confused on this D issue and like you, i ate very healthily and supplemented D3 and fish oil for several years before i started feeling sick.
according to what you've learned, what lab values do you think constitute a high D 1,25? and a low D 25? mine, taken last month, were 45 (1,25) and 39 (25) - do you think that makes me a candidate for trying to reduce (or at least not supplementing) with D3?
thanks!
-------------------- Increasingly ill over past 10 yrs; treating since October '08. Posts: 180 | From Philadelphia, PA | Registered: Oct 2008
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posted
the first D lab, 2 months after the onset of illness, was 28. i have had two others and the numbers were 27 and 28. Then I had the the D 1,25 tested too. D was 30.5 and D 1,25 was 34.5.
I found it strange since I had stopped supplementing D before last lab, and yet it went up.
The reference ranges (normal) are 32-100 for d and 15.9-55.6 for D 1,25. If you want to know what Marshall thinks "normal" is, head over to the MP study site.
BAsed on the numbers I would not call me a "prime candidate" for Marshall-type treatment, but based on lab trends and based on how I felt, I decided to add a little Marshall to my protocol.
I'll keep you posted on the D and D 1,25 lab findings; I should hear in a couple weeks. Hope this helps. Good luck with your research.
-------------------- enjoy the day.
-jmb Posts: 208 | From Maryland | Registered: Dec 2008
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posted
thanks for the info, jmb - do keep us posted on what your hear ~ your D labs!
out of curiosity, which aspects of the MP are you following? just the benicar? or specific antibiotics, as well?
thanks again!!
-------------------- Increasingly ill over past 10 yrs; treating since October '08. Posts: 180 | From Philadelphia, PA | Registered: Oct 2008
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posted
This new MP paper really adds nothing to the mix.
The theory in it may or may not be right. Who knows?? Most likely it's a little bit right somewhere, but mostly wrong everywhere else. But, either way, there's no new science here that I can see. It is another hashing out of the same theories.
Interestingly, all the references on the key points come from people involved with the MP or from the big man himself. Also interesting, was after spending a good bit of time trashing the idea of observational studies and causation, they turned around and used one when it suited their needs -- vitamin d associated with brain lesions.
Funny how that one study is okay, but all the others, hundreds if not thousands by now, that show the *possible* benefits of d are dismissed.
I don't know what to think, but at this point would prefer a normal d level to a deficiency (which I had, and may have again until summer).
Posts: 845 | From Eastern USA | Registered: Jul 2006
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