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Borrelia burgdorferi reduces VDR expression
 Moderated by: Prof Trevor Marshall Page:  First Page Previous Page  1  2  3  4  5  Next Page Last Page  
 

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Aunt Diana
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 Posted: Tue Nov 17th, 2009 10:46

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Good luck with your doc. Be sure to print out the article on Amy Proal's website http://www.bacteriality.com re: Vitamin D. She explains it in simple terms.



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Lyme 1987, neuro cardio fatigue achiness brain fog depression, anxiety. Pacemaker, D.1,25 32; D <5; 12/07 <6, hydrocodone, lorazapam, benedryl, zantac, colase, Noirs, cover-up or avoid sun, house <30lux. Feb 08 Phase 3. 6/08 D <4, D1,25
paulalbert
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 Posted: Tue Nov 17th, 2009 11:01

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Everything you say is pretty much right except re: #5, we are also concerned that 25-D will bind and inactivate the VDR. Also, re: #6, when Benicar binds the VDR it turns it on transcribing enzymes which reduce high levels of 1,25-D, which reduces the chances that high 1,25-D interferes with other receptors - many of which also play key roles in immune function.

If you want to know what Marshall says about what is happening to cause your vitamin D metabolites to be out of whack, check out this article:
http://mpkb.org/doku.php/home:pathogenesis:vitamind:mechanisms

That said, I wouldn't go too deep into the molecular biology or the bacteria. You could say that it has been our experience that people simply do not get better when they have high levels of 25-D. You could also point out that MP patients take a medication that binds to and activates the Vitamin D Receptor, so you are in a completely different boat than most other people with an inflammatory disease. And then say, if you have any questions, have a look at this peer-reviewed paper.
http://autoimmunityresearch.org/transcripts/AR-Albert-VitD.pdf

Paul



____________________
Diag CFS 6.03 / sympt since 9.02 / exercise, food intol, sleep prob / 1,25D: 16, 4.06; 1,25D:27, 25D:26 7.04; 1,25D:43, 25D:6 6.05; 1,25D:17, 25D:8 8.05; / MP: 7.04 / Ph. 3 / Bacteriality
Cynthia S
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 Posted: Tue Nov 17th, 2009 17:05

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3,4, and 5 seem to leave out the suppression of the immune system by the VDR itself being blocked.  Here is a summary I put together for Bill-K in the TH1 questions forum:

"A) The VDR is responsible for a great deal including
  1) part of innate immunity
  2) a feedback system controlling the level of 1,25D

B) Several other nuclear receptors are responsible for many things including
  1 )part of innate immunity

C) 25D (and D2 & D3  also) blocks the VDR and shuts it down resulting in, among other things
  1) From A1, suppression of the immune system to a degree 
  2) From A2, disregulation of 1,25D allowing 1,25D to go too HIGH resulting in
      a)1,25D docking in other nuclear receptors where it does not belong shutting them down resulting in
             1) From B1, further suppression of the immune system

So you see, high 1,25D does suppress the immune system and is accounted for in the MP.  And unfortunately, as you can see, 25D has a double whammy effect on the immune system."

Cynthia



____________________
MP start 10/08,break 1/16 - 9/16, Spondylitis'97,early Diverticulosis'98,early AMD'08,Calcium anomaly'95,TypeII Diabetes(?)'02,Degenerative hip disease'12, 25D=14.3ng/mL 10/15 (preMP 125D/25D=47/43) https://marshallprotocol.com/forum30/13911-2.html
thelymelight
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 Posted: Sun Nov 22nd, 2009 08:11

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Okay I am getting my notes together and constructing a document I can read to my Endo at my next appt.

Is it the 1-25 being too high that causes the innate immune system to shut down?

If so, at what level does it start to do this...or what level is considered acceptable and by whose standards?  I remember reading something in the past about the Merck Manual...Is this where we are getting our numbers from or is this the standard book in medicine?

I ask b/c when I first mentioned the MP to her in 2005 (on the recommendation of my G.P. at the time)...As he felt of all the info, I have ever brought to him on treatments for chronic Lyme /CFS.....he said this (MP) makes the most sense to me as it is scientifically based..

Anyways back in 2005, I had my first 1-25 D levels checked and they were 173 pmol/L (or 72.08 pg/ML) which is HI as the range here in Canada at that time was 30 - 120 pmol/L

At that time my Endo said my levels weren't really that high as labs were now changing the acceptable levels of 1-25 D to be up to 150 pmol/L.

As of Sept 2008 (8 months of being on Olmesartan & NO Minocin) my 1-25 levels dropped to 73 pmol/L , which is 30.41 pg/ML and my 25-D is now 14 nmol/L or 5.6 ng/ML

Is my 1-25D level too low now?

Thanks!!!:D




____________________
MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
jcwat101
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 Posted: Sun Nov 22nd, 2009 09:13

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Both a high 1,25-D and a high 25-D can contribute to suppression of innate immune function according to the MP perspective.

I discuss this in the NY Annals paper (Waterhouse et al, see http://mpkb.org ).

Your 1,25D is fine now and so is your 25D.  Yes, we use the Merck manual limit.  I think others raise the limit because they don't understand what a high 1,25D means.  You might also show your doctor the paper by Blaney et al (also in the KB).

Joyce Waterhouse


PS  The MP perspective is that it is not necessary to measure 1,25-D once one has started the protocol.  One might review the KB with regard to measuring D metabolites and related documents for more on this.

Last edited on Sun Nov 22nd, 2009 12:10 by jcwat101



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20 yrs with CFS/FM/Lyme/IBS, food sensitivities; 1,25D/25D 8/04:64/11 http://SynergyHN.wordpress.com
Joyful
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 Posted: Sun Nov 22nd, 2009 18:50

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Lisa, this article, " Test: 1,25-dihydroxvitamin D (1,25-D)", in the MP KB gives some information on the lab ranges also.



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Marysue
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 Posted: Sun Nov 22nd, 2009 20:37

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Joyce,
Thanks so much for mentioning your article here. I had printed out the "six key papers" and have been working through reading them all but hadn't finished yours yet. Now I have and....wow--what a great explanation of the impact of VDR dysregulation all in one place. I've been flipping around between 4-5 different links to information and trying to piece it all together. Each link covered part of it, and some were more detailed than I could fully grasp.
You and your "et al partners" (Tom Perez and Paul Albert) did a great job explaining it all in a very readable format. For anyone who hasn't read it yet, here is a direct link to the full 11-page preprint:

Reversing Bacteria-Induced Vitamin D Receptor Dysfunction is Key to Autoimmune Disease
Pages 5-7 in particular cover the impact of high vitamin D levels on innate immunity and using serum levels for diagnostic purposes.

Thanks again for all your hard work.:)
Marysue



____________________
MP Apr09 (no breaks)| CFS/FM,infert/endometriosis, Autism Spec | hypotension, cardiac IP, chronic muscle/joint pain, severe light sensitivity, sensory/auditory processing | last 25D=12.5 Sep'11
thelymelight
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 Posted: Thu Nov 26th, 2009 08:03

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When you see so many reports in the news about how Vit D is good for your immune system and that it can help reduce cancers etc...

Is there actual research proving this?  OR....Are the researchers just making a conclusion (without any proof) that low levels of 25- D contribute to/cause cancer....because they find that so many people who get cancer, have these low levels of 25-D and thus are making an assumption.

Just wanting to get my facts accurate...As I know the Endo is probably going to say to me, that everything I am telling her is wrong and incorrect about our high 1-25D & low 25-D's and that we need Vit D to prevent cancers etc....

Thanks!! :)



____________________
MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
paulalbert
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 Posted: Thu Nov 26th, 2009 08:07

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Here's the ol' KB article on cancer and vitamin D:
http://mpkb.org/doku.php/home:pathogenesis:vitamind:cancer

This article may also be helpful:
http://mpkb.org/doku.php/home:pathogenesis:vitamind:mechanisms

Best,
Paul



____________________
Diag CFS 6.03 / sympt since 9.02 / exercise, food intol, sleep prob / 1,25D: 16, 4.06; 1,25D:27, 25D:26 7.04; 1,25D:43, 25D:6 6.05; 1,25D:17, 25D:8 8.05; / MP: 7.04 / Ph. 3 / Bacteriality
thelymelight
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 Posted: Thu Nov 26th, 2009 10:08

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Tanks Paul..will take a look!!



____________________
MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
Joyful
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 Posted: Thu Nov 26th, 2009 13:36

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Lisa,

Paul has written some other good articles in the MP knowledge base too...

See especially:
Mistaking correlation for causation in vitamin D studies
(http://mpkb.org/doku.php/home:pathogenesis:vitamind:correlation)
Also:
Assessing the published literature
Immunosuppression and insufficient followup in vitamin D studies
Koch's postulates
Latitude studies on vitamin D and disease
Palliative vs. curative treatments



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Marysue
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 Posted: Thu Nov 26th, 2009 17:53

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Joyful, thanks for those extra links.
In the "Assessing the published literature" section, #5 states, The concept of the “blood-brain barrier” has lost meaning in today's world of molecular genomics.2
And, there is a link to this pubmed article/abstract:
http://www.ncbi.nlm.nih.gov/pubmed/19228962
Could someone (maybe Paul:)) explain this article to me. I get that it has something to do with contradicting current thinking about the blood-brain barrier since you referenced it, but I don't understand what the article is saying enough to make the connection.

Marysue



____________________
MP Apr09 (no breaks)| CFS/FM,infert/endometriosis, Autism Spec | hypotension, cardiac IP, chronic muscle/joint pain, severe light sensitivity, sensory/auditory processing | last 25D=12.5 Sep'11
paulalbert
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 Posted: Fri Nov 27th, 2009 16:48

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Marysue,

Well, according to Trevor and co., the blood-brain barrier is this idea that all types of stuff - chemicals, drugs, bacteria - are incapable of passing the barrier, but this study and various others suggest the opposite.

Here's the Wikipedia article repeating some of the folklore:
http://en.wikipedia.org/wiki/Blood-brain_barrier

Best,
Paul



____________________
Diag CFS 6.03 / sympt since 9.02 / exercise, food intol, sleep prob / 1,25D: 16, 4.06; 1,25D:27, 25D:26 7.04; 1,25D:43, 25D:6 6.05; 1,25D:17, 25D:8 8.05; / MP: 7.04 / Ph. 3 / Bacteriality
Marysue
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 Posted: Fri Nov 27th, 2009 21:39

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Thanks Paul.

The descriptions of the various diseases associated with the blood-brain barrier listed there (in Wikipedia) are interesting. Hmmmm....more examples of "bacterial involvement" regardless of whether the blood-brain barrier actually exists as stated or not.

Marysue



____________________
MP Apr09 (no breaks)| CFS/FM,infert/endometriosis, Autism Spec | hypotension, cardiac IP, chronic muscle/joint pain, severe light sensitivity, sensory/auditory processing | last 25D=12.5 Sep'11
jcwat101
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 Posted: Sat Nov 28th, 2009 04:41

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My recollection is that the point is that the barrier is not totally absent but that it is just not as effective as previously thought.  Some things don't get through very well, but others do.  And how much of a barrier it is may also vary according to the individual and the circumstances and what substance or cell type is at issue.

Joyce Waterhouse



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20 yrs with CFS/FM/Lyme/IBS, food sensitivities; 1,25D/25D 8/04:64/11 http://SynergyHN.wordpress.com
paulalbert
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 Posted: Sat Nov 28th, 2009 07:35

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Good point, Joyce. I didn't mean to imply that everything gets through.

Paul



____________________
Diag CFS 6.03 / sympt since 9.02 / exercise, food intol, sleep prob / 1,25D: 16, 4.06; 1,25D:27, 25D:26 7.04; 1,25D:43, 25D:6 6.05; 1,25D:17, 25D:8 8.05; / MP: 7.04 / Ph. 3 / Bacteriality
thelymelight
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 Posted: Sat Nov 28th, 2009 14:53

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Thanks Joyful for the additional links to articles



____________________
MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
thelymelight
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 Posted: Wed Dec 23rd, 2009 07:43

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UPDATE with BONE SPECIALIST :

Okay folks, here’s how my appt went with the Bone Specialist.

She actually took the time to listen to me explain some of the info behind the MP and she did take a quick look at some of the research papers I brought her…(this is a step forward from when I saw her last year).

While she may still not quite understand all the workings of the VDR & innate immune system etc..She still disagrees with me keeping my 25-D (Vitamin D stores so low).

She acknowledges that 1-25 is what build bones/density…But she said I will develop SOFT BONES without enough D stores, which is what the body needs to assist in absorbing Calcium….This is different than having less dense bones, which is where the 1-25 D comes in.

She has had patients who have had normal 1-25 D levels, yet still had ‘fractures and when they went in and did a bone biopsy their bones were all MUSHY (Soft Bones) So she said just because you have a normal 1-25 D, doesn’t mean you are not a risk for developing Osteomalacia…soft bones….

She also said you can’t rely on the Merck Manual for 1-25 D levels, as each lab uses a different assay for their test, they are not all the same…

She also made some rude comment that b/c Dr. Marshall is not an M.D., he really doesn’t understand how all the physiology works (or something to that affect, can’t remember the word she used right now)..So then I said well the Dr. who is overseeing my care while on the MP, is very knowledgeable of the protocol and “IS” an M.D….She then said, Yes, but he isn’t a bone specialist…..I think no matter what I say, she would have an answer for everything.:X

While I respect Dr. Marshall’s discoveries & research very much,  I feel I also need to respect and be open to where she is coming from ie - her education, knowledge and first hand experience dealing with patients, as a Bone specialist/calcium disorders clinician… 

When I looked up info on the Knowledge Base site under “Concerns for Physicians” I see concern #4 is  re: “Avoiding consumption of Vit D leads to Osteoporosis” when I explored the link further,  there are only 3 studies quoted, that dispute Vitamin D supplementation can prevent Osteoporosis etc…But there is no mention of Vitamin D preventing SOFT BONES…which I would suspect is an entirely different thing…

My concern is: Does my Bone Specialist have a valid point about keeping my Vitamin D stores up, to assist with calcium absorption so as to prevent developing SOFT BONES?

If not, then why?


Is it possible we are overlooking something important here? :?



____________________
MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
Prof Trevor Marshall
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 Posted: Wed Dec 23rd, 2009 09:15

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Bone matrix is dependent on estrogen homeostasis, not on Vitamin D. The estrogen receptor is expressed by the VDR. If your bone specialist did not stress the importance of estrogen to bone matrix then she is way out of her depth.

We have already been there, done that, years ago.

Get another bone specialist :)

..Trevor..


http://www.nsbri.org/HumanPhysSpace/focus6/ep_development.html
 
http://endo.endojournals.org/cgi/content/abstract/138/7/2919

http://www.ncbi.nlm.nih.gov/pubmed/12682916
 

leroybrown
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 Posted: Wed Dec 23rd, 2009 14:51

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I wonder if bone marrow is too?



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I just know that something good is going to happen
And I don't know when - Kate Bush
Aplastic anemia Apr/10, PRCA Jan/09, Agranulocytosis 1991
25D = 25 1,25D = 58 Aug 18/09|25D<4.8 Mar/10|10.8 Nov/12
Sep '09 q8h Nov '09 q6h

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