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25D does not activate VDR
 Moderated by: Dr Trevor Marshall  

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Frans
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 Posted: Wed May 7th, 2008 18:47

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Hi all,

I just came across the following paper, PMID 18398421

They gave people 60.000 iu of cholecalciferol for 8 weeks and after that, they concluded:

The PBMC VDRmRNA expression showed no significant change after cholecalciferol supplementation, making clear VDR is not activated.


Sounds interesting, doesn't it?

I cannot view the fulltext however, so maybe someone can and find out if VDR activity was actually downregulated ?

I want to try to find more papers showing 25D does not activate VDR, maybe others can help dig around pubmed?

Sincerely, Frans



____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
Frans
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 Posted: Wed May 7th, 2008 20:57

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Another interesting paper if I am not mistaken, see PMID 17286279

It states:

"25D inhibits growth of these cells but does not trigger apoptosis or induce CYP24 expression"

seemingly implying that at least several transcriptional activities are actually hampered by 25D, since CYP24 expression, but especially triggering apoptosis (which would make tumors smaller) would be expected from a fully operating VDR

Perhaps because the levels opf 25D were nor high enough (yet) to totally shut down the receptor? I don't know, maybe someone can check the full paper?

Sincerely, Frans



____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
Dr Trevor Marshall
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 Posted: Wed May 7th, 2008 22:02

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Personally, I am not the least bit interested in this topic. I have shown that 25-D inactivates the VDR in exquisite detail, and even the King (or, in UK, the Queen) cannot change the way the body works.

There are a lot of people who think they are experts in understanding the way that Vitamin D works, but unless they take the time to understand the genes transcribed by the VDR then their 'knowledge' is (by definition) a small subset of totality, and their opinions are of little value. At this time we need to be quite prepared to tell them that. This is the 21st Century, and mankind is facing a crisis. It deserves better from those who call themselves "Vitamin D experts".

Here is a paper (that Joyce recently called to my attention) which confirms the metabolic interactions shown in  Figure 1 of my BioEssay, especially the way in which 1,25-D shuts down the PXR and thereby shuts down both CYP3A4 (and hence they observed low levels of 24,25-D) and also CYP27A1 (and hence they observed low levels of 25-D).
http://www.ncbi.nlm.nih.gov/pubmed/9241280
Of course, you will need to get the full text from a library to go through the detailed study results :)

 Here is my position, as I elucidated the other day in the Autism thread:
My BioEssays response, just published this month:
http://www.ncbi.nlm.nih.gov/pubmed/18404718
http://AutoimmunityResearch.org/Bioessays_reply_may08_preprint.pdf
in answer to the letters:
http://AutoimmunityResearch.org/BioEssays_May08_letters.pdf
"Dr Boucher has highlighted many of the difficulties confronting clinical medicine as it expands its knowledge-base from the level of tissues, as seen under the microscope, to that of individual genes and proteins, interacting at the sub-microscopic scale of the molecule. Even though there are decades of clinical studies attempting to delineate the association between health, disease, and the Vitamin D metabolites, any study conducted without reference to genes, or transcription, must necessarily lead to an incomplete characterization."
..Trevor..
 

Last edited on Wed May 7th, 2008 22:07 by Dr Trevor Marshall

Frans
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 Posted: Wed May 7th, 2008 22:33

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Trevor, I know, and I understand and believe what you are showing us, not a doubt in my mind.

The problem is that a lot of people are scared silly by papers like that from Lappe et al.

Now, I have worked through that particular paper and am thoroughly disturbed that a piece of hogwash like that actually got published.

My only goal is to enthuse as many people as possible for the MP, explain that they are being brainwashed, so I am trying to find out as much as possible to cast doubts on those so-called vit. D experts.

dr Stephen Cannell posted a letter on the vit D council website about the MP that made my blood curl and I am preparing a reply for some sites that have referred to that paper and Lappe's paper as being the holy grail...

Your replay to the editor of BioEssays should definitely help in that regard.

Bottomline is, I want to help, cannot sit still, you are clearly more patient than a lot of us  :)

Sincerely, Frans



____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
Dr Trevor Marshall
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 Posted: Wed May 7th, 2008 22:36

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As the great Max Planck observed "Science progresses one funeral at a time."

There is no way you are going to change the minds of the luddites. Focus on locating, and helping, those whose minds are open.

..Trevor..

Martin78
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 Posted: Fri May 9th, 2008 23:36

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Frans, if you register at:

https://docline.gov/loansome/login.cfm

You can order fulltext papers from your nearest library- I use this service alot, the papers cost aprox. 10 EUR and the library I use (University of Oslo) mailes very fast.

As you surely already know some paper are available free full text, like this one:

http://www.ncbi.nlm.nih.gov/pubmed/17945003?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Look out for the square logo in the right corner: "free full text".

Now, if you study this paper it will describe a population study (n>500) with a very high median value of 1,25D.

One of the authors of this paper WAS (I dont think I will see him again) my endo. this autumn whos task was to investigate my 1,25/cal metabolism.  I confronted him with the significant difference between his median values and the Danish pop. study used on the mp-site. He claimed the difference were due to different analyzing methods. I will investigate this further, as I dont have alot of confidence in this endo.

He is regarded as a "calcium" expert and authority, so I find it very strange that he didnt react to my individual variance of calcium levels of beeing 7%, when normal variance should be less than 1,8%. My 1,25 was also consitently around 170 pmol three tests in a row, which he described as "only slightly elevated". Further my PTH was undetectable (>0,6). He also made some remarks around CFS patients I found very disturbing, it was like he denied the diagnose to actually excist. Qoute:"You have probably heard about these ME patients who belives they are so sick"

This guy is frightening me!

I didnt care because I knew I had experienced vitaminoverdosis symptoms long before I even knew that vitamin D exsisted in the blood. so I knew my 1,25 was hyper-homeostatic anyway, thats what kept my so "stubborn" against his claims that my levels very only "slightly" and "almost unsignificantly elevated".

But, anyway. Frans (or others) if you would have any ideas about why the means are so different I would welcome any thoughts on the subject.

BR

Martin

 

Last edited on Sat May 10th, 2008 00:05 by Martin78



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Sjøgrens Syndrome|Fatigue|wt loss|itch|Plantar Fac.|pain|ancle|legs|ches|irritat|depr| hypercalcemia|initial 125D 98|Probe Apr08|Valium| 25D30 Jan15.09|Ph1 Jan15.09|visit
Martin78
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 Posted: Mon May 12th, 2008 19:48

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Trevor, I dont expect you to have time to compare the exact population studies in question, but I would guess that you have studied quite a few population studies of 1,25 levels, and that you had some reason for choosing/deciding that the Danish one was to be the most reliable.

What is your thoughts about why these studies shows so different 1,25 means?

The mean 1,25 (for one group of the cohort (Norwegians)) in the study I gave a link to was around 120pmol (!), how can that be??

Can you give me some clues, just from the top of your mind? Are there different lab. techinal analyzing methods that can give these variations? And if so, how do we know if all the members that posts their test-results are using the same analysing methods? Allthough many comes from Quest, many also comes from different labs all over the world..(?)

BR

Martin

Last edited on Mon May 12th, 2008 20:01 by Martin78



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Sjøgrens Syndrome|Fatigue|wt loss|itch|Plantar Fac.|pain|ancle|legs|ches|irritat|depr| hypercalcemia|initial 125D 98|Probe Apr08|Valium| 25D30 Jan15.09|Ph1 Jan15.09|visit
shamutooth
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 Posted: Mon May 12th, 2008 20:47

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I'm by no means a molecular biologist,but a little bit of wisdom would surely lead people to wonder how mankind has been able to survive up till the early part of last century without D supplementation? Wouldn't we have died off as a species if the authors of these papers are correct? Especially disturbing to me is the intense media coverage of increasing Vitamin D intake,as I've seen how pervasive and misleading the media is in my now full time career trading bond and commodity futures.You learn quickly that people lie but numbers don't...



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MCS,CFS,IBS,insomnia,anxiety,depression,started Doxy July'04, MP Sept. 04; Benicar 40mg 3/day; Phase 2 started 2/2/05; 6/28/05 D results 25D=29,125D=47;11/13/05 25D=10

schesche
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 Posted: Wed May 14th, 2008 01:24

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i liked your last remark...observational science is full of lies..because it is people who think they know something through observation and conclusion without using molecular science as a base--what they are observing  is often flawed--

what i find is many people with TH1 symptoms...go improving when they go to the sea and sun--a warmer climate
if u try to explain to them that the effects are  due to immunosuppression they will and don´t want to understand..( i observed this in myself since earliest childhood..being austrian and australian--cold climate(inflammation) --warm climate(feeling great)...i was sure the sun was good for me, for 35 years...

 they(the patients)  are interpreting it--wrongly



people lie (to themselves) but numbers don´t--

How do you make a  swine learn calculus?

u won´t! even if u feed it all the goodies in the world as a reward




Last edited on Wed May 14th, 2008 01:26 by schesche



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Freddie Ash
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 Posted: Wed May 14th, 2008 02:01

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HI ALL

This is Fred in WV.  This might be a good place to post this.  Our local paper puts a QUOTE OF THE DAY each day and today's said this:

      "THERE IS NO GREATER IMPOTENCE IN ALL THE WOLD LIKE KNOWING YOU ARE RIGHT AND THAT THE WAVE  OF THE WORLD IS WRONG, YET THE WAVE CRASHES UPON YOU."  Norman Mailer

Remember, we are all in this together and I am pulling for us.

Your friend in Sarcoidosis

Freddie



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Freddie: dx-sarc 2/82 lymph; skin, eyes, joints, esophagus, intestines, spleen, heart,lungs-25D-7; 125-D43

 Current time is 12:45



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