Jump to content
RemedySpot.com

Re: Article on Vitamin D

Rate this topic


Guest guest

Recommended Posts

>

> http://trevormarshall.com/BioEssays-Feb08-Marshall-Preprint.pdf

>

> I would be be interested in any thoughts about it

Hi athan;

There are some things in the article by Trevor Marshall that I do

agree with, and others that I don't. I'll try to explain as best as I

can, and I hope that I don't loose you (and other readers) in the

process.

First, I do agree that vitamin D is not only a vitamin, but also an

important hormone with lots of biological effects, including causing

changes in the expression of a huge number of genes. The number of

changes in gene expression regulated by the active metabolite (1,25-

dihydroxyvitamin D) binding to the vitamin D receptor (VDR) is much

too large for the human brain to comprehend .... we need a computer

model of all the interactions to begin to accurately predict all the

biological responses.

Because vitamin A (retinol) does something similar ... i.e. is

metabolized in two steps to compounds (retinoic acids) that bind to

receptors (retinoic acid receptor (RAR) and retinoid X receptor

(RXR)) that then bind to a whole bunch of other receptors (including

VDR, PXR, LXR, PPAR) that affect expression of a multitude of

genes .... shouldn't we also call vitamin A a hormone? And why stop

there, since beta-carotene is metabolized in 2 steps to retinoic

acid, should we call carrots a hormone? And since docosahexaenoic

acid (DHA) (found in fish oil) binds to RXR and PPAR, causing a large

number of changes in gene expression, should we call DHA a hormone?

Shouldn't FDA also be regulating how many carrots we eat or how much

fish we eat, or fish oil supplements we take? The bottom line is that

a lot of nutrients have a marked effect on gene expression, and there

is not really a need to single-out vitamin D.

Second, I do agree that low values of 25-hydroxyvitamin D (the form

of vitamin D that is usually measured) CAN be the result of the

disease process. In the case of inflammatory bowel disease and

cholestatic liver diseases like PSC and PBC, there is good evidence

that absorption of vitamin D from the digestive system is impaired.

In the case of inflammatory bowel disease the level of 25-

hydroxyvitamin D (the main storage form of vitamin D) tends to be

reduced, and this level correlates with bone mineral density

(especially in males). Not surprisingly, then, supplementation with

vitamin D (and calcium) tends to rectify the metabolic bone disease

associated with IBD. This would not be expected if you believe

everything said in the Marshall article!

Could vitamin D deficiency tend to make the disease worse? Sure!

Because vitamin D plays an important role not only in bone metabolism

and the immune system (including how T cells migrate to various sites

in the body, and how much anti-bacterial peptides are produced, and

how strong the epithelial barrier is in the gut, and how much of the

inflammatory cytokine tumor necrosis factor alpha is produced),

deficiency of vitamin D would not be good for you in the long run.

Similarly, prolonged vitamin A deficiency would not be good for you

because vitamin A also regulates how and where T cells migrate, how

strong the epithelial barrier is in the gut, and how much IgA is

produced in the gut. The best way to rectify any deficiencies is

through supplementation .... and I am certainly all for this except

that this has to be done with caution to avoid potential toxicity

from over-doses.

The article by Trevor Marshall has some strong points. I like his

Figure 1, showing that the pregnane X receptor (PXR) is involved in

regulating not only 25-hydroxyvitamin D synthesis, but also 1,25-

hydroxyvitamin D catabolism. Because PXR is markedly down-regulated

in ulcerative colitis, this probably means that in ulcerative colitis

there would be impaired conversion of dietary vitamin D (or sunshine

generated vitamin D) to 25-hydroxyvitamin D. In principle, this

metabolism could be restored by taking rifampin, which is a PXR

activator (and used to control pruritus in PSC and PBC patients).

However, the long-term effects of rifampin therapy on 1,25-

hydroxyvitamin D catabolism are a concern to me [my son is taking

rifampin]. Will long-term treatment with rifampin require higher

vitamin D intakes to prevent depletion of vitamin D reserves? ... I

don't know.

While the article by Marshall is a bit controversial, it does get us

all thinking about what differences we might make to our long-term

health if we make sure we don't become nutrient/vitamin/hormone

deficient, and avoid taking too much of any one

nutrient/vitamin/hormone. Something that Marshall did not really

elaborate on was that the VDR actually pairs up with RXR to effect

changes in gene expression. What's the activator of RXR? Many suggest

that it is 9-cis retinoic acid, a metabolite of vitamin A. But others

point out that this metabolite cannot be reproducibly measured, and

that the best candidate 'natural' ligand for RXR is actually

docosahexaenoic acid (DHA). Regardless of who is right on this

specific point, does this mean that in order for VDR to function

properly, you also need either DHA of vitamin A? It's not just one

hormone/vitamin/nutrient that matters, but rather it's best to have a

good balance for everything to work properly!

I love Marshall's idea that certain bacteria might actually be

producing compounds that bind to VDR and prevent it from working. In

fact that's essentially the same idea that I have had about PSC,

namely that some as yet unidentified bacteria in the gut produces a

retinoic acid derivative that binds to RXR and prevents it from

working properly, disrupting bile, lipid, xenobiotic and bone

metabolism, bile transport, and the immune system.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

P.S. I tried to avoid using references this time, but would be glad

to provide any if anyone is interested in more detail.

Link to comment
Share on other sites

Join the conversation

You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

Loading...
×
×
  • Create New...