Marshall Pathogenesis and Protocol

[Guest guest]

I know this issue has been raised a few times here before. But I'm hoping that

at some

point we may see a critical review of the Marshall pathogenesis and protocol

from

someone at the WAPF.

The Marshall pathogenesis goes something like this. Th1-mediated inflammatory

diseases (such as IBD, RA, sarcoidosis, etc.) are caused by a chronic infection

by cell well

deficient (CWD) bacteria, also known as L-form bacteria. These bacteria, which

are able to

survive within macrophages, stimulate the activity of Nuclear Factor Kappa B.

NF Kappa B

then activates a variety of genes that cause the release of inflammatory

cytokines,

including TNF-alpha and interferon gamma, which produce the symptoms (swelling,

pain

and fatigue) commonly observed in " autoimmune " diseases.

This is where vitamin D comes in. According to the Marshall pathogenesis, as a

person

falls ill with inflammatory disease, ligands created by the Th1 pathogens

(L-form bacteria)

and exogenous 25-D (vitamin D metabolite) from diet, supplements and excessive

sun

exposure inactivate the Vitamin D Receptor (VDR).

Under normal conditions, the VDR transcribes an enzyme called CYP24 which breaks

down

excess 1,25-D. But when the receptor is blocked, it is no longer able to create

a sufficient

level of CYP24, causing 1,25-D to rise. Furthermore, the cytokines released by

the

immune system in response to the Th1 pathogens cause the production of excess

Protein

Kinase A (PKA). As levels of PKA rise, the protein causes increased production

of the

enzyme CYP27B1. Since CYP27B1 regulated the amount of 25-D converted into

1,25-D,

an excess of the enzyme causes increased conversion of the two metabolites,

elevating

1,25-D even further.

Hypervitaminosis-D symptoms result from a toxic level of the active form of

Vitamin D in

the body. Symptoms may include fatigue, insomnia, irritability, kidney stones,

night

sweats, tinnitus, muscle pain and stiffness, digestive issues, etc. etc.

According to the Marshall pathogenesis, the low levels of 25-D often found in

patients

with autoimmune disease is a *result* of the disease process rather than a

*cause*. A

high level of 1,25-D naturally down-regulates the level of 25-D. Therefore,

while 1,25-D

rises as part of the inflammatory disease process, 25-D remains low, often

despite

supplementation.

The treatment (Marshall Protocol) involves two strategies. The first is to

reduce D levels

elevated by the disease process until the body can again regulate it normally.

Avoiding

supplements and foods containing vitamin D, and avoiding *all* sun exposure in

some

cases (to the point of not venturing outdoors during the day, and using blackout

shades

over the windows at home) is " essential " .

The second strategy involves medication originally developed to treat high blood

pressure

- an angiotensin receptor blocker (ARB), Olmesartan (Benicar). After starting

Olmesartan,

pulsed, low-dose antibiotics are added to the program. The antibiotics are

chosen for

their activity against the L-form bacteria causing the Th1 inflammatory

response.

There is certainly some evidence to support several aspects of the Marshall

pathogenesis

and protocol, and it certainly can't be dismissed out of hand. I have many

questions and

criticisms, which I have actually raised on various Marshall Protocol websites.

But I am no

molecular biologist, and I am hoping someone from the WAPF with a more thorough

understanding of microbiology and vitamin D metabolism, in particular, can shed

some

light.

Here are a few links that might be useful:

http://bacteriality.com/2007/09/15/vitamind/

http://bacteriality.com/2008/02/23/misconceptions/

http://bacteriality.com/2007/11/28/sense/

Here's an article of Dr. Marshall's that was published in BioEssays in Feb.

2008:

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