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Understanding chronic disease
About the Marshall Protocol

The Marshall Protocol is a medical treatment being used by physicians worldwide to treat a variety of chronic inflammatory and autoimmune diseases including (but not limited to) Sarcoidosis, Chronic Fatigue Syndrome, Fibromyalgia, Crohn’s Disease, and Rheumatoid Arthritis. While other treatments for chronic disease use palliative medications in an effort to cover up symptoms, the Marshall Protocol is a curative treatment, which addresses the root cause of the problem.

Information about the treatment can be found at the study site, marshallprotocol.com. The site is run by the staff of the Autoimmunity Research Foundation, a California-based non-profit agency. Over 200 health professionals are members of the site, and discussions are moderated by a group of volunteer nurses. There is no charge to use the website or the treatment and all patients are welcome to participate.
The FDA has already granted orphan product designations for two of the Foundation’s six applications - Sarcoidosis, and Post Treatment Lyme Disease Syndrome (PTLDS, commonly known as chronic Lyme). The Foundation continues to work with the FDA to make effective therapies available in an even wider array of chronic diagnoses.

Chronic Disease
Chronic diseases (termed Th1 illnesses), are caused when certain individuals accumulate large amounts of L-form bacteria, bacteria that have changed form and lost their cell walls. Although researchers have known about L-form bacteria for over a century, up until recently they have not fully understood their role in causing chronic disease. Because they lack a cell wall, many antibiotics are unable to kill them directly and they cannot be detected by standard laboratory tests.

Unlike other forms of bacteria, L-form bacteria have also developed the ability to remain alive and proliferate undetected inside macrophages, the very cells of the immune system that the body uses to kill invading pathogens. Once inside these cells, they cause our own cells to release inflammatory cytokines (proteins that often generate pain and/or fatigue).
Bacteria outside macrophages are also able to contribute to chronic disease by grouping together into communities called biofilms. The bacteria inside a biofilm produce a protective protein matrix that allows them to more effectively evade the immune system and develop resistance to antibiotics.

The ability of L-form and biofilm bacteria to proliferate in the body is directly related to the vitamin D receptor (VDR). Critically important to the body, the Vitamin D Receptor (VDR) controls the innate immune system – the body’s first line of defense against infection. It’s also responsible for turning on/off a wide array of genes and chemical pathways. One of the VDR’s myriad jobs is to control expression of antimicrobial peptides (AMPs), proteins that kill bacteria, viruses and fungi.

Although casually referred to as a vitamin by some members of the medical community, molecular biologists have long realized that the precursor form of vitamin D (25-D) is really a steroid. Recent research has shown that levels of 25-D over 20 ng/ml can bind and inactivate the VDR, which subsequently shuts down the innate immune system.

Certain species of bacteria also produce substances that can bind and inactivate the VDR in a manner similar to 25-D. Consequently, people who are infected with L-form bacteria and consuming vitamin D are no longer able to produce the AMPs or turn on the innate immune system. This allows their bacteria to proliferate and spread.

When the innate immune system can no longer function, people have a very hard time keeping other pathogens under control. They often find that childhood viral infections reactivate, or that they acquire Candida (pathogenic yeast) and Mycoplasma as well. Thus, every person who starts the MP has a different mix of pathogens to kill depending on what microbes they have encountered during various stages of life. A person’s unique mix of pathogens is often referred to as their “toxigenic pea soup.”
L-form bacteria have evolved mechanisms that allow them to both mutate and alter the expression of the genes inside the cells they infect. These effects on the genes result in changes in the cellular environment that make it easier for new pathogens to invade the cell - creating a snowball effect where, as a person acquires more pathogens, it becomes even easier for them to pick up a diverse array of other infectious agents. This process is known as successive infection.

Since L-form bacteria can survive in the sperm and egg, and evidence is growing that they can also pass through the placental barrier, these pathogens can be passed from parent to child – meaning that Th1 illnesses often run in families. In addition, the pathogens may be easily passed to an infant soon after birth, during the period before the adaptive immune systems is up and running.

The activated form of vitamin D (1,25-D) is a hormone. Often called the “master hormone” 1,25-D directly controls the pathways that regulate the body’s other hormones including the thyroid, sex, and stress hormones.
Unlike its inactive counterpart, 25-D, that inactivates the VDR in healthy individuals, 1,25-D binds and activates the VDR. But in individuals who have 25-D and bacterial proteins blocking the VDR, 1,25-D is forced out of the receptor and into the surrounding environment.

Furthermore, in healthy individuals, the VDR transcribes an enzyme called CYP24. CYP24 breaks down excess 1,25-D, ensuring that the level of 1,25-D in the body stays in the normal range. But in chronically ill individuals, the VDR (which is blocked by bacterial susbstances) can no longer transcribe CYP24. The level of 1,25-D in the body becomes significantly elevated since there is no CYP24 to keep it in check.
Another enzyme called CYP27B1 normally regulates the amount of 25-D converted into 1,25-D. When more CYP27B1 is produced, conversion occurs at a greater rate. In addition, the cytokines released by the immune system in response to L-form bacteria activate a protein called Protein Kinase A (PKA). PKA in turn activates CYP27B1, causing more 25-D to be converted to 1,25-D.

As all three processes cause the amount of 1,25-D to rise to an unnaturally high level, the master hormone can no longer correctly regulate the thyroid, stress and sex hormones. Many patients find that they have difficulty tolerating stress, changes in temperature and a variety of other issues that result from the dysregulated hormonal pathways. Also, when levels of 1,25D rise above 42 ng/ml, calcium begins to be leached from the bones, a process that results in osteoporosis and osteopenia.

The body also produces 1,25-D in response to sunlight on the skin and bright light in the eyes. Excessive exposure to these sources of light helps drive the disease process. Most patients on the MP must take certain precautions, described on the web site, to avoid too much sun/bright light.

The Treatment
Patients on the Marshall Protocol take a medication called Olmesartan (called Benicar in the United States), which is able to bind and activate the VDR by pushing 25-D and bacterial proteins out of the receptor. Patients also lower levels of 25-D in the body by avoiding the kinds of vitamin D present in various foods. These measures renew the body’s ability to turn on the innate immune system and produce the anti microbial peptides. The immune system is then able to kill L-form bacteria and is once again able to manage viral and other co-infections.

At the same time, MP patients take pulsed, low-dose antibiotics. Antibiotics taken in this manner are much more effective against bacteria in biofilms and are able to greatly weaken L-form bacteria so that the patient’s own immune system is then able to destroy them. The antibiotics weaken the bacteria by blocking their ribosomes, which they need to produce proteins that help them survive and reproduce. It’s important to understand that when L-form bacteria die, there is a temporary change in a patient’s immunopathology.

Immunopathology refers to the changes in the immune system that result from bacterial death (another term sometimes used is the Jarisch-Herxheimer or “Herx” reaction). Dying bacteria release toxins into the bloodstream, stimulate the production of inflammatory cytokines, and generate temporary hormonal imbalances. This means that once a patient begins the MP, each dose of antibiotic will cause them to feel bad for the period of time it takes their immune system to deal with the consequences of CWD bacterial die-off.

Before starting the MP, many people may feel that they have improved through consuming vitamin D and taking steroids such as prednisone. In reality, these compounds inactivate the VDR, preventing the immune system from effectively killing CWD bacteria. Since it is the killing of CWD bacteria that generates an increase in painful symptoms, people may experience short-term relief when using vitamin D or prednisone as their immune system shuts down and less bacteria are killed. However, in reality, this situation allows the bacteria to spread more easily.

Applicable Illnesses
Patients on the MP have dozens of different medical conditions. As evidenced by members’ reported progress on the marshallprotocol.com website, nearly all experience a powerful immunopathological reaction after taking a dose of antibiotics.
Many patients report great improvement, while some appear to be approaching complete recovery.
Some of the diseases patients are currently using the MP to treat include (but are not limited to):

• Sarcoidosis
• Chronic Fatigue Syndrome
• Fibromyalgia
• Chronic Lyme Disease
• Rheumatoid Arthritis
• Multiple Chemical Sensitivity (MCS)
• Myasthenia gravis
• Psoriasis
• Osteoarthritis
• Hashimoto’s Thyroiditis
• Uveitis
• Cardiac Arrhythmia

Here is a more complete list of diseases. [includes Parkinson's]

Apart from the symptoms or diagnosis indicating Th1 disease, the easiest way to find out if the Marshall Protocol may be applicable to your disease is to get a blood test and check the level of your D Metabolites. This test can detect the elevated level of 1,25D often seen in patients with chronic disease, but must be done correctly in order to be of any value.

Patients can also use a therapeutic probe to determine whether the MP can be applied to their illness. A therapeutic probe refers to a trial period during which a person tests whether or not the taking the MP medications results in immunopathology or other symptom changes.

Because patients must carefully manage their immunopathology, it takes several years to complete the MP. Severely ill patients may need 3-5 years to reach a state of remission. However, once on the MP, most patients begin to notice improvements little by little.

Patients must work with their own doctor while on the treatment. There are instructions on how to request a list of doctors who use the MP in your area.

Phase One Guidelines give detailed instructions regarding dosages, etc…. One must follow the guidelines carefully to avoid the risk of serious reactions from immunopathology reactions due to the bacterial killing.
For a thorough article on the Marshall Protocol published in the Townsend Letter for Doctors and Patients see parts one and two.

About Professor Trevor Marshall Ph.D.
Trevor Marshall, Ph.D., is a biomedical researcher. In 2002, Marshall published a pathogenesis for sarcoidosis followed in 2004 by the definitive paper in Autoimmunity Reviews “Sarcoidosis Succumbs to Antibiotics.” He has since written several papers and given numerous presentations that detail the pathogenesis of chronic disease. He has derived many of his findings by using molecular modeling.
Marshall is currently active on the medical conference circuit. Among his many endeavors, he was invited by the Food and Drug Administration (FDA) Center for Drug Evaluation and Review in March 2006 to give a presentation in their “Visiting Professor” lecture series. In 2006, he co-authored a book chapter about Vitamin D dysregulation.
Marshall has hosted two conferences on “Recovering from Chronic Disease,” the first in Chicago in 2005, and most recently in Los Angeles in 2006. In 2007, Marshall was appointed Adjunct Professor in the School of Biological Sciences and Biotechnology at Murdoch University in Australia.

Autoimmunity Research Foundation
The directors and members of the ARF work to:
1. educate doctors and patients about the Marshall Pathogenesis and Protocol.
2. communicate with researchers in the field of autoimmunity and Th1 disease.
3. run the MP’s study web sites, marshallprotocol.com and sarcinfo.com
4. gain FDA designation for medications used in conjunction with the MP

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