Tutorial - An overview of the Marshall Protocol: the science, the treatment, and the guidelines

Type: Tutorial
Presenter: Amy Proal
Date: 2008
Notes: 87 minutes
See also: PDF version of presentation

Hi. My name is Amy Proal. In the following video I will be discussing the Marshall Protocol, a curative medical treatment for chronic inflammatory disease. The treatment is a phase II open-based internet trial monitored by the FDA. There are currently thousands of patients on the treatment, who suffer from a wide array of chronic diseases. Nearly all patients who have reached the later stages of the treatment are reporting improvement and recovery. The Marshall Protocol is based on a plethora of molecular and clinical evidence, and in the following video I hope to discuss, in the simplest terms possible, the science that forms the backbone of the treatment. I will lay out the basics of the treatment itself in detail.

“Nobody can pretend to know the complete life cycle and all the varieties of even a single bacterial species. It would be an assumption to think so.” These are the words of Ernest Alnquist, a friend of Louis Pasteur, and one of the first scientists to realize, around 1895, that classical forms of bacteria can transform into smaller forms that lack cell walls.

In 1934, a German scientist named Emmy Klieneberger-Nobel also used novel culturing techniques to mutate the bacteria in her Petri dish into cell wall-less forms.

She named the wall-less variants L-forms after the Lister Institute where she worked. In the years that followed, she studied many other species of L-forms and published several papers describing their characteristics and behavior. She once said that “the L-form is an entity of its own as different from classical bacteria as the tadpole from the frog.”

Hundreds of scientists picked up where Nobel and her colleagues left off. Many of them are listed in a 2005 paper in the Journal of International Medical Research that reviews the clinical significance of the L-form as an infectious agent, and discusses the work of a great number of researchers who over the past century, have cultivated the L-form and implicated it in a wide array of diseases.

Among these researchers was Emil Wirostko at Columbia University who began to culture and photograph L-forms after taking white blood cells from the liquid inside the eyes of patients with sarcoidosis, juvenile rheumatoid arthritis, and Crohn’s disease. He observed the pathogens under an electron microscope. He published 20 papers on the pathogens, each of which are filled with pictures of them such as this one which is a TEM photograph of a monocyte taken from the vitreous of the eye of a sarcoidosis patient. Look closely and you'll see that hundreds of tiny bacterial colonies in the shape of coccoid bodies have parasitized the phagocyte.

So much information has been gathered about these pathogens– the way they grow, reproduce, move, change shape, how they can be cultured– that researchers such as Lida Mattman, who worked at Wayne State University, and Gerald Domingue, another top expert on L-form bacteria who served for years as a professor at Tulane University, have published entire textbooks that detail how L-form bacteria persist in the tissues and change form during their lifecycles. Like Witrosko's work, these textbooks, along with many of the hundreds of papers published on L-forms, are filled with pictures clearly showing the persistent pathogens in the tissues of people with nearly every disease that the MP can potentially treat.

In fact, Mattman cultured these wall-less forms of bacteria from the blood samples of patients with over 20 incurable illnesses - illnesses such as Parkinson's, MS pulmonary thrombosis, and sarcoidosis. Here is a list of just some of the bacterial species she found capable of transforming into the L-form.

Here are several pictures taken by Domingue showing L-form bacteria. Taken under a scanning electron microscope they show L-form bodies harvested from the blood and an L-form within a kidney cell, among others. Papers are still published today on L-form bacteria. A month ago researchers from the Institut Jacques Monod in Paris published a paper in the medical journal BioEssays in which they repeat the fact that L-form bacteria are very likely behind most diseases of unknown cause, stating “Of special interest for human health is the formation of L-forms as a consequence of specific antibiotic treatments, and the potential involvement of L-forms in persistent and relapsing infections.”

L-form bacteria are simply part of the natural lifecycles of classical bacteria. Under certain conditions, they mutate from classical bacteria, losing their cell walls in the process. However the pathogens also exist naturally in the environment. 7 Because they cannot be killed by pasteurization or chlorination, L-form bacteria can be found in milk, food, and water. They can be transmitted via sperm, intimate contact, and can be passed from mother to child during childbirth. Since they are too small to be filtered during the purification processes used in pharmaceutical manufacturing procedures, they can be transmitted through injectable medicines. They have even been cultured from dry soil.

Let's pause for a moment to watch a quick video of L-form bacteria in the blood of a patient with CFS as viewed under a darkfield microscope. The video was taken by British clinician Andy Wright. Here you can see L-form bacteria encased inside a protective biofilm sheath. Now, in these later slides, the patient's blood has been aged in the laboratory. As the blood ages, the bacterial colonies reach a point where they expand and burst out of the cell, causing the cell to burst as well. Then they extend as huge, long tubules which are presumably the way the pathogens spread to other cells. Some may argue that these long bacteria filled tubules are just the result of cell death. But for one thing, cell death, or apoptosis, doesn't result in long strands. Apoptosis also doesn't result in structures this small.

L-form researcher Josep Casadesus of Spain recently stated that every bacterial species almost certainly has the capability of transforming into the L-form. Meanwhile, Dave Relman, a microbiologist at Stanford University in California, has stated that our current culturing techniques have only allowed us to detect and name about .04% of all bacteria that will eventually be identified. With such a vast number of potential L-forms out there. it's easy to see how they could cause a wide variety of inflammatory diseases. It's not an exaggeration to say that the mainstream medical community has sorely underestimated the diversity of bacteria and their potential to cause disease.

How do L-form bacteria survive? Unlike other forms of bacteria, L-form bacteria have 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 a macrophage, L-form bacteria are able to delay the process of apoptosis, or programmed cell death, allowing them to thrive inside the cell for a period of time even longer than 45 days. However, L-form bacteria are also able to infect nearly every other tissue of the body.

Beta-lactam antibiotics are designed to attack the bacterial cell wall and include penicillin, amoxicillin, and the cephalosporins. These antibiotics are able to kill classical bacteria but are completely ineffective against L-form bacteria, which have lost their cell walls. In fact, Klieneberger-Nobel first discovered that beta-lactam antibiotics actually promote the formation of L-form bacteria. These results have been confirmed over and over again, to the point where the beta-lactam antibiotics are used repeatedly to culture L-form bacteria in the lab. So while penicillin and the other beta lactams are very effective at stopping acute infection, they actually foster chronic infection.

L-form bacteria cause inflammation and painful symptoms by taking control of a protein called Nuclear Factor Kappa B. They are able to activate proteins that increase the activity of Nuclear Factor Kappa B, which subsequently moves to the nucleus or center of the cell. Once there, it turns on a variety of genes that cause the release of inflammatory cytokines, proteins that generate pain and fatigue. These cytokines include interferon gamma and TNF alpha.

Bacteria outside the macrophages, which may possess cell walls, can also greatly contribute to the pathogenesis of 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 administered in a standard manner.

According to JW Costerton at the Center for Biofilm engineering at Montana State University, “Bacteria that attach to surfaces aggregate in hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections.”

So from now on I will refer to L-form, biofilm, and any other persistent, ideopathic bacterial forms - even species yet to be discovered- collectively as the Th1 pathogens. The Th1 pathogens are a tremendously large microbiota that have been thoroughly researched, yet largely ignored by mainstream medicine. This is despite the fact that they have existed with man for millenia. After all, the neolithic ice man was said to have died from arthritis and heart disease. Later, I will discuss the major reasons why the Th1 pathogens have found it substantially easier to spread during the past century and at the present moment.

So if the Th1 pathogens exist, and have been studied for over 100 years, why have they been largely ignored?

One reason is that since they grow so slowly it's hard to connect their presence to disease symptoms that manifest much later in time.

But when it comes down to it, L-form bacteria would get far, far more attention were it not for a single factor: they don’t grow in a standard Petri dish using the usual culture methods. Since the vast majority of mainstream researchers have failed to familiarize themselves with the very different laboratory techniques needed to grow L-forms, it’s no wonder that most doctors are oblivious to the bacteria making their patients sick.

According to Relman, “Features of a number of important but poorly explained human clinical syndromes strongly indicate a microbial etiology. In these syndromes, the failure of cultivation-dependent microbial detection methods reveals our ignorance of microbial growth requirements.”

Furthermore, since they are able to persist inside the macrophages for such extended periods of time, few of the Th1 pathogens die, and only tiny amounts of bacterial proteins and genetic material reach the bloodstream at any given time; an amount so small that a PCR test cannot pick them up. L-forms also cannot be detected with antibody testing, since antibodies only form in response to bacteria that have died.

Finally, research on L-form bacteria was largely quelled by researchers who were unable to duplicate the findings of their more meticulous colleagues.

Mattman and other researchers spent decades figuring out how to correctly culture the L-form. Applying their techniques correctly requires rigorous adherence to specific guidelines. Mattman has said, over and over again that other research teams would try to duplicate her studies but misinterpret just one of the steps required to correctly grow the bacteria. When their results inevitably failed, they reported to the medical community that, in their eyes, cell wall-less variants of bacteria did not exist. They dismissed Mattman's studies by saying her samples had been “contaminated.”

There is also little incentive for scientists to study the L-form. Since the bacteria can be killed by simple low-dose antibiotic therapy, drug companies have little interest in investing money into related research. Researchers studying the L-form often find themselves with very little grant money but must still work long, tedious hours in the lab.

As Domingue states, “It is generally agreed among scientists that L-form bacteria are extraordinarily intriguing, interesting tools for biological study, yet the most neglected area of research has been on the role of these organisms in disease, particularly in host-pathogen interactions.”

Because of these circumstances, doctors are not taught about L-form bacteria in medical school, which is why they are largely unaware of their presence.

Bacteria inside protective biofilms were first viewed in the 1700s by scientist Anton Van Leeuwenhoek, who scraped the plaque biofilm from his teeth and observed what he referred to as the “animalculi” inside them under his primitive microscope. However, it was not until the 1980s and 90s that scientists actually began to appreciate the reality that attached bacteria can be organized into biofilm colonies in extensive ways. This was largely due to the fact that the advanced laboratory techniques, molecular methods, and powerful microscopes used to view biofilm bacteria have only recently been invented.

Unfortunately, the advances that allow for a better understanding of biofilm bacteria were created at the same time as the sequencing of the human genome. At that point, most scientists were convinced that a simple answer to disease could be found in our genes. Interest in biofilm bacteria,and the research grants that would accompany such interest, were diverted to projects on genetics. However, since genetic research has failed to uncover any causes of any chronic disease, biofilms are finally - just over the past few years - being given the credit they deserve as serious infectious entities, capable of causing a wide array of chronic illnesses.

It follows that autoimmune and inflammatory diseases are almost certainly illnesses caused by the Th1 pathogens.

When it comes down to it, the concept of autoimmune disease doesn't make much sense and many would say it has run its course.

Look up autoimmune disease on Wikipedia. Some researchers favor the Clonal Deletion Theory, Clonal Anergy Theory. Then, there is the Idiotype Network theory, And don’t forget the Clonal Ignorance theory, the Supressor Population theory, or the Regulatory T-cell theory.

These and other suspiciously complex explanations can’t help but invoke Occam’s Razor which states that in the absence of other factors the simplest explanation is usually the right one. Why then, is it so hard to appreciate that inflammatory diseases are the result of infection?

Why would the human body, which has evolved so elegantly over the course of millions of years, retain such a debilitating flaw?

According to evolutionary biologist Paul Ewald, “The fact is, the immune system functions just fine in a large proportion of the population. The only logical way to explain the immune activation seen in patients with “autoimmune disease” is to suggest that there is some sort of agent pushing the immune system off balance. This argument is only strengthened by the fact that the same evolutionary forces that would cause a serious disease to be weeded from the population would also cause those people whose immune systems are prone to self-destruction to be eliminated from the population.”

Furthermore, bacteria are an extremely logical cause of inflammation. Acute forms of bacteria are already known to cause inflammation. According to Relman “An inflammatory immune response—one of the body’s primary means to protect against infection—defines multiple established infectious causes of chronic diseases, including some cancers. Inflammation also drives many chronic conditions that are still classified as (noninfectious) autoimmune or immune-mediated. Both [the innate and adaptive immune systems] play critical roles in the pathogenesis of these inflammatory syndromes. Therefore, inflammation is a clear potential link between infectious agents and chronic diseases.”

The CDC agrees. In a 2006 paper they state that, “The epidemiologic, clinical, and pathologic features of many chronic inflammatory diseases are consistent with a microbial cause. Infectious agents have emerged as notable determinants, not just complications, of chronic diseases. To capitalize on these opportunities, clinicians, public health practitioners, and policymakers must recognize that many chronic diseases may indeed have infectious origins.”

And a bacterial pathogenesis for chronic disease makes sense. Every major disease that scientists have found a cause for has, in the end, been linked to a pathogen. Whereas centuries ago doctors who treated patients with leeches and bloodletting wondered about the cause of tuberculosis, polio, syphilis, leprosy, even the plague - it wasn’t long before these diseases were linked to pathogens.

The good thing is that the Th1 pathogens can now be killed.

Another reason doctors don't search for L-form and other persistent forms of bacteria is that up until very recently, even if they were able to identify them, there was no way to kill them.

That changed recently when biomedical researcher Trevor Marshall, who is also an adjunct professor at Murdoch University in Australia, began to study the pathogens and their effects on the innate immune system. After decades of research and several key discoveries that have been confirmed by a wide body of molecular and clinical data, Marshall was able to create a treatment, dubbed the MP, that effectively kills the Th1 pathogens. Marshall's discoveries include new insights about how the Th1 pathogens affect the immune system at the molecular level and how the immune system works in the first place. These discoveries have allowed him to not only create the MP, but to also form a very accurate pathogenesis for chronic inflammatory diseases such as CFS.

Marshall's background in biomedical engineering has allowed him to approach chronic disease from a novel perspective. For example, Dr. Leroy Hood at the Johns Hopkins School of Medicine, among others, has made the point that the pioneering researchers and doctors of tomorrow will have to be trained in engineering and computer science in order to understand the body’s “circuits” and feedback pathways. According to Hood, medical research has stagnated for wont of systems thinking, the kind of inquiry which is the hallmark of someone with a background in biomedical engineering.

By using molecular modeling software Marshall has been able to take a definitive rather than an interpretive approach to medicine.

Despite not having a medical degree, Marshall is still frequently invited to lecture on medical issues. Over the past two years he has given presentations to the FDA, the American Academy of Environmental Medicine, and the Days of Molecular Medicine Conference in Karolinska Sweden. He will also be chairing a session about vitamin D and the VDR at the upcoming 2008 International Conference on Autoimmunity in Portugal.

What are some of Marshall's discoveries?

Front and center to Marshall's pathogenesis of chronic disease is the Vitamin D Receptor, a fundamental nuclear receptor that controls the activity of the innate immune system - the body's first line of defense against intracellular infection. It also controls the transcription of many families of antimicrobial peptides and the transcription of hundreds of genes. Scientists at McGill University in Canada have released a recent paper stating that the receptor may actually transcribe around 27,000.

Antimicrobial peptides (AMPs) are potent, broad-spectrum antibiotics that the body creates naturally. They kill many kinds of bacteria, including strains that are resistant to conventional antibiotics. They have also been shown to target enveloped viruses, fungi and even transformed or cancerous cells.

Thus, the VDR is essentially the gatekeeper to the innate immune system. It's importance and action are widely understood and accepted by mainstream molecular biologists, in fact, an average of one new paper on the VDR appears in Medline each day.

Since it is now understood that chronic inflammatory diseases are bacterial in origin, it's easy to realize that the VDR is of utmost importance in keeping the Th1 pathogens under control.

In 2007, Marshall discovered a species of gliding bacteria that creates a substance (the sulpholipid capnine) that is able to bind the VDR and block its activity. Eureka! This discovery strongly suggests that other pathogens can create similar substances, each of which can potentially block the VDR and diminish its ability keep bacteria in check.

It's almost certain that other bacteria create VDR-blocking substances because doing so is such a logical survival mechanism for any form of pathogen.

If the Vitamin D Receptor is not functioning correctly, it’s no stretch to think that dysfunction will occur. First, the expression of thousands of genes is thwarted. Then, the innate immune system slows down. Finally, production of the AMPs decreases – meaning that bacteria in the body find it exceptionally easy to spread.

So, by creating one single substance to block the VDR, the Th1 pathogens can, in a knockout blow, disable the receptor that would otherwise activate numerous pathways to interfere with their ability to persist in the body.

Does anything else shut off the Vitamin D Receptor?

Let’s start with this fact: the vast majority of doctors touting the benefits of vitamin D are not aware of discoveries made by researchers in the field of molecular biology, which have clearly shown that the “vitamin” D derived from diet and supplements is not a vitamin, but a secosteroid with immunosuppressive properties when elevated.

There are several forms of vitamin D. The form of vitamin D we get from food, supplements and excessive sun exposure is called D3. D3 is converted by the liver into 25-D, which functions as a secosteroid. Then there is 1,25-D - the activated form of vitamin D which functions as both a secosteroid and a hormone. It is produced inside various types of cells, including those of the immune system and the kidneys, as well as in response to sunlight. Both 25-D and 1,25-D bind the VDR.

Scientists have known for quite some time now that the different forms of vitamin D are immunomodulatory. For example, according to a paper published by the Institute of Biomedical Research in Birmingham, England, “The active form of vitamin D, [1,25-D] is a potent immunomodulatory secosteroid”

Scientists have also long recognized that there are two different main forms of vitamin D. It's just that up until Marshall's research they have made the assumption that both forms, 25-D and 1,25-D, activate the receptor. That's wishful thinking.

1,25-D does activate the VDR and keep it on. But Marshall, one of the first to study 25-D at the molecular level, discovered that the secosteroid actually SLOWS the activity of the VDR until the level of 25-D becomes high enough that it shuts the receptor off. The immunosuppressive effect of 25-D starts around 20 ng/ml. This makes sense. If you think of the VDR as a switch that controls innate immunity, it is logical that the body would create one form of vitamin D to turn it on and another to turn it off.

This slide shows the molecular structures of the various forms of vitamin D. The only difference between 25-D and 1,25-D is that 25-D is missing one alpha hydroxylation that stabilizes helix 12 - a hydroxylation that is known to be essential to binding the promoters which allow for activation of the VDR.

Although most researchers are still unaware of Marshall's models of 25-D and the VDR, they are nevertheless starting to pick up on immunosuppressive effect. For example, a 2007 paper published in Rheumatic Diseases states “On the whole, Vitamin D confers an immunosuppresive effect in autoimmune disease.

What this means is that if patients ingest high levels of vitamin D - be it through food or supplements containing the secosteroid - they will start to slow, rather then activate the activity of their innate immune systems.

Some may argue that Marshall's models may not be accurate, but they are supported by a tremendous amount of clinical data from the MP study site. If MP patients are to kill an optimal level of bacteria, they must remove, rather then add, vitamin D to their diets. It is only after lowering their levels of 25-D to under 20 ng/ml that the immune systems of most patients have the strength to put the antibiotics used by the treatment to work. This trend has applied to each of the thousands of patients now on the treatment.

Studies support the fact that long-term supplementation with vitamin D has very negative effects. For example, researchers at Duke University found that elderly men and women who consumed higher levels of calcium and, in particular, vitamin D are significantly more likely to have greater volumes of brain lesions, indicating regions of damage that can increase risk of cognitive impairment, dementia, depression and death. The team found that vitamin D intake was the only variable that retained a significant correlation with the brain lesions when analyzed by a multivariate analysis.

What happens when bacterial substances and 25-D block the VDR?

When the innate immune system can no longer function because the VDR is blocked, people have a very hard time keeping other pathogens under control. They often find that childhood viral infections reactivate, they acquire new viruses, or they succumb to Candida (pathogenic yeast) and Mycoplasma as well. Since the immune system is suppressed, they also find it easier to acquire even more of the Th1 pathogens which in turn create even more substances that block the VDR. This creates a snowball effect, where, as a person picks up an increasing load of pathogens, they also become increasingly immunosuppressed.

But what about Vitamin D deficiency?

Right now you may be thinking…whoa this doesn't make sense. I've heard that patients with chronic disease are actually deficient in vitamin D. In fact, many researchers will tell you we are living in an era of vitamin D deficiency. Unfortunately, in what is also a medical mistake of rather epic proportions, researchers have failed to consider the rather logical alternate hypothesis, which is that vitamin 25-D levels in patients with chronic disease are low as a RESULT rather then a CAUSE of the inflammatory disease process.

In a recent BioEssay's paper Marshall flushed out many of pathways that regulate vitamin D metabolism in order to show exactly how the inflammatory disease process causes levels of 25-D to drop. 25-D is of course, the sole vitamin D metabolite that doctors now test in order to determine what they call deficiency. You are now looking at a figure of vitamin D metabolism taken from the paper.

In individuals with chronic disease, bacterial-induced blockage of the VDR prevents transcription of the enzyme CYP24A1, which normally breaks down excess 1,25-D. Activation of Protein Kinase A (PKA) by bacterial cytokines also causes increased production of the enzyme CYP27B1, resulting in increased conversion of 25-D into 1,25-D.

Both processes cause the amount of 1,25-D to rise to an unnaturally high level. When 1,25-D is elevated it begins to downregulate, through a receptor called the PXR, the level of pre-vitamin D converted to 25-D. This leads to less production of 25-D and a lower level of the metabolite detected on blood tests.

Thus it's clear that if doctors were to test for the level of BOTH vitamin D metabolites they would recognize a clear pattern that is not indicative of deficiency, but of disease - namely a higher than normal level of 1,25-D and a lower than normal level of 25-D in patients who have accumulated the bacteria that cause chronic inflammatory diseases. It is incredibly important then, that doctors start to test both metabolites rather than just 25-D and that they begin to look at the dysregulation of the vitamin D metabolites as a sign of disease rather than a condition that requires extra supplementation with vitamin D.

Numerous clinical studies have confirmed that the level of the hormone 1,25-D rises in patients with many chronic diseases. Chronically ill patients starting the Marshall Protocol sometimes have a level of 1,25-D exceeding five or six standard deviations above the “standard” value.

In fact, since a dysregulated vitamin D ratio is a sign that a patient is suffering from an inflammatory disease, doctors can test a patient's levels of 25-D and 1,25-D in order to confirm that the MP will indeed work for a particular patient.

How does a high level of 1,25-D affect the patient?

Unfortunately, when 1,25-D reaches a certain threshold, it binds not just the VDR, but many of the body’s other nuclear receptors, displacing the metabolites that are meant to be in the receptors under normal conditions.

Those nuclear receptors affected by 1,25-D are receptors that regulate the body's hormones - the glucocorticoid receptor, the alpha and beta thyroid receptors, the adrenal receptors, and the progesterone receptors among others.

This means that when 1,25-D is high, it competitively displaces cortisol, T3, T4, and other metabolites from their target nuclear receptors. This causes havoc on the body's hormonal pathways. That's why patients with chronic disease begin to suffer from numerous hormonal abnormalities.

Furthermore, each of the nuclear receptors also transcribes various families of antimicrobial peptides. In a recent article published in BMC Bioinformatics, a team of researchers found that the glucocorticoid receptor controls 20 families of AMPs, the androgen receptor 17, and the Vitamin D Receptor 16, out of 22 analyzed.

So the displacement of their normal metabolites by 1,25-D causes a decrease in AMP production, generating yet another immunosuppressive effect. Since the AMPs serve as natural antibiotics, the body's ability to kill bacteria is significantly hindered.

Based on the above, it's clear that restoring the competence of the Vitamin D Receptor is the key to recovery from chronic inflammatory disease

The Marshall Protocol does this. How?

Patients on the Marshall Protocol take a medicine called Olmesartan (Benicar in the US) that binds and activates the VDR by pushing 25-D and bacterial proteins out of the receptor.

Olmesartan was carefully chosen over other drugs in its class because according to molecular modeling data, it binds the Vitamin D Receptor and some of the other nuclear receptors in a manner that most effectively activates the immune system response. Other drugs also bind the same receptors as Olmesartan but fail to activate them at the correct level.

Once on Olmesartan, the patient’s own immune system regains the strength to kill the Th1 pathogens, that, as I will describe later, have already been greatly weakened by antibiotic therapy. Olmesartan makes such a difference in activating the immune system that some patients find that once on the medication, they begin to kill bacteria before they have even started the antibiotics. In order for the immune system to function correctly at all times of day, Olmesartan must be taken every 6-8 hours.

As Olmesartan restores the activity of the VDR, patients on the MP also lower levels of 25-D in the body by avoiding the kinds of vitamin D present in various foods. This includes the vitamin D present in foods fortified with the secosteroid, as well as natural sources of vitamin D such as seafood, mushrooms, egg yolks, and others.

These measures renew the body’s ability to turn on the innate immune system and produce the antimicrobial peptides. The immune system is then primed to kill the Th1 pathogens with the help of antibiotics. It is once again able to manage viral and other co-infections. Thus, there is no need for doctors to treat co-infections before patients start the MP, as data from the MP study site indicates that most co-infections clear up naturally as the activity of the innate immune system is restored by Olmesartan and bacterial death.

It should be noted that Olmesartan also binds other receptors involved in the immune system response. Recently, Marshall has elucidated additional modes of action of Olmesartan on the nuclear receptors that control the immune system.

By definition Olmesartan is an Angiotensin II Receptor Blocking (ARB) drug. When Olmesartan binds and blocks the Angiotensin Receptor, it decreases levels of Nuclear Factor Kappa B, a protein that, as previously discussed, stimulates the release of inflammatory cytokines. The drop in cytokines results in less inflammation and oxidative stress. As inflammation drops, the antibiotics can also perfuse the tissues more effectively.

The drop in inflammation stimulated by Olmesartan makes some patients feel better, allowing them to more easily tolerate the increase in symptoms generated by bacterial die-off, something I will discuss later.

Olmesartan strengthens the innate immune system so that it is primed to kill the Th1 pathogens. Still, Marshall's research has determined that the Th1 pathogens must be weakened by carefully chosen antibiotics before the immune system can finish them off.

Over the past few decades, Marshall has studied this data and figured out the safest, most effective antibiotics to use against the Th1 pathogens.

He discovered that a class of antibiotics called bacteriostatic antibiotics has the potential to weaken the Th1 pathogens if administered in the correct manner. Bacteriostatic or “Protein Synthesis Inhibitors” are a class of antibiotics that work by disabling bacterial ribosomes - small, dense, structures that allow the pathogens to replicate and survive. This group of antibiotics includes the tetracyclines, such as minocycline and demeclocycline. This class of antibiotics has also been shown to interfere with the ability of bacteria to create exoproteins, (proteins on their surfaces), making it easier for the immune system to kill the pathogens.

The base antibiotic of the MP is minocycline. In the Journal of Postgraduate Medicine, Burke Cunha and team argue that a benefit of bacteriostatic antibiotics is that when taken orally, they are just as effective as when administered using intravenous therapy. Cunha also argues that minocycline is the antibiotic of choice because of its “superior intracellular mechanism of activity and an excellent safety profile.”

One of the great benefits of minocycline when compared to other tetracyclines is that it has better lipid solubility. This means it can more easily penetrate the central nervous system and the inside of cells. Minocycline is also very effective against the bacterial species Staphylococcus which is one of the most widely implicated pathogens in chronic disease.

All bacteria use their ribosomes to create a variety of proteins in order to survive and the Marshall Protocol is designed to make that task progressively harder. Bacteria have one ribosome, the 70S ribosome, which is divided into two sections - the 30S ribosomal subunit and the 50S ribosomal subunit. Minocycline binds to the 30S ribosomal subunit, preventing bacteria from creating proteins necessary for survival and protein synthesis. One molecule of minocycline inhibits one 30S bacterial ribosome from manufacturing proteins. This low antibiotic to ribosome ratio proportionately controls the rate of bacterial death.

However, minocycline must be combined with other antibiotics if the patient is to fully target all the different species of bacteria involved in causing chronic disease. According to Marshall, “Long term therapy with any single antibiotic will cause the killing of bacteria susceptible to that antibiotic, and the repopulation of the tissues with bacteria resistant to that antibiotic. So your bacterial load may well be increasing while your original symptoms improve.”

As a result, the Marshall Protocol uses other carefully selected antibiotics in conjunction with minocycline, allowing the 30S and 50S ribosomal subunits to be blocked at the same time.

Patients on the treatment begin by taking pulsed, low-dose minocycline, but soon add other antibiotics into the mix, until their bacterial load is reduced to the point where they are able to tolerate the ribosomal blockage generated by taking different combinations of three antibiotics at one time. One of the phase 2/3 antibiotics that blocks the 50S ribosomal subunit is an azolide antibiotic that has excellent tissue penetration and persists in the tissues for weeks.

The MP does use one antibiotic that does not work by inhibiting protein synthesis. It works by inhibiting dihydropteroate synthase, an enzyme that allows bacteria to use folic acid. Since folic acid is an essential precursor in the synthesis of several of the base pairs needed to create DNA, inhibition of the enzyme stops pathogens from creating the genetic material they need to survive.

When patients are taking two antibiotics at the same time, they are in what is referred to as phase II. When they are taking combinations of 3 MP antibiotics, they are considered to be in phase 3. There are a total of 5 antibiotics used by the MP which each patient eventually combines into a variety of different 3 antibiotic combinations.

Because each of the three classes of bacteriostatic antibiotics used by the Marshall Protocol affect different ribosomal subunits and target different mechanisms of protein synthesis, a bacterial species would have to develop three different mutations in order to survive in their presence. To date, no bacterial species has been shown to have this ability.

I mentioned that the MP uses pulsed, low-dose antibiotics. Why?

Standard methods that use high-dose, constant levels of antibiotics are unable to effectively eliminate L-form and biofilm bacteria. The reason lies with the fact that, aside from their ability to block bacterial ribosomes, bacteriostatic antibiotics also have effects on the immune system. Unfortunately, some of these effects are immunosuppressive. For instance, the tetracycline antibiotics have been widely recognized as being able to inhibit various functions of phagocytes, the white blood cells that engulf and kill bacteria. These effects seem to be independent of their antibacterial effect.

These immunosuppressive properties decrease the amount of L-form and biofilm bacteria killed by the immune system. This is why some people report feeling better on high-dose antibiotics. The high levels of antibiotic prevents the immune system from killing the Th1 pathogens, resulting in a temporary decrease in the toxins the pathogens release as they die and the inflammatory cytokines produced by the immune system in response to their death. However, in reality, the Th1 pathogens a person has accumulated remain alive and find it easier to spread to new tissues and organs.

The most effective way to avoid this problem is to use low doses of pulsed antibiotics. Pulsed dosing refers to administering a dose periodically, such as every 48 hours, rather than once or several times daily. When taken in this manner, the immunosuppressive effects of the antibiotics are minimized but their ability to weaken bacterial ribosomes remains intact. Patients gradually increase the dosage of the pulsed antibiotic, so that species of bacteria that are susceptible to all different concentration levels will eventually be targeted.

A report in the European Journal of Clinical Microbiology found that treating the bacterial species Staphylococcus aureus with only 1/32 of the minimum inhibitory dose of clindamycin (a very small dose!) resulted in enhanced uptake of the bacteria by white blood cells called polymorphonuclear cells, and enhanced killing of the pathogens by another class of white blood cells called phagocytes. Not surprisingly, the team found that only bacteriostatic antibiotics (the class of antibiotics used by the MP) possess this ability. Antibiotics that work by blocking cell wall production were unable to elicit such an effect.

Similarly, researchers at the University of Iowa found that subinhibitory concentrations of the bacteriostatic antibiotic azithromycin significantly decreased biomass and maximal thickness in both forming and established biofilms. These extremely low concentrations of azithromycin inhibited biofilms in all but the most highly resistant isolates.

The advantage of pulsed dosing has been demonstrated in the past. It has long been known that pulsing levels of the hormone GNRH is most effective against infertility. Similarly, intermittent doses of antibiotics seem to disrupt the immune system’s natural state of homeostasis, thus provoking a greater immune response.

Recent research has also demonstrated that pulsing antibiotics can be a superior way of targeting treatment-resistant biofilm bacteria. According to researchers at Tulane University, who mathematically modeled the action of antibiotics on bacterial biofilms, “exposing a biofilm to low concentration doses of an antimicrobial agent for longer time is more effective than short time dosing with high antimicrobial agent concentration.” Several studies have shown that even when administered in low, pulsed doses, the bacteriostatic antibiotics are still able to decrease the production of bacterial exoproteins.

Sounds good so far, right? So I hate to tell you about immunopathology, but I must……

The Th1 pathogens have evolved mechanisms that allow them to live for long periods of time within the cells and, when alive, generally persist without generating too many symptoms. It is when the Th1 pathogens die that they begin to cause a major increase in symptoms for the host. Thus, as patients start to kill bacteria on the MP, with each dose of antibiotic they experience a reaction referred to as the Jarisch Herxheimer or immunopathology.

Immunopathology occurs because, after bacteria die, the associated release of toxins and cellular debris occurs faster than the body can process them via the kidneys and liver. Bacterial death is also accompanied by the release of cytokines. All of the above cause a temporary rise in disease symptoms. 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 Th1 bacterial die-off.

The severity of immunopathology differs from person to person depending on bacterial load and the species of bacteria that need to be killed. Patients can adjust their level of antibiotics, and consequently adjust the severity of their immunopathology. Patients who are severely ill generally experience stronger immunopathology, whereas patients who start the Marshall Protocol during earlier stages of illness often find that they are able to work and manage a high level of activity despite the rise in symptoms.

Immunopathology is unavoidable, and it is the hallmark of the MP. Patients must be willing to feel worse before they feel better.

Since immunopathology must be carefully managed, the Marshall Protocol takes several years to complete. The average treatment time for a person with a very severe case of CFS is 3-5 years. Those people with more mild cases of CFS can expect the treatment to progress much more quickly. However, it's a comfort to know that, in all cases, immunopathology generally decreases as patients progress to later stages of the treatment, allowing them to become more and more active as time goes on.

Because people on the MP note an increase in symptoms once they have started medication, the presence of the immunopathological reaction is proof positive that the body is indeed killing bacteria – which in turn means that bacteria are undoubtedly driving the disease process in the first place.

A devil’s advocate would be hard-pressed to explain MP patients’ consistent immunopathology in any other way. After all, both Benicar and the antibiotics used by the MP have excellent safety profiles, so rises in symptoms can seldom, if ever, be attributed to the side effects of these medications.

Nothing but calculated and controllable bacterial death can explain immunopathology. And nothing but the absence of bacterial death can explain why patients who complete the MP - who are taking just as much Benicar as the day they started, along with the highest dose of antibiotics allowed by the treatment - find that the medications no longer elicit immunopathology. Why? Because all their bacteria have been killed - a reality supported by the fact that their symptoms have resolved.

On a personal note, I could tell on day one that the MP was working because of the fact that I experienced calculated symptoms of IP. I actually welcomed the increase in symptoms because, before the MP, my symptoms had served only to remind me of the fact that my health was deteriorating. But after starting the MP, a rise in symptoms indicated that I was killing bacteria and slowly improving. As my boyfriend used to say, “Once on the MP you go to bed every night with less bacteria then you had the day before. It's a good feeling, and my new mindset helped me get through some tough periods of immunopathology.

I should also add that immunopathology also occurs in the brain. This means that symptoms of brain fog, memory loss etc are also affected by the antibiotics and also clear up as the treatment progresses. “Brain herx, or mental immmunopathology” is likely a term you will become quite familiar with if you start the MP. Symptoms of “brain herx” can usually be effectively managed by adjusting antibiotic dosage.

With the concept of immunopathology in mind we can now go back and further examine why we hear about so many positive studies on vitamin D and why steroids are so often used to treat inflammatory disease.

25-D, like prednisone, acts like a steroid, slowing the activity of the innate immune system. In fact, molecular models show that both 25-D and prednisone have a five member steroidal ring and a six member steroidal ring with methane in both cases. The only difference is that the bond between two carbons on 25-D has been cleaved by an electrocytic reaction, making 25-D a secosteroid rater than a steroid. If inflammatory diseases are considered to be autoimmune or the result of an overactive immune system, slowing the immune system with a steroid or vitamin D might seem like a good idea. Such actions also make the patient feel better because, as the immune system slows, so does bacterial die-off and hence immunopathology.

But when one understands that inflammatory diseases are caused by the Th1 pathogens, the entire scenario becomes reversed. Prednisone, just like elevated 25-D, prevents the immune system from killing bacteria. Patients experience short-term relief and resolution of symptoms as the die-off slows down. But nobody would ever claim that prednisone actually cures “autoimmune” diseases. Instead, in the long run, patients taking prednisone generally become much more ill and require increasing amounts of palliative medication. The same occurs with vitamin D. Short term “benefit”, long-term harm.

This is why we see so many positive studies on D. Researchers track their study subjects only for a period of time long enough to notice the temporary drop in inflammation and palliation that results from the actions of the secosteroid. Rarely, if ever, do they follow their subjects for 15, 30 years - the time needed to see that patients who take vitamin D are not recovering and are almost certainly acquiring more of the Th1 pathogens, causing them to suffer from more disease symptoms or new diseases altogether in the long run.

This is an extreme example, but a study published in the April 2000 Archives of Internal Medicine found that five patients confined to wheelchairs with severe weakness and fatigue were able to walk after supplementing with 300,000 IU’s of vitamin D (a huge amount!) over a period of six weeks. Sadly, the patients were not “cured” and, not surprisingly, there has been no follow-up study. They were simply feeling the effect of a temporary decrease in cytokine and toxin release that resulted after the high levels of vitamin D completely shut down their innate immune systems. In fact, one of the patients actually died in the weeks during which vitamin D was administered.

So we desperately need more long-term studies on vitamin D to convince mainstream medicine of 25-D's immunosuppresive effects. Right now doctors only notice that their patients seem to feel temporarily better when taking the secosteroid and misinterpret this as a sign of success.

There's no need to worry about bone mass

But what about the long-held misunderstanding that vitamin D enhances bone mass? It's been engrained into our heads, perhaps more by companies trying to sell products fortified with vitamin D than actual scientists.

A problem with many studies on bone mass is that participants are given both calcium and vitamin D supplements at the same time. If participants demonstrate a small increase in bone density, which of the two supplements should be given credit for their improvement? Based on what we know about the actions of elevated 25-D, certainly the calcium, not the vitamin D, accounts for any positive changes in bone mass noted among study participants.

The largest meta-analysis of calcium and vitamin D trials in people over 50 was recently published in the Lancet. It combined the results of 29 randomized trials in which researchers had given participants supplements of calcium and vitamin D. The researchers state on page 663 of their paper that the “addition of vitamin D supplementation was not shown to offer additional risk reduction over and above the use of calcium alone.”

There are many studies with similar results, particularly studies released in the last few years. There are a few that even show, correctly, that vitamin D actually causes bone mass to decrease in the long term. However, we hear less about these studies as negative results don't usually interest the media who are content to think of vitamin D as the sunshine vitamin. You can read more about osteoporosis in an article on my website, Bacteriality.

The benefits you have surely heard concerning vitamin D and cancer are almost certainly the result of the fact that cancer is also an inflammatory disease that has been tied to bacteria. Not surprisingly then, more accurate studies on cancer and vitamin D are hardly finding a positive correlation between the two.

In fact, the latest study by the National Cancer Institute - the first study to actually look at the relationship between measured vitamin D in the blood and subsequent total cancer deaths - failed to show an association between baseline vitamin D status and overall cancer risk in men, women, non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and persons younger than 70 or 70 years or older. The researchers did find an association between vitamin D and colorectal cancer risk, most likely for reasons that could be explained by 25-D's immunosuppressive properties.

Returning to the concept of infection……it's important to understand that many different species of bacteria cause each form of chronic disease.

Modern medicine’s understanding of the body as a series of discrete systems blinds the profession to the nature of bacterial infections, which care nothing of such categories. Is it merely a coincidence that some sarcoidosis patients have dyslexia, some fibromyalgia patients have gastrointestinal problems, some CFS patients also have arthritis? When we pause to think about this reality it becomes all too clear that chronically ill patients are suffering from system-wide dysfunction which is best explained by infection.

This analogy essentially applies to most diseases of “unknown cause” which the medical community has labeled with an array of different names but, in reality, all result from the same pathogenesis - namely infection with different species of the Th1 pathogens. Once the immune system is weakened by these bacteria, viruses, fungi, and protozoa can also thrive.

It's important to understand that each person's symptoms results from a large mix of Th1 pathogens, each of which causes different symptoms. Take, for example, bacterial biofilms. A single biofilm may contain up to 30, 50, 60 different species of bacteria inside and there are probably millions of biofilm communities in people with inflammatory disease.

This means that Robert Koch's postulates, which state that only one type of pathogen can cause one type of disease, are clearly outdated. The Marshall pathogenesis makes it clear that a person’s symptoms arise from the unique mix of pathogens they collect over a lifetime, meaning that no two people are alike. Surely this explains why most people who end up at the doctor’s office have symptoms that could be attributed to multiple conditions. What name you give these symptoms doesn’t really matter.

The fact that some conditions are not currently diagnosed as illness doesn’t matter either. What we're observing among patients on the MP study site is that most suffer from what might be most accurately called a Th1 spectrum disorder.

Another phenomenon that must be taken into account when trying to imagine the load of pathogens that cause any one person's symptoms is that of horizontal gene transfer. Horizontal gene transfer is a process in which organisms swap genetic material. They often do this by trading plasmids, circular molecules of DNA that can replicate independently of a pathogen’s other genetic material.

As James Lake, a researcher at the Molecular Biology Institute at the University of California, puts it, “Increasingly, studies of genes and genomes are indicating that considerable horizontal gene transfer has occurred between bacteria.” In fact, due to increasing evidence suggesting the importance of the phenomenon in organisms that cause disease, molecular biologists such as Peter Gogarten at the University of Connecticut have described horizontal gene transfer as “a new paradigm for biology.”

What does this mean?

This transfer of DNA among pathogens means that once harmless microbes can acquire properties that allow them to cause problems for the host. As Relman has stated, “The mobile nature of gene islands, transported between bacteria via plasmids or phages, creates the potential for acquired virulence in previously innocuous microbes. This concept should inspire some reflection the next time one receives a culture report reading 'normal flora.'

The bottom line - every person's mix of pathogens is unique, each inflammatory disease is the result of infection with many different species of pathogens, and it's impossible to isolate any specific species of bacteria as being soley responsible for causing any one inflammatory disease.

If inflammatory diseases arn't caused by faulty genes, then why do they run in families?

The Th1 pathogens 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 . For one thing, these mutations often lead to an environment inside the cell that makes it easier for new pathogens to invade the nucleus.

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 definitely run in families. In addition, the pathogens may be easily passed to an infant soon after birth, during the period before the adaptive immune system is up and running.

So it's clear to those who understand Marshall's pathogenesis of chronic disease that most researchers are making a big mistake in assuming that the correlation between disease symptoms and mutated genes implies that genes - rather than the pathogens creating the genetic mutations - are responsible for the progression of an illness.

Clearly, humans accumulate a plethora of infections during their lifetimes, and it is the genetic mutations which result from active infection that play a major role in what is commonly thought of as “genetic susceptibility.” In the vast majority of diseases, parents do not pass on defective genes to their children. Instead, they often pass on L-form bacteria, which are the real underlying factor responsible for causing the symptoms of Th1 disease.

It comes as no surprise then, that after billions of dollars spent on research, not one gene therapy, not even research on the classic genes implicated in causing cystic fibrosis, has proven effective.

Are Olmesartan and the MP antibiotics safe?

Although they do so for many other drugs, the FDA has set no unsafe upper limit for Olmesartan. The FDA bases its safety data on ‘post-marketing experience’ - how many adverse events have been linked to the drug – and for olmesartan, they are negligible. There has been no dose detected that results in an adverse event.

In fact, the FDA guidelines for Olmesartan, state that:

* The guidelines allow a dosage of “40 mg Q6hr” (the dose used by patients on the MP) * Benicar dosing must be individualized. * The overall frequency of adverse events is not dose-related.

A recent study published in the Journal of of Pharmacology found Olmesartan to be safe and well tolerated at doses of up to 160 mg/day.[1] Animal studies in mice, with Benicar doses up to 480 times the human dose of 40 mg per day (relative to body weight), showed that Benicar is not carcinogenic. Many other studies confirm the safety of Olmesartan at doses used by the MP. Here are just a few of them….

Furthermore, since the anti-inflammatory actions of Olmesartan actually protect organs, and reduce damage to the body from cytokines, any assessment of “safety” should take these properties into account.

The protective effects of ARBs include the ability to:

* prevent migraines * inhibit liver fibrosis and aid liver healing * protect the kidneys in diabetic nephropathy * reduce insulin resistance * protect the heart from damage from inflammation in myocarditis * protect the mitochondria from age-associated damage from oxidation

When it comes to the antibiotics, minocycline has been used for decades in a variety of medical therapies. Recently, a multicenter double-blind placebo-controlled trial concluded that minocycline was safe and effective in patients with mild to moderate rheumatoid arthritis and supported its use (alone or as adjunctive therapy) in rheumatic diseases. Tetracyclines have been also used effectively in urogenital, gastrointestinal, and lower respiratory tract infections.

There is no evidence that long-term use of the antibiotics used by the Marshall Protocol leads to resistant species forming. In fact, minocycline was introduced in 1968 and, since that time, virtually no organisms have developed resistance to the medication, despite the fact that for decades it has been widely prescribed in efforts to control teenage acne.

According to the Physicians Protocol for using antibiotics in rheumatic disease, “Minocycline tends not to cause yeast infections.” Some infectious disease experts even believe that it has a mild anti-yeast activity.

For most patients, another hallmark of the MP is photosensitivity

Because people with inflammatory disease suffer from a dysregulated vitamin D metabolism, patients often become photosensitive when they start the treatment.

The exact mechanisms behind why people on the MP become sensitive to light are largely unknown. One thing is certain – light sensitivity is not a side effect of the Marshall Protocol medications, except in the sense that some patients report that increasing their level of antibiotics, and thus their immunopathology, causes their light sensitivity to increase. This suggests that there may be a connection between bacterial load, more intense bacterial killing, and light sensitivity.

There is, however, no doubt about the fact that once L-form bacteria dysregulate a person’s vitamin D metabolism, light in the eyes, through mechanisms not yet fully understood, can generate symptoms in many other areas of the body. In patients with inflammatory disease, light in the eyes can also stimulate a portion of the brain called the amygdala that in turn generates an increase in neurological symptoms.

Similarly, exposure to sunlight and heat from the sun – which further dysregulates the body’s level of 1,25-D - can lead to neurological as well as physical reactions that are poorly understood.

This means that patients who start the Marshall Protocol are required to buy special sunglasses that block a greater spectrum of the sun’s rays than normal sunglasses.

When first starting the treatment, they are also highly encouraged to avoid sunlight by wearing thick dark clothing and closing the shades on windows that get direct light. Here is a picture of me blocking sun during my first year on the MP. Despite my precautions, I am still ironically being hit by a beam of light.

Once immunopathology has begun, patients get a better idea of the nature of their bacterial load and their ability to tolerate light. Some (generally more ill) patients find that they can hardly tolerate the rise in symptoms generated by light exposure during the first phases of the treatment. and are forced to shut out all natural light, while turning indoor lighting down to 30 lux, which is similar to the mood lighting of a romantic restaurant. These people learn to adapt their lifestyle, if needed, to accomplish necessary outdoor tasks and enjoy social outings after sunset.

Other patients find that they have trouble seeing when wearing their sunglasses and that when they take them off, or are exposed to moderate amounts of sunlight, they don’t feel a rise in symptoms. If this proves to be the case, the patient is not required to keep wearing his glasses, although erring on the side of caution is always advised.

People who are forced to work in an environment where they must tolerate some symptoms of light exposure should be encouraged by the fact that patients have succeeded on the MP under these conditions.

Nevertheless, the goal of every MP patient is to reach a state where they will once again be able to tolerate a normal amount of light. As bacterial load decreases and dysregulated vitamin D metabolism is corrected, light sensitivity also subsides. Thus, as patients forge ahead and kill bacteria, they are gradually able to tolerate more and more light.

In other words, if you start the MP no, you will not have to wear sunglasses five years from now.

While light avoidance is part of the Marshall Protocol, supplements are not. This brings me to a very important subject.

It's very important that neither doctors nor patients modify the MP in any way.

The Marshall Protocol has a no supplement policy unless the patient needs to take the supplement for a marked deficiency. Patients are also encouraged to cut down on any prescription drugs to those that are only absolutely necessary.

These guidelines are based on the reality that the body works by setting up a delicate balance between the receptors and molecules that control numerous complex feedback pathways, many of which are intertwined. Any substance, whether or not it is listed as a drug, can bind the receptors that control these feedback pathways. In the absence of research that tells us which receptors a supplement or drug affects, we have absolutely no idea what pathways it may be altering if it enters the body. It could bind a receptor that interferes with immune function, or dysregulate a pathway that regulates important hormones.

Data has shown that, once on the MP, most of the body’s healing processes work better if they are left alone.

As Marshall describes on the MP study site, it’s important to understand that the body does not work by having specific “levels” of any particular substance. Instead, as described above, it works by setting up a balance between all the various metabolites. So it is generally useless to try and force the body to have a particular level of any one metabolite when the body’s own homeostasis is working to lower it for some reason – a reason that is often associated with the disease process itself. All metabolites should come back into balance as the MP medicines kill off the pathogens making patients sick.

Patients must follow the MP as written and as counseled because safety is at stake. Not following the MP exactly as written may force the patient to deal with intolerable immunopathology. Taking the antibiotics when not using Benicar, dosing the antibiotics at higher levels than directed, or not pulsing them, may also significantly decrease or completely stop immunopathology from occurring. This will make the patient feel better, but they are not getting better.

So what are the recovery rates?

The MP has a 100% response rate. What that means is that essentially every person to start the Marshall Protocol, and these are people with quite an array of diseases, is reporting immunopathology - which of course indicates bacterial death and thus eventual recovery. One must remember that the MP is only five years old. The vast majority of patients to start the MP were very, very sick and only started about three years ago. So the majority of patients on the treatment are reporting recovery that is often significant, but are still experiencing immunopathology.

As you can see in these photos, I was bedridden when I started the MP and just last week was able to travel half way across the world to participate in a medical conference. I can't even describe how much better I feel and how much clearer my head feels.

Although most patients on the MP will need another year or two before reporting full recovery, they are following in the footsteps of people who did start the MP about five years ago that are in a state of remission. Since nearly every patient on the MP is responding in the same exact manner to the MP meds as the fully-recovered patients, there is little doubt that they too will reach a state where they no longer experience immunopathology and are no longer symptomatic.

Since the Th1 pathogens have also been implicated in what is now referred to as “normal aging” - if you think about it many of the symptoms of aging such as aches, pains and memory loss are also symptoms inflammatory disease - people to reach the end of the MP often report that they not only feel completely better, but actually younger than when they started. Some report that they feel better than they ever knew was possible because, in retrospect, they realize that they harbored Th1 pathogens during their entire lives. Those people to reach the end of the MP do not relapse. When all their bacteria are killed they end up like any other healthy person out there.

Unfortunately, many of our current patients took steroids and other immunosuppresants for years before the MP, allowing their bacterial load to spread to a point where it takes a long time to be eliminated. So it's important to stress that the sooner one starts the MP after the onset of disease symptoms, the easier it will be. Those people to start the MP early should find their immunopathology is easier to tolerate and they require a much shorter period of time to recover.

So one of the keys to quelling chronic disease in the years to come is for patients to start the Marshall Protocol at the first sign of inflammatory symptoms.

Here are some quotes from people who have successfully recovered thanks to the MP: I'm going to skim over them quickly, but full versions of interviews with these patients, and interviews with other recovered patients can be found on my website, Bacteriality.

Carol Morgan suffered from CFS, fibromyalgia, sarcoidosis

Now she states, “I can do just about anything I want. My fatigue has been replaced with renewed energy. I have better balance and agility. I have strength and muscle tone in my legs again, and my back/neck issues are totally gone. I can now lift, twist, and engage in all kinds of movement. The pain and swelling in my stomach, legs, and feet are gone. My digestion and sleep patterns have normalized. My hair is growing back thickly again; and every time I go to the hair dresser, she says, 'Ah! I’m so glad you’re beyond that!' For the most part, my headaches and blurriness are gone, although I may have a slight headache here and there, which is quickly dampened or eliminated with an extra Benicar.

My blood pressure readings are back to normal, and the chest pain and pressure have disappeared. The TMJ and teeth sensitivity have resolved. Plus, my two trigger fingers have returned to normal. I have reduced my thyroid meds to a level that is less than half of what they used to be.

Really, all my symptoms are gone or greatly improved. Some of them were so bad that I feel like I’m 1000% better. There is no doubt in my mind that the MP has literally saved my life.”

Paul Albert suffered from CFS and depression

Today Paul says, “In many respects, you’re talking to someone who is doing better than ever. The sleep has been really good. To bed at 11:30 and up at 8. I might wake up during the night once, just long enough to check the time before I fall back asleep. Also, I have a great new job. I’m working on lots of fun projects. It is somewhat demanding, but I definitely have the energy for it. I play racquetball with my buddy on the weekends. I can spend lots of time in the sun. I’m more social at work and in general, I’m not put off by people.

Gus Wilkinson suffered from sarcoidosis, psoriasis, insomnia

Today he states, “I have no lung symptoms at all. My insomnia is completely gone. Sleep is blissful, it’s wonderful. No kidney stones, no night sweats. The only thing left is a very small amount of psoriasis. I would say maybe 1% of my body is covered with psoriasis. But before I started the MP I had psoriasis over about 70% of my body. A host of other symptoms are gone as well. I have so much more energy and my mood is better. I think my wife and kids have nearly forgotten my grumpy, sickly and lethargic cocooning days. Also, before the MP, I had an uncontrollably high blood pressure, which averaged out at about 170/105. After a while on the MP, my blood pressure settled down to an average of 90/60. I have clear before/after lung x-rays. I have granulomas in the x-rays taken before I started the MP and no granulomas are visible in my current x-rays. Well, the MP literally cured ALL my health problems. Before starting the MP I had no idea that all my symptoms were connected and were all the result of bacterial infection. So it was a real eye opener when all my symptoms responded to the treatment. So although I started the MP for sarcoidosis, it fixed everything else as well…a real bonus!”

Ival Myer suffered from rheumatoid arthritis and dyslexia

Now he says, “The lower back pain has completely gone away. The pain in my hands is 100% gone. My toes are still curled up but they don’t hurt anymore. I think the ligaments are definitely loosening up. The flu-like feeling is gone. The fatigue is much better. I’ve been able to start working again. I work in the office of the collision shop but I’m starting to get back out to the cars. I’m convinced that I will live longer because I’m doing the Marshall Protocol. Clearly these bacteria are what bring the elderly down. But I’m not going to have any! It’s a good feeling to know that you’re going to age with, let’s say, dignity and grace. When someone asks me 'Now how old are you?' I say, '45. I would’ve been 48 but I was sick for three years.' That reflects how much younger I feel.”

How can doctors or patients determine what makes someone a good candidate for the MP?

As mentioned before, doctors can test the levels of a patient's vitamin D metabolites. A low 25-D and a high 1,25-D is a good indicator that the patient is suffering from a disease the MP can treat. If these tests are performed, it's extremely important that the 1,25-D sample is frozen. If the sample is not frozen, the 1,25-D results are useless.

It's important that doctors who plan to use the D tests realize that several medicines are able to interfere with the levels of the vitamin D metabolites. These meds include some antifungals and immunosuppressants. For example, prednisone lowers 1,25-D by 25-40%.

Similarly, if person is supplementing with large amounts of vitamin D, their level of 25-D may be artificially skewed upwards, and the 25-D result will not prove conclusive.

Because of these variables, it’s extremely important that even if the D tests prove inconclusive, people considering the MP do what is referred to as a therapeutic probe. A therapeutic probe is simply a way of saying that a patient should start the Marshall Protocol medications. If they are infected with the Th1 pathogens, Olmesartan will likely cause expected hormonal adjustment symptoms and minocycline will almost always provoke immunopathology within the first month or two of treatment.

These reactions are proof positive that the patient is infected with L-form bacteria and thus should be given priority over the D tests to decide if a person should start the MP. This is particularly true if the person is displaying obvious symptoms of Th1 disease or has been diagnosed with one of the illnesses that the MP has been shown to successfully treat.

Patients must also be willing to understand the science and guidelines of the Protocol, follow it exactly as recommended, and discontinue any contraindicated medications and therapies. Patients must have access to, and be able and willing to use, the Internet to utilize the study site forums. Patients should understand and accept immunopathology as unavoiable and the fact that the resolution of their disease may take several years. Financial resources to cover doctor’s visits, blood tests, sunglasses, and medications must be available. Patients must be willing to make necessary lifestyle adaptations including the avoidance of sun, bright lights, and vitamin D-containing foods and supplements. Lastly, but most importantly, it's important that a patient have adequate social support.

What I have discussed is controversial but…..

If the claims made by vitamin D advocates are correct, and the idea of “autoimmune disease” is correct, then why is the rate of chronic disease increasing as we add an ever-greater amount of vitamin D to the food supply and doctors continue to treat their patients with immunosuppressive drugs?

Chronic diseases have been around for centuries. Shakespeare and Beethoven are rumored to have suffered from chronic symptoms resembling those of sarcoidosis or CFS. The difference is that over the past few decades the rate of chronic disease has escalated to the point where we are now in the midst of a literal epidemic.

Is it merely a coincidence that during the 20th century:

1. We are living during a moment in history when vitamin D supplementation is at an all time high. After all, we have added vitamin D to the food chain – to the point where today not just milk but butters, juices, cereals, grain and pasta products, cheeses and soy milk are all fortified with the secosteroid.

2. We have started to routinely give patients anti-inflammatory drugs, ranging from over the counter anti-pyretics and anti-histamines, to prescription steroids, such as prednisone, in order to suppress what is incorrectly regarded as inflammatory response by an immune system that has lost control (e.g autoimmune disease).

3. We have started to equate tanned skin with beauty – meaning that excessive sun exposure at the beach and the use of tanning beds has become commonplace.

4. We frequently administer the beta-lactam antibiotics such as penicillin, which kill most classical forms of bacteria during acute infection but cause the formation of L-form bacteria in the process.

It's food for thought.

How can patients find an MP doctor?

Patients on the MP must work with their own physician. Materials to present to physicians are available on the study site. Patients can also request a list of doctors in their area who already have patients on the MP from the study site moderators.

We strongly encourage doctors to join the Private Section for Medical Professionals on the site where they can discuss the treatment with other professionals and get feedback about treating patients.

What organization runs the Marshall Protocol?

The MP is run by Autoimmunity Research Foundation (ARF) - a non-profit, California-based organization. ARF is working with physicians around the world to effectively apply the Marshall pathogenesis. The FDA has already granted orphan product designations for two of its six drug applications - in Sarcoidosis and in PTLDS. The Foundation continues to work with the FDA who actively monitor the study site.

The Board of Directors is comprised not only of medical professionals, but also patient advocates and research support teams. The Board and patients are composed of people from all around the world.

Some may ask why ARF is not conducting a double blind placebo-controlled study…….

The Marshall Protocol is unique because researchers conducting standard blinded study trials currently base their conclusions on data that reveals only a small (usually 5-20%) difference in statistical significance between those patients given treatment and those to receive a placebo. But the response rate (and by that I mean the number of people who experience immunopathology) of those patients taking part in the current phase II trial of the Marshall Protocol is essentially 100% - not to mention the fact that the treatment is also based on a very solid scientific model.

To date, the positive response of patients to the treatment is so definitive that to blind a separate study on the MP raises an ethical dilemma. For one, because the Marshall Protocol takes so many years to complete, it just isn’t ethical to give sick, suffering patients a placebo for multiple years—not when so many people die from these diseases every day.

So instead, the MP is part of a phase II clinical trial monitored by the FDA. Because the MP is a study as well as a treatment, once a patient becomes a member of the study site, ARF volunteer research staff advise participating doctors and patients through the Organization’s forums, free of charge. In turn, members are required to post symptoms in weekly progress reports on the MP site so that the nursing staff can be aware of any blips in progress and can help identify potential problems before they arise, during a time when the patient may not have access to their doctor. Patients should visit the website www.marshallprotocol.com for details and the study inclusion criteria.

ARF has recently set up a website called Curemyth1.org that is a great place for people interested in the MP to ask questions about the treatment before starting it. Questions are answered 24 hours a day by patient advocates.

Gaining acceptance

Those of us on the MP feel a great sense of excitement about Dr. Marshall's research and its potential to impact people with such a wide range of terrible chronic diseases. In fact, I feel we are living during a very exciting time in history. For millenia, the Th1 pathogens have been evolving in ways that have allowed them to gain the upper hand by taking advantage of our body's receptors and feedback pathways. Now, thanks to Dr. Marshall's molecular data, and the wide body of clinical evidence being collected on the MP study site, humans can finally dominate the Th1 pathogens, allowing people to live normal, pain-free lives once again.

I am so excited about my own recovery thus far that I dedicate as much time as possible to writing for my website, Bacteriality. On the site, I try to simplify scientific concepts related to the MP and write in language that the average person can understand. The site also contains interviews with doctors and scientists whose work contributes to the MP pathogenesis as well as interviews with patients who are recovering thanks to the MP.

I feel honored to be part of such an exciting scientific movement that will lead to some of the greatest paradigm shifts ever made in medicine.

Everyone else at Autoimmunity Research Foundation is a volunteer for similar reasons. All services on the site are provided free of charge and Autoimmunity Research Foundation makes money only from donations. The moderators, the patient advocates, and Dr. Marshall all work for free because, like me, they realize that the Marshall Protocol has the potential to affect the lives of millions and change the concept of chronic disease as we know it.

Change in the medical world is a slow process. As German philosopher Arthur Schopenhauer once stated, “All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.”

Full acceptance of the MP by mainstream medicine will require doctors and researchers to rethink everything they have been trained to believe and approach disease through a vastly different lens. Such change takes time, particularly since many prestigious researchers will have to admit that the work that has brought them respect and tenure is not correct. Yet every day, more doctors and researchers are accepting Marshall's work and his pathogenesis for chronic disease is being discussed and presented at some of the most prestigious medical conferences in the world.

When Barry Marshall, a colleague of Dr. Marshall's at Adelaide University in Australia, first discovered that stomach ulcers are caused by h.pylori bacteria, it took twenty years before his discovery was accepted by mainstream researchers. When he first put forth his hypothesis, people walked out of his presentations and he was largely scorned. But decades later he won the Nobel Prize.

I urge you be open-minded towards Dr. Marshall's research and it is my sincere hope that you will join me in spreading word about the immunosuppresive actions of 25-D, the unbiquitous presence of the Th1 pathogens in people with inflammatory disease, the importance of the vitamin D receptor, and all the other aspects of Marshall pathogenesis. As word spreads, there is great hope that chronic inflammatory diseases will become a disease of the past.