Grappling with uncertainty about the Marshall Protocol

The Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop. is an explanation for how all chronic inflammatory diseases share a single pathology. The Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP) is a therapy designed to address that pathology. One of the barriers in the way of widespread acceptance of the theory is that it contradicts so many commonly held assumptions about medicine:

• vitamin D “deficiency” causes or exacerbates disease
• vitamin D is therapeutic in patients with chronic disease
• bacteria are mostly beneficial
• diseases caused by bacteria are caused by a single species
• if patients take a therapy which makes them feel better in the short-term, that means they are getting healthier in the long-term

The MP study site does not have the resources to support amateur scientists who offer up theories that build upon the work of the Autoimmunity Research FoundationNon-profit foundation dedicated to exploring a pathogenesis and therapy for chronic disease. (ARF), nor it does have the resources to explain how a study reconciles with the latest ARF research.

To do the MP, patients must ultimately make the decision for themselves and must make the decision realizing that, at least for now, one or more experts will disagree with that choice.

People also seem to have trouble grappling with root causes. They may point to a sign or symptom of disease: low blood pressure, elevated cholesterol, trouble sleeping, low levels of a hormone, etc., and conclude that a certain factor causes the disease. The problem with this line of thinking is that the disease does not go away when that factor is remedied–when medications are used to increase cholesterol or medications are used to decrease blood pressure. On the other hand, patients who take regular doses of olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. and pulsed, low doses of antibiotics do see improvement in their underlying disease.

While the theory behind the MP is no more complicated than a number of others, it does require reassessing certain basic assumptions, the embrace of which has led to escalating rates of chronic disease. High school biology classes, to say nothing of medical schools, do not talk about nuclear receptorsIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affect transcription. or how supplementing with vitamin D may be immunosuppressive. To make matters even more difficult, with a couple of exceptions, the media repeats the old ways of thinking. This is especially true when it comes to coverage of vitamin D.

Consider the MP as consisting of a series of hypotheses about vitamin D, about bacteria, and about the nature of the innate immune system. Each of these hypotheses is supported by molecular science, much of which is described in this Knowledge Base and in peer-reviewed papers and presentations given by members of the Autoimmunity Research Foundation research team.

The point of all the work that has gone into the papers, presentations, and this Knowledge Base is that well-educated people–be they researchers, clinicians, or motivated patients–can understand it and make a critical evaluation of the science and its relevance to patients.

In fact, most patients who succeed on the Marshall Protocol internalize much of the science behind it or have a physician (or family member or friend) who does. As a theory, the Marshall Pathogenesis and Marshall Protocol are not perfect, as no scientific theories are; but it does have strong explanatory power. Autoimmunity Research Foundation and its members are confident that its basic claims about the nature of chronic disease should keep researchers busy for decades.

For a person who still has doubts about the MP science, perhaps an empirical or observational approach is warranted. Patients should look at what the MP predicts and ask themselves if their reactions are consistent with what has been experienced by every other patient who has succeeded on the MP:

• “Do I get an increase in the symptoms of my disease, known as immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed., when taking olmesartan (Benicar)–a medication that is otherwise used to lower blood pressure, of all things?”
• “Do I feel calculated increases in the severity of my symptoms following each dose of antibiotics?”
• “Do I feel the temporary immunosuppression caused by antibiotics?”
• “While the olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. blockade is in place, am I photosensitiveAbnormal sensitivity to sunlight and bright lights. Also referred to as "sun flare" or "light flare."?” While this reaction tends to be somewhat variable, those patients who do experience it have added evidence that the MP is working.

Questions arise when a patient can't understand the basic scientific concepts behind the MP. Cognitive dysfunction, also known as brain fog, is a common symptom reported among patients with inflammatory disease. It may be difficult, if not impossible, for such patient to fully understand the science.

A second issue is how the MP may or may not apply in an individual's particular circumstances. A patient may want to know, for example, what role a hormone plays in the disease process or if a particular medication interferes with progress on the MP. According to the Marshall Pathogenesis, the signs and symptoms of chronic disease are downstream effects or end-results of the underlying disease process. As for the thousands of medications and supplements that patients with inflammatory disease take, it is often hard to say exactly how they affect immune function. Practically speaking, it is impossible for the ARF research team to model the interaction of every substance's relationship with the body's key nuclear receptors.

Another common source of questions is recent studies. PubMed has tens of millions of studies. Some of them, many in fact, seem to contradict the conclusions put forth in the Knowledge Base or in the ARF research team's published papers. Often, a critical thinker may be able to apply the evidence and criticisms in the Knowledge Base to a study and make sense of it.

An example: one study concluded that vitamin D might lower the incidence of colorectal cancer.¹ A critical thinker might realize that the study was only for four years and might even be able to find studies over a longer period, which contradicted the original study's findings.²

Using statistical inferences, John P. A. Ioannidis concluded in the prestigious journal PLoS Medicine that half of published research must be wrong.³ The arguments of that paper are beyond the scope of this article; but in grappling with a confusing study, it's seriously worth considering how Ioannidis could be right.

Karhausen wrote, “Actually, there is no experience of causation: events do not wear their causal credentials on their faces.”⁴ Many of the statements a reader sees in the context of a scientific paper is dependent on interpretation. The point of the MP is that several of those key interpretations are wrong.

For this reason, studies from PubMed should always be read with the critical eye of a university professor.

Because the MP science is so new and different, it does contradict dozens (or probably hundreds) of studies that have been done in the past. It especially contradicts studies done on populations, as opposed to research that investigates the workings of the immune system at the molecular level.

I have seen many instances of new (and understandably skeptical) members challenging MP science with other medical studies that contradict it. This asks Dr Marshall to explain why each of these studies came to their conclusions erroneously, or, to reconcile their findings with his own. This is an incredibly time consuming request, as it asks Dr Marshall to explain everyone else's science.

This is also a highly unrealistic expectation, as it will probably take decades of research to fully reconcile MP findings with conventional science. No one (as yet) has a full understanding of the complete workings of the immune system, as it is incredibly complex. There are innumerable contradictions between the thousands of studies out there. This simply attests to the fact that nobody understands it all. How can we realistically expect anyone to explain and reconcile all findings to date?

DaveW