Confronting 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 Protocol (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
  • if patients take a therapy which makes them feel better in the short-term, that means they are getting healthier in the long-term
  • diseases caused by bacteria are caused by a single species

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 Foundation (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.

One pathology, one treatment

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, anemia, 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 frequent doses of olmesartan (Benicar) and in some cases, pulsed low doses of antibiotics do see improvement in their underlying disease.

Evaluating the Marshall Protocol

We as scientists are very good at studying what we know. But the unknown is out of reach, and what it may take… is someone who just has what might seem like a crazy idea, but the means to pursue it, and find that there are new links between the human microbiomeThe bacterial community in the human body. Many species in the microbiota contribute to the development of chronic disease., and diseases that today we don't really think of as having any underlying microbiological component.

Claire Fraser-Liggett, Director of the Institute for Genome Sciences at the University of Maryland, BBC Radio 4 program about the Human Microbiome

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 receptors 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.

Empirical approach

Related article: Therapeutic probe

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:

On evidence

from a 2010 article in The Scientist by Mike Rawlins, chairman of NICE

The discomfort of many clinicians comes from the fact that the data are derived mainly from clinical trials, which exclude the elderly and people with multiple problems. Yet in the “real world” of medicine, particularly general practice, most patients are elderly and most have multiple problems. So can the “evidence” be applied to these patients? Unthinking application of multiple evidence-based guidelines may cause serious problems

Getting answers to questions

Grappling with brain fog

Questions arise when a patient can't understand the basic scientific concepts behind the MP. Cognitive dysfunctionThe loss of intellectual functions such as reasoning; memory loss; and other neurological abilities that is severe enough to interfere with daily functioning., also known as brain fogThe loss of intellectual functions such as reasoning; memory loss; and other neurological abilities that is severe enough to interfere with daily functioning., 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.

How does the MP apply to me?

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.

Understanding studies

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. See 2), 3), 4), 5) and select OXFORDacademic to read the comments.

Using statistical inferences, John P. A. Ioannidis concluded in the prestigious journal PLoS Medicine that half of published research must be wrong.6) 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 wrote7), “Actually, there is no experience of causation: events do not wear their causal credentials on their faces.” 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.

Patient inquiries

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?


Frequent question

It has been mentioned that others who have been on the MP for awhile and had a relatively quiet IP period will typically have a big IP wave. Can you give me more info on this? How bad does it get for people & how long does it typically last?

Support volunteer replies:

In the first 2 or 3 years on MP, the immune system begins to become active, and firstly goes after the easier to control microbes, the more recent infections. I guess often planktonic…

Researchers have estimated that 60-80 percent of microbial infections in the body are caused by bacteria growing as a biofilm A structured community of microorganisms encapsulated within a self-developed protective matrix and living together. – as opposed to planktonic (free-floating) bacteria

This includes sub-clinical or undiagnosed conditions which were building up unnoticed. In my case by the second year I had flare-ups followed by disappearance of symptoms which I formerly thought to be normal aging.

When MP is maintained for many years, the recovering immune system is dealing with biofilm.

At this point individual difference in patient status and response becomes much more obvious.

As before, it is again impossible to predict how long any bout of IP will last, how it will manifest, whether it will become intolerable. Often people give up, they decide they would rather feel better now and take the risk of feeling much worse when older.

Sometimes a person decides the MP “does not work” for them ….but it is very likely that MP is working 'too well' at the time, with great quantities of cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. being produced by death of microbes in biofilm. Our job as support team includes asking MPeers to 'phone home' with information and experiences which will help others, often ways of ameliorating nasty IP whether physical or pharmaceutical. There is no easy or short term way, we wish there were.

===== Notes and comments =====

Excellent article!!!

Evidence: A Seductive but Slippery Concept Medical guidelines based on so-called scientific evidence are not a panacea.

The discomfort of many clinicians comes from the fact that the data are derived mainly from clinical trials, which exclude the elderly and people with multiple problems. Yet in the “real world” of medicine, particularly general practice, most patients are elderly and most have multiple problems. So can the “evidence” be applied to these patients? Unthinking application of multiple evidence-based guidelines may cause serious problems, says Mike Rawlins, chairman of NICE.

===== References =====

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