Note: A number of patients with CFS, FM, and other chronic illnesses such as lupus and Lyme disease are reporting success with the experimental Marshall Protocol, originally developed for relieving the symptoms of patients with the "Th1" inflammatory disease sarcoidosis. (See the Marshall Protocol message board at http://www.marshallprotocol.com, and "A Journey Towards Complete Recovery from Chronic Fatigue Syndrome" at http://www.immunesupport.com/library/showarticle.cfm/id/6569
Following is an exclusive interview conducted in July 2004 with Trevor Marshall, PhD, who devised the highly demanding and still-controversial protocol, which must be administered under the care of a physician. He explains why he believes it may work for certain CFS and FM patients, and others. (See disclaimer at end of article.)
Question: Please introduce yourself by giving some background on your medical training and practice.
Trevor Marshall, PhD: I graduated Bachelor of Engineering (w/w statistics) from the University of Adelaide in 1974. I spent a year in Papua New Guinea teaching at the University of Technology in Lae, and then spent 6 years teaching at Curtin University in Western Australia. During that tenure I received my Masters Degree and commenced my PhD Research at the University of Western Australia, in Biomedical Engineering. It was an exciting time. Another UWA student, Dr. Barry Marshall (no relation) had just discovered that the bacterium Helicobacter Pylori was the cause of stomach ulcers, and the teaching hospital where we did our clinical research ("Sir Charles Gairdner") was full of "new ideas." My mentors were convinced that we needed to develop a totally different approach to medicine.
I researched Infertility and Cryptochidism with Ted Keough and Diabetes in Tim Welborn's group. Ted found a way to treat infertility by pulsatile infusion of a hormone called GnRH, and resolved Cryptorchidism without surgery, using pulsatile infusions of the hormone LHRH. Tim's group explored the continuous infusion of insulin in Diabetes.
After moving to the USA in 1982 I took some time off to study with Mike Albisser's group at the Hospital for Sick Children in Toronto. "Sick Kids" was a world leader in diabetes research at the time, and our research team included MDs and PhDs from all over the world. It was an amazing experience, and my doctoral thesis, "Mathematical Modeling of the Insulin Glucose Homeostasis in Healthy and Diabetic Individuals", was accepted in 1985.
Soon after that, I came to the realization that sunlight was a factor in immune disease, but it took many years for all the elements of the Th1 immune reaction to gel together in my mind. Late in 1999 I noticed that a new class of drugs, "Angiotensin Receptor Blockers' (ARBs), were affecting the psyche of Sarcoidosis patients. Since I knew that ARBs should not have any such effect I commenced a full-time sabbatical in early 2001 to try and figure out exactly what was happening. The result of that research was a pathogenesis for sarcoidosis, published in 2002. Since then we have conducted an Internet-based study of ARB and antibiotic therapy in sarcoidosis, and are now exploring how our success can be generalized to all the Th1 immune diseases. The Autoimmunity Research Foundation is acting as a focus for our current efforts (http://autoimmunityresearch.org).
Question: A number of patients with Chronic Fatigue Syndrome (CFS), Fibromyalgia (FM), and other chronic illnesses report they're finding success following your sarcoidosis treatment protocol. Could you explain what CFS, FM, and sarcoidosis patients might have in common that could explain this?
Trevor Marshall, PhD: Sarcoidosis is a Th1 inflammatory disease which can damage the lungs, heart, eyes, brain, liver, kidneys and soul. Patients are still being told it has no known cause and no known cure.
Tiny "pleomorphic" bacteria have been photographed living within the cells of the immune system of sarcoidosis patients. Emil and Barbara Wirostko produced stunning electron microscope photographs of immune phagocytes each containing hundreds of tiny bacterial forms, around 0.01 to 0.025 microns in diameter, living in colonies within the very cells (phagocytes) which are supposed to kill these bacterial parasites. One of the Wirostko photographs can be found at http://www.autoimmunityresearch.org/wirostko-fig3.jpg It is important to understand that these bacteria are "coccoid" (round, and very, very small), 10 to 100 times smaller than the shapes these same pleomorphic bacteria will take when they enter the bloodstream.
We found that you can measure a hormone (in the blood) resulting from the Th1 inflammation produced by these tiny bacteria, and that it is elevated in Sarcoidosis patients. It is also often elevated in CFS patients, indicating that the inflammation of CFS is often very similar to that of Sarcoidosis.
Question: Some researchers (including Garth Nicolson, PhD at The Institute for Molecular Medicine in Huntington Beach, California) and physicians believe that multiple co-infections including bacterial and mycoplasmal infections, play a key role in the onset and pathology of CFS and FM. To what extent are bacterial and mycoplasmal infections involved in sarcoidosis, and do you believe your methods for treating those infections in sarcoidosis apply to CFS and FM patients?
Trevor Marshall, PhD: Multiple co-infections of antibiotic-resistant bacteria can act in unison because many of the species have evolved a similar technique for evading the immune system.
These bacteria live in the cytoplasm of phagocyte cells, and directly stimulate a protein called NuclearFactor-kappaB to cause the continuous release of inflammatory chemicals, a Th1 cytokine cascade. This is the source of the inflammation driving the CFS symptoms.
Where our work diverges from that of Dr. Nicolson is the manner in which we control the hormones Angiotensin II and 1,25-dihydroxyvitamin-D so as to weaken the defense mechanism of these tiny bacteria, and allow the immune system itself to start to recognize and kill them. We then use common (oral) antibiotics, at a very low dosage, to help the immune system deal with the parasites. It is the immune system which kills these tiny resistant microbes, helped along by low-dose antibiotics.
Question: What is your treatment protocol for bacterial and mycoplasmal infections?
Trevor Marshall, PhD: Our treatment protocol is split into two phases. The first phase lasts for about three months and is focused on getting the bacterial load down to a point where the endotoxins are no longer life-threatening. Then, in phase 2, we use additional (low-dose) antibiotics, making it almost impossible for the resistant bacteria to evade the immune system.
Phase 1 is available online at http://SarcInfo.com/phase1.pdf
We focus on blocking genetic protein transcription, the process whereby the tiny bacteria use the bacterial 30S and 50S Ribosomal Nucleic Acid subunits to produce the proteins they need to hide from the immune system. In phase 2 we block multiple pathways for 50S RNA synthesis, which allows the immune system to recognize (and kill) even the strains which have evolved a resistance to standard antibiotics.
Question: How do you go about improving immune function in your patients, what is your protocol for that objective which could cross over from sarcoidosis to CFS and FM patients?
Trevor Marshall, PhD: The two hormones critical to this inflammatory process are Angiotensin II and the seco-steroid 1,25-dihydroxyvitamin-D.
Blockade of Angiotensin II weakens these bacteria to the point where they can be more easily killed, and reducing the 1,25-D makes it harder for the bacteria to slip in and out of the cells they have infected.
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We use the Angiotensin Receptor Blocker "Olmesartan Medoxomil" (Benicar/Olmetec/Votum), dosed approximately every 6 hours, to blockade the Angiotensin II receptors in the inflamed tissue.
The seco-steroid 1,25-D is the active hormone resulting from sunlight on our skin, and the Vitamin D we ingest. Both these sources of 1,25-D have to be attenuated if these bacteria are to be killed.
Question: Are you currently treating any patients with CFS and/or FM, or have you in the past? If so, what is your strategy for treating these patients?
Trevor Marshall, PhD: I am a researcher with a PhD, not an MD, and I cannot treat patients directly. I help their physicians understand the disease process, so that those physicians can work with the patients to cure the disease. We are also working with several LLMDs (Lyme literate Medical Doctors).
I, and my colleagues, have published a number of papers describing all the elements of our discoveries, and, during 2002, we set up a clinical trial at the Internet site http://www.SarcInfo.com so that we could track the progress of the first patients using our protocol.
Also [a message board was created] called "MarshallProtocol" (http://www.marshallprotocol.com), and CFS and FM patients have used the information from that site to work with their physicians to implement the protocol… It seems the protocol is working just as well for these CFS and FM sufferers as it did for the sarcoidosis patients, most of whom have progressed to "cure" over the last two years.
Question: In one of your recent research articles, you discuss "Lessons from Lyme Disease." Many chronic Lyme patients experience symptoms very similar to CFS and FM, and in fact, it is not unusual for someone with Lyme disease to be mis-diagnosed with CFS or FM. Could you discuss this issue, and talk a bit about how you diagnose and treat patients with Lyme and other spirochetal diseases?
Trevor Marshall, PhD: Whether the inflammation (which gives rise to the CFS and/or FM symptoms) is caused by Borrelia, Bartonella, Chlamydia, or any other bacterium with the ability to change into these tiny pleomorphic shapes (also called "L-forms," "Cell Wall Deficient," "Cystic," "Mycoplasma"), the inflammation needs to be treated the same way. The microbes seem to be resistant to standard antibiotics, even IV antibiotics, and have to be killed by our immune system itself. We have defined what is necessary to achieve that.
Diagnosis can often be done from bloodwork assay. If the level of 1,25-dihydroxyvitamin D in the blood is elevated (above 38-45pg/ml), or the 25-hydroxyvitamin-D depressed (below 20 ng/ml) then it is pretty certain that a Th1 process is in play (note: all blood must be frozen during transit to the labs for these tests to be accurate).
Sometimes it is quicker and cheaper to apply the angiotensin blockade as a "therapeutic probe." If there are profound psychic and systemic effects from using Benicar, a drug which usually only changes the blood pressure, then that is a pretty good indication of the presence of Th1 inflammation, and an indication it is worth starting on our protocol.
Question: For those patients out there struggling with dubious diagnoses, do you recommend any specific laboratory tests to determine what infections they might have?
Trevor Marshall, PhD: Unfortunately today's laboratory tests are of little use until the immune system starts to recognize these intracellular invaders. Hundreds of these tiny bacteria can live inside a single cell. They are too small to be seen with conventional optical microscopes. The host cells live for a relatively long time. There is little apoptosis (cell death), so very few bacteria are released into the bloodstream, and they are hard to detect with lab equipment.
Because they live in stable symbiosis with our immune system, there are no antibodies created. The bacteria live within the cells in stable colonies which cannot be attacked by the body's normal defenses. Lab tests will not find antibodies to these bacteria.
PCR (polymerase chain reaction testing) is capable of sensing the occasional cell apoptosis, but the resulting low DNA concentrations would be regarded as insignificant by most labs.
The biochemical symbiosis is so delicate that it is virtually impossible to culture these bacteria outside the body. Just as the bacteria causing Leprosy (mycobacterium leprae) and the bacteria causing Syphilis (treponema pallidum) are nearly impossible to culture, I expect it is unlikely we will be able to culture these Th1 pleomorphs until we fully understand the biochemistry needed to sustain them. No lab has been able culture these bacteria up to this point in time (with the possible exception of Lida Mattman's research at Wayne State University).
So I guess the next task for us is to start working with labs to help devise tests which can produce a reliable diagnosis.
Question: Do you have any parting advice for CFS and FM patients seeking appropriate, effective treatment?
Trevor Marshall, PhD: I would just say don't take "no" for an answer. For the last 100 years sarcoidosis patients have been told that there is no known cause and no known cure for their disease (much the same prognosis being given to CFS and FM patients). The diagnosis of chronic sarcoidosis is regarded by pulmonologists as irreversible, they know their patient is dying, and that it is just a matter of time.
Yet the sarcoidosis folks who have been helping us develop our protocol, are becoming healthy again. Not just 10 percent, or 25 percent, but close to 100 percent are recovering their lives and their families. They have variously reported regaining cognitive focus, stamina, and stable gait, and resolving chronic pain, paresthesias and visual disturbances. Some have been able to discard wheelchairs, braces and supplementary oxygen.
"It is not the antibacterial therapy" that is helping these patients, say 'the experts,' "it is just spontaneous remission." Well, personally, I don't care what they call it, most of us will take this antibiotic-induced "spontaneous remission" any day, as long as it gives us back our health, our lives and our families. Don't take "no" for an answer.
Disclaimer: The content of this article reflects the views of Professor Trevor Marshall, PhD. ProHealth/ImmuneSupport.com does not endorse this or any other specific protocol as a treatment or cure for CFS or FM.
Note: This information has not been evaluated by the FDA, and is not meant to diagnose, treat, cure, or prevent any disease. It is very important that you never make any change in your health support plan without the careful review and approval of your professional healthcare team.