Proal AD, Albert PJ, Marshall T
Autoimmun Rev8p677-81(2009 Jul)
The Marshall Protocol (MP) is the name given to a therapy devised by Professor Trevor Marshall. Based on the pathogenesis Marshall has proposed for chronic inflammatory disease, the MP is aimed at targeting bacteria, fungi, viruses, and other microbes that appear to interact to cause chronic inflammatory diseases.
Marshall (and colleagues) have hypothesized that chronic inflammatory diseases, including many autoimmune diseases, are caused by dysbiosis of a metagenomic microbiotaThe community of bacterial pathogens including those in an intracellular and biofilm state which cause chronic disease.: communities of microbial pathogens, many of which persist intracellularly. A recent peer-reviewed paper describes this Pathogenesis in more detail.1)
Supported by Autoimmunity Research Foundation, the MP has been available since 2002 and has been used in a wide range of chronic inflammatory illnesses.
A significant number of patients diagnosed with sarcoidosis, post-treatment chronic Lyme syndrome, chronic fatigue syndrome, uveitis, Hashimoto’s thyroiditis, rheumatoid arthritis, fibromyalgia, diabetes type II, psoriasis, lupus (SLE), multiple sclerosis, and a number of other diagnoses are showing a promising response from being treated with the Protocol.
In determining whether a patient can be successfully treated with the MP, a specific chronic disease diagnosis is not as important as the clinical assessment by a knowledgeable health care provider, the results of a therapeutic probe, and outcome of the vitamin D metabolites blood test.2)
According to the Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop., chronic inflammatory disease is characterized by dysregulation of the nuclear receptorIntracellular 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 affects transcription. pathways which control the innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease.. For example, the Vitamin D nuclear receptorA nuclear receptor located throughout the body that plays a key role in the innate immune response. (VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response.) expresses many of the body's antimicrobial peptidesBody’s naturally produced broad-spectrum antibacterials which target pathogens. (along with TLR2A receptor which is expressed on the surface of certain cells and recognizes native or foreign substances and passes on appropriate signals to the cell and/or the nervous system.). In addition to down-regulation of expression of the VDR itself by many common bacteria and viruses, antagonistic microbial metabolites incrementally block ligands from activating it. Ingested vitamin D slows activity of the receptor in this same manner, preventing the body from killing the pathogens at the heart of the disease state. That is why avoidance of ingested vitamin D (in food and supplements) is essential for the innate immune system to function correctly while patients are on the MP.3) 4)
The MP uses multiple daily dosing of olmesartan medoxomil (Benicar, Olmecip, Olmetec) to re-activate the Vitamin D Nuclear Receptor, dislodging bacterial ligands in the process. This drug was developed as an Angiotensin II Receptor Blocker (ARBA drug which is an angiotensin receptor blocker. One of the ARBs is olmesartan (Benicar). Not all ARBs activate the Vitamin D Receptor.) but it has multiple actions in the human body when dosed as defined by Marshall. In addition to immunostimulation via the VDR, 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. also reduces inflammatory cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. production by inhibiting the NF kappa-B transcription pathway. This inhibits, among other things, the release of TNF-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells., helping to protect the organs from effects of excessive inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue..
Additionally, several pulsed, low-dose, bacteriostatic oral antibiotics may optionally be used. Four bacteriostatic antibiotics: minocycline, clindamycin, sulfamethoxazole-trimethoprim (Bactrim DS), and demeclocycline (Declomycin) have been found useful, as also formerly was azithromycin (Zithromax). Minocycline directly acts in an immunosuppressive manner on the PXR nuclear receptor, and this biochemical action may be useful in pulsing 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. to (for example) a 48 hour cycle.
N.B. azithromycin is no longer recommended for use while on the MP.
Seriously ill patients may develop photosensitivityAbnormal sensitivity to sunlight and bright lights. Also referred to as "sun flare" or "light flare." during the healing process, so avoidance of direct and indirect sunlight may be necessary. Patients may need to protect their eyes from bright lights to prevent further retinal damage and reduce neurological symptoms due to inter alia, the effect of ocular 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. production on the brain.
Patients may also develop sensitivity to skin exposure to sunlight, and/or find that they need to avoid skin exposure to sunlight in order to maintain the low blood levels of vitamin D required by the Protocol. However, some patients do not experience significant photosensitivity during recovery, and those who do often find it more manageable several years into the therapy.
Trevor Marshall and the rest of the Autoimmunity Research Foundation research team have been active in publishing papers and making presentations before learned bodies.
Marshall's recent presentations can be viewed in order to get a more detailed description of the Marshall Pathogenesis and Protocol.
|Marshall TG||2015 May||Preventive Medicine 2015||Innovative methods of diagnosis, treatment and rehabilitation||Moscow, Russia|
|Marshall TG||2012 June||Molecular Basis of Clinical Medicine||What can microbial genomes tell us about human health?||Saint Petersburg, Russia|
|Lindseth IA||2012 May||8th International Congress on Autoimmunity||Treatment of chronic fatigue syndrome as an immunological disorder||Granada, Spain|
|Marshall TG||2012 May||8th International Congress on Autoimmunity||The microbiome, which feeds a myriad of autoimmune diseases||Granada, Spain|
|Goetze-Pelka R||2011 November||Autoimmunity Congress Asia||Psychiatric and neurologic comorbidities as systemic dysfunctions||Singapore|
|Marshall TG||2011 May||NeuroTalk 2011||The human microbiome is the mechanism fueling neurodegenerative disorders||Dalian, China|
Main article: Physicians' concerns about the Marshall Protocol
Over the years, physicians have voiced various concerns about the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis., concerns ranging from the safety of higher doses of olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. to concerns about long-term antibiotic use. The Autoimmunity Research FoundationNon-profit foundation dedicated to exploring a pathogenesis and therapy for chronic disease. has assembled articles, well-grounded in scientific research, which address these concerns. Physicians who choose to use and administer the MP do so on the basis of the available evidence.
Access to the Marshall Protocol study site is available for health professionals upon request. Health Professionals are welcome, and will be manually joined into the database after sending an email to Moderators@MarshallProtocol.com listing their desired username and password. Health professionals are granted access to the Private Section for Health Professionals.
In addition to the Private Section for Health Professionals, health professionals have the option to contact Dr. Marshall at TM@AutoimmunityResearch.org or (818) 584-1201.
To ensure success, physicians are asked to encourage their patients to carefully study this Knowledge Base. This site provides additional instructions, helpful hints, and support that will greatly ease a practitioner’s emotional support workload and smooth the patient’s path to recovery.
Trevor also mentioned that we probably do need to develop a “cover letter” which may take more time.