Science behind Marshall Protocol

When patients on the MP kill bacterial pathogens they experience a reaction called immunopathology. Immunopathology is an increase in one's present symptoms of Th1 inflammation, or a return of previous Th1 inflammatory symptoms, that is caused largely by cytokines generated by the immune response and endotoxins released from dying bacteria. Occasionally, immunopathology will consist of a new symptom or abnormal lab value (e.g., elevated creatinine, elevated liver enzymes, low white blood count, etc.) due to the occurrence of subclinical bacterial inflammation that has been revealed by Olmesartan's activation of the immune system. Immunopathology is a necessary part of recovery. The amount of immunopathology a patient experiences on the Marshall Protocol (MP) is correlated with disease severity and bacterial load. Patients who are less sick will have comparatively less-strong immunopathology.

Immunopathology is sometimes used synonymously with the “Jarisch-Herxheimer reaction” or “herx.”

Many MP patients who have experienced prolonged periods of immunopathology have reached stages of significant improvement or remission. This serves to validate the conclusion that immunopathology is a necessary result of chronic bacterial death, and a precursor to disease reversal. The MP is not unique in this regard. A number of other diseases and/or therapies generate immunopathological or immunopathological-like reactions.^{1 2 3}

Lab work and patient reports can be used to track clinical signs of immunopathology.

The Marshall Protocol (MP) employs rotating combinations of bacteriostatic antibiotics at pulsed low dosesAdministration of an antibiotic periodically such as every 48 hours and in amounts small enough that the immunosuppressive effects of the antibiotics are minimized. for maximum effectiveness. The type of bacterial pathogens the MP targets are chronic forms, bacteria that grow much more slowly than acute forms.

For some physicians, the long-term use of the Marshall Protocol (MP) antibiotics inspires concern about bacterial resistance. However, the MP includes several measures to minimize, if not entirely eliminate, any chance that bacteria could become resistant to long-term use of antibiotics:

• carefully selected antibiotics, one of which is minocyclineBacteriostatic antibiotic used by Marshall Protocol patients., an antibiotic which has been in use for over 40 years yet continues to be effective against MRSA⁴ and to reduce disease severity even after follow-up several years later⁵
• pulsed-low dosing of antibiotics – often below the minimum inhibitory concentrationThe lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Dosing at well below the MIC improves the MP's effectiveness against slow-growing chronic pathogens and reduces the likelihood of resistance. – so as not to create “persister cells” or suppress the production of the body's natural antibiotics, the antimicrobial peptides
• varying combinations of antibiotics reduce the likelihood that a bacterium could develop resistance by subverting the use of a given antibiotic
• regular dosing of olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor., a medication which is a Vitamin D Receptor agonistA substance such as olmesartan (Benicar) or 1,25-D which activates the Vitamin D Receptor and transcribes the genes necessary for a proper innate immune response. and is effective in activating the immune system against antibiotic-resistant diseases

The evidence that the MP is not creating resistant communities of bacteria comes in low levels of co-infections such as Candida among the MP cohort as well as the unmistakable immunopathological reactionA temporary increase in disease symptoms experiences by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed., which cannot be explained through any other way except as an indication of bacterial die-off.

Antibiotics are typically dosed at levels above the minimum inhibitory concentrationThe lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Dosing at well below the MIC improves the MP's effectiveness against slow-growing chronic pathogens and reduces the likelihood of resistance. (MIC) so as to reduce the likelihood of bacterial resistance. While the MIC may be relevant for acute infections, dosing at that level can still suppress the immune response and aid the growth of chronic infections including those implicated in chronic inflammatory disease. For instance, some antibiotics, when administered at high dosages, have been widely recognized as being able to inhibit various functions of phagocytes.⁶ These effects seem to be independent of their antibacterial effect.⁷

The Marshall Protocol uses subinhibitory dosage levels of antibiotics. Dosing at well below the MIC improves the MP's effectiveness against chronic pathogens and further reduces the likelihood of bacterial resistance. Pulsed dosing greatly reduces the incidence of biofilm persister cells.⁸ The presence of a sustained immunopathological response is evidence that the MP uses antibiotics in such a way that it does not suppress the immune system.

Patients on the Marshall Protocol (MP) take olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor., a drug whose actions are fully known, every six hours. A substantial body of research supports the use of 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. as a part of a curative therapy for chronic disease. In general, olmesartan tends to be prescribed for its antihypertensive properties due to the fact that is an angiotensin receptor blocker.

For the purposes of the MP, olmesartan has two primary actions: it reduces 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. by blocking the Nuclear Factor-kappaB cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. pathway and it is an agonist of the Vitamin D 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.). As a VDR agonistA substance such as olmesartan (Benicar) or 1,25-D which activates the Vitamin D Receptor and transcribes the genes necessary for a proper innate immune response., olmesartan activates 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.. Research supports the safety of the doses used by MP patients. Olmesartan has minimal interactions with other drugs and is one of the safest drugs on the market.

Some patients and healthcare providers have expressed concerns about the safety of higher than typical doses of olmesartan (Benicar).

Ample research supports the fact that olmesartan is one of the safest and has the most gentle side effects profiles of almost any drug on the market – as opposed to Benicar HCT, which contains a thiazide and is harmful.

I feel there are simply no adverse reactions or negative side effects that I need to worry about while taking the Marshall Protocol medications. It is an extremely safe approach. Personally, I believe overtreating this condition is preferable than undertreating as the side effects of both antibiotics and Benicar are so minimal compared to the risk of [disease] recurrence.

Greg Blaney, M.D.

As a matter of course, markers of kidney function including blood urea nitrogen (BUN) and creatinine will fluctuate while a patient is on the Marshall Protocol (MP).

There is a tendency for some physicians to become alarmed by these fluctuations, particularly if a patient has kidney disease. However, for the vast majority of patients these test results are an expected part of the healing process. In fact, a wide range of research shows that olmesartan is therapeutic for kidney disease.