Safety of Marshall Protocol antibiotics

For some physicians, the long-term use of the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (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 MRSA¹⁾ and to reduce disease severity even after follow-up several years later²⁾
• 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 peptidesBody’s naturally produced broad-spectrum antibacterials which target pathogens.
• 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 125-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.

According to the Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop., chronic inflammatory disease is caused by bacterial pathogens that proliferate by dysregulating the Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response., a 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. which plays the key role in innate immune function. Though fastidious and difficult-to-culture, the bacteria which cause this disease process have proven themselves to be resistant to any number of antibacterial therapies. One need look no further than the plethora of antibacterial treatments that fail to cure chronic diseases. In fact, the Marshall Pathogenesis points to the use of these therapies, which appear not to address the ultimate cause of chronic disease, as being one of the principle reasons why rates of acute and chronic infection, especially treatment-resistant forms, have escalated in recent decades.

Drawing on a range of clinical and molecular evidence, the Marshall Protocol guidelines purposefully forbid use of those medications and dosing strategies that have proven to allow for the proliferation of chronic (and acute) pathogens. The medications used by the MP are used in a manner that will kill communities of bacteria that have not and cannot be killed by other antimicrobial therapies.

The Marshall Protocol uses rotating combinations of various broad-spectrum antibiotics effective against a variety of bacterial species. All but one of these antibiotics (Bactrim DSSulfa antibiotic used by patients on the Marshall Protocol. Combination of sulfamethoxazole and trimethoprim. Works by blocking bacterial folic acid synthesis.) are in the tetracycline family.

The MP's base antibiotic is minocycline. Minocycline is broad-spectrum, and has been safely used for decades in a variety of medical therapies.

Even though it has been in use for for over forty years, minocycline continues to be successfully used for a variety of conditions from acne to MRSA, a bacterium responsible for difficult-to-treat infections in humans. One 2008 study of antibiotic effectiveness against community-associated methicillin-resistant (CA-MRSA) and methicillin-sensitive Staphylococcus aureus (MRSA) found that minocycline killed 100% of the former and 97.1% of the latter.³⁾

Minocycline has been deemed safe and effective (alone or as adjunctive therapy) in patients with mild to moderate rheumatoid arthritis or rheumatic diseases. ⁴⁾ Tetracyclines have been used effectively in urogenital, gastrointestinal, and lower respiratory tract infections.⁵⁾

For most individuals, minocycline is well-tolerated. Cunha writes that minocycline is the “antibiotic of choice” because of its “superior intracellular mechanism of activity and an excellent safety profile.”⁶⁾ Minocycline binds to the 30S ribosomal subunit of a bacteria as well as the body's pregane X nuclear receptor (PXR), both actions having the potential to contribute to bacterial death.

The other MP antibiotics have similar safety profiles.

In the treatment of inflammatory diseases, immunosuppression, Labro writes, is “the basis for antibiotic action.”⁷⁾ The Marshall Protocol guidelines take issue with the conclusion that antibiotics should be used to interfere with immune function.

Standard methods that use high dose and/or constant levels of antibiotics are unable to effectively eliminate the Th1 pathogens, including L-formDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria. and biofilmA structured community of microorganisms encapsulated within a self-developed protective matrix and living together. bacteria. The reason lies with the fact that aside from their ability to block bacterial ribosomes, bacteriostatic antibiotics also inhibit the immune system. This may be why a number of other antibacterial therapies generate short-term symptomatic remission but no long-term disease resolution.

One telling study looking at tetracycline's (the specific drug, not the family of drugs) “antibacterial” effects found that it temporarily reduced the appearance of acne, but without inhibiting the proliferation of Propionibacterium acnes, which has a role in causing acne.⁸⁾

[There is a] lack of correlation between the drug dose regimen [for Propionibacterium acnes] and cutaneous bacterial counts.

Marie Labro ⁹⁾

In order to take advantage of the MP antibiotics' antibacterial effects, MP patients take comparatively low doses of antibiotics – at well below the minimum inhibitory concentration. For example, the highest dose of minocycline used by MP patients is only 100 mg every other day, and often only a portion of azithromycin (Zithromax)Bacteriostatic antibiotic used by Marshall Protocol patients. Has relatively long half-life. is only taken every ten days. Some patients have reported on the Marshall Protocol Study Site that a single bottle of azithromycinBacteriostatic antibiotic used by Marshall Protocol patients. Has relatively long half-life. lasts for a year or more. By way of comparison, when it is prescribed for acne, minocycline is taken 200-400mg daily.

Over the course of the treatment, patients find that as their sensitivity to the MP antibiotics drops, are they are able to discontinue taking all antibiotics or take them only intermittently.

Varying combinations of antibiotics reduce the likelihood that a bacterium could develop resistance by subverting the use of a given antibiotic.

In practice, the antibiotics used by the Marshall Protocol actually have a somewhat ancillary role. The chief antibacterial is olmesartan (Benicar).

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 recurrence.

Greg Blaney, M.D.

Although the cohort of MP patients is high-risk with a number of co-morbidities, very few, if any, patients have reported additional co-infections such as Candida or acute bladder infections. As patients report in their online progress reports, these infections invariably resolve after being on the MP antibiotics for several years.

Aside from long-term symptom resolution, the primary indication of treatment efficacy is the presence of the immunopathological reaction. Immunopathology is a temporary increase in disease signs and symptoms experienced by Marshall Protocol patients and is due to the destruction of bacteria and human cells infected by bacteria.

The generation of the immunopathological response among the MP cohort, which includes patients with dozens of different inflammatory diseases, is near universal. Many patients experience elevated 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. while taking only a fraction of a dose of antibiotics – for example 25mg of azithromycin (Zithromax) which is 1/10 of the dose the drug is normally prescribed – or even on 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. alone.

The conclusion that the immunopathological reaction is due to bacterial die-off is a valid one. No other explanation successfully accounts for how olmesartan, a drug which has only one documented side effect – causing dizziness in 3% of patients taking the drug vs. 1% in placebo – could generate this response.

That the MP is able to generate sustained immunopathology and therefore bacterial die-off where other therapeutic interventions have not strongly suggests that the treatment is not fostering the growth of resistant bacterial communities.