Related article: Pulsed low-dose antibiotics
Related article: Pulsed low-dose antibiotics
A high-dose antibiotic therapy is any treatment which uses antibiotics at a large enough dose that the immune response is suppressed more than it is not.
Antibiotic protocols and treatments other than the Marshall Protocol have been widely prescribed for certain Th1 diseasesThe chronic inflammatory diseases caused by bacterial pathogens. including rheumatoid arthritis and Lyme disease. However, the evidence for these treatments' efficacy is limited to short-term improvement and patients tend to relapse.
Although the Th1 diseases are caused by bacterial pathogens, these alternatives to the Marshall Protocol are ineffective for at least several reasons. For one, antibiotics given in high enough doses interfere with immune activity. With a weakened inflammatory response, a patient's symptoms may temporarily improve, but not because the pathogenic bacteria which drive the Th1 diseases have been eradicated.
Also, these protocols do not use olmesartan (Benicar) to activate the Vitamin D Receptor. Protocols which do not generate sustained immunopathology are ultimately not effective against the Th1 diseases.
At sufficiently high doses, all antibiotics, including those used by the Marshall Protocol, interfere with immune activity. Many of these antibiotics appear to be immunosuppressive in dose-dependent fashion.
In the absence of a robust immune response, inflammation is reduced, and a patient's symptoms temporarily improve – but not because the pathogenic bacteria which drive the Th1 diseases have been eradicated. In fact, the inflammatory response is invaluable to the body's fight against both acute and chronic infections. Compromising it may reduce signs and symptoms of disease, but it has been shown to exacerbate disease over longer periods of time, a conclusion validated by controlled trials.
The absence of inflammation is undoubtedly one of the principal reasons why patients report feeling better on high-dose antibiotics. It is also why the guidelines for the Marshall Protocol recommend doses of antibiotics low enough to avoid the problem of uninterrupted immunosuppression. 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.
Note that formulations which keep antibiotic concentrations at artificially high concentrations such as extended-release minocycline1) have a similar immunosuppressive effect as high-dose antibiotics.
In the last several years, various observations have emerged suggesting the manner in which antibiotics suppress the immune response, a few of which are listed below:
Moreover, pre-exposure to agents that selectively inhibit protein synthesis (30S or 50S subunit inhibitors) or DNA metabolism (DNA gyrase) mitigated subsequent tPMP-1 [an antimicrobial peptide] induced killing of an otherwise susceptible S. aureus strain in vitro.
Michael Yeaman 2)
You can put a patient on [high-dose] antibiotics, and it may seem that the infection has disappeared. But in a few months, it reappears, and it is usually in an antibiotic-resistant form.
The immunosuppressive properties of antibiotics have been long known. Labro states that the tetracycline family of antibiotics – four of which are a part of the MP's guidelines – are desirable because they inhibit “detrimental” phagocyte activity.3)
To that end, most researchers have assumed, consistent with the autoimmuneA condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body theory of disease, that using antibiotics to reduce immune activity would improve disease.
On the basis of this understanding, scientists have put forth work concluding that the tetracyclines are anywhere from somewhat to very effective against reactive arthritis,4) rheumatoid arthritis,5) scleroderma,6) and periodontal disease.7) Other diseases for which minocycline, a kind of tetracycline, has been proposed include stroke, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease.8) 9)
One study compared the use of hydroxychloroquine (Plaquenil) to minocycline in early seropositive rheumatoid arthritis patients.10) As a part of the study, one set of patients received 200mg of minocycline per day – four times as much as minocycline as an MP patient would ever take. That arm of the trial had a better outcome at the end of the study, but the absence of any supportive follow up research or longitudinal studies is revealing.
Indeed, a number of studies have been able to demonstrate the “effectiveness” of a given antibiotic-based therapy on the basis of immunosuppression. Yet, these treatments do nothing to eradicate the bacteria causing the inflammation in the first place. This is true even of purportedly antibacterial treatments.
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.11) In her review, “Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or 'Immuno-Fairy Tales'?”, Labro argues exactly this.
[There is a] lack of correlation between the drug dose regimen [for Propionibacterium acnes] and cutaneous bacterial counts.
M.T. Labro 12)
Earlier on in the paper, Labro concludes that when it comes to treating inflammatory diseases, immunosuppression is “recognized as the basis for antibiotic action.”13)
Antibacterial treatments which reduce inflammation but fail to destroy bacteria have been known to lead to exacerbation and onset of both acute and chronic infections. These infections include Candida.
For this reason, the doses of antibiotics used by patients on the Marshall Protocol are a fraction of what other treatments use. In fact, the only time MP patients take more antibiotics is in order to mange an intolerable 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.: as little as an additional 50mg of minocycline can provide temporary symptom relief.
In a 2006 trial appearing in BMJ (nicknamed the CLARICOL trial), 13,702 patients with a history of myocardial infarction or angina pectoria (chest pain) were given two weeks' treatment with clarithromycin 500 mg/day or matching placebo. Mortality was significantly higher in the clarithromycin arm as a result of significantly higher cardiovascular mortality. The authors concluded: “Short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality. The long term safety of clarithromycin in patients with stable ischaemic heart disease should be examined.”14)
These results are consistent with the explanation that immunosuppressive therapies exacerbate inflammatory diseases.
Fallon et al treated patients diagnosed with Lyme disease with intravenous ceftriaxone (Rocephin) for a period of 24 weeks.15) While patients in the experimental arm of the trial experienced improvement in pain, fatigue, and physical functioning, these changes were short-lived. According to Fallon:
The improvement… was not sustained to week 24…. 10 weeks of IV ceftriaxone followed by 14 weeks of no antibiotic is not an effective strategy.
B.A. Fallon, et al. 16)
The study also revealed that more than one quarter of antibiotic-treated patients had significant adverse effects necessitating treatment termination.
In a letter to the editor, one physician writes:
140 g of ceftriaxone should have eliminated any spirochetes present in these patients…. In sum, this is now the fourth randomized blinded trial of prolonged antimicrobial therapy in patients previously treated for Lyme disease. Like the other three, it clearly demonstrates the absence of any lasting improvement in cognitive function. Given the considerable risk of serious adverse events from prolonged [high-dose] antibiotic treatment, it is time to look elsewhere for an effective management strategy to help patients with persistent cognitive symptoms after treatment for Lyme disease. Clearly, enough is enough.
John J. Halperin MD 17)
Other controlled trials have found no improvement in treatment outcome when the length of the study was extended.18)
Related article: Palliative vs. curative treatments
According to the Marshall Pathogenesis, patients must generate immunopathology in order to recover from chronic inflammatory disease. To this end, regular dosing of olmesartan (Benicar) is critical. Olmesartan's action as a VDR agonist allows Marshall Protocol patients to activate their 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.. This is evident in patients taking MP antibiotics who do not begin killing bacteria until they take olmesartan.
Under the care of one of the few treating doctors in Canada, I did six more years of high-dose antibiotics. I did experience immunopathology in response to taking many of them, but my symptoms never came close to resolving. Sometimes I would seem to reach a plateau, but then I would inevitably relapse. It seemed like the antibiotics were helping me somewhat, but taking them at high doses was like taking three steps forward and two steps backwards. When I had IV rocephin for three months, I started to feel like I was making no progress at all - it was three steps forward, three steps backwards. I think this pattern might have gone on forever if I hadn’t found the Marshall Protocol.
Ken L., Bacteriality inteview
It took me about eight months on [the Road Back Protocol, which uses 200 mg of minocycline three times a week but no olmesartan] to be certain that I was improving. It takes some people twelve or more months. During that interval it makes the disease unstable – good days and bad days, good weeks and bad weeks. It isn't like the predictable, reliable herxing on the MP, but I believe it is herxing nonetheless…. I got tremendous relief from that protocol but ultimately switched to the MP to see if I could could move to a full cure. I was pretty much pain free when I started the MP last September, but I started a whole new round of herxing when I started the MP.
John McDonald