Many people who are chronically ill are given antibiotics. But are these medications working in the correct manner to kill the pathogens responsible for their disease? New molecular modeling research strongly suggests that the stealth pathogens responsible for causing a wide array of chronic diseases can only be killed if carefully chosen antibiotics are taken in a very specific manner.

In what is emerging as a new understanding of chronic disease, researchers are increasingly implicating what are often referred to as the Th1 pathogens in a wide array of illnesses previously considered to be of unknown cause or “autoimmune” in nature. “It is our contention that several diseases that are usually regarded as ‘autoimmune’ or ‘idiopathic’, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, sarcoidosis and psoriasis, are caused by infection with related slow-growing bacteria,” states G.A.W. Rook in the journal Immunology Today.[1]

The Th1 pathogens are hypothesized to be an intraphagocytic, metagenomic microbiota of bacteria, meaning that they are able to persist inside the cells of the immune system as well as group into colonies called biofilms. The bacteria inside a biofilm produce a protective matrix that allows them to more effectively evade the immune system and develop resistance to antibiotics administered in a standard manner. Essentially, high-dose antibiotics fail to eliminate all the cells that form a biofilm, leaving what are referred to as persister cells behind. The persister cells are eventually able to re-create the biofilm, allowing it to thrive again. [2] There is a tremendous number of different species of these chronic pathogens.

Many of the bacteria that compose this microbiota are in what is referred to as the L-form. For over a century, scientists have realized that classical bacteria can transform into small forms that lack cell walls. These pathogens are known as L-form bacteria. Researchers have currently identified over 50 different species of bacteria capable of transforming into the L-form, and it is likely many other bacteria also have this ability. Brown et al have found evidence of L-form bacteria in the blood of more than 60% of healthy controls.[3] In fact, the diseases generated by L-form bacteria are far more common than currently realized, and are often only noticed as subtle signs of aging, such as osteoporosis, obesity, fatigue and arthritis.[4][5]

Unlike other forms of bacteria, L-form bacteria have developed the ability to remain alive and proliferate undetected inside macrophages, the very cells of the immune system that the body uses to kill invading pathogens. Once inside the macrophages, it becomes much more difficult for antibiotics to penetrate the interior of the cell and come in contact with these bacteria.

Beta-lactam antibiotics including penicillin, amoxicillin and the cephalosporins are also designed to attack the bacterial cell wall. These antibiotics are able to kill classical bacteria but are completely ineffective against L-form bacteria, which have lost their cell walls. In fact, in 1934, German scientist Emmy Klieneberger-Nobel first discovered that beta-lactam antibiotics actually promote the formation of L-form bacteria.[6][7]

However there are other classes of antibiotics, and the sequencing of the human genome has allowed scientists to figure out exactly how these types of antibiotics work at the molecular level. Every antibiotic is different at the molecular level and possesses unique qualities that allow it to effectively target different species of pathogens. Over the past few decades, biomedical researcher Trevor Marshall, PhD, has studied this data and figured out what is believed to be the safest, most effective antibiotics to use against L-form bacteria. He used this data to create a medical treatment known as the Marshall Protocol.[8]

Marshall discovered that a class of antibiotics called bacteriostatic antibiotics have the potential to weaken L-form bacteria if administered in the correct manner. Bacteriostatic, or “Protein Synthesis Inhibitors” are a class of antibiotics that work by disabling bacterial ribosomes – small, dense, structures that allow the pathogens to replicate and survive. This group of antibiotics includes the tetracyclines, such as minocycline and demeclocycline. This class of antibiotics has also been shown to interfere with the ability of bacteria to produce proteins on their surfaces called exoproteins. This makes it easier for the immune system to kill the pathogens.[9][10]

In the Journal of Postgraduate Medicine, Burke Cunha and team argue that there is an increasing number of “cases emerging of certain infectious diseases against which [bacteriostatic antibiotics] are especially effective, such as ehrlichiosis, Lyme disease, and methicillin-resistant Staphylococcus aureus (MRSA) infection. The researchers argue that another benefit of bacteriostatic antibiotics is that when taken orally, they are just as effective as when administered using intravenous therapy. According to Burke, minocycline is the antibiotic of choice because of its “superior intracellular mechanism of activity and an excellent safety profile.”[11]

A tetracycline antibiotic docked into the 30s ribosomal subunit; taken from riboworld.com

One of the great benefits of minocycline when compared to other tetracyclines is that it has better lipid solubility. This means it can more easily penetrate the central nervous system and the inside of cells. Minocycline is also very effective against the bacterial species Staphylococcus which is one of the most widely implicated pathogens in chronic disease.

Meg Mangin at Autoimmunity Research Foundation states, “All bacteria must create a variety of proteins in order to survive and the Marshall Protocol is designed to make that task progressively harder.” Bacteria have one ribosome, the 70S ribosome, which is divided into two sections – the 30S ribosomal subunit and the 50S ribosomal subunit. Minocycline binds to the 30S ribosomal subunit. Under normal conditions, the 30S ribosomal subunit sends out a helix-like molecule that decodes the sequences of genetic code (RNA) necessary for a bacterium to create proteins necessary for survival. When minocycline binds the 30S ribosome it blocks and prevents this helix-like molecule from initiating the process that results in protein synthesis. One molecule of minocycline will inhibit one 30S bacterial ribosome from manufacturing proteins. [12] This low antibiotic to ribosome ratio proportionately controls the rate of bacterial death.

However, according to the Marshall Protocol guidelines, minocycline must be combined with other antibiotics in order to fully target all the different species of bacteria involved in causing chronic disease. As a result, the Protocol uses other carefully selected antibiotics in conjunction with minocycline, allowing the patient to target the entire spectrum of L-form bacteria.

According to Marshall, “Long term therapy with any single antibiotic will cause the killing of bacteria susceptible to that antibiotic, and the repopulation of the tissues with bacteria resistant to that antibiotic. So your bacterial load may well be increasing while your original symptoms improve.”

Consequently, patients on the treatment begin by taking pulsed, low-dose minocycline. However, they soon add other antibiotics into the mix, until their bacterial load is reduced enough that they are able to tolerate different combinations of three antibiotics at one time.

Minocycline prevents bacteria from decoding sequences of RNA; taken from riboworld.com

“[The Marshall Protocol] uses Minocycline as a base, and adds other symbiotic bacteriostatic antibiotics,” says Marshall, “specifically to make sure that no species can escape. The molecular genomic science is clear and precise. The Marshall Protocol is unique in its avoidance of the mechanisms leading to antibiotic resistance.” He has presented the modes of action of the Marshall Protocol antibiotics at several conferences. At the Chicago conference “Recovering from Chronic Disease,” he presented 3-D models of a bacterial ribosome, and showed where and how each antibiotic docks into the ribosomal RNA in order to prevent protein synthesis, and how the Marshall Protocol antibiotics do this synergistically, without the possibility of interaction.

Note: The antibiotics used by the Marshall Protocol must be very carefully managed so as not to provoke immunopathology that is too strong for the patient to handle. Consequently, I will not reveal the names of the other antibiotics used by the treatment, as I do not want patients to take them without first working closely with a doctor. Both doctor and patient should study and follow the protocol guidelines carefully in order to implement it safely. The Phase One Guidelines describe how to start the treatment correctly.

One of the antibiotics used in conjunction with minocycline is an azolide antibiotic that targets the other subunit of the 70S ribosome – the 50S ribosomal subunit. When this antibiotic binds this section of the ribosome it blocks bacterial proteins from being assembled and exiting through a pore in the bottom of the ribosome. Several other antibiotics are also able to block the 50S ribosome, but the azolide antibiotic used by the Marshall Protocol is unique in that it also forms a bond with a region of bacterial genetic material called 23S RNA – further preventing protein synthesis. This azolide also has superior tissue penetration than other antibiotics in its class, meaning that the drug can persist inside the tissues for weeks. As a result, this antibiotic is not taken as often as the others. In later phases of the treatment this antibiotic is combined with another antibiotic that blocks different regions of the 50S ribosomal subunit, further preventing proteins from being assembled.[13]

Two researchers at the Max Planck Institute in Germany have put together a website that brings together the research of several different scientists who have used molecular modeling software to reveal how minocycline and azolide antibiotics can block the ability of bacteria to synthesize proteins.

Another antibiotic used by the Marshall Protocol works by interfering with the ability of bacteria to create and replicate their DNA. This antibiotic inhibits dihydropteroate synthase, an enzyme that allows bacteria to use folic acid. Since folic acid is an essential precursor in the synthesis of several of the base pairs needed to create DNA, inhibition of the enzyme will stop the pathogen from creating the genetic material it needs to survive.

Because each of the three classes of bacteriostatic antibiotics used by the Marshall Protocol affect different ribosomal subunits and target different mechanisms of protein synthesis, a bacterial species would have to develop three different mutations in order to survive in their presence. Consequently, Marshall argues that when the Marshall Protocol antibiotics are taken in the correct manner, “Statistically, the chance that bacteria will evolve that cannot be killed by the MP is so close to zero it is inconsequential.”

An azolide antibiotic docked into the 50s ribosomal subunit; taken from riboworld.com

Several variables affect how a patient will respond to the antibiotics used by the Marshall Protocol. Marshall argues that these factors include:

1. Patient’s prior exposure to the antibiotics

2. Strength (or weakness) of the patient’s own immune system

3. Species of bacteria present

4. Concomitant health problems – e.g. kidney failure

5. Concomitant infections – e.g. fungal, viral

6. Medications being taken by the patient

One antibiotic that the Marshall Protocol does not use is doxycycline. Doxycycline is not nearly as wide-spectrum an antibiotic as minocycline and does not kill as many L-form bacterial species. It also has effects on the brain that can stimulate feelings of euphoria. Marshall argues “These are both dangerous characteristics because they can make people prematurely think they have ‘conquered’ their infection.”[14]

The Marshall Protocol antibiotics must be taken in conjunction with Benicar

The ribosome blockades initiated by the Marshall Protocol antibiotics greatly weaken L-form bacteria but are unable to actually kill the pathogens. Consequently, patients on the treatment take a medication called Benicar that activates the innate immune system. Molecular modeling has revealed that Benicar binds and activates the Vitamin D Receptor – a fundamental receptor of the body that controls the activity of the innate immune system.

“To us, Benicar is not a “medication.” It is a method of turning-on your body’s VDR (Vitamin D Receptor). This is a key part of the immune system, and transcribes over 1000 genes which affect body processes from calcium homeostasis to cancer metastasis,” states Marshall.

Once on Benicar, the patient’s own immune system has the strength to kill bacteria that have already been greatly weakened by antibiotic therapy. Benicar makes such a difference in activating the immune system that some patients find that once on the medication, they begin to kill bacteria before they have even started the antibiotics. In order for the immune system to function correctly at all times of day, Benicar must be taken every 6-8 hours.[15]

Marshall says that this use of Benicar along with the MP’s unique antibiotic regime “significantly tilts the advantage in favor of the immune system which is actually the most effective ‘antibiotic’.

But Benicar also binds other receptors involved in the immune system response. Recently, Marshall has elucidated additional modes of action of Benicar on the nuclear receptors that control the immune system.[16]

By definition Benicar is an Angiotensin II Receptor Blocking (ARB) drug. When Benicar binds and blocks the Angiotensin Receptor, it decreases levels of Nuclear Factor Kappa B, a protein that stimulates the release of inflammatory cytokines – proteins that generate pain and fatigue. These cytokines include interferon gamma and TNF-alpha. The drop in cytokines results in less inflammation and oxidative stress. As inflammation drops, the antibiotics can also perfuse the tissues more effectively.[17]

The drop in inflammation stimulated by Benicar makes some patients feel better, allowing them to more easily tolerate the increase in symptoms generated by bacterial die-off. In fact, if a patient feels that their immunopathology is too strong, they can take extra Benicar in order to help palliate the inflammatory response.

Benicar was carefully chosen over other ARBs because according to molecular modeling data, it binds the above receptors and the Vitamin D Receptor in a manner that most effectively activates the immune system response. Other ARBs also bind the same receptors as Benicar but fail to activate them at the correct level.[18]

A molecular model showing Benicar activating the vitamin D receptor; created by Trevor Marshall

Although Benicar is a mild antihypertensive agent, even patients who have very low starting blood pressure (80/50) have tolerated it well. The maximum hypertensive effect usually occurs in the 20-40 mg range. Taking higher doses has little, if any, additional effect on blood pressure.

Therefore, taking Benicar more often will not continue to lower blood pressure or deplete sodium more than the usual 40 mg dose. Patients must be sure to get plain Benicar without hydochlorothiazide added (HCT). Adequate sodium and water intake is advised. As noted in The Townsend Letter for Doctors and Patients: “Benicar was well tolerated in safety evaluations (1). Examples of some of the documented protective effects of ARBs include the ability to:

1. prevent migraines[19]

2. inhibit liver fibrosis and aid liver healing[20]

3. protect the kidneys in diabetic nephropathy[21]

4. reduce insulin resistance[22]

5. protect the heart from damage from inflammation in myocarditis[23]

6. protect the mitochondria from age-associated damage from oxidation[24]

Meg Mangin at Autoimmunity Research Foundation states, “The combination of [Benicar] to engage the immune system with the safe, wide-spectrum, symbiotic antibiotics used during the later stages of the Marshall Protocol seem to effectively eliminate all strains of antibiotic-resistant bacteria.”

As noted in the Phase 1 Marshall Protocol guidelines, Benicar is a critical component of the Marshall Protocol. Without it, the immune system is unable to fully utilize antibiotics to kill L-form bacteria. This is evident in patients taking MP antibiotics who do not begin killing bacteria until they take Benicar.[25]

Low-dose pulsed antibiotics are most effective against L-form and biofilm bacteria

Standard methods that use high dose, constant levels of antibiotics are unable to effectively eliminate L-form and biofilm bacteria. The reason lies with the fact that aside from their ability to block bacterial ribosomes, bacteriostatic antibiotics also have effects on the immune system. Unfortunately, some of these effects are immunosuppressive. For instance, the tetracycline antibiotics have been widely recognized as being able to inhibit various functions of phagocytes, the white blood cells that engulf and kill bacteria.[26] These effects seem to be independent of their antibacterial effect.[27]

These immunosuppressive properties decrease the amount of L-form and biofilm bacteria killed by the immune system. This is why some people report feeling better on high-dose antibiotics. The high levels of antibiotic prevents the immune system from killing these forms of bacteria, resulting in a temporary decrease in the toxins the pathogens release as they die and the inflammatory cytokines produced by the immune system. However, in reality, the person’s L-form bacteria remain alive and find it easier to spread to new tissues and organs.

The most effective way to avoid this problem is to use low doses of pulsed antibiotics. Pulsed dosing refers to administering a dose periodically, such as every 48 hours, rather than once or several times daily. When given in this manner, the immunosuppressive effects of the antibiotics are minimized but their ability to weaken bacterial ribosomes remains intact. Patients gradually increase the dosage of the pulsed antibiotic, so that species of bacteria that are susceptible to all different concentration levels will eventually be targeted.

A report in the European Journal of Clinical Microbiology found that treating the bacterial species Staphylococcus aureus with only 1/32 of the minimum inhibitory dose of clindamycin (a very small dose!) resulted in enhanced uptake of the bacteria by white blood cells called polymorphonuclear cells, and enhanced killing of the pathogens by another class of white blood cells called phagocytes. Not surprisingly, the team found that only bacteriostatic antibiotics (the class of antibiotics used by the MP) possess this ability. Antibiotics that work by blocking cell wall production such as penicillin, cefotiam, peperacillin, and vancomycin where unable to elicit such an effect.[28]

Similarly, researchers at the University of Iowa found that subinhibitory concentrations of the bacteriostatic antibiotic azithromycin significantly decreased biomass and maximal thickness in both forming and established biofilms. These extremely low concentrations of azithromycin inhibited biofilms in all but the most highly resistant isolates. In contrast, subinhibitory concentrations of gentamicin, which is not a bacteriostatic antibiotic, had no effect on biofilm formation. In fact, biofilms actually became resistant to gentamicin at concentrations far above the minimum inhibitory concentration.[29]

The advantage of pulsed dosing has been demonstrated in the past. It has long been known that pulsing levels of the hormone GNRH is most effective against infertility. Similarly, intermittent doses of antibiotics seem to disrupt the immune system’s natural state of homeostasis, thus provoking a greater immune response. When antibiotics are taken in low, pulsed, doses, they are also able to effectively eliminate biofilm persister cells in a way that high-dose antibiotics cannot.[2]

Recent research has also demonstrated that pulsing antibiotics can be a superior way of targeting treatment resistant biofilm bacteria. According to researchers at Tulane University who mathematically modeled the action of antibiotics on bacterial biofilms, “exposing a biofilm to low concentration doses of an antimicrobial agent for longer time is more effective than short time dosing with high antimicrobial agent concentration.”[30] Several studies have shown that even when administered in low, pulsed doses, the bacteriostatic antibiotics are still able to decrease the production of bacterial exoproteins.[2]

The MP antibiotics generate changes in immunopathology

The Th1 pathogens have evolved mechanisms that allow them to live for long periods of time within the cells, and when alive, generally persist without generating too many symptoms. It is when the Th1 pathogens die that they begin to cause a major increase in symptoms for the host, since as they die they release large amounts of toxins and cytokines, proteins that generate pain and fatigue. Additionally, as the Th1 pathogens die, the cell that they have parasitized dies as well, and cellular debris is released into the bloodstream. This means that once patients begin the MP, each dose of antibiotic will cause them to feel bad for the period of time it takes their immune system to deal with the consequences of L-form bacterial die-off.[31][32]

The severity of the immunopathology reaction differs from person to person depending on bacterial load and the species of bacteria that need to be killed. Patients can adjust their level of antibiotics, and consequently adjust the severity of the immunopathology response. Patients who are severely ill generally experience stronger immunopathology, whereas patients who start the Marshall Protocol during earlier stages of illness often find that they are able to work and manage a high level of activity despite the rise in symptoms.

Since immunopathology must be carefully managed, the Marshall Protocol takes several years to complete. However immunopathology generally decreases as patients progress to later stages of the treatment, allowing them to become more and more active as time goes on.

Because the Marshall Protocol takes a long time to complete and patients are understandably eager to reach a state of wellness, some people try to raise the dose of their antibiotics too quickly. Unfortunately, this can result in symptoms that are so strong that the patient decides to quit the treatment. Consequently, as described on the Marshall Protocol study site, the cliché, “slow and steady wins the race” can certainly be applied to the manner in which patients should correctly ramp their antibiotics. If a patient feels that their immunopathology has reached an intolerable level there are several mechanisms they can use to dampen the reaction which are discussed in this forum on the Marshall Protocol study site.

Before starting the Marshall Protocol, some patients with chronic inflammatory disease report having trouble tolerating many antibiotics. In most cases, it is discovered that these perceived “allergies” are actually due to the antibiotics provoking changes in immunopathology. According to the Townsend Letter for Doctors and Patients, “Experience with the MP indicates that if the antibiotics are started at low enough dosages, they are generally well tolerated, although patients will usually experience immunopathology responses. The pattern of reaction to the antibiotics are not typical of allergies or toxic side effects, in that they usually manifest as exacerbations of the patient’s usual symptoms, and the reactions decline with subsequent doses as the bacterial load is reduced.”

The tetracycline antibiotics may improve bone health

The tetracycline antibiotics also offer patients an advantage when it comes to bone health. Several studies have shown that the tetracycline antibiotics used by the treatment can increase bone mass.

Researchers at the University of Portugal found that just 1 mug/ml of the tetracycline antibiotics “significantly increased proliferation of human bone marrow and osteoblastic cells without altering their functional activity.” In fact they reported that exposure to the antibiotics actually caused a significant increase in the number of bone cells and amount of bone matrix.[33]

Similarly, researchers at the National Institute of Health in Maryland published a study which found that treating mice with minocycline modestly reduced bone reabsorption and substantially stimulated bone formation.

The team concluded that “oral minocycline can effectively prevent decreases in bone mineral density… through its dual effects on bone resorption and formation.”

Activating the Vitamin D Receptor allows the body to effectively create its own antibiotics

Antimicrobial peptides (AMPs) are actually potent, broad-spectrum antibiotics that the body creates naturally. The AMPs have been shown to kill gram-negative and gram-positive bacteria, including strains that are resistant to conventional antibiotics such as Mycobacterium tuberculosis and other cell wall deficient bacteria. They have also been shown to target enveloped viruses, fungi and even transformed or cancerous cells.[34]

The AMPs kill bacteria in a variety of different ways. These include disrupting cell membranes, interfering with metabolism, and targeting machinery inside the cell. In many cases the exact mechanism of killing is not known. In addition to killing bacteria directly, the AMPs have been shown to have a number of immunomodulatory functions that may be involved in the clearance of infection, including the ability to alter host gene expression, inhibit cytokine production, and promote the healing of wounds.

Recent research has revealed that the Vitamin D Receptor controls the activity of numerous AMPs.[35][36][37]

Unfortunately, in chronically ill individuals, L-form bacteria create substances that are able to bind and decrease the activity of the Vitamin D Receptor.[38] 25-D, the precursor form of vitamin D (at levels over 20ng/ml) also binds and deactivates the receptor.[39] Patients who avoid vitamin D and use the Marshall Protocol to kill L-form bacteria allow the VDR to regain function. They also take a medication called Benicar that molecular modeling shows is able to further activate the VDR. All these measures return the Vitamin D Receptor to an active state where it can turn on the pathways that create the AMPs.

The Marshall Protocol antibiotics can be used safely and effectively

Minocycline has been used for decades in a variety of medical therapies. Recently, a multicenter double-blind placebo-controlled trial concluded that minocycline was safe and effective in patients with mild to moderate rheumatoid arthritis and supported its use (alone or as adjunctive therapy) in rheumatic diseases.[40] Tetracyclines have been also used effectively in urogenital, gastrointestinal, and lower respiratory tract infections.[41]

There is no evidence that long-term use of the antibiotics used by the Marshall Protocol leads to resistant species forming. In fact, minocycline was introduced in 1968, and since that time, virtually no organisms have developed resistance to the medication. Minocycline is also one of the few antibiotics that remains active against the bacterial species Methicillin-resistant Staphylococcus aureus (MRSA), despite the fact that for decades, it has been widely prescribed in efforts to control teenage acne.

According to the Physicians Protocol for using antibiotics in rheumatic disease, “Minocycline tends not to cause yeast infections. Some infectious disease experts even believe that it has a mild anti-yeast activity. Women can be on this medication for several years and not have any vaginal yeast infections.”[42]

It is important that patients who begin the Marshall Protocol take their antibiotics exactly as directed. Taking the antibiotics when not using Benicar, dosing the antibiotics at higher levels than directed, or not pulsing them, will significantly decrease or completely stop immunopathology from occurring. Patients may feel better temporarily, but they are no longer killing bacteria.

“Please understand that the Marshall Protocol may seem simple, but it has a lifetime of my own research behind it. Anything you change will likely get you into trouble,” says Marshall.

Furthermore, taking medications or supplements that are not part of the Marshall Protocol can impair the body’s ability to correctly put the antibiotics to use.

Marshall argues, “We have to remember that there are many species we are fighting against. Second, the immune system is so finely balanced between not killing them, and killing them, so that small changes to our lifestyle, or to our food, or caused by other drugs we are taking, might stop the immune system from killing the bacteria. If there is no killing the patient will generally feel better.”

But, if taken correctly, the Marshall Protocol antibiotics, in conjunction with Benicar, have great potential to induce improvement and recovery. “There are plenty of people who show that if the treatment is done in the correct manner, healing is possible,” says Belinda Fenter of Autoimmunity Research Foundation.

REFERENCES

  1. Rook, G. A., & Stanford, J. L. (1992). Slow bacterial infections or autoimmunity? Immunology Today, 13(5), 160-4. [↩]
  2. Lewis, K. (2007). Persister cells, dormancy and infectious disease. Nature reviews. Microbiology, 5(1), 48-56. [↩] [↩] [↩]
  3. Brown, S. T., Brett, I., Almenoff, P. L., Lesser, M., Terrin, M., Teirstein, A. S., et al. (2003). Recovery of Cell Wall-Deficient Organisms From Blood Does Not Distinguish Between Patients With Sarcoidosis and Control Subjects. Chest, 123(2), 413-417. [↩]
  4. Nikkari S, McLaughlin IJ, Bi W, Dodge DE, Relman DA. Does Blood of Healthy Subjects Contain Bacterial Ribosomal DNA? J. Clin. Microbiol. 2001 May 1;39(5):1956-1959. [↩]
  5. Marshall, T. G. (2006). Immunity & Ageing. Comments: Is inflammaging an auto[innate]immunity sub clinical syndrome? [↩]
  6. Wang, H., & Cheng, Z. (1998). [Observations of characteristics of the mechanisms of biological oxidation of cell wall-deficient bacteria]. Wei sheng wu xue bao = Acta microbiologica Sinica, 38(5), 396-9. [↩]
  7. Mursic, V. P., Wanner, G., Reinhardt, S., Wilske, B., Busch, U., Marget, W., et al. Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants. Infection, 24(3), 218-26. [↩]
  8. Marshall, T., & Marshall, F. E. (2003). Antibiotics in Sarcoidosis – Reflections on the First Year. Journal of Independent Medical Research. [↩]
  9. Herbert, S., Barry, P., & Novick, R. P. (2001). Subinhibitory Clindamycin Differentially Inhibits Transcription of Exoprotein Genes in Staphylococcus aureus. Infect. Immun., 69(5), 2996-3003. [↩]
  10. Tanaka, M., Hasegawa, T., Okamoto, A., Torii, K., & Ohta, M. (2005). Effect of Antibiotics on Group A Streptococcus Exoprotein Production Analyzed by Two-Dimensional Gel Electrophoresis. Antimicrob. Agents Chemother., 49(1), 88-96. [↩]
  11. Cunha, B. Antimicrobial Therapy Symposium: New uses for older antibiotics. (1997). Postgraduate Medicine. [↩]
  12. Antibiotics bounds to the 30s subunit. Riboworld. [↩]
  13. Antibiotics bound to the 50s subunit. Riboworld. [↩]
  14. Cell Wall Deficient Bacteria and the Marshall Protocol. (2007). Marshall Protocol Study Site. [↩]
  15. Marshall, T. G. (2006). VDR Nuclear Receptor Competence is the Key to Recovery from Chronic Inflammatory and Autoimmune Disease. [↩]
  16. Marshall, T. G., Lee, R. E., & Marshall, F. E. (2006). Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. Theoretical biology & medical modelling, 3, 1. [↩]
  17. Marshall TG, Fenter, B. J., & Marshall, FE. (2004). Putative Antibacterial Mechanisms for Angiotensin II Receptor Blockers. Journal Of Independent Medical Research. [↩]
  18. Marshall, T. G. (2006a). Molecular genomics offers new insight into the exact mechanism of action of common drugs – ARBs, Statins, and Corticosteroids. [↩]
  19. Tronvik, E., Stovner, L. J., Helde, G., Sand, T., & Bovim, G. (2003). Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA : the journal of the American Medical Association, 289(1), 65-9.”>Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA : the journal of the American Medical Association, 289(1), 65-9. [↩]
  20. Kurikawa, N., Suga, M., Kuroda, S., Yamada, K., & Ishikawa, H. (2003). An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells. British journal of pharmacology, 139(6), 1085-94. [↩]
  21. Fan, Y., Baba, R., Nagai, Y., Miyatake, A., Hosomi, N., Kimura, S., et al. (2006). Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan. Hypertension research : official journal of the Japanese Society of Hypertension, 29(3), 169-78. [↩]
  22. Okada, K., Hirano, T., Ran, J., & Adachi, M. (2004). Olmesartan medoxomil, an angiotensin II receptor blocker ameliorates insulin resistance and decreases triglyceride production in fructose-fed rats. Hypertension research : official journal of the Japanese Society of Hypertension, 27(4), 293-9. [↩]
  23. de Cavanagh, E. M. V., Piotrkowski, B., Basso, N., Stella, I., Inserra, F., Ferder, L., et al. (2003). Enalapril and losartan attenuate mitochondrial dysfunction in aged rats.The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 17(9), 1096-8. [↩]
  24. de Cavanagh, E. M. V., Piotrkowski, B., Basso, N., Stella, I., Inserra, F., Ferder, L., et al. (2003). Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 17(9), 1096-8. [↩]
  25. Autoimmunity Research Foundation. (2006). Phase One Guidelines: Guidance for Physicians. [↩]
  26. Labro, M. (2000). Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or “Immuno-Fairy Tales”? Clin. Microbiol. Rev., 13(4), 615-650. [↩]
  27. Golub, L. M., Ciancio, S., Ramamamurthy, N. S., Leung, M., & McNamara, T. F. (1990). Low-dose doxycycline therapy: effect on gingival and crevicular fluid collagenase activity in humans. Journal of periodontal research, 25(6), 321-30. [↩]
  28. Milatović, D. 1982. “Effect of subinhibitory antibiotic concentrations on the phagocytosis of Staphylococcus aureus. ” European journal of clinical microbiology 1(2):97-101. [↩]
  29. Starner, Timothy D et al. 2008. “Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms.” Antimicrobial agents and chemotherapy 52(1):137-45. [↩]
  30. Cogan, N. G., Cortez, R., & Fauci, L. (2005). Modeling physiological resistance in bacterial biofilms. Bulletin of mathematical biology, 67(4), 831-53. [↩]
  31. Mangin M. (2004). Observations of Jarisch-Herxheimer Reaction in Sarcoidosis Patients. Journal Of Independent Medical Research, 2(1):1. [↩]
  32. Marshall, T. G., Fenter, B. J., & Marshall, F. E. (2005). Antibacterial Therapy Induces Remission in Sarcoidosis. Journal of Independent Medical Research. [↩]
  33. Gomes, P. S., & Fernandes, M. H. (2007). Effect of therapeutic levels of doxycycline and minocycline in the proliferation and differentiation of human bone marrow osteoblastic cells. Archives of Oral Biology, 52(3), 251-259. [↩]
  34. Antimicrobial peptides. (2007). Wikipedia. [↩]
  35. Schauber, J., Dorschner, R. A., Coda, A. B., Büchau, A. S., Liu, P. T., Kiken, D., et al. (2007). Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. The Journal of clinical investigation, 117(3), 803-11. [↩]
  36. Wang, T., Nestel, F. P., Bourdeau, V., Nagai, Y., Wang, Q., Liao, J., et al. (2004). Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. Journal of immunology (Baltimore, Md. : 1950), 173(5), 2909-12. [↩]
  37. Brahmachary, M., Schonbach, C., Yang, L., Huang, E., Tan, S., Chowdhary, R., et al. (2006). Computational promoter analysis of mouse, rat and human antimicrobial peptide-coding genes. BMC Bioinformatics, 7(Suppl 5), S8. [↩]
  38. Marshall, T. G. (2007). Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides. Nature Precedings. [↩]
  39. Marshall, T. G. (2006d). Molecular mechanisms driving the current epidemic of chronic disease. [↩]
  40. Tilley, B. C., Alarcón, G. S., Heyse, S. P., Trentham, D. E., Neuner, R., Kaplan, D. A., et al. (1995). Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Annals of internal medicine, 122(2), 81-9. [↩]
  41. Lauhio, A., Leirisalo-Repo, M., Lähdevirta, J., Saikku, P., & Repo, H. (1991). Double-blind, placebo-controlled study of three-month treatment with lymecycline in reactive arthritis, with special reference to Chlamydia arthritis. Arthritis and rheumatism, 34(1), 6-14. [↩]
  42. Mercola, J. (1999). Physicians’ Protocol for Using Antibiotics in Rheumatic Disease. [↩]