May 19, 2010
Inflammatory diseases may be caused by bacteria Inflammatory diseases may be caused by bacteria . .
Australian scientist Trevor Marshall’s drug therapy is based on the idea that many inflammatory diseases such as rheumatoid arthritis are caused by stealthy bacteria that hide inside of healthy cells and tissues, writes Ron Falcone.
The Marshall Protocol: A New Hypothesis in Rheumatism Treatment
The Marshall Protocol (MP) was named after an Australian scientist Trevor Marshall, and is based on the idea that many inflammatory diseases like rheumatoid arthritis (RA) are caused by stealthy bacteria that hide inside of healthy cells and tissues. Specifically, the MP involves a method of drug therapy designed to undermine the suspected bacteria and reverse the inflammatory process.
Conventional approaches to diseases like RA involve giving toxic drugs that suppress inflammation. But Marshall argues that such drugs temporarily relieve symptoms and don’t address the underlying cause of the disease. And in one of Marshall’s more controversial views, he stipulates that vitamin D---now believed by many to help diseases like arthritis---may actually worsen the condition.
The Bacteria Connection
The idea that inflammatory diseases are caused by an infection is not new. Shortly after World II, Dr. Thomas McPherson Brown of the Rockefeller Institute, isolated tiny bacteria called mycoplasma from the joints of a rheumatoid arthritis (RA) patient.
Claiming to observe the mycoplasma triggering an immune response in animals and humans, Brown developed an antibody test and then announced he’d found the primary cause of RA. Brown also reported positive responses from patients treated with minocycline, an antibiotic used against mycoplasma.
Over the years, thousands of patients were reportedly helped by Brown’s treatment. In addition, numerous scientific papers showed a guilt-by-association link between bacteria and inflammation. But Brown continually faced opposition from doctors who argued that inflammatory diseases are the result of an autoimmune problem (i.e., a faulty immune system attacking its own tissues).
This is still the prevailing view in medicine. Nonetheless after years of contentious debate, a 1995 government-sponsored trial known as MIRA (or Minocycline In Rheumatoid Arthritis) reported that more than half of patients so treated had improved.
The MIRA results were initially criticized, because patients who received a placebo instead of the actual drug also reported positive results. However a careful review later revealed that many of the patients were also secretly taking anti-inflammatory drugs; it was apparent that the positive mincocyline results had therefore been underestimated.
While the MIRA study seemed to vindicate Brown, his bacterial theory is still looked at circumspectly. That’s because mainstream science argues that a cause and effect has yet to be proven via the time honored tenets of “Koch’s Postulates”.
Named after a 19 century German scientist, Koch’s Postulates require four steps: isolation of a microbe from diseased tissue or blood; growing that microbe on a culture plate; exposing a healthy test animal to the microbe; and then seeing if the same disease for which the microbe is suspected of causing makes the animal sick. According to critics, these steps have not been completed with respect to RA and similar diseases. [Ed: Click here for an article about why animal experiments are unscientific when it comes to human health].
Marshall argues that inflammatory bacteria are so small and genetically unstable, Koch’s Postulates are not a valid means of isolating them. In fact, new research is casting an entirely different light on how bacteria are identified, and this may lead to better methods than the century’s old Postulates are able to provide.
The New Bacteria Paradigm
Cutting edge science is now able to study bacterial DNA without the use of traditional culture methods, and some of its findings are challenging the very foundations of microbiology. Scientists have discovered, for example, that enormous amounts of bacteria exist in the human body---the ratio being an incredible 10 bacterial genes to 1 human.
(One theory holds that bacteria coexist peacefully in a healthy body, but during periods of stress or disease, can invade healthy cells and throw a monkey wrench in the genetic machinery. This can lead to severe inflammation). Scientists have also found that bacteria can swap genes and form new or hybrid species previously unrecognized. They explain that such DNA transfer occurs so fast, trying to link a particular bacterium to a disease is not always possible.
Complicating things even further, many bacteria are proving to be highly unstable outside of the body, making them extremely difficult to study. This becomes evident as researchers now find that only 1% of bacteria in study samples can be cultured via traditional methods.
Based on all these findings, Marshall and others point to the following associations between bacteria and inflammation that they say aren’t based on Koch’s Postulates:
1.Markers associated with (RA) are often elevated in people with chronic bacterial infections, suggesting a link
2.Bacteria have been observed inside of white blood cells in people with juvenile arthritis, and in such diseases of “unknown origin” as chronic fatigue syndrome; these bacteria can form antibody-resistant sheaths called “biofilms” which allows them to spread from cell to cell
3.Chemicals which block immune system cells are produced by bacteria, and abnormal blood tests confirm that process in people with inflammatory disease
4.Anti-bacterial treatments often result in disease flare-ups followed by a predictable relief of symptoms. This suggests that large numbers of bacteria involved in the disease process are being killed
5.Bacteria not associated with the human body---for example species found on the ocean floor---have been isolated from tissues suggesting that many species share common genes; this also makes such bacteria difficult or impossible to categorize via traditional methods
6.Many areas of the body such as blood or hip joints normally considered “sterile” have been found to harbor bacteria; this challenges the common assumption that microbes isolated from unexplained diseases are simply “contaminants”.
How Bacteria Shut Down the Immune System
Marshall believes that bacteria which he calls “Th1 pathogens” attack the very immune cells designed to fight them. Once nestled inside, the pathogens block proteins used to fight infections and they also shut down the cells’ ability to summon help through a highly complex system called the “Vitamin D Receptor” (or VDR). The VDR is found inside immune system and other bodily cells.
Normally, the body uses a derivative (or metabolite) of vitamin D known as 1,25D to “switch on” the receptor. Once turned on, an immune response is then triggered against infections. But in people with inflammatory disease, bacteria have inserted themselves in the VDR’s machinery, blocking 1,25D’s switching ability. Scientists call this blocking action “down regulation” and Marshall thinks this is one of the hallmarks of inflammatory disease. Now, microbes can remain hidden inside the cells they’ve taken hostage and flourish there indefinitely.
Bacteria also block an enzyme responsible for producing normal levels of 1,25D. This creates high levels which works to the bacteria’s advantage. One might assume that more 1,25D is better because it can turn on more vitamin D receptors. But the problem is, it’s not being used by the VDR; instead, the metabolite floods cells where it’s not needed, and this can cause a worsening of symptoms.
For example, too much 1,25D can over stimulate chemical messengers called cytokines which alert the body to disease and help activate antibodies. While extremely important to immunity, over stimulation of cytokines can also cause them to attack healthy tissues. In fact, one of the leading theories of inflammation involves faulty cytokines, and new drug therapies like Enbrel are designed to block them.
But Marshall warns that inflammation is caused by a malfunctioning vitamin D receptor and unless treated as such, will never be cured.
1,25D and Its Effects On Other Organs
Not only does 1,25D wreak havoc with the VDR, it can affect tissues and organs leading to a cluster of misdiagnosed “diseases”. For example, 1,25D can bind with the thyroid and prevent that gland from making thyroid hormone. This might explain why in a recent study of 100 patients with rheumatoid arthritis (RA), 24 also suffered from Hashimoto’s Thyroiditis.
Patients with RA and thyroid disease might typically be treated with synthroid and other drugs that restore hormone levels. But if thyroid disease is actually being caused by Th1 pathogens, drugs won’t cure the underlying problem. In addition, thyroid medications can cause such affects as weight gain (also a known issue with RA).
An impaired vitamin D receptor might also cause other disease states including some cases of diabetes, Chron’s disease, psoriasis and others.
1,25D And Vitamin D “Deficiency”
Doctors determine “normal” vitamin D levels by measuring another of its metabolites called 25D. But during inflammatory disease, an interesting thing happens.
25D is normally formed in the liver after being converted from sunlight or dairy products. However, excess 1,25D blocks an enzyme involved in this conversion, leading to a drop in 25D levels. It’s almost as though bacteria have “figured out” that abnormal metabolite levels benefit them and allow their continued growth and safer occupation inside the cells they’ve taken hostage.
Many in the medical community now think that low 25D levels are a sign of a vitamin D deficiency. Understandably, some address this issue by recommending increased supplementation with the vitamin. However Marshall argues that this practice only suppresses an already impaired immune system and creates a false sense of benefit similar to that conferred by anti-inflammatory drugs. Over the long haul, he worries that such strategies will allow pathogens to gain an even stronger foothold, eventually overtaking the body and any efforts of medicine to quell disease symptoms.
The Marshall Protocol
One of the cornerstones of the Marshall Protocol (MP) involves a medicine usually used for high-blood pressure, named Olmesartan (also known as “Benicar”). Minocycline and other antibiotics are also used, and vitamin D restriction is usually advised.
Olmesartan binds with the VDR and is believed to dislodge the bacterial molecules which have taken it over. This helps to switch the receptor back on and resume normal immune function. Olmesartan also helps return 1,25D levels back to normal because the enzyme which regulates it is now functioning again. This reduces inflammation caused by 1,25D activated cytokines. As inflammation abates, bodily tissues can better absorb antibiotics which might otherwise have a tough time doing so.
While Dr. Brown believed that minocycline directly attacks mycoplasma, other mechanisms might explain its benefits. These include blocking of genetic proteins necessary for bacteria to survive, and stimulation of the immune system. Zithromax, another drug used in the MP, also blocks key bacterial proteins.
It is notable that many antibiotics may not have any effect against Th1 pathogens because these have been found to lack cell walls; penicillin for example, kills by attacking bacterial cell walls. In addition, scientists who study Th1 pathogens find they sometimes grow better when exposed to penicillin and other antibiotics.
If true, this is a troublesome finding considering that penicillin has been approved for the treatment of RA. (One exception is when patients have streptococcus infections which are penicillin-sensitive; the administration of penicillin in such patients requires careful monitoring and can’t be given for very long periods, as organisms can develop resistance).
If the theory behind the MP is correct, then it follows that such treatment would result in the destruction of large colonies of sequestered bacteria inside millions of bodily cells; this would also mean that patients should expect to experience side effects from the dying or killed organisms.
In fact, many patients do report a worsening of their symptoms unrelated to drug side effects before eventually improving. This effect is known as the Jarisch-Herxheimer (or “Herx”) reaction and it occurs because the body is responding to increasing levels of dead bacteria.
(Interestingly, it was the Jarisch-Herxheimer phenomenon that initially cued Dr. Brown to suspect a bacterial cause for inflammatory diseases; he noticed that patients receiving gold salts---now known to have some antibacterial properties---would often feel sicker before improving).
Marshall calls Herx reactions “immunopathologies” and considers them a positive sign; the more pronounced the reaction, the more effective the treatment is believed to be. And indeed, studies of people on the MP appear to show a statistical correlation between immunopathology and eventual improvement in symptoms. For this reason, Herx reactions are cited as proof that bacteria are the prime factor in inflammatory diseases.
Not all MP patients experience reactions but when they do, symptoms can last more than a few weeks and are sometimes intense. These can often be controlled by adjusting doses of Olmesartan which helps modify inflammation.
In a recent study of 54 patients representing 20 different types of inflammatory diseases, 81% reported “continued improvements” over the course of several years while undergoing treatment with the MP.
Vitamin D Restriction
Because Marshall believes that vitamin D and its metabolites act as hormones which suppress the immune system in sick people, one of the goals of treatment is to restrict intake of, or exposure to the vitamin.
This includes avoidance of sunshine and foods rich in vitamin D. Some patients who are severely ill avoid sunlight completely while others less so. Because MP drugs cause photosensitivity, patients are urged to use special sunglasses. They’re also advised to avoid foods that may not be thought of as being vitamin D rich. These include tuna, egg yolks, sunflower oil and even some beers.
The duration of treatment can last several years because the Marshall Protocol is designed to destroy a minimal amount of bacteria over a lengthy period. This is said to lessen Herx reactions and other toxic effects to the body while also restoring an immune system long compromised by disease.
What The Future Holds
The medical profession doesn’t recognize Marshall’s Protocol nor any of Dr Brown’s early theories. It still holds to the 50-year-old concept that inflammatory diseases are a problem of autoimmunity.
Consequently, the treatments of choice remain medicines that suppress symptoms---many over the course of a lifetime and at considerable expense and sometimes danger to the health of patients.
Given the billions of dollars generated annually in the dispensing of, and research into anti-inflammatory drugs (and the general reluctance of orthodox medicine to explore an infectious cause), it doesn’t appear likely that the current treatment paradigm will change ant time soon.
But while the MP has yet to be proven via standard clinical trials, the following point is raised: for all of orthodox medicine’s progress, it has failed to isolate a primary cause of inflammatory disease; nor can it speak in terms of a cure. Therefore, what justifies the orthodox treatment paradigm to the exclusion of all others?
Medical journalist and author Ron Falcone attended the University of Bridgeport, CT in 1973. After writing articles for major periodicals such as Woman's Day and Your Health, he began work on a non-fiction account of the life of controversial cancer physician Virginia Livingston. Eventually, this project morphed into the Complete Guide to Alternative Cancer Therapies (Citadel Press 1995).
In 1995, Ron established and operated a medical information company, Cancer Treatment Search Services. In 1997 he authored Natural Medicine For Breast Cancer (Dell Health) and a year later, Natural Medicine For Prostate Problems (Dell Publishing). His latest article appeared in New Dawn Magazine (December 2009). Ron also contributes to Wikipedia, having written most of the draft for the entry on “cancer bacteria”, and recently contributing the entry on “Virginia Livingston”. He is also the creator and host of The Cancer Bacteria Homepage.
He currently lives near Orlando, Florida in the US with his wife Anne and their two children.