[i]``The human body does not require sunlight, nor foods containing Vitamin D, in order for it to function correctly. The human body can manufacture all the Vitamin D it needs from its own 7-dehydrocholesterol. Clinical medicine is just plain wrong on its understanding of the actions of Vitamin D.'' Trevor Marshall
The Marshall Protocol (MP), which claims to cure CFS and FM, is a very polarizing topic. People are either really for it, or really against it. Seduced by the molecular modeling and hope of a cure, I was on the protocol for almost two years. However, after almost landing in ER and experiencing a permanent deterioration in all my CFS symptoms, I have learnt first-hand of the dangers and risks of the MP, none of which I was warned. The MP worsened my existing CFS symptoms such as fatigue, sleep dysfunction, muscle and joint pain and created new symptoms such as neuropathy, parenthesisa, breathing difficulties, cardiac pain and tinnitus which have persisted. Thus I feel that it is my duty to warn others who may be considering the MP, which continues to attract many new patients, of all the hidden risks so that they can make a fully informed decision about whether to undertake this protocol.
The Marshall Protocol claims to be a curative treatment for illnesses caused by cell wall deficient bacteria. Given that various credible researchers such as Nicholson and De Meirleir have found mycoplasma in between 50-68% of CFS and FM patients, the MP seems to be a logical treatment option.[ii] (However it is unclear whether mycoplasma are the causative agent for CFS or FM or a secondary infection.) However, just because mycoplasma may be involved in your condition, it does not necessarily follow that the Marshall Protocol is either a safe or effective therapy.
Invented by electrical engineer Trevor Marshall PhD, the Marshall Protocol was initially designed for the treatment of sarcoidosis, a Th1 disease in which granulomas form in the lungs and where vitamin D pathways appear to be deregulated (this is generally not the case with CFS). The treatment is based on the premise that 25 vitamin D is immunosuppressive, that the cell wall deficient bacteria are converting excessive amounts of it into 1,25 vitamin D which creates inflammation in the body and thus disease symptoms. Consequently the Marshall Protocol advocates:
1. Eliminating exogenous sources of vitamin D including both dietary and sunshine. (This is includes blocking windows and installing low watt globes). 2. The use of Benicar in high doses which partially blocks the vitamin D receptor and inhibits certain inflammatory processes. 3. The use of different combinations of low pulsed antibiotics in order to eliminate the bacteria. The elimination of vitamin D in tandem with the use of Benicar is claimed to switch on the innate immune system so that it `sees' the bacteria. Marshall claims that the antibiotics don't directly kill the bacteria, but merely latch on to their RNA subunits, weakening them, and allowing the immune system to eliminate them. This theory, none of the elements of which have ever been tested in a lab, has since been rolled out to all autoimmune diseases as well as CFS and FM all of which Marshall claims are Th1 conditions and thus have the same pathogenesis and can all be cure by his protocol.
Who is Trevor Marshall? Before I tackle the safety of the MP directly I think there is value in having a look at who Trevor Marshall is as the protocol has been wholly created by him and is not endorsed by any other researcher. While there has been some interest in his theories lately, there is little support in the biomedical or molecular modeling communities for the protocol to be applied to patients in its present form.
Trevor Marshall trained as an electrical engineer and did his PhD thesis with the Department of Electrical Engineering on modeling insulin production and flows in diabetic patients (using mathematical equations). Although he spent some time in the early 1980s modeling reproductive hormones, he spent most of his career working on electronic engineering and IT, including running YARC, a printer technology company, from 1988 until its bankruptcy in 2000. During this time YARC, headed by Marshall, was involved in over a dozen litigations at the Superior Court of California, predominantly as the defendant. The most interesting being Joseph La Bruna v. YARC Systems Corporation (2001) where the court found that Marshall ``made representations and promises and concealed and omitted the true facts knowing such representations, promises and concealments and omissions to be false. They were made with the intention of deceiving, defrauding and misleading the plaintiff, and to induce him to act in reliance thereon.''[iii]
After YARC went bankrupt, Marshall devoted himself to reading as much as he could on sarcoidosis, from which he suffered, and devised the Marshall Protocol in order to rid himself of the disease. After he and a small group of other sarcoidosis patients began noting improvements in their condition, Trevor Marshall decided to create a study site on the web for other sarcoidosis patients in 2002 and then in 2004 decided that all autoimmune illnesses, as well as CFS and FM, were Th1 illness and had the same pathogenesis as sarcoidosis and opened the study site up to all these conditions.
It is important to note that Trevor Marshall has little research experience in chronic illnesses and no formal training or research experience in microbiology, biochemistry or drug administration. While Trevor Marshall promotes himself as a Biochemical Engineer his PhD was in electrical engineering and consists of many equations modeling the effects of insulin in diabetic patients. His area of expertise is computer modeling, rather than medicine. His understanding of immunology is based on his own readings of various scientific literature.
How was the Marshall Protocol devised? Trevor Marshall devised the protocol in order to treat his own sarcoidosis. He read into the discipline as an outsider and created a theory from his own research and personal experiences. He then wrote a computer model based on his research. The current Marshall Protocol is an extrapolation of the sarcoidosis theory to all autoimmune conditions which Marshall claims are all Th1 illness. (CFS is not considered an autoimmune condition and is considered a Th2 dominate illness not Th1 dominant illness). No objective lab work or animal testing was performed in order to determine the safety or efficacy of the treatment. Trevor and a few compatriots who were sarcoidosis patients simply experimented with various drugs on themselves. While Marshall has presented his model at a number of conferences now, he has not published any scientific papers on the full protocol itself in any peer reviewed journals. There is no support for his work in the biomedical community as he has not presented any objective data to support his claims.
Is it a cure? The protocol is promoted as a curative treatment yet there is no evidence of this yet. The statement is made based solely on Marshall's theoretical model not patient outcomes. After 5 years, no CFS patients are permanently of all the medications (including Benicar) and completely `cured'. While some patients have improved on the antibiotics, many of them have relapsed when they have stopped taking them and many still have just steadily deteriorated.A couple of CFS patients who had improved on the protocol and were held up as 'success stories' relapsed after stopping the antibiotics after 3-4 years on the protocol. Other patients stopping the protocol have also developed urinary tract infections, cancer and osteoporosis after extended periods on the MP. If you read the Phase 2 and 3 web boards on the www.marshallprotocol.com (you need to be a member in phase 2 or 3 to have access to these) you will see that the health of many people deteriorated while on the MP and they have had difficulty clawing it back.[iv] You will not hear about this or any such dangers on the public access Marshall Protocol site or www.curemyth1.org or www.bacteriality.com. There only the success stories are advertised.
The time promised for full remission on the Marshall Protocol was initially 12-18 months, then it became 2-3 years, then 3-5 years now 8-10 years is being bandied about. These are all Marshall's projections, none of these claims are based on fact or outcomes. That's an awfully long time to be on antibiotics and out of the sun.
Hidden Risks Marshall claims that his protocol is perfectly safe for use by adults and children but does not provide any evidence to back this claim up. In fact the protocol involves many risks none of which are disclosed on the Marshall Protocol site, namely:
1. The risk of being out of the sun for extended periods of time will invariably deregulate your hormones. Vitamin D is a hormone that is critical to numerous of functions in the body. Long term vitamin D deprivation is associated with an increased the risk of osteoporosis, rickets and cancer. Vitamin D plays an important role in both the adaptive and innate the immune systems and has been found to be responsible for the synthesis of antimicrobial peptides.[v] Marshall thinks that clinical medicine is completely wrong, that vitamin D is always immunosuppressive and dismisses the health risks associated with vitamin D deprivation because they do not fit in with his theories.
2. Modulating the immune system for prolonged periods in a way that has not been tested in a lab or on animals can have all sorts of dangers. Marshall has based his protocol on a computer simulation which is underpinned by his assumptions, rather than lab tests. Medical science does not yet fully understand what various receptors and components in the immune system do and what happens if you shut some of them down. For example, if you block Angiotensin II Receptor, which Benicar does, wound healing is impaired. Any number of feedbacks or alternative pathways could result none of which are known or can be predicted in a computer model. We simply don't have enough information to make definitive claims yet.
3. The risk of taking antibiotics over long periods of time can create resistant strains of bacteria. This is especially a risk where patients are exposed to concentrations of antibiotics which are below the minimum concentration required for killing bacteria as on the Marshall Protocol. Bacteria have a number of ways in which to avoid being detected or killed by antibiotics particularly when they are exposed to them over a long period of time. Indeed resistance to macrolides (which are used in the MP) is an increasingly growing problem. [vi] Marshall claims that it is the immune system, not the antibiotics doing the killing, that the antibiotics simply weaken the bacteria and make them more susceptible to being killed by the immune system, but there is no evidence of this. You just have to trust his theory that vitamin D is always immunosuppressive (which no one else agrees with) and its absence activates the immune system. One must also consider damage that long term impacts of antibiotic use can have on bacteria in the gastrointestinal tract.
4. Side effects of the drugs themselves: o Benicar: The Marshall Protocol recommends the use of Benicar at four times the recommended dose for extended periods. � Benicar is a very effective antihypertensive agent and also decreases aldosterone levels. CFS specialist Dr. Cheney states that this can be problematic in CFS patients who already often have low blood volume and low aldosterone levels. � The safety of Benicar has only been tested on humans for up to a year and only at half of the dose recommended by the Marshall Protocol. It has only been tested on rats for up to 2 years, yet the protocol requires patients to remain on Benicar for several years.[vii] o The antibiotic Minocycline can have a number of side effects especially when used over the long term. Many of these are similar to the rise in symptoms that patients are told to expect from bacterial die back.[viii] So it is impossible to tell whether patients on the MP are experiencing bacteria die back or just a drug side effect. o Other antibiotics used in the MP are not typically used over the long term so little is known about their safety over extended periods.
Patient Care Every symptom encountered on the site is attributed by the moderators to toxins released due to bacterial die back or 'Jarisch Herxheimer Reaction' (or 'herx'). Symptoms can be acute and varied and can include cardiac symptoms, breathing difficulties, vomiting, depression etc...Some of these may be dangerous drug reactions others merely exacerbation of disease symptoms. Moderators constantly assure patients on the internet web boards that these symptoms are an indication of bacterial die back, that their medication dosage should merely be adjusted and at best some palliation may be required. No other alternative causes such as allergic reactions, drug toxicity, disease exacerbation, vitamin D deficiency are ever suggested as these symptoms are never contemplated as possibilities on the MP, despite the fact that vitamin D deficiency is known to create depression, muscle and joint pain.[ix] Patients on the MP are encouraged to drive their 25 vitamin D levels to below 12ng/ml on Phase 2 and 3 of the protocol, which is severely deficient, the recommended vitamin D levels being 32-65ng/ml.
Interestingly the moderators who are advising patients on how to interpret symptoms and how to adjust their medication are all themselves Marshall Protocol patients. They have all yet to finished the protocol and are still ill (to varying degrees) and see the protocol as their only way out of the disease. They all cling to the protocol as it represents hope, the only road to health and gives them a sense of control over their illness. As such, they are all very devoted to the protocol which inevitably clouds their judgment when advising patients on how to interpret symptoms and adjust their medications or whether the patients ought to be on the protocol at all. The overriding goal of the MP site is not to achieve the best possible outcome for the patient, but to push the patient through the protocol, as it is automatically assumed that in the end this will be in the patient's best interest. Thus patients are encouraged to `hang in there' even when their symptoms are quite acute and dangerous and are assured that this is a sign of bacterial die back and thus part of the healing process. This has resulted in a number of patients ending up in emergency wards.
Validity of Data While the Marshall Protocol site claims to be a study site, the evidence used to support the MP on the site is not objective. Any positive post by a patient on the Marshall Protocol.com site is put up in the success stories section even though the improvement may be temporary and the patient has subsequently felt worse. The only way to verify this is to read all of a patients posts in the Phase 2/3 forum which are off limits to anyone not in phase 2 or 3. A handful of people have improved on the MP but it is a much smaller number than the success stories page would have you believe and improvement is based on self reporting. There is no way of knowing what percentage of people who started the MP have subsequently improved because anyone who stops the MP, due to an adverse reaction to the protocol is discounted. No one is interested in why they dropped out and none of this is followed up or documented. One only needs to scan the membership list (which has date of commencement and number and date of patient posts) to see how high the dropout rate is. These patients are simply dismissed as not being tough or dedicated enough, or not complying with the rules. Only those who stay on it for over a year are eligible for inclusion in any `study'. So far the only study conducted was a voluntary retrospective survey that was sent out to a random selection of patients. Obviously those having more success with the protocol are more likely to stay on it as well as respond to a survey. The patient feedback was retrospective and based on self reporting so this study (which was conducted by a patient as well) has more holes in it than Swiss cheese. This is the data that Marshall cites at conferences in order to prove the efficacy of the MP.
Interestingly no one is off all the MP medications and actually cured themselves of anything except perhaps Trevor Marshall. The number of CFS patients who have not relapsed going off the antibiotics is still in single digits. Most patients are plugging away on 3 different types of antibiotics, Benicar often with anti-inflammatories, pain killers, sleep meds etc...and claiming they feel better or that they will 'turn the corner soon'. It is difficult to know what is a drug effect and what is genuine improvement as Benicar and Minocycline do have an anti-inflammatory effect which could be mistake for genuine healing and, as state previously, most MP patients have experienced a worsening of symptoms when discontinuing the antibiotics which is ongoing (see patient comments on the following web boards).[x] This all implies that at best the antibiotics were palliating their symptoms and at worse suppressing their own immune systems allowing bacteria to proliferate and possibly breeding new antibiotic resistant strains of bacteria on the way.
Patients often persist on the Marshall Protocol despite being in great pain as cling to the hope of a cure and they are told by moderators that these symptom exacerbations are a sign of healing. Thus often patients do not quit until their symptoms become so intolerable that they are forced to stop. Interestingly, of the 40 MP the patients at my doctor's clinic who persisted into Phase 2 (most dropped out in phase 1 due to acute symptoms), half them have experienced a worsening of CFS symptoms as a result of the MP and they have often developed new CFS symptoms including orthostatic intolerance, anxiety, neuropathy, muscle and joint pain, light sensitivity, digestive problems and depression. The other half managed to return to their pre-MP level of health after a couple of months (these people usually have spent less time in Phase 2.) Interestingly, none of the ex-MP patients from my clinic have experienced any symptoms improvement after stopping the MP. One would think that if bacteria were indeed being killed by the protocol, that at least someone would feel better after all that herxing.
Conclusion Perhaps the biggest folly of the Marshall Protocol is the belief that what happens in a computer simulation will be directly replicated in the human body. The human body is vastly complex system with multiple pathways and feedback loops. The idea of calculating the drug affinity of a few receptors on a computer, running a simulation, and then confidently claiming that this will be replicated in the human body is na�ve and dangerous. Molecular modeling is a starting point for research, it provides a general direction for lab work, avoiding the needle in the haystack approach to research which wastes time. But all of this needs to be validated step by step in the lab before being rolled out to desperate patients as cure, especially when it contradicts many current lab findings, as the Marshall Protocol does.[xi] Patients on the MP are expected to trust the results of one computer model, however unfortunately theory does not neatly translate into reality. We don't know enough about how bacteria and the immune system work to build reliable models at this stage.
So in summary the risks of going on the Marshall Protocol include: - Risks associated with having low vitamin D for extended periods of time include immune suppression, risk of cancer, rickets and osteoporosis. - Risk of modulating the immune system in untested ways with unknown consequences. - Risk of taking Benicar at four times the recommended doses for prolonged periods of time with unknown consequences. - Risk of developing bacterial resistance and proliferation from being on antibiotics for long periods of time and a worsening of your condition.
These are substantial health risks to be taking in light of the lack of evidence to support the claim of a cure for CFS and FM by the Marshall Protocol. So if mycoplasma are found to be contributing to your condition, it may be best to consider other treatment options.
[iii] JOSEPH LA BRUNA VS YARC SYSTEMS CORP, Superior Court of California, County of Ventura (2001) Case number: CIV201956 ; A summary of this and other cases can be read at http://www.sarkoidose.de/apboard/use...t_upload&id=23; The list of court cases the YARC and Marshall were involved in can be found by typing `YARC' into the Case Enquiry search box (for Civil cases) at the Superior Court of California, County of Ventura website found at: http://www.ventura.courts.ca.gov/vent_frameset_puba.htm
I tried again and was able to cut and paste the post today. This person gives a very good (and fair) overview of the dangers of this protocol.
Posts: 845 | From Eastern USA | Registered: Jul 2006
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dmc
Frequent Contributor (1K+ posts)
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Thank you for posting this.
Posts: 2675 | From ct, usa | Registered: Jan 2004
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