Concerns about progress on the Marshall Protocol

The exact nature of a patient's progress on the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP) can be variable. Depending on the level of inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue., location of infection, exposure to light, dosing of antibiotics, and any number of other variables, patients can experience everything from a minimal to a strong 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..

There is no evidence that the MP worsens a patient's health. If anything, the strong exacerbation of symptoms due to antibiotics, known as 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., is an indication that the MP is working all too well. For patients who are experiencing intolerable immunopathologyAn unbearable or unsafe severity of bacterial die-off reaction., there are a number of strategies available. Patients who do not seem to be reacting to the combination of olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. and antibiotics have options as well.

In the interests of safety, it is important that patients proceed on the MP at a conservative pace, leaving themselves a margin due to the highly variable nature of immunopathology.

Pulsed low-dose antibiotics and frequent administration of olmesartan (Benicar) work to kill intraphagocytic and other pathogenic forms of bacteria. When bacteria die, endotoxins and inflammatory cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. are released at the site of infection, causing an increase in symptoms such as pain and fatigue. For example, patients with the lung disease sarcoidosis may notice that their coughing spells get worse. Those with psoriasis may notice a flare in their skin symptoms. In laymen's terms, one must feel worse before getting better.

From day to day and week to week, MP patients' symptoms wax and wane in semi-predictable fashion and occur in expected locations. Occasionally, however, patients may notice new symptoms occurring in organs not known to be infected. The MP does not and cannot create new inflammation.

In cases where people have trouble grasping this concept, the biggest hurdle is to get them through the first phase of the treatment when the immunopathology is often strongest. If I have any dropouts, they come from this group – the people who can’t intellectually grasp the idea that they need to feel worse before they get better.

Greg Blaney, MD

The immunopathological reaction (sometimes referred to as the Jarisch-Herxheimer reaction) is widely accepted as an indication of progress and, according to the literature, has been observed in at least ten different diseases and conditions.

It is noteworthy that anxiety often is a symptom of the disease process. Given that the MP is, after all, a multi-year treatment, succeeding on the MP requires a conviction that the cause of one's inflammation is intracellular, pleomorphic bacteria, and that the elimination of these bacteria will eventually result in resolution of the inflammation and recovery from disease.

At some point in the Protocol, many patients find their immune system becomes much more active and immunopathology symptoms may increase. At this point, there may be a need to reduce or stop antibiotics, while staying on Benicar alone. This is completely expected and is consistent with the stages of illness and recovery. Rather than being a sign of “treatment failure,” the need to reduce antibiotics is actually a result of improved immune function.

Patients whose immunopathology is intolerable have a number of options, including the following:

• Lower one's dose of antibiotics. Typically, the most effective way to manage immunopathology.
• Take a break from taking antibiotics. Breaks tend to be more effective in the earlier stages of treatment before the immune response becomes more self-sustaining.
• Discontinue minocyclineBacteriostatic antibiotic used by Marshall Protocol patients. for a period of time and prove to yourself that it is the antibiotic which is making you feel worse.
• Dose minocycline more frequently, 50mg every day. This may “turn off” immunopathology and may be a better option than discontinuing antibiotics altogether, which can actually exacerbate immunopathology.
• Increase olmesartan (Benicar) dosing frequency to every six hours, around the clock. Typically, if a patient's symptoms are a result of immunopathology, the increase in olmesartan (Benicar) will help alleviate them.
• Assess light exposure to determine whether any relief might be derived from decreased exposure. Sometimes, MP patients are extremely light sensitive in the beginning of the MP and any excess light exposure makes them feel considerably worse than they would feel without the excess light.
• Change nothing and just “ride it out” to see if or when there is a window of feeling some improvement. Sometimes it take several weeks before a patient feels any better.

The expected increase in symptoms that MP patients experience can be alarming, especially when those symptoms are potentially life-threatening. A patient with severe cardiac inflammation may have to endure frightening arrhythmias or chest pain before the heart muscle is free of inflammation. A patient with shortness of breath and coughing may experience a worsening of those symptoms before pulmonary function improves. Symptoms of severe depression are no less scary.

One common mistake MP patients make is to underestimate how much exposure to light can drive immunopathology. As a general rule, the more life-threatening a patient's symptoms, the more judicious he or she should be when it comes to regulating light exposure.

Of course, patients experiencing any kind of symptoms that appear life-threatening are advised to promptly consult with their physicians.

MP patients do not always recognize immunopathology. Mental or neurological immunopathologyA temporary exacerbation of neurological symptoms due to bacterial death. Requires careful management by physicians. may be particularly hard to notice given that life events can color the perception of the MP's effect on one's mind. Many patients have benefited by recording their progress in a log or journal or by asking a friend or family member to offer feedback on progress.

The following checklist should help identify any reasons why patients fail to generate the expected immunopathological reaction.

• Antibiotic recently introduced – Have you just begun taking an antibiotic? If it is less than two weeks since you began the antibiotic, it can sometimes take a couple of weeks to “kick in.” Always be cautious when starting new antibiotics or new antibiotic combinations.
• Antibiotic dosing – Have you considered extending the time between doses of antibiotics, which you would usually take every 48 hours to every 72 hours?
• Expired antibiotics – Are you using expired antibiotics, which have lost potency?
• Antibiotics perfusing the tissues – Have you considered that the antibiotics have not reached the infected tissue? Mild exercise or a warm bath can increase circulation and may be in order. Please exercise caution. Heating up the body can cause strong immunopathology.
• Medications and supplements – Have you discontinued all unnecessary prescription or over-the-counter medications and supplements? A number of substances have unknown immunomodulatory effects.
• Regular dosing of Benicar – Are you taking Benicar 40mg every six hours around the clock and never missing a dose?
• Past use of Prednisone – Have you been taking Prednisone? Sometimes the immunosuppressive effects of corticosteroids can be felt for months later.
• Low-carb diet – Have you considered limiting intake of carbohydrates as per the suggested low-carb diet?
• Food containing vitamin D – Are you diligently avoiding all foods and supplements that contain or may contain vitamin D?
• Avoiding other immunomodulatory foods – Are you avoiding foods which contain high levels of chlorogenic acid? Are you avoiding soy and soy products?
• Eye protection – Are you wearing NoIR sunglassesSpecial sunglasses worn by Marshall Protocol patients to block light. at all times, both indoors and outdoors? Do you wear them to watch TV and when you are on the computer? Do you wear them when facing bright oncoming headlights at night? Is your computer monitor brightness turned down?
• Light avoidance – Have you been avoiding natural light and bright artificial lights? Do you go outside during the daytime? How often? For how long? Do you cover up from head to toe when you cannot avoid going out during the day? Is your house darkened to 30 lux?
• Any changes of note – Have you changed in the following: foods, light exposure, exercise, medications?
• 25-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. in range – Many patients do not start experiencing strong immunopathology until their 25-D is below a certain level. The decrease in stores of vitamin D can sometimes take months to accomplish. According to Trevor Marshall, PhD: “The 25-D seems to be the most critical factor as to whether the immune system is able to start working. Any level of 25-D above about 20ng/ml is likely to be acting as an immunosuppressant, with an action very similar to that of corticosteroidsA first-line treatment for a number of diseases. Corticosteroids work by slowing the innate immune response. This provides some patients with temporary symptom palliation but exacerbates the disease over the long-term by allowing chronic pathogens to proliferate..”

Every so often, reports of “treatment failure” surface. The MP has a number of requirements, which are non-negotiable, and, if violated, can result in failure. For example, one cannot make progress on the MP while consuming significant levels of vitamin D or taking immunosuppressants. Continuing to take supplements with unknown effects can be problematic as well.

Another issue relates to the fact that the MP is a curative therapy. For many of the sickest patients – people who have five, six or more co-morbidities – this may mean five or more years of treatment.

So long as symptoms of immunopathology continue and elevated blood markers of bacterial die-off (such as BUN), there are bacteria being killed and to be killed.

The range of time it takes seriously ill patients to recover on the Marshall Protocol is not entirely without precedent in medicine. The first-line treatment for for tuberculosis infection takes six months¹ – and that's only a single genus as opposed to a metagenomic microbiota. It's also worth noting that recovery from tuberculosis also involves an immunopathological-type reaction.²

Patients should try to consider their responses to the MP medications logically. The safety profile of olmesartan (Benicar) as well as the safety profile of the MP antibiotics are excellent. The single best explanation for why a patient symptoms are worse is that the immune system is becoming stronger and microbes are being killed.

Patients who are sick with Th1 disease are understandably eager to become well. But, especially for patients who are very ill, achieving desired results from the MP can take several years or more. Over that length of time, there is strong evidence that the MP is effective. On the other hand, there is no current evidence that one can speed up progress on the MP beyond a certain pace.

In fact, trying to excessively hasten the pace of the MP has a number of disadvantages:

• Especially when patients have cardiac, respiratory or neurological symptoms, patients could be putting their lives in danger.
• Patients could have an episode of intolerable immunopathology, which could require a visit to the emergency room and set back one's progress even further.
• Killing too many bacteria in a short period of time could result in tissue damage.
• Patients could become discouraged, both physically or mentally.
• In Phase One, going too fast could result in a failure to kill all the bacteria susceptible to minocycline alone.

Finding the optimal and safest pace to succeed with the MP is a matter of trial and error. There is, of course, such a thing as being too cautious: conceivably, bacteria could repopulate tissues already cleared by one antibiotic. Patients are advised to work closely with their physician to find the right combinations of antibiotics at the right time.

MP patients are advised to dose their antibiotics such that they leave themselves a margin between the level of their current symptoms and “intolerable.” The variable nature of immunopathology necessitates this approach.

Here are some suggestions for getting well in the safest and smoothest manner, without getting side-tracked or delayed:

• Give new antibiotics two weeks to “kick in” before increasing a dose.
• Stay at each dose level for at least three doses before increasing. A dose may kick in suddenly and unexpectedly after several doses at the same dose level.
• If you are experiencing intolerable symptoms at any given dose level, stay at the dose level longer.
• Make changes cautiously, especially when other factors and life events could result in debilitating symptoms. These symptoms include: extra stress, added activity, an infection, difficult menses, etc.
• Try a break from the MP to help determine what symptoms are disease baseline (pre-MP) and what are immunopathology. Note that some patients do not feel better with a short break and need the antibiotic(s) to keep symptoms manageable.
• If in doubt, always choose the more cautious action.

It is hard for some of us to pace ourselves and go slowly. Many of us are used to pushing ourselves to the limit and have learned to be tough and almost obsessive in order to make it in our lives. We have had to overcome punishing levels of symptoms in order to make it under the burden of these illnesses. However, for the Marshall Protocol, remember, discretion is the better part of valor. Don’t treat your body too harshly. The illness has done that too much already. The fable of the tortoise and the hare really does apply here: the slow and steady ones are better able to make it to the finish line.

Joyce Waterhouse, PhD

Patients with ALS, unlike those who have any other chronic Th1 disease, have a fast-progressing illness and need to be more aggressive in progressing on the MP to kill bacteria as quickly as possible.