Marshall Protocol

This document is a one-article summary of key issues related to the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis., especially as it is relevant to physicians. Many of the topics covered here are reviewed in greater depth throughout the Knowledge Base.

An active community of recovering patients has been a cornerstone of our success. While the physician is responsible for patient care, patients can do a lot of the footwork, retrieving information so that the physician can make fully informed decisions. Indeed, without active participation of the patients in our study, we do not support or license the public use of this therapy. We urge physicians to encourage patients to take advantage of the following three websites:

• MPKB.org – The Marshall Protocol Knowledge Base contains links to the latest peer-reviewed research from ARF as well as articles about hundreds of topics and written for a variety of audiences.
• CureMyTh1.org – Short for “Cure My Th1 DiseaseAny of the chronic inflammatory diseases caused by bacterial pathogens.,” CureMyTh1.org is open to all. At CureMyTh1.org, patients can ask questions about the MP, find a doctor, and share symptom reports. CureMyTh1.org is moderated by patient advocates.
• MarshallProtocol.com – This site helps patients and physicians better understand the Marshall Protocol. MarshallProtocol.com is currently open to new patients by invitation and contains patients' symptoms reports and science-related discussions. Healthcare providers are encouraged to join the Private Section for Health Professionals forum on the MarshallProtocol.com study site, which is open by email request. MarshallProtocol.com is moderated by Professor Trevor Marshall, members of the research team, and patient advocates.
• AutoimmunityResearch.org – At this site one can learn more about the Foundation that supports the Marshall Protocol and explore the full implications of a metagenomic pathogenesis of chronic disease.
• Bacteriality.com - Amy Proal's interviews with MP patients, together with articles about the science underlying the protocol.

Main article: Science behind immunopathology

The Marshall Protocol has been used in a variety of chronic inflammatory diseases. The gold standard for evaluating whether the MP is warranted is the therapeutic probeA brief trial of the Marshall Protocol to see if it will generate an immunopathological response. The "gold standard" for testing whether a patient is a good candidate for the MP., a brief trial of the Marshall Protocol to see if olmesartan medoxomil and minocyclineBacteriostatic antibiotic used by Marshall Protocol patients. will generate an immunopathological response. The results from a vitamin D metabolites test, while less definitive, may also suggest the presence of treatable condition. For an automated interpretation of the vitamin D metabolites, consult the Vitamin D Metabolite Calculator.

Other patient groups:

• pregnant/lactating women – Both olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. and minocycline, the two mainstay medications of the MP, are contraindicated during pregnancy and while breastfeeding. Women of childbearing age on the MP should take adequate contraceptive precautions.
• children – Children with a range of diseases and conditions can be treated with the MP. There are more than a dozen in the study cohort who are doing well. The FDA recently approved the use of olmesartan for hypertensive children ages 6-16.

Before commencing therapy, physicians and patients should familiarize themselves with the pre-MP checklist, which reviews the medications, eye protection, and possible lifestyle modifications necessary for treatment success and safety.

1. Some patients with severe forms of disease may develop strong 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. that is difficult to control - While most patients can adjust their antibiotics to tolerate immunopathology successfully on a day-to-day basis, patients with severe forms of disease may develop strong immunopathology that is difficult to control. Physicians should help their patients internalize the strategies for managing immunopathology. Knowing how to manage the MP independently on a day-to-day basis will serve patients well should an urgent situation occur. Patients should be urged to seek support from the Foundation's websites.
2. For sicker patients, immunopathology can be physically and mentally challenging – Support from a knowledgeable doctor and family/friends becomes of paramount importance. Unless the patient has a good insight into IP and other inconveniences of the treatment, the patient should not start treatment.
3. Patients physically dependent on multiple palliative drugs will generally have considerable difficulty weaning from those drugs, a necessary precursor to allowing the innate immune system to function properly, and induce recovery. Our members have had success weaning from 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., but psychotropic drugs and some painkillers have proven very difficult to wean

The following is a summary of common medications that has the potential to interfere with the MP. A more complete list of medications is available in the Non-MP treatments article.

• antibacterials – Sulfusalazene, Plaquenil and Methotrexate are antimetabolite antibiotics with actions similar to BactrimSulfa antibiotic used by patients on the Marshall Protocol. Combination of sulfamethoxazole and trimethoprim. and may produce unwanted or uncontrolled immunopathology. They must be discontinued before starting the MP.
• antibiotics – Olmesartan greatly potentiates the action of many antibiotics. Consequently, a severe or life-threatening 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. may result if non-MP antibiotics are prescribed. Olmesartan protects vital organs from the cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. storm, and it must not be withdrawn. If a non-MP antibiotic is temporarily needed for an acute infection, Please follow the instructions in the Notice for emergency medical personnel.
• anticoagulants – Olmesartan may profoundly affect the anticoagulant dosing requirement. It is absolutely essential to closely monitor any patient on anticoagulant therapy.
• antifungal agents – Medicines such as Diflucan and Lamisil are known to interfere with vitamin D metabolism and are generally contraindicated.
• antiviral agents – Antivirals may have profound effects on the immune system as well as a number of serious adverse effects. Routine use is generally contraindicated for MP patients.
• bisphosphonates – May cause calcium deposition into the soft tissues, reduced organ function and possible osteonecrosis of the jaw.
• calcium supplements – Should be avoided in the presence of hypercalciuria or hypercalcemia. Those without these conditions should generally consume 1000-1500 mg calcium daily, preferably from foods, but if this is not possible, calcium supplements without vitamin D are acceptable.
• corticosteroids – Therapy will not be effective while corticosteroids are suppressing the immune system. Begin or continue the gradual weaning process with the assistance of palliation from olmesartan. ACTH and cortisol production may be monitored to assess adrenal function.
• diuretics – Some diuretics including the thiazides are contraindicated for MP patients. If a diuretic is necessary, Lasix is preferred.
• folic acid (Rx or OTC) – Folic acid makes it easier for occult bacteria to replicate and create new DNA. Consuming a balanced diet low in supplemental folic acid should provide adequate folic acid.
• hormonal replacement therapy (e.g. progesterone, estrogen and testosterone) – Because hormonal supplementation can interfere with the activity of many of the nuclear receptorsIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affect transcription., hormonal supplementation is contraindicated. However, under certain circumstances, patients may continue hormone replacement therapy, until they are able to wean from it. See article on hormonal replacement therapy.
• interferon – Interferon therapy is immunosuppressive, reducing in number both cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. and immune cells.
• IVIG – IVIG is derived from the blood of a pool of more than a hundred apparently healthy individuals. There is a significant likelihood that species from the microbiotaThe bacterial community which causes chronic diseases - one which almost certainly includes multiple species and bacterial forms. of these people might spread to the microbiota of a Th1 patient.
• statins – Statins have a range of documented negative side effects and have been shown to exacerbate certain kinds of chronic disease. Some compete for the VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response. binding pocket. They are contraindicated.
• thyroid supplements – Need for these supplements may change within a day or two of being on olmesartan alone. Monitor thyroid function closely and adjust the level of thyroid supplementation downward as needed.
• TNF-alpha blockers – Tumor necrosis factor-alpha or TNF-alpha is a cytokine critical for effective immune surveillance. Anti-TNF drugs, also known as TNF-alpha blockers, are drugs which interfere with the body's production of TNF-alpha. While olmesartan also reduces levels of TNF-alpha, it does so by blocking the initial generation of the substance rather than disabling free-floating TNF-alpha after the cytokine has been produced.

Patients on the MP must avoid all food and drink that contains supplemental vitamin D or high levels of naturally-occurring vitamin D. MP patients must avoid foods and drinks high in chlorogenic acidAn antioxidant and phenolic compound which in ways that are not yet fully clear can modulate and/or suppress the immune response – particularly coffee, concentrated juices, and supplements and multivitamins containing added folic acid. A low-carbohydrate, insulin-resistant diet is recommended for MP patients but is not required. Specific nutritional imbalances should in some cases be corrected, but this requires proper understanding of both the MP and the nutritional needs of the body by a health professional.

Patients on the MP often benefit from wearing special glasses that block a broader spectrum of light and in many cases must cover their skin when in the sun. Further guidelines are available at the Knowledge Base articles on Eye protection and Skin protection.

Example of immunopathology – Patients on the MP tend to experience temporary increase in several antibody titers, and a decline in latter stages of treatment.⁸

Most patients on the MP experience temporary but well-defined increases in various markers of disease state and 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., consistent with an immunopathological response. It is helpful, but not necessary, to measure % lymphocytes, C-Reactive Protein, alkaline phosphatase, triglycerides, relevant autoantibodies, and serum ACE, to track systemic inflammation. Doctors may want to assess kidney function by testing creatinine or BUN and measure other indicators specific to each patient for a baseline and retest as appropriate. Some lab work – commonly HGB, HCT, eGFR, creatinine and BUN – may become temporarily abnormal, due to immunopathology reactions, until the inflammation resolves.

For example, a higher than usual BUN and creatinine is not an indication that olmesartan should be discontinued but a sign that immunopathology may be occurring in the kidneys or other nearby organs. In most cases where physicians have allowed such levels to remain temporarily out of range, BUN and creatinine have returned to range as bacterial die-off in the kidneys subsides. For as long as they remained on Olmesartan, there has been no dialysis needed in the MP cohort.

If these markers indicate dysfunction sustained for more than several months, it may be advisable to use one or more methods to lower immunopathology levels.

There are two main vitamin D metabolites:

• 1,25-dihydroxyvitamin DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. (1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol.) – The presence of high levels of the active hormone of vitamin D in patients suggests an ongoing chronic inflammatory disease process.⁹ However, the absence of elevated levels does not mean a patient cannot benefit from treatment particularly since non-MP therapies such as TNF-alpha blockers and other unknown drugs and interventions can affect 1,25-D levels. Whenever possible, use the lab Quest Diagnostics. Although they have recently ceased to routinely freeze the blood samples, as we find necessary, if the patient insists that they do so, they will freeze the sample. Note that measuring a patient's 1,25-D level is only useful prior to beginning olmesartan.
• 25-hydroxyvitamin 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. (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. ) – Unlike 1,25-D, serum samples of 25-D need not be frozen. 25-D, an immunosuppressive secosteroid,¹⁰ serves as a general indication of immune function with levels higher than 25 ng/ml suggesting immunosuppression via supplementation or sunlight exposure. Patients on the MP restrict consumption of vitamin D in order to reduce their 25-D to the therapeutic range: at or below 12 ng/ml. Levels of 25-D should be tested every 6-12 months. Be aware that as 25-D levels fall, immunopathology may increase, sometimes dramatically.

If the vitamin D metabolite tests do not indicate Th1 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. but clinical observation suggests otherwise, a short course of the MP (1 to 2 months) should be used as a therapeutic probe. A longer time period may be needed if 25-D levels remain high, as a therapeutic probe is often not effective unless 25-D levels fall below 25 ng/ml.

Consult the Vitamin D Metabolite Calculator for suggestions on interpreting this lab data.

Benicar is a weak hypotensive. Benicar's ability to reduce blood pressure is unrelated to the rise in symptoms that is associated with its VDR activating properties. Source: FDA label for Benicar

The primary indication for olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. is as a mild hypotensive drug. As one can see from the FDA label for Benicar (right), the dose response curve for Benicar is asymptotic, with higher dosages of the drug having incrementally smaller decreases in blood pressure. For example, the difference between 40mg and 80mg of olmesartan results in a decrease of no more than 1mm Hg.

It is important to understand that olmesartan’s effect on blood pressure is limited if we are to appreciate that a decline in systolic pressure greater than 15mm Hg of mercury cannot solely be due to olmesartan’s hypotensive action, but is also likely to include the result of disease processes.

The widespread destruction of bacteria and human cells infected by bacteria can lower blood pressure. Though this isn’t true of all bacterial forms, when some forms of bacteria are destroyed, they release endotoxins,¹¹ the bioavailability of which can lead to a steep decline in blood pressure.¹²

If a patient suffers low blood pressure before the MP, low blood pressure will return as a symptom of immunopathology while on the MP. In these cases, we have observed that patients who remain on the MP dosage of olmesartan see their blood pressure eventually return to a normal range as immunopathology subsides.

Medications that raise blood pressure, such as fludrocortisone and dopamine, are contraindicated, both because they would do nothing to slow bacterial die-off and because they may have deleterious effects on immune function.

The U.S. Food and Drug Administration has set no safe limit for olmesartan medoxomil (Benicar), as no dose-related adverse events have been identified to this point. FDA post-marketing-experience has shown that Olmesartan has one of the safest profiles of any drug on the market. Note that this does not apply to the combination drugs, such as 'Benicar HCT', which contains a thiazide and is harmful, and should NEVER be used with an MP dosing schedule.

The label for olmesartan medoxomil states that the drug is well-tolerated. Adverse events were similar to those experienced by the placebo group. Adverse events were generally “mild, transient and not related to dose.” The frequency of adverse events also had no relationship to the dose of olmesartan.

A 2001 study published in the Journal of of Pharmacology found olmesartan to be safe and well tolerated at dosages of up to 160 mg/day.¹³

In placebo-controlled trials, the only side effect that occurred in more than 1 percent of olmesartan-treated patients vs. placebo-treated patients was dizziness (3 percent vs. 1 percent).¹⁴

The relevant Knowledge Base article reviews the safety profile of olmesartan/Benicar in greater detail.

1. Test vitamin D metabolites – Following the vitamin D metabolites testing instructions. Remind the drawing lab that the 1,25-D sample must be clotted no more than 30 minutes before centrifuge and the resulting serum must be frozen for shipment. Consult the Vitamin D Metabolite Calculator for suggestions on interpreting this lab data.
2. Restrict dietary vitamin D intake – Patient must restrict all supplements and foods high in Vitamin D. It is recommended that, over the course of treatment, the patient reduce 25-D to the therapeutic target of approximately less than 12 ng/ml. Retest 25-D periodically to make sure 25-D is dropping toward the lower end of the therapeutic range. Many members of the observational cohort have kept their 25-D below 5 ng/ml for many years, without any adverse effect.
3. Withdraw or begin to wean contraindicated therapies – For patients weaning from Prednisone or Cortef, olmesartan can greatly relieve withdrawal symptoms and help ensure weaning success. It is recommended that olmesartan be started a week or two before beginning to wean. See the weaning guidelines for detailed instructions.
4. If necessary, avoid light exposure – If necessary to avoid the symptoms of photosensitivityAbnormal sensitivity to sunlight and bright lights. Also referred to as "sun flare" or "light flare.", patients should avoid outdoor light and bright indoor lights by staying indoors as much as possible, using heavy curtains or window shades, and covering up well whenever venturing outside during daylight hours. Patients may also need to protect their eyes indoors.
5. Begin olmesartan – Commence therapy by prescribing 40mg pure olmesartan medoxomil every six hours (e.g.: 6am, noon, 6pm, midnight) to interrupt the inflammatory cycle and reduce the severity of potential immunopathology. Olmesartan medoxomil is the only angiotensin receptor blocker (ARB) that activates the patient’s immune system. “No substitutions” should be written on the prescription. Avoid any combination formulation such as Benicar hydrochlorothiazide (Benicar HCT). Because patients often begin to feel worse when decreasing light and/or vitamin D, olmesartan should be prescribed concurrently with the previous steps, so that it can palliate any resulting immunopathology while the 25-D levels are decreasing. Patients should keep several weeks’ supply of olmesartan in reserve to use in case it is needed to treat intolerable immunopathologyAn unbearable or unsafe severity of bacterial die-off reaction..
6. Wait for patient to stabilize on olmesartan – It usually takes two to three weeks to stabilize symptoms on the olmesartan blockade alone. Some patients may need more time. Depending on the patient's bacterial load and a host of other factors, some patients initially feel better on olmesartan, some worse, and some don't experience any change. All three reactions are normal.
7. Begin minocycline – Prescribe the first MP antibiotic, brand name or generic minocycline, at 25 mg every 48 hours. Do not use less or a substitute such as doxycycline. As with the other MP antibiotics, patients may need to divide the contents by opening a capsule or using a pill cutter. While using minocycline and olmesartan alone, patients can begin to learn the nature of their immunopathology, and how, in conjunction with their physician, they can adjust their antibiotics to elicit tolerable immunopathologyA state in which a patient has maintained an acceptable intensity of bacterial die-off reaction. The primary goal of the Marshall Protocol.. The following is only a partial list of typical immunopathology symptoms: fatigue, muscle weakness, rash, headache, photosensitivity, pain anywhere, numbness, nausea, diarrhea, constipation, ringing in the ears, toothache, sinus congestion, nasal stuffiness, fever/chills, flu-like body ache, cough, irritability, depression, sleep disturbances and “brain fog.”
8. Increase dosage of minocycline – When patients want to increase the strength of their immunopathological reaction, they typically increase their dosage of minocycline, in increments of 25 mg (q48h), until they reach 100mg. It is strongly recommended that patients should stay at each dosage for at least a week and should not increase the antibiotic until their immunopathology at a particular dosage has declined to a low level. Sudden increases in immunopathological reactions may occur at any time as the immune response strengthens. Patients should familiarize themselves with the managing immunopathology article to manage symptoms. The response may even necessitate reducing or temporarily stopping some or all of the antibiotics for an extended period of time. This is not uncommon and should not be regarded as a setback, but rather as a sign of progress.
9. Add a second and then third antibiotic – There is no urgency for patients to take more or higher doses of antibiotics if symptoms become too uncomfortable. Olmesartan plays the most critical role in the recovery process. See more below.

Patients who are still experiencing significant immunopathology from 100mg of minocycline alone are not yet ready to add a second antibiotic because the two antibiotic combination, especially when ZithromaxBacteriostatic antibiotic used by Marshall Protocol patients. Has relatively long half-life. is used, is much stronger than minocycline alone.

When ready to experience additional immunopathology, patients begin to take a second antibiotic in conjunction with their minocycline (which is still taken q48h). Typically, that second antibiotic is Zithromax (azithromycin)Bacteriostatic antibiotic used by Marshall Protocol patients. Has relatively long half-life.. But often, patients and their physicians choose to use clindamycinBacteriostatic antibiotic used by patients on the Marshall Protocol. .

• When to use Zithromax as a second antibiotic – Patients with significant psychological symptoms such as depression, anxiety, intrusive thoughts, or obsessive-compulsive behavior should use Zithromax, because clindamycin can sometimes exacerbate these symptoms and is usually tolerated better at later stages of the treatment.
• When to use clindamycin as a second antibiotic – Clindamycin doesn't linger in the tissues like Zithromax, so it is easier to control the immune system reactions. Clindamycin is helpful for patients who are very sick and may not be able to tolerate the relatively prolonged effect of Zithromax. Patients who have had extreme difficulty tolerating minocycline alone may need to progress to use it in combination with a different antibiotic such as Bactrim DSSulfa antibiotic used by patients on the Marshall Protocol. Combination of sulfamethoxazole and trimethoprim. Works by blocking bacterial folic acid synthesis. or demeclocyclineBacteriostatic antibiotic used by patients on the Marshall Protocol. before taking Zithromax.

A special consideration for patients with high levels of 25-D – For those patients who have been supplementing for years, vitamin D can remain in the tissues for months or years even when they are abstaining from further vitamin D consumption and outdoor light exposure. In the case of patients who are severely ill, it may be prudent to wait until their 25-D levels have dropped below 12 ng/ml before administering Zithromax. However, in less serious cases, physicians may use their discretion to increase antibiotics even in the presence of a higher level of 25-D so long as patients are aware they may have to take measures to control higher levels of immunopathology when their 25-D levels do drop.

After completing a two-antibiotic combination, patients may add a third antibiotic and rotate combinations as desired. Appropriate dosing combinations include:

• CMZ – clindamycin + minocycline + Zithromax (considered by some patients to be the most potent combination)
• BCD – Bactrim DS + clindamycin + demeclocycline
• BCM – Bactrim DS + clindamycin + minocycline
• BDM – Bactrim DS + demeclocycline + minocycline
• BDZ – Bactrim DS + demeclocycline + Zithromax
• BMZ – Bactrim DS + minocycline + Zithromax
• CDM – clindamycin + demeclocycline + minocycline
• CDZ – clindamycin + demeclocycline + Zithromax
• DMZ – demeclocycline + minocycline + Zithromax

For a more detailed discussion on the MP antibiotics including combination strategies, examples of progression through the MP, and general tips, please read the Knowledge Base article, Dosage and administration of Marshall Protocol antibiotics.

ARF has prepared a Notice for emergency medical personnel treating a Marshall Protocol patient. Important points from that document include the following:

• Do not withdraw olmesartan – In a critical care situation, it is essential to continue oral olmesartan, even in the presence of hypotension, as abrupt withdrawal can be life-threatening. Along with routine lifesaving procedures, it is essential to continue oral olmesartan 40mg dosing every four hours, with 20mg SL p.r.n., until symptoms subside - even if an NG tube is necessary. If B/P is extremely low (mean arterial pressure <55), continue olmesartan as above and increase fluid volume with 0.9 NS or packed red cells.
• antibiotics – Unless patients have reached a late stage of the treatment, using high dosages of the MP antibiotics has the potential to greatly increase immunopathology as the antibiotics leave the patients' system. Therefore, we recommend patients not be treated with MP antibiotics. Flouroquinolone antibiotics are generally well tolerated although instances of tendon damage have been reported; the patient should be advised of the FDA black-box warnings. Cephalosporins, Claforin, and the macrolide Biaxin are usually tolerated.
• corticosteroids – Do not give corticosteroids in any form or by any route (injected, inhaled, oral or IV) as they will lead to metabolic instability.
• epinephrine or norepinephrine – Adverse reactions may occur if epinephrine or norepinephrine is used to raise B/P or treat anaphylaxis. Use epinephrine and norepinephrine only for cardiac arrest. Local anesthetics containing epinephrine may cause adverse events (tachycardia, psychosis), and the epinephrine may hinder anesthesia.

For the details of these recommendations, please consult the Notice for emergency medical personnel.

In an emergency, physicians may call Trevor Marshall at 805-492-3693.

The length of time it takes for antibiotics to no longer have an effect is variable. Determining factors include how long the antibiotics stay in one's system. Due to its unusually long half-life, Zithromax can remain in the tissues for a month or more. In addition, the self-sufficiency of the immune system is an important factor. Some patients may find their immune response is relatively self-sustaining due to the body's own increased antimicrobial peptide production, and thus it will take longer for the immunopathology to wane. If the patient is stopping antibiotics for the purpose of minimizing immunopathology, in some cases it may be preferable to stay on either 100 mg minocycline every other day or take it daily for its palliative effects (many of which are the result of its effect on the PXR nuclear Receptor, see Bioessay, Figure 1).

To discontinue both antibiotics and olmesartan, patients should first discontinue their antibiotics following the above instructions. If necessary, olmesartan should be weaned gradually, only after the antibiotics have been discontinued and over the course of several weeks. Note that the immune response may remain activated for a period of time even after discontinuing olmesartan.

An alternative to discontinuing olmesartan alone is to wean the patient across to another ARB, valsartan (Diovan), 80mg every 6 hrs (80 mg is one quarter of a 320mg Diovan tablet). The patient reduces the olmesartan dosage (e.g., from 40 mg to 30mg to 20mg to 10mg to 0) while simultaneously ramping the valsartan (e.g. 0 to 20mg to 40mg to 60mg to 80mg). The length of time the organ protection from the valsartan will be needed depends on how long it takes the immune system to shut down again. This ARB does not activate the immune system, but does protect organs and provide a little palliation. The patient can be weaned across in 2 to 3 days.

Patients who stop olmesartan are terminating their recovery.