Managing immunopathology (IP)
Patients' goal during the MP should be to maintain
tolerable immunopathology as they get well. In cases where IP is becoming intolerable, certain strategies are available including:
- Adjust olmesartan (Benicar) - Depending on which of olmesartan's two main properties a patient experiences most strongly during a particular period of treatment, increasing or decreasing the dose may help manage immunopathology. For some, taking olmesartan sublingually (under the tongue) can provide immediate relief.
- Minocycline as a palliative – Minocycline taken more frequently such as every 12-24 hours, it may help reduce symptoms of immunopathology.
- Take palliative medications – A range of symptom-specific palliative medications can be relied upon in the case of intolerable immunopathology - enquire in the forums at MarshallProtocol.com
- Light restriction. Sunlight to the skin and eyes can exacerbate symptoms and make symptoms intolerable. This is individual. However, if experiencing intolerable symptoms one will want to reassess their response to every type of light exposure. Indoor lighting above 30 lux or any type of fluorescent lighting has been enough provoke intolerable symptoms for some patients, even when wearing NoIR sunglasses.
Strategy #1: Adjust olmesartan
Taking more frequent or higher doses, or less frequent and lower doses, of
olmesartan (Benicar) is often effective at
Marshall Protocol patients – roughly 80% or so – feel either substantially
better or worse when taking olmesartan. Knowing which kind of patient a person is can help decide which course to take in case of intolerable immunopathology.
It is important to experiment during times of relative well-being to see which strategy is most successful.
Increasing olmesartan increases its anti-inflammatory effect
A
potent anti-inflammatory, olmesartan decreases levels of Nuclear Factor Kappa B, a protein that stimulates the release of inflammatory
cytokines - proteins that generate pain and fatigue.
Olmesartan has been
shown to be safe in higher than typical doses. As a temporary replacement for
standard dosing for olmesartan, which is 40mg every six hours, patients can:
- take 40mg of olmesartan every four hours or more frequently; some patients have reported a benefit from taking olmesartan as frequently as every three hours
- lower the dose to 20mg every two to six hours, but only if that reduces symptoms
When in a crisis, never discontinue Benicar, or increase the dosing interval beyond 6 hours.
Also, there is the option of taking Benicar sublingually, that is, under one's tongue. Some people in the midst of a crisis situation have found it helpful to combine 40mg oral doses at the regular time with an
additional 20mg of sublingual Benicar (at minimum three hour intervals) around the clock.
Swallowed olmesartan, which in non-emergency situations is preferred, usually takes between 90 and 300 minutes to be absorbed by the GI tract, depending on whether the stomach is full. Chewing and then putting Benicar under one's tongue can drastically cut the amount of time it takes for the medication to be absorbed.
The sublingual route of medication administration uses the thin epithelium and rich network of capillaries on the underside of the tongue to gain rapid absorption and drug action. Drugs absorbed from the sublingual route have a rapid effect since they enter the bloodstream directly without being metabolized by the liver or being affected by gastric and intestinal enzymes.
Decreasing olmesartan lessens its immune-activating effect
A
Vitamin D Receptor agonist, olmesartan turns on the immune response, which can lead to immunopathology. Ideally, a Marshall Protocol patient would take 40 mg of olmesartan 4-6 times a day. The dosing interval is most important, as
VDR receptors are quickly liganded and/or broken down by bacterial kinases, with a mean useful lifespan of 3-6 hours. Provided the dosing is kept frequent, every 4-6 hours, immunopathology can sometimes be reduced if the Benicar (
olmesartan medoxomil) dosing is lowered to 20 mg every 4-6 hours. More usually, the loss of palliation at the lower dose makes this approach untenable.
A patient or physician should never stop olmesartan in a
crisis situation without a slow weaning schedule. The innate immune system remains active after the olmesartan is withdrawn, but the organ-protection offered by the olmesartan is lost, leading to potential organ failure. If
discontinuation of the Protocol is necessary, a physician should consult Prof. Marshall to discuss therapeutic options.
Olmesartan has multiple effects: anti-inflammatory, immune stimulating and anti-hypertensive. Activation of the innate immune system via olmesartan activation of the VDR can on its own cause immunopathology (IP) or herx. Early on, this impact may dominate, and the anti-inflammatory effects may not be sufficient to lessen the intensity of the IP. In these circumstances or in anticipation of the possibility of that occurring, ramping up olmesartan over a few days is a wise option. If though the lower dose of olmesartan cause an increase in symptoms, upward adjustment of olmesartan is initiated.
In conclusion, there can be circumstances where some variation in the established protocol may be necessary but this is uncommon and should not be seen as a change of treatment direction for the vast majority of patients. This lower dose is only temporary and almost everyone will ultimately tolerate and benefit from higher dose olmesartan.
Greg Blaney, M.D.