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Benicar-OlmecipConcern has been expressed about the importance of taking enough Benicar® to prevent “organ damage” during Inflammation Therapy (IT) This article explains how to best avoid possible tissue damage related to the recovery process.

The disease process of many types of chronic illnesses causes tissue damage during years of ineffective attempts by the immune system to eliminate intracellular bacteria. This abnormal inflammation causes varying degrees of “bystander” (incidental) tissue destruction or fibrosis. See Immune System.

The concern about organ damage arises because Inflammation Therapy enables the immune system to mount an effective assault on the persistent pathogens that are believed to be the root cause of chronic inflammatory diseases. This results in a temporary increase in inflammation due to the presence of endotoxins released by the dying bacteria and cellular breakdown products (Jarisch-Herxheimer reaction) that is reflected in increased symptoms or a negative change in lab results. See Patient Safety During Immunostimulative Therapies.

There is speculation that this unavoidable increase in inflammation during the prolonged recovery process may cause tissue destruction or fibrosis but there is no evidence that this does or will occur.

The degree of increased inflammation that may cause tissue damage isn’t known so it’s important that IT be expertly managed to avoid an excessive increase in inflammation.

Controlling Herxheimer reactions (immunopathology) to maintain tolerable symptoms and/or acceptable lab work is the best way to ensure that the therapeutic (necessary and unavoidable) inflammation of IT is minimized and organs are protected.

Benicar® (olmesartan) is both pro-inflammatory by one purported biochemical mechanism and anti-inflammatory by at least several different mechanisms so proper dosing is essential to control Herxheimer reactions.

Benicar® appears to activate the vitamin D Receptor (VDR) which enables transcription of the anti-microbial peptides needed to kill the bacterial pathogens. Because this results in increased Herxheimer reactions and inflammation, Benicar® can be termed pro-inflammatory (immune-activating). Benicar®’s activation of the VDR is dose-proportionate and can occur at relatively low doses. Limiting VDR activation results in less inflammation and, thus, provides a degree of protection from tissue damage.

Benicar® also has an anti-inflammatory action - slowing down cytokine production via the inflammatory pathway Nuclear Factor-Kappa Beta, thereby reducing inflammation. This immunosuppressive action of Benicar® may provide a degree of protection from tissue damage.

The dose of Benicar® needed to control Herxheimer reactions and inflammation varies.

The Benicar® dose needs to be individualized based upon individual variations in biochemistry.

Increasing the dose of Benicar® sometimes (but not always) provides enough of an anti-inflammatory effect to reduce Herxheimer reactions (as evidenced by symptoms).

There is evidence that Benicar® is organ protective most of the time in most people. However, there is no evidence to support the claim that olmesartan must always be taken at high doses to avoid supposed organ damage. Nor is there evidence to support the claim that it's dangerous to take a lower dose of Benicar® or that organ failure will occur if Benicar® is discontinued.

In some patients the VDR activation of Benicar® trumps (outweighs) its other effects of immuno-suppression and palliation. Patients might feel better on a higher dose, but have too many waste products build up from Herxheimer reactions.

This study suggests that more olmesartan (Benicar®) may not always be better for organ protection. "The reason that middle or high doses of olmesartan were not as effective for cardio-protection is unknown."
Olmesartan, a novel AT1 antagonist, suppresses cytotoxic myocardial injury in autoimmune heart failure

Abnormal kidney function

Patients with impaired kidney function may do better with a smaller dose of Benicar®. Studies show that in patients with renal insufficiency, serum concentrations of olmesartan were elevated compared with subjects with normal renal function.

The dogma that mega-dosing of olmesartan is needed for organ protection has not been shown to be the case in a number of patients with kidney problems; a number of whom we have seen improve with lower olmesartan dosing. The statistics often quoted about most patients experiencing elevated BUN or creatinine on higher doses Benicar® or all patients tolerating serious alterations in lab tests by increasing Benicar® has no basis in fact. Patients whose lab tests did not improve on high-dose Benicar®, or those whose symptoms increased to intolerable on high-dose Benicar® stopped reporting at other websites (and were lost to follow-up) so claims cannot be made about their welfare.

Extra Benicar® is acceptable for short-term palliation when symptom levels are intolerable, but when kidneys begin to be too profoundly affected this is not a good option. It’s best to lower Benicar® and adjust antibiotic doses (while practicing strict light avoidance) to decrease kidney waste products by modulating the immune response to reduce herxing.

Long-term very high dose Benicar®

Immune system function is extremely complex. Nuclear Factor kappa-B pathways control aspects of inflammation and immune system function. Steroids like prednisone provide a strong NF kappa-B blockade and interfere with immune system function by other pathways as well. Benicar® (at high doses) also blocks NF kappa-B pathways and taking too much Benicar® (240mg a day or more) could be detrimental in the long run because some NF kappa-B activation may be necessary to have a competent immune system. For example, high-dose Benicar® may block the production of anti-microbial peptides (AMPs) such as Defensins. Benicar® is an analog of 1,25-D dehydroxyvitamin-D (similar in chemical structure) and, like elevations in 1,25-D, high-dose Benicar® may limit macrophage responses.

Summary

If intolerable Herxheimer reactions are not decreased and/or lab work is not improved by increasing Benicar® in the short-term, it can be assumed that Benicar®’s pro-inflammatory effect predominates over its anti-inflammatory effect. In that case, reducing the dose of Benicar® may reduce symptoms and improve lab work suggesting that this strategy provides the desired organ protection.

To complicate matters, Benicar®’s actions can be highly individual; at different points in treatment the action of Benicar® can be more/less anti-inflammatory or more/less pro-inflammatory. Therefore, it’s essential that Inflammation Therapy be individualized based upon each patient’s unique mixture of both inflammatory and anti-inflammatory responses to Inflammation Therapy. Some patients may need to take a lower dose of Benicar® for the duration of Inflammation Therapy. More Benicar® is not always better, and a total blockade of the NF-kappa-B pathway may not be ideal in the longer term. See this study.

It’s paradoxical that Benicar® is both immune activating and immunosuppressive at the same time by differing mechanisms. The same paradox is found in at least one and perhaps all of the bacteriostatic antibiotics that are used during Inflammation Therapy.

Therefore, Benicar® and IT antibiotic doses need to be adjusted up or down (or antibiotic combinations changed) to successfully control Herxheimer reactions and thus, minimize the risk of organ damage.