HIGH-DOSE OLMESARTAN MEDOXOMIL RESOLVES SYMPTOMS OF AUTOIMMUNE AND INFLAMMATORY DISEASES

Meg Mangin, R.N. Chronic Illness Recovery Chronic inflammation is a sign of immune system dysfunction. A probable cause is found in the ability of cell wall deficient bacteria to invade nucleated cells. These pathogens may persist within cellular cytoplasm by using strategies to evade destruction. One of those strategies appears to be down-regulation of the vitamin D receptor (VDR) which is activated by 1,25(OH)2D (calcitriol). This is suggested by the presence of elevated calcitriol in many diseases linked to an inflammatory process.

High-dose Olmesartan The angiotensin receptor blocker olmesartan medoxomil (brand name Benicar®), when dosed at 20-40mg q6h, appears to be an agonistic VDR ligand which up-regulates the bacterially-inhibited VDR. This was postulated by molecular modeling. It is evidenced by: ● a reduction in calcitriol following olmesartan administration. ● Jarisch-Herxheimer reactions which indicate increased AMP transcription and elimination of intracellular bacteria. Olmesartan is the only ARB that, like calcitriol, reduces the inflammatory protein angiotensin II.

Incompetent VDR

Wirostko TEM of L-form

Normally, calcitriol production is tightly self-regulated by the kidneys, with the end product down-regulating its own further production. In contrast, production of calcitriol within extra-renal tissues is controlled by cytokines. When extra-renal cells are parasitized by bacteria, calcitriol production is stimulated and renal control is lost. Elevated calcitriol suggests the immune system recognizes the presence of parasitic pathogens and is making a futile attempt to combat them by increasing production of calcitriol in order to up-regulate the VDR and transcribe antimicrobial peptides (AMPs). The result is sustained inflammation and tissue damage.

"Have any symptoms resolved? YES!!!!! Almost all of them!!!" LeAnne (Crohn's, Lyme)

Elevated calcitriol is reduced with highdose olmesartan.

Conclusion Persistent infection may induce non-resolving inflammation by down-regulating the vitamin D receptor (VDR). The use of high-dose olmesartan to enhance VDR expression, along with very low-dose oral antibiotics, appears to eliminate the offending bacteria; resulting in reduction of inflammatory markers and resolution of inflammatory symptoms. Sarcoidosis and several rheumatic diseases have been treated successfully with this strategy.

Diagnosis

Measure both 25(OH)D and 1,25(OH)2D. Proposed hypothesis for excess 1,25(OH)2D production in bacterially-stimulated extra-renal tissues.

Research Needed

85% of autoimmune subjects had elevated 1,25(OH)2D without hypercalcemia.

Proposed hypothesis for dysregulated vitamin D metabolism caused by intracellular pathogens.

Activation Immunotherapy Olmesartan Medoxomil

Acts on RAS

Safety Profile

Low HTN Dose

Case Reports and Clinical Study

Proposed hypothesis for restoring renal control of 1,25(OH)2D with olmesartan.

Elevated Calcitriol

Dysregulated Vitamin D Metabolism

Olmesartan Treatment Overview

● Olmesartan 20-40mg q6h ● Low-dose, oral antibiotics ● Minocycline 25-100mg qod ● Azithromycin 31-125mg q10days ● Clindamycin 37-150mg qod ● No immunosuppressants ● Maintain 25(OH)D below 30ng/mL

Therapeutic Response

Olmesartan is a VDR ligand. Computer modeling suggests olmesartan modulates immune system by agonizing the VDR.

Treatment Effect The up-regulated VDR can transcribe AMPs needed to kill pathogens.

References 1. Wirostko E, Johnson L, Wirostko W. JRA Inflammatory Eye Disease, Parasitization of Ocular Leukocytes by Mollicute-like Organisms, J Rheumatol. 1989 Nov;16(11):1446-53. 2. Blaney GP, Albert PJ, Proal AD. Vitamin D metabolites as clinical markers in autoimmune and chronic disease. Ann N Y Acad Sci. Sep 209;1173:384-90. 3. Onwuamaegbu ME, Belcher RA, Soare C. Cell wall-deficient bacteria as a cause of infections: a review of the clinical significance. J Int Med Res. Jan-Feb 2005;33(1):1-20. 4. Ferrario C. Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil. Vasc Health Risk Manag. 2009;5(1):301-14. 5. Ichikawa S, Takayama Y. Long-term effects of olmesartan, an Ang II receptor antagonist, on blood pressure and the renin-angiotensin-aldosterone system in hypertensive patients. Hypertens Res. Nov 2001(24(6)):641-6. 6. Arao T, Okada Y, Mori H, Nishida K, Tanaka Y. Antihypertensive and metabolic effects of highdose olmesartan and telmisartan in type 2 diabetes patients with hypertension. Endocr J. Jan 2013; 2013;60(5):563-70.

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