Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol
Open Access
- 7 April 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 12, 655739
- https://doi.org/10.3389/fimmu.2021.655739
Abstract
Vitamin D3 (cholecalciferol) is a secosteroid and prohormone which is metabolized in various tissues to the biologically most active vitamin D hormone 1,25(OH)2D3 (calcitriol). 1,25(OH)2D3 has multiple pleiotropic effects, particularly within the immune system, and is increasingly utilized not only within prophylaxis, but also within therapy of various diseases. In this context, the latest research has revealed clinical benefits of high dose vitamin D3 therapy in autoimmune diseases. The necessity of high doses of vitamin D3 for treatment success can be explained by the concept of an acquired form of vitamin D resistance. Its etiology is based on the one hand on polymorphisms within genes affecting the vitamin D system, causing susceptibility towards developing low vitamin D responsiveness and autoimmune diseases; on the other hand it is based on a blockade of vitamin D receptor signaling, e.g. through pathogen infections. In this paper, we review observational and mechanistic evidence for the acquired vitamin D resistance hypothesis. We particularly focus on its clinical confirmation from our experience of treating multiple sclerosis patients with the so-called Coimbra protocol, in which daily doses up to 1000 I.U. vitamin D3 per kg body weight can be administered safely. Parathyroid hormone levels in serum thereby provide the key information for finding the right dose. We argue that acquired vitamin D resistance provides a plausible pathomechanism for the development of autoimmune diseases, which could be treated using high-dose vitamin D3 therapy.This publication has 89 references indexed in Scilit:
- Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D and other factorsCritical Reviews in Clinical Laboratory Sciences, 2010
- Glucocorticoid regulation of the vitamin D receptorThe Journal of Steroid Biochemistry and Molecular Biology, 2010
- Confirmation of association between multiple sclerosis and CYP27B1European Journal of Human Genetics, 2010
- Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-βPLoS Pathogens, 2009
- Vitamin D Status: Measurement, Interpretation, and Clinical ApplicationAnnals of Epidemiology, 2009
- Expression of the Multiple Sclerosis-Associated MHC Class II Allele HLA-DRB1*1501 Is Regulated by Vitamin DPLoS Genetics, 2009
- Inactivation of the Human Vitamin D Receptor by Caspase-3Endocrinology, 2009
- Interleukin-17 Production in Central Nervous System-Infiltrating T Cells and Glial Cells Is Associated with Active Disease in Multiple SclerosisThe American Journal of Pathology, 2008
- T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγImmunity, 2008
- Guillain-Barré Syndrome and Preceding Infection with Campylobacter, Influenza and Epstein-Barr Virus in the General Practice Research DatabasePLOS ONE, 2007