Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol

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.

The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications

“…However, it should be noted that this is far from being proven, and more research is needed to address this point. Another possibility is that bacterial metabolites contribute to the disease by interfering with the estrogen receptor and Vitamin D receptor pathways, as the latter is also involved in development of autoimmune disorders, which often occur as comorbidities of ME/CFS as mentioned previously, but this topic remains to be addressed [ 64 , 78 , 79 ]. Last, when searching for a possible mechanism for how dysbiosis influences ME/CFS pathogenesis, the gut-brain-axis, and the autonomic and enteric nervous systems should also be considered [ 60 , 80 ].…”

VDR Polymorphic Variants Are Related to Improvements in CRP and Disease Activity in Patients with Axial Spondyloarthritis That Undergo Anti-TNF Treatment

“…On the contrary, Th-2 cytokines, such as IL-4, IL-5, and anti-inflammatory cytokines IL-10 and transforming growth factor β (TGFβ), are promoted [ 34 , 36 ]. As a result, the shift of an inflammatory to a more tolerant immune status is promoted, which may explain the protective effects of vitamin D against autoimmune diseases [ 37 ]. However, despite the beneficial effects of 1,25(OH)2D supplementation in experimental autoimmune models, the application of vitamin D derivatives in clinical practice is currently limited to topical use for the treatment of psoriasis.…”

Single Treatment of Vitamin D3 Ameliorates LPS‐Induced Acute Lung Injury through Changing Lung Rodentibacter abundance

“…Therefore, it potentially due to the hypothesis of vitamin D resistance proposed. [31] However, the levels of ACE2, which as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, [32] was downregulated by long-term vitamin D3 supplementation. In line with previous study, [33] our data indicate that supplementation of vitamin D3 might benefit to treatment the coronavirus disease 2019 (COVID-19) by reduc-ing the ACE2 levels.…”