EC Clinical and Medical Case Reports

Vitamin D is increasingly recognized as a pleiotropic prohormone with extensive non-skeletal actions that shape immune, metabolic, neuroprotective, and barrier-tissue homeostasis. Immune cells, including macrophages, dendritic cells, monocytes, and lymphocytes, express both the vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1), enabling intracellular conversion of 25-hydroxyvitamin D into calcitriol and conferring direct control over the innate and adaptive immunity. Vitamin D deficiency is widespread, affecting 15.7% of the global population and exceeding 50% when insufficiency is included, with disproportionately high prevalence in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, autoimmune thyroid disease, and type 1 diabetes, as well as metabolic disorders including type 2 diabetes and metabolic syndrome. Current evidence supports the concept of vitamin D as a threshold nutrient, with serum 25-hydroxyvitamin D concentrations above 40 - 50 ng/mL required to achieve full beneficial effects and prevent chronic diseases. Interindividual variability in responsiveness, captured by the vitamin D response index, reveals distinct high-, mid-, and low- responder phenotypes, with roughly one-quarter of individuals requiring substantially higher doses to elicit comparable biological responses of vitamin D. This literature review focuses on the non-skeletal functions of vitamin D and some autoimmune and metabolic diseases that are greatly associated with vitamin D deficiency. It aims to clarify the pathophysiological mechanisms that may link vitamin D deficiency to those diseases and to evaluate the therapeutic potential of vitamin D supplementation.

Keywords: Vitamin D; Vitamin D Receptor (VDR); Autoimmune Diseases; Vitamin D Deficiency

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