EC Clinical and Medical Case Reports

Review Article Volume 9 Issue 3 - 2026

Vitamin D Between Non-Skeletal Functions and Autoimmune Diseases: Pathophysiological Perspectives and Therapeutic Potential: A Literature Review of the Current Clinical Evidence

Samuel Saad1*, Herman Lebovitch2, Akram Mahreen2, Khalid M Alzwahereh2, Mina Zakher3 and Cyril Ibrahim4

1MBBCh MD, Collection of data and review of literature/Research FellowCardiovascular Diseases/Mayo Clinic, Rochester, Minnesota, USA
2MD, Collection of data and review of literature
3Research volunteer undergraduate, Collection of data and review of literature
4Research volunteer undergraduate, fixing grammar mistakes and downloading material from the internet

*Corresponding Author: Samuel Saad, MBBCh MD, Collection of data and review of literature/Research Fellow Cardiovascular Diseases/ Mayo Clinic, Rochester, Minnesota, USA.
Received: May 25, 2026; Published: July 09, 2026



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 non-skeletal effects; immunomodulatory effects; vitamin D supplementation; Vitamin D Receptor (VDR); Autoimmune Diseases; Vitamin D Deficiency

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Samuel Saad., et al. “Vitamin D Between Non-Skeletal Functions and Autoimmune Diseases: Pathophysiological Perspectives and Therapeutic Potential: A Literature Review of the Current Clinical Evidence”. EC Clinical and Medical Case Reports 9.3 (2026): 01-16.

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