Vitamin D Metabolism in Health and Disease

Abstract

Vitamin D, a secosteroid hormone synthesized in the skin via UVB exposure or obtained from dietary sources, is critical in numerous physiological processes. Its metabolism involves hepatic hydroxylation to 25-hydroxyvitamin D [25(OH)D], the main circulating form, followed by renal conversion to the biologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], which binds to the vitamin D receptor (VDR) to regulate gene expression. CYP2R1, GC, and VDR genetic polymorphisms influence vitamin D status and functional outcomes. Beyond its classical role in calcium-phosphate homeostasis and skeletal health, vitamin D modulates immune function, cardiovascular health, neuroprotection, and cellular proliferation. Deficiency, defined as serum 25(OH)D <20 ng/mL, is a global health concern linked to osteoporosis, autoimmune diseases, metabolic disorders, and increased infection susceptibility. Risk factors include limited sun exposure, obesity, malabsorption syndromes, and genetic predisposition. This review synthesizes current evidence on vitamin D metabolism, genetic determinants, pleiotropic physiological functions, and the clinical implications of deficiency, emphasizing the need for targeted screening and personalized supplementation strategies to optimize health outcomes.