Vitamin D: Physiology, Pharmacology and Clinical Evidence for Supplementation—A Narrative Review

Vitamin D is a nutrient and prohormone obtained from diet and supplements and synthesized in the skin. It is essential for calcium and phosphate homeostasis and skeletal health and influences multiple extra-skeletal processes, yet deficiency remains common worldwide. This narrative review summarizes vitamin D sources, physiology, metabolism, pharmacokinetics, clinical relevance and safety and outlines the distinct pharmacokinetic profiles and clinical roles of vitamin D, calcidiol and calcitriol and its analogues. Evidence consistently supports vitamin D, combined with calcium, for preventing and treating deficiency-related skeletal disorders in high-risk populations, and in specific conditions such as malabsorption, chronic kidney disease, hypoparathyroidism and frailty. In vitamin D-replete populations, large trials show limited extra-skeletal benefits, apart from modest effects on cancer mortality and progression from prediabetes to Type 2 diabetes. Untargeted screening is not recommended. Future research should prioritize targeted supplementation, standardized assays and identification of populations most likely to benefit from supplementation.