Vitamin D3 — Fat-soluble vitamin / prohormone
Cholecalciferol (D3) is hydroxylated in the liver to 25(OH)D (calcifediol) and then in the kidney (and locally in tissues) to 1,25(OH)2D (calcitriol), the active hormone. Calcitriol binds the vitamin D receptor (VDR), a nuclear receptor expressed in >200 tissue types. Regulates calcium/phosphorus absorption, modulates >1,000 genes, suppresses parathyroid hormone, exerts anti-inflammatory effects through T-regulatory cell induction, and supports innate immunity via cathelicidin upregulation. Observational and interventional data link deficiency to increased risk of fractures, autoimmune disease, cardiovascular events, depression, and all-cause mortality.
Overview
This page is part of Hormonaly's evidence-graded compound library. All clinical claims are linked to peer-reviewed sources via our dual-layer citation verification pipeline.
Compound Class
Fat-soluble vitamin / prohormone
Mechanism of Action
Cholecalciferol (D3) is hydroxylated in the liver to 25(OH)D (calcifediol) and then in the kidney (and locally in tissues) to 1,25(OH)2D (calcitriol), the active hormone. Calcitriol binds the vitamin D receptor (VDR), a nuclear receptor expressed in >200 tissue types. Regulates calcium/phosphorus absorption, modulates >1,000 genes, suppresses parathyroid hormone, exerts anti-inflammatory effects through T-regulatory cell induction, and supports innate immunity via cathelicidin upregulation. Observational and interventional data link deficiency to increased risk of fractures, autoimmune disease, cardiovascular events, depression, and all-cause mortality.
Regulatory Status
OTC dietary supplement. Ergocalciferol (D2) and Cholecalciferol (D3) FDA-approved prescription forms exist for deficiency treatment.
Evidence Level
High — multiple large RCTs and meta-analyses (VITAL, D-HEALTH, FIND). Endocrine Society and USPSTF guidelines support supplementation in deficiency.