Vitamin D3 (Cholecalciferol) for Stage IV Cancer
Also known as: Cholecalciferol, Calcitriol, 25-hydroxyvitamin D
Vitamin D deficiency is associated with worse cancer outcomes across multiple tumor types, and supplementation may improve survival.
Mechanism of Action
Calcitriol induces cancer cell differentiation, inhibits proliferation via p21/p27 upregulation, promotes apoptosis, inhibits angiogenesis, and modulates anti-tumor immune responses through VDR signaling in T cells, dendritic cells, and macrophages.
General mechanism: Secosteroid hormone. VDR-mediated gene transcription affecting calcium, immunity, neurotrophic factors, cell differentiation, and apoptosis.
Current Evidence
VITAL trial showed 25% reduction in cancer mortality in the vitamin D group (not incidence). Multiple meta-analyses support survival benefit with supplementation. 2000-4000 IU/day appears optimal.
Clinical Status: VITAL trial positive for cancer mortality. Standard supportive care in many oncology centers.
Safety Profile
Safe at recommended doses (1000-4000 IU/day). Hypercalcemia at very high doses. Monitor 25(OH)D levels. Rare: kidney stones.
Key Research Questions
- What serum 25(OH)D level optimizes anti-cancer immune function?
- Does vitamin D supplementation enhance checkpoint inhibitor response?