Impact of Vitamin D Status on Pancreatic Cancer Risk and Outcomes

Vitamin D (VD), a fat-soluble prohormone, exerts diverse effects on cellular proliferation, differentiation, and immune modulation, with accumulating evidence supporting its role in pancreatic ductal adenocarcinoma (PDAC) biology. Experimental studies demonstrate that VD and its analogs can inhibit PDAC cell growth and remodel the tumor microenvironment, potentially contributing to tumor suppression. Epidemiological data indicate that VD deficiency is prevalent among PDAC patients and is associated with increased inflammatory biomarkers and reduced overall survival, particularly in early-stage disease. However, meta-analyses reveal inconsistent associations between circulating 25-hydroxyvitamin D levels and PDAC incidence, while higher levels may be linked to improved survival but not reduced risk of disease onset. The clinical utility of VD supplementation for PDAC prevention or treatment remains uncertain, with ongoing debate regarding optimal dosing, timing, and patient selection. This narrative review synthesizes current evidence on the mechanistic, epidemiological, and clinical relevance of VD in PDAC. Particular emphasis is placed on existing knowledge gaps and the need for well-designed clinical trials to clarify the potential therapeutic and prognostic role of VD in pancreatic cancer.