Vitamin D Level in Blood Serum and Its Connection with Helicobacter pylori Infection: A Systematic Review

Helicobacter pylori (H. pylori) is widely recognized for its role in gastric pathologies, including ulcerative disease and malignant transformation of the gastric mucosa. Lower serum concentrations of 25-hydroxyvitamin D may impair immune responses, potentially influencing colonization dynamics and persistence of H. pylori infection. A systematic review was conducted to critically evaluate the current evidence on the association between serum vitamin D levels and H. pylori infection. PubMed, Scopus, Cochrane Library, and Web of Science databases were comprehensively searched for relevant articles from their inception until May 28, 2025. Twenty observational studies, including 167,903 cases, were included in the review. Our results suggest a possible link between vitamin D deficiency and the risk of H. pylori infection, as the H. pylori-positive population was more likely to have lower vitamin D levels than the negative population. However, we could not confirm causality. In addition, vitamin D receptor (VDR) gene polymorphism, particularly rs2228570 (FokI), rs7975232 (ApaI), and rs1544410 (BsmI), as well as the TLR4 gene (rs4986790 and rs4986791), were significantly associated with H. pylori infection and vitamin D status. Our findings provide a strong base for further research into vitamin D's role in gastric immunity and its utility as a modifiable risk factor in managing H. pylori infection.