Combined Molecular Hydrogen and Vitamin C Treatment in Irradiated Normal and Cancer Cell Models: An Exploratory In Vitro Study and Case Reports.

Background: Radiation therapy is widely used to treat cancer but frequently causes normal tissue toxicities that compromise patients' quality of life, highlighting the need for strategies that protect healthy tissue without reducing antitumor efficacy. Here, we investigated whether a redox-modulating intervention combining vitamin C and molecular hydrogen could mitigate radiation-induced injury while preserving or enhancing anticancer effects. Methods: Normal endothelial cells together with breast cancer and glioma cell lines were treated with vitamin C and hydrogen before and/or after irradiation, followed by assessments of cell viability, apoptosis, reactive oxygen species (ROS), and epithelial-mesenchymal transition (EMT)-associated gene expression. To explore the potential clinical relevance of these findings, two patients undergoing radiotherapy received the combination treatment as supportive care. Results: In normal cells, the combination treatment increased post-irradiation viability and reduced intracellular ROS levels, consistent with a cytoprotective antioxidant effect. In contrast, cancer cells exhibited reduced viability and increased apoptosis following the combined treatment, effects that were further enhanced by irradiation. In glioma cells, the combination treatment also suppressed the expression of EMT-associated genes. In the two clinical cases, improvements in radiation-associated toxicities were observed, including dermatitis, oral mucositis, gastrointestinal symptoms, and hair loss, along with improved treatment tolerability. Conclusions: Collectively, these exploratory findings suggest that the combination of vitamin C and hydrogen produces distinct responses among the cell models examined, with increased viability and reduced ROS in HUVECs and reduced viability, increased apoptosis, and altered EMT-associated gene expression in the cancer cell lines. These findings warrant further investigation of this combination as a potential adjunct to radiotherapy.