Progress in Hydrogen Anti-Tumor Research

The high incidence and mortality of tumors have caused a heavy medical burden worldwide. In the short term, there is a lack of effective means to cure tumors. How to prevent tumors and prolong the survival of tumor patients is the primary goal, and hydrogen is expected to play a role in this field.

Anti-Cancer Mechanisms of Hydrogen

Hydrogen exerts its anti-tumor effects through multiple pathways:

• Selective Antioxidant — H₂ selectively neutralizes cytotoxic reactive oxygen species (ROS) such as hydroxyl radicals (·OH) and peroxynitrite (ONOO⁻), while preserving beneficial signaling ROS.
• Anti-Inflammatory — Inhibits the NF-κB pathway, reducing tumor-promoting inflammatory cytokines including IL-6, TNF-α, and IL-1β.
• Anti-Angiogenic — Suppresses VEGF expression, limiting blood supply to tumor tissue.
• Pro-Apoptotic — Activates caspase pathways and upregulates pro-apoptotic proteins in cancer cells.
• Immune Modulation — Enhances NK cell activity and T-cell-mediated anti-tumor immunity.

Synergistic and Toxic Effects

Research has revealed that hydrogen can enhance the efficacy of conventional anti-tumor therapies while reducing their side effects. In combination with chemotherapy, hydrogen has been shown to protect normal cells from drug-induced oxidative damage, improving patient tolerance and treatment outcomes.

However, certain dosage-dependent toxic effects have been observed in high-concentration hydrogen exposure studies, emphasizing the importance of controlled delivery methods.

Combination Therapy

Hydrogen-based combination therapies represent the most promising clinical direction:

• Hydrogen + Chemotherapy — Reduces chemotherapeutic side effects (nausea, neuropathy, cardiotoxicity) while maintaining anti-tumor efficacy.
• Hydrogen + Immunotherapy — Enhances PD-1/PD-L1 inhibitor response rates by modulating the tumor microenvironment.
• Hydrogen + Radiation — Protects normal tissue from radiation-induced damage through selective ROS scavenging.
• Hydrogen + Targeted Therapy — Synergistic effects observed with EGFR inhibitors and CDK4/6 inhibitors in preclinical models.

Clinical Research Progress

Several clinical trials have been registered or completed, evaluating hydrogen therapy in cancer patients. Early results show improvements in quality of life scores, reduced inflammatory markers, and enhanced treatment tolerability. The lack of reported adverse effects positions hydrogen as an ideal adjunct therapy.

Hydrogen Administration Methods

Current delivery methods include hydrogen-rich water, hydrogen gas inhalation, hydrogen-rich saline injection, and solid-state hydrogen products (tablets, patches, dressings). Solid-state hydrogen donors are gaining attention for their portability, sustained release, and targeted delivery capabilities.

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