A Systematic Review and Meta-Analysis: Does Molecular Hydrogen Exert Radioprotective Effects Without Compromising the Antitumor Efficacy of Radiotherapy or Concurrent Chemoradiotherapy?

Radiotherapy and concurrent chemoradiotherapy (CCRT) are widely used for cancer treatment but are frequently associated with radiation-induced toxicities. Molecular hydrogen has been proposed as a potential radioprotective agent because it protects normal tissues from oxidative damage. However, an important concern is whether molecular hydrogen also protects tumor tissues. This systematic review and meta-analysis aimed to evaluate whether molecular hydrogen preserves tumor response while providing radioprotection in cancer patients receiving radiotherapy or CCRT. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for conducting this review. Eligible studies were English-language original clinical studies of adult cancer patients (≥18 years) treated with radiotherapy or CCRT and receiving molecular hydrogen for radioprotection. Three electronic databases (PubMed, Embase, and Web of Science) were searched from inception to 8 July 2026. Seven studies involving 222 patients were qualitatively synthesized, of which 3 involving 130 patients were included in the meta-analysis. The random-effects model was used. The risk of bias was evaluated with validated tools. The risk ratio (RR) was used to estimate the pooled tumor response. Molecular hydrogen did not significantly affect tumor response compared with the control group (RR = 0.98, 95% CI 0.83-1.15). Sensitivity analysis restricted to randomized controlled trials yielded a broadly consistent result (RR = 0.99, 95% CI: 0.84-1.17). The narrative synthesis further indicated that molecular hydrogen reduced radiation-induced toxicities, improved quality of life, and did not adversely affect hematological parameters. In conclusion, this systematic review and meta-analysis suggest that molecular hydrogen may have radioprotective effects in cancer patients receiving radiotherapy or concurrent chemoradiotherapy, with the currently available evidence showing no significant reduction in tumor response. This review was registered with INPLASY (INPLASY202680108).