Does Hydrogen-Rich Water Reduce Oxidative Stress in Patients with Chronic Mountain Sickness? A Randomized, Blinded, Controlled Trial

Zhang, Fengying, Yang Zhong, Qiuyue Li, Doudou Hao, Zhiyou Shi, Suying Zhu, Qian Zhang, and Yunhong Wu. Does Hydrogen-Rich Water Reduce Oxidative Stress in Patients with Chronic Mountain Sickness? A Randomized, Blinded, Controlled Trial. High Alt Med Biol. 00:00-00, 2025. Background: Oxidative stress is implicated in the pathogenesis of chronic mountain sickness (CMS), providing a rationale for antioxidant therapies. This study evaluated the safety and efficacy of hydrogen-rich water (HRW) as a potential antioxidant in individuals with CMS. Methods: We conducted an 8-week, randomized, blinded, placebo-controlled trial at the Tibetan Hospital of Nagqu, China. Adults with untreated CMS (defined by Qinghai score) were randomly assigned (1:1) to receive 990 ml/day of HRW or placebo using a dynamic minimization method. Participants, clinicians, and investigators were blinded to treatment allocation. The primary efficacy endpoint was change in oxidative stress biomarkers from baseline to week 8, including catalase, glutathione, malondialdehyde (MDA), superoxide dismutase, 8-hydroxy-2'-deoxyguanosine, and total antioxidant capacity (T-AOC). Safety was assessed by adverse event reporting. This trial has been completed and is registered at chictr.org under the identifier ChiCTR2400082685. Results: From July 3 to December 24, 2024, 60 participants were randomized; one in the placebo group did not receive treatment and was excluded from the analysis. At week 8, HRW produced greater changes in MDA and T-AOC compared with placebo: MDA, +2.11 (95% CI: 1.13-3.09; p < 0.001); T-AOC, +2.86 (95% CI: 0.09-5.64; p = 0.043). In participants with body mass index (BMI) ≥24, the increase in MDA was more pronounced (Δ+2.57; p = 0.02 for interaction). Adverse events occurred in 50% (15/30) of the hydrogen group and 37% (11/29) of the placebo group; dizziness was the most common. Conclusion: HRW demonstrated both pro-oxidative and antioxidative effects in CMS. However, it did not reduce oxidative stress-induced damage and may increase oxidative risk in individuals with higher BMI.