Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction, yet it currently lacks FDA-approved treatments. Molecular hydrogen (H2), administered primarily as hydrogen-rich water (HRW), has emerged as a potential therapeutic candidate due to its selective antioxidant effects, anti-inflammatory activity, and support of mitochondrial and cellular homeostasis. These mechanisms align with several biological abnormalities implicated in ME/CFS, including oxidative stress, chronic inflammation, and impaired energy metabolism. This narrative mini-review summarizes mechanistic evidence relevant to ME/CFS and evaluates three developmental clinical studies of HRW in this population.

Although early trials are small and methodologically limited, moderate-dose HRW consumed over extended durations has demonstrated feasibility and preliminary benefits in reducing fatigue and improving physical function, with generally mild side effects. Overlapping findings in Long COVID further suggest potential applicability across related post-viral fatigue conditions. Key limitations include small sample sizes, reliance on self-report outcomes, and the absence of objective biomarkers.

Future research should prioritize larger, rigorously controlled trials incorporating remote biometric and biochemical assessments to clarify mechanisms of action and identify responsive subgroups. Overall, molecular hydrogen represents a promising, low-burden adjunctive therapy warranting further investigation in ME/CFS.

Source:Friedberg F and LeBaron TW (2026) Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale. Front. Med. 13:1760210. doi: 10.3389/fmed.2026.1760210 https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1760210/full (Full text)

Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial

Abstract:

Background: Given the absence of effective medical treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the testing of a new intervention that may ameliorate potentially pathologic levels of oxidative stress, sympathetic arousal, and inflammation may yield symptomatic improvements.

Objective: To explore in a pilot study, the possible beneficial effect of molecular hydrogen (H2) for the symptoms and functional limitations of ME/CFS.

Methods: Twenty-three subjects were randomized to H2 or active placebo which involved drinking up to five glasses daily of hydrogen-enriched water or placebo water for 28 days. Assessments included: (i) self-report fatigue, physical function, and stress; (ii) salivary C-Reactive Protein (inflammation), Uric Acid (antioxidant status), and Alpha-Amylase (sympathetic function); and (iii) heart rate variability (parasympathetic activity). Data were analysed with Wilcoxon rank-sum tests.

Results: Completion rate for the primary outcome measure of fatigue severity was 100% for the 11 hydrogen participants and 91.7% (n = 11) for placebo participants. No significant changes were found on self-report or biological variables in the active vs. placebo treatment conditions. A small, but significant reduction in fatigue was found in the placebo condition. Adverse effects led to treatment discontinuation in 27.2% of H2 subjects. All severe- and moderate-intensity effects were found in the active treatment condition. Adverse effects were not significantly associated with any demographic or symptom variable.

Conclusions: Therapeutic molecular hydrogen did not yield improvement on any biological or symptom measure in individuals with ME/CFS. Dosage reduction might benefit any future trial of hydrogen therapy in this illness.

Source: Fred Friedberg & Dennis Choi (2022) Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2038519