Hydrogen-Based Therapeutics for Oxidative Stress Management

Hydrogen-based therapeutics have emerged as a versatile and safe modality to counteract oxidative stress across a wide range of pathological conditions. Molecular hydrogen (H₂) exhibits selective scavenging of deleterious radicals, notably hydroxyl radicals and peroxynitrite, while sparing physiologically important reactive oxygen species involved in cell signalling. Administration routes include inhalation of H₂ gas, oral ingestion of hydrogen-rich water, intravenous or intraperitoneal injection of hydrogen-saturated saline, and novel biomaterial platforms that enable site-targeted delivery and controlled release. Mechanistic insights reveal that H₂ modulates redox-sensitive signalling pathways, such as the activation of the Nrf2 antioxidant network, suppression of pro-inflammatory cytokine expression and attenuation of lipid peroxidation. Furthermore, H₂ influences secondary messengers, including calcium-dependent gene regulation mediated by oxidised phospholipid species, thereby extending its impact to gene expression and cellular homeostasis. Preclinical and early clinical studies suggest potential therapeutic applications in cardiovascular, neurological, metabolic and inflammatory disorders, offering a promising adjunct to existing antioxidant strategies. The global significance of hydrogen therapy lies in its minimal toxicity, ease of administration and broad mechanistic profile that addresses fundamental processes of redox imbalance and inflammation.

Research from Nature Portfolio

Recent foundational work has elucidated the molecular basis of hydrogen’s regulatory effects on gene expression. In a cell-free system, H₂ was shown to suppress the free-radical chain reaction of linoleic acid peroxidation, thereby altering the profile of oxidised phospholipid mediators. Exposure of cultured cells to these mediators modulated calcium-dependent signal transduction and reshaped transcriptional programmes associated with oxidative stress response. In parallel, sensitive measurement techniques employing gas chromatography have characterised hydrogen kinetics in blood and tissues following diverse delivery routes. These studies established the temporal profiles of H₂ distribution after oral, intravenous or inhalational administration, providing critical data to optimise dosing regimens and therapeutic windows for future clinical translation.

Hydrogen-Based Therapeutics for Oxidative Stress Management publication trend

The graph below shows the total number of articles in hydrogen-based therapeutics for oxidative stress management across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative stress: An imbalance between the production of reactive oxygen species and antioxidant defences, leading to cellular damage.

Reactive oxygen species (ROS): Chemically reactive molecules, including free radicals and peroxides, derived from oxygen metabolism.

Lipid peroxidation: The oxidative degradation of lipids in cell membranes, resulting in altered membrane integrity and signalling.

Nrf2 antioxidant pathway: A cellular defence mechanism governed by the transcription factor Nrf2 that induces expression of antioxidant and cytoprotective genes.

Biomaterial-based delivery: The use of engineered materials to transport and release therapeutic agents in a controlled and targeted manner.

References

1. The Landscape of Smart Biomaterial‐Based Hydrogen Therapy. Advanced Science (2024).
2. Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles -. Medical Gas Research (2015).
3. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Scientific Reports (2016).
4. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes. Scientific Reports (2014).
5. A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress. Molecules (2019).
6. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. Journal of Lipid Research (2013).