Inhaled Molecular Hydrogen Therapy (H₂)
Scientific Evidence, Clinical Applications & Mechanisms
What Is Inhaled Molecular Hydrogen Therapy?
Inhaled molecular hydrogen (H₂) therapy is a medical gas intervention in which low concentrations of hydrogen (typically 2–4% mixed with air or oxygen) are administered via inhalation. Hydrogen is increasingly recognized for its unique biological properties, particularly its role as a selective antioxidant, immunomodulator, and cytoprotective signaling molecule.
Unlike conventional antioxidants, molecular hydrogen does not indiscriminately suppress reactive oxygen species (ROS). Instead, it selectively neutralizes the most damaging radicals while preserving physiological redox signaling that is essential for cellular function.
1. Why Inhaled H₂ Is a Unique Antioxidant
Selective Neutralization of Cytotoxic Radicals
The foundational study by Ohsawa et al. (2007) demonstrated that inhalation of 2% hydrogen gas markedly reduced brain infarct size and neurological deficits in a rat model of cerebral ischemia–reperfusion injury. Mechanistically, hydrogen selectively scavenged hydroxyl radicals (•OH) and peroxynitrite (ONOO⁻)—the most cytotoxic reactive species—while leaving beneficial signaling molecules such as superoxide, hydrogen peroxide, and nitric oxide intact.
This selectivity is critical, as these physiological ROS play essential roles in cellular signaling, immune defense, and mitochondrial adaptation.
Rapid Diffusion to All Tissues
Hydrogen is the smallest and lightest molecule in nature, non-polar and electrically neutral. As summarized by Ohta (2012) and Hong et al. (2010), inhaled H₂ diffuses rapidly across cell membranes, mitochondrial membranes, and the blood–brain barrier, reaching subcellular compartments that conventional antioxidants cannot effectively access.
Clinical takeaway:
Inhaled molecular hydrogen is a selective, tissue-penetrating antioxidant that targets the most harmful oxidative species without disrupting normal cellular signaling.
2. Sports Performance and Physical Recovery
Performance Enhancement in Healthy Adults
A randomized, placebo-controlled crossover trial by Javorac et al. (2019) showed that 7 days of inhaling 4% hydrogen gas for 20 minutes per day significantly increased peak running velocity (~4.2%) and torso muscle strength in healthy adults.
Vascular Protection During Intense Training
In professional rugby players, Zhao et al. (2024) demonstrated that inhaled hydrogen attenuated the exercise-induced decline in nitric oxide bioavailability during high-intensity training, suggesting improved endothelial function and reduced oxidative stress.
Ongoing Clinical Research
A registered randomized controlled trial (NCT07130942) is currently investigating inhaled hydrogen’s effects on exercise performance, muscle damage, and gene expression related to stress resilience and anti-cancer pathways in healthy young adults.
Clinical positioning:
Inhaled H₂ can be positioned as an adjunct for athletic performance, vascular protection, and recovery, with human RCT data already supporting short-term benefits.
3. Neuroprotection and Neurological Disorders
Acute Ischemic Stroke (Human RCT)
In a randomized controlled clinical study, Ono et al. (2017) found that patients with acute cerebral infarction receiving hydrogen gas inhalation alongside standard therapy showed better neurological outcomes (NIHSS), improved functional independence (Barthel Index), and reduced MRI lesion intensity compared to controls.
Broader Neuroprotective Evidence
Reviews by Iketani & Ohta (2017) summarize extensive preclinical evidence showing that inhaled hydrogen reduces brain edema, preserves blood–brain barrier integrity, and improves neurological outcomes in models of stroke, traumatic brain injury, neonatal hypoxia–ischemia, and subarachnoid hemorrhage.
Neurodegenerative Disease
In Parkinson’s disease, human trials show mixed but safe results (Yoritaka et al., 2021), while animal models demonstrate reductions in neuroinflammation and dyskinesia without impairing dopaminergic therapy (Nascimento et al., 2023).
Clinical framing:
There is solid human evidence for acute neuroprotection (stroke), with promising but still emerging data for chronic neurodegenerative diseases.
4. Pulmonary and Respiratory Conditions
Asthma and COPD (Human Studies)
A prospective clinical study by Wang et al. (2020) demonstrated that a single 45-minute hydrogen inhalation session significantly reduced inflammatory cytokines (IL-4, IL-6) in patients with asthma and COPD.
COPD Exacerbations and Respiratory Failure
Recent reviews and clinical studies (Zajac et al., 2025; Shogenova et al., 2024) indicate that hydrogen–oxygen inhalation during COPD exacerbations and respiratory failure is feasible, safe, and associated with improved inflammatory and gas exchange parameters.
Clinical message:
Inhaled H₂ has human evidence supporting reduced airway inflammation and oxidative stress in asthma and COPD, with excellent safety.
5. Autoimmune and Inflammatory Diseases
Preclinical studies summarized by Tian et al. (2021) show that hydrogen inhalation downregulates pro-inflammatory cytokines (TNF-α, IL-6, IL-17) and inflammatory signaling pathways across multiple organ systems.
In a randomized double-blind trial, Maruyama et al. (2025) found that hydrogen inhalation improved gut microbiota diversity and inflammatory profiles in ulcerative colitis, although larger studies are needed to confirm clinical remission effects.
Clinical honesty:
Evidence is strong at the mechanistic and preclinical level, with early human trials suggesting benefit as an adjunctive anti-inflammatory therapy.
6. Oncology: Supportive and Adjunctive Use
Immune Function and T-Cell Exhaustion
In patients with stage IV colorectal cancer, Akagi & Baba (2019) reported that long-term hydrogen inhalation reduced PD-1–positive exhausted CD8⁺ T cells and improved survival outcomes when used alongside chemotherapy.
Radiotherapy-Induced Toxicity
Studies by Hirano et al. (2021) show that hydrogen inhalation during radiotherapy attenuated bone marrow suppression without compromising tumor response.
Clinical Positioning in Cancer Care
Hydrogen therapy is positioned as a supportive adjunct—reducing treatment toxicity and supporting immune function—not as a standalone anti-cancer therapy.
7. General Healing, Fatigue, and Systemic Protection
Hydrogen’s protective effects against ischemia–reperfusion injury (Ohsawa et al., 2007) and radiation-induced tissue damage (Qian et al., 2013) support its role in tissue protection and recovery. Reviews on fatigue (Lucas et al., 2021) highlight hydrogen’s suitability for oxidative stress–driven acute and chronic fatigue states.
8. Systemic Immune Modulation
Human studies (Chen et al., 2021) show that high-flow hydrogen inhalation modulates lymphocyte populations, suggesting an immune-balancing effect rather than immune suppression. This aligns with oncology and autoimmune findings where hydrogen reduces chronic inflammation and immune exhaustion while preserving host defense.
Clinical Summary
Based on current human and preclinical evidence, inhaled molecular hydrogen therapy:
- Acts as a selective antioxidant, targeting harmful radicals without disrupting cellular signaling
- Provides neuroprotection, with human RCT evidence in acute stroke
- Reduces airway inflammation in asthma and COPD
- Supports exercise performance, recovery, and vascular health
- Modulates immune function and inflammation
- Serves as a supportive adjunct in oncology, reducing treatment-related toxicity
While some applications are supported by robust human trials and others by emerging data, inhaled hydrogen therapy demonstrates a strong safety profile and a growing scientific foundation.
Medical Disclaimer
Inhaled molecular hydrogen therapy is part of an integrative medical approach and is not intended to replace standard medical diagnosis or treatment. Indications and outcomes may vary, and therapy should be supervised by a qualified physician.
References (MLA – Key Inhalation Studies)
- Ohsawa, Ikuroh, et al. Nature Medicine, 2007.
- Javorac, Dejan, et al. Biology of Sport, 2019.
- Wang, Shuo-Ting, et al. QJM, 2020.
- Ono, Hirohito, et al. Journal of Stroke and Cerebrovascular Diseases, 2017.
- Akagi, Junji, and Hideo Baba. Oncology Reports, 2019.
- Hirano, Shigeo Ichikawa, et al. Medical Gas Research, 2021.
- Chitapanarux, Imjai, et al. OncoTargets and Therapy, 2024.
- Tian, Yiming, et al. Frontiers in Physiology, 2021.
- Maruyama, Tetsuro, et al. Biomedicines, 2025.
- Zajac, Daniel, et al. International Journal of Molecular Sciences, 2025.
- Ohta, Shigeo. Mitochondrion, 2012.