Authors: Deryugina A.V., Danilova D.A., Brichkin Y.D., Taranov E.V., Nazarov E.I., Pichugin V.V., Medvedev A.P., Riazanov M.V., Fedorov S.A., Smorkalov A.Y., Makarov E.V.
Source: Medical Gas Research, Volume 13, Issue 2 (2023), Pages 59–66
https://doi.org/10.4103/2045-9912.356473

Background

Molecular hydrogen (H₂) has emerged as a therapeutic and preventive medical gas with potential benefits in a variety of disease states. Its antioxidative and cytoprotective properties suggest possible applications in perioperative care, particularly where oxidative stress is a known contributor to tissue damage.

Objective

To assess the role of molecular hydrogen as an anaesthetic adjunct during cardiopulmonary bypass (CPB) surgery for acquired valvular defects, focusing on its effects on red blood cell (RBC) function and cardiac performance indicators in the early postoperative period.

Methods

This prospective, randomised clinical trial involved 24 patients undergoing elective cardiac surgery with CPB at a specialised cardiothoracic hospital in Nizhny Novgorod, Russian Federation. Patients were randomly assigned to one of two groups:

• Hydrogen group (n = 12): received 1.5–2.0% molecular hydrogen via face mask using a ventilator breathing circuit alongside anaesthesia, beginning immediately after tracheal intubation and continuing throughout the surgery.

• Control group (n = 12): received standard anaesthesia without hydrogen administration.

Blood samples were collected from peripheral veins and the radial artery at four time points:

1. Immediately after induction of anaesthesia

2. Prior to CPB initiation

3. Immediately after CPB termination

4. 24 hours post-surgery (early postoperative period)

Results

Compared to the control group, the hydrogen-treated group exhibited:

• Increased electrophoretic mobility of RBCs

• Enhanced RBC metabolism

• Reduced erythrocyte aggregation

The most pronounced reduction in oxidative stress markers was observed 24 hours after surgery. Additionally, statistically significant differences in myocardial contractile function indicators were recorded on postoperative Days 1 and 3 in favour of the hydrogen group.

Conclusion

Inhaled molecular hydrogen positively influences red blood cell functionality and appears to contribute to a more favourable recovery profile in the early postoperative period. These findings support the protective role of molecular hydrogen and suggest its potential as a beneficial perioperative intervention in cardiac surgery.

Citation

Deryugina AV, Danilova DA, Brichkin YD, Taranov EV, Nazarov EI, Pichugin VV, Medvedev AP, Riazanov MV, Fedorov SA, Smorkalov AY, Makarov EV. Molecular hydrogen exposure improves functional state of red blood cells in the early postoperative period: a randomised clinical study. Medical Gas Research. 2023 Apr–Jun;13(2):59–66.
https://doi.org/10.4103/2045-9912.356473

Authors: Alexis R. Cole, Francesca Sperotto, James A. DiNardo, Stephanie Carlisle, Michael J. Rivkin, Lynn A. Sleeper, John N. Kheir
Source: Critical Care Explorations, Volume 3, Issue 10 (2021), Article e543
https://doi.org/10.1097/CCE.0000000000000543

Background

Ischaemia-reperfusion injury is a common and clinically significant problem in critically ill patients, for which no targeted therapy currently exists. Inhaled molecular hydrogen (H₂) has demonstrated protective effects against ischaemia-reperfusion injury in preclinical models of shock, stroke, and cardiac arrest.

Objective

To investigate the safety of inhaling 2.4% hydrogen gas in medical air, administered via high-flow nasal cannula (HFNC), at exposure durations sufficient for future clinical efficacy trials.

Methods

A prospective, single-arm clinical trial was conducted with eight healthy adult volunteers (aged 18–30 years). Participants were assigned to receive 2.4% H₂ in medical air via HFNC at 15 L/min for durations of 24 (n = 2), 48 (n = 2), or 72 hours (n = 4).

Monitored parameters included:

• Vital signs

• Pulmonary function tests

• 12-lead electrocardiogram (ECG)

• Mini-Mental State Examination (MMSE)

• Comprehensive neurological examination

• Serological testing for haematological, hepatic, renal, pancreatic, and cardiac markers

• Participant-reported symptoms

All adverse events were adjudicated by two independent physicians and reviewed by an external data safety monitoring board (DSMB).

Results

• All eight participants completed the study without early discontinuation.

• No clinically significant adverse effects were observed in any subject.

• Vital signs, pulmonary function, MMSE scores, neurological assessments, ECG, and laboratory findings showed no clinically relevant changes compared to baseline.

• Minor laboratory deviations included non-significant increases in haematocrit and platelet count, with no indication of organ injury.

Conclusion

Inhalation of 2.4% hydrogen gas in medical air for up to 72 hours appears to be well-tolerated and safe in healthy adults, with no clinically meaningful adverse effects. These findings support the feasibility of prolonged hydrogen gas inhalation and provide foundational safety data for future trials involving critically ill patients, including those with cardiac arrest.

Citation

Cole AR, Sperotto F, DiNardo JA, Carlisle S, Rivkin MJ, Sleeper LA, Kheir JN. Safety of Prolonged Inhalation of Hydrogen Gas in Air in Healthy Adults. Crit Care Explor. 2021 Oct 8;3(10):e543.
https://doi.org/10.1097/CCE.0000000000000543

Authors: Rahman M.H., Bajgai J., Sharma S., Jeong E.S., Goh S.H., Jang Y.G., Kim C.S., Lee K.J.
Source: Antioxidants, Volume 12, Article 1241 (2023)
https://doi.org/10.3390/antiox12061241

Background

Molecular hydrogen (H₂) is gaining recognition as a versatile therapeutic gas with reported benefits in multiple disease states, including neurodegenerative conditions such as Alzheimer’s disease (AD). While its antioxidant and anti-inflammatory effects have been observed in experimental settings, clinical data on its cognitive impact and safety in diverse adult populations remain limited.

Objective

To evaluate the safety and potential cognitive benefits of hydrogen gas inhalation in community-dwelling adults aged 40 to 70 years, with a specific focus on markers of oxidative stress, inflammation, and dementia-related biomarkers.

Methods

A total of 54 participants aged 40–70 years were enrolled in a 4-week single-arm, open-label study. All subjects received inhalation therapy with molecular hydrogen gas (H₂) for a specified duration each day. Pre- and post-treatment assessments included:

• Complete and differential white blood cell (WBC) counts

• Levels of reactive oxygen species (ROS) and nitric oxide

• Beta-site APP-cleaving enzyme 1 (BACE-1) – a key enzyme involved in amyloid precursor protein metabolism

• Amyloid beta peptides (Aβ), total tau (T-tau)

• Brain-derived neurotrophic factor (BDNF)

• Vascular endothelial growth factor A (VEGF-A)

• Monocyte chemoattractant protein-1 (MCP-1)

• Pro-inflammatory cytokines such as interleukin-6 (IL-6)

Results

• No adverse effects were observed in WBC counts post-inhalation, suggesting good tolerability and systemic safety.

• Significant reductions were recorded in oxidative stress biomarkers (ROS and nitric oxide) following treatment.

• Notably, markers associated with cognitive decline and neurodegeneration, such as BACE-1, Aβ, IL-6, and others, were reduced post-treatment.

• In contrast, neuroprotective biomarkers, particularly BDNF, showed increased levels, indicating potential for neuronal support and cognitive benefit.

Conclusion

This study demonstrates that daily hydrogen gas inhalation is safe and well-tolerated in healthy adults aged 40–70 and may have beneficial effects on cognitive biomarkers, especially those linked to Alzheimer’s disease. The findings support further investigation into hydrogen inhalation as a non-invasive, preventive or adjunctive therapy for age-related cognitive impairment and early-stage dementia.

Citation

Rahman MH, Bajgai J, Sharma S, Jeong ES, Goh SH, Jang YG, Kim CS, Lee KJ. Effects of Hydrogen Gas Inhalation on Community-Dwelling Adults of Various Ages: A Single-Arm, Open-Label, Prospective Clinical Trial. Antioxidants. 2023;12(6):1241.
https://doi.org/10.3390/antiox12061241