" Cardiovascular diseases (CVDs) are one of the major health concerns worldwide. They contribute to most of the deaths, and the numbers are still upsurging . According to the world health organization report 2016, cardiovascular diseases are the leading reason of morbidity and mortality globally and were responsible for 17.9 million deaths, representing 31% of all worldwide casualties. Cardiovascular diseases are a group of medical conditions of the heart & blood vessels, such as coronary heart disease (CHD), heart failure, rheumatic heart disease, hypertensive heart disease, and stroke. Among heart diseases, stroke and ischemic heart disease are the leading cause of death and disability (3). Furthermore, coronary artery disease is another common heart ailment. It also contributes to deaths and disabilities at a massive level as well as accelerates the economic burden. It is estimated that around 23.3 million people may die of this disease by 2030 "

Hydrogen Therapy in Cardiovascular and Metabolic Diseases

"Hydrogen (H2) is colorless, odorless, and the lightest of gas molecules. Studies in the past ten years have indicated that H2 is extremely important in regulating the homeostasis of the cardiovascular system and metabolic activity. Delivery of H2 by various strategies improves cardiometabolic diseases, including atherosclerosis, vascular injury, ischemic or hypertrophic ventricular remodeling, intermittent hypoxia- or heart transplantation-induced heart injury, obesity and diabetes in animal models or in clinical trials. " Source

Inhalation of Hydrogen Attenuates Progression of Chronic Heart Failure

Continuous damage from oxidative stress is an important mechanism that facilitates Chronic Heart Failure CHF. We summarize that molecular hydrogen as a safe antioxidant could mitigate progression of CHF via inhibiting apoptosis modulated by p53. Therefore, we propose that inhalation of H2 as a safe, convenient and inexpensive therapy may serve as a new antioxidant in the prevention and treatment of CHF in clinic in the future. Source

Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease

Molecular Hydrogen and Heart Attacks

"Hydrogen treatment was found to significantly reduce the area of damaged heart muscle. Scientists observed that the left ventricular function after heart attack was improved and the hydrogen resulted in a positive effect on the heart remodelling. The positive effects were explained by expression of antioxidant enzymes in the mitochondria." Source

"Molecular hydrogen uses its anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms to relieve cardiac diseases and improve the overall health of the patients. These action mechanisms of hydrogen may work in synchronization to offer cardioprotective effects and improve cardiac morphology and function."

Clinical studies

Most of the studies related to the role of hydrogen inhalation therapy in cardiovascular diseases are carried out in animal models. Remarkably, the therapy showed quite promising results in relieving disease conditions without exerting any side effects. Additionally, the palpable research studies offer valuable insights to design this therapy for human clinical trials and develop a low-cost and effective treatment method for cardiovascular diseases ".

"However, one pilot study on hydrogen gas inhalation is available that was conducted by researchers in 2017. The study included twenty patients with ST-elevated myocardial infarction (STEMI) (a severe type of heart attack) and assigned them to either a hydrogen inhalation group (1.3% hydrogen gas with 26% oxygen) or a placebo group (26% oxygen). Following this, they measured the cardiac salvage index on day 7 and onwards after primary percutaneous coronary intervention (PCI). The results showed a significant increase in cardiac salvage or recovery from day 7 onwards in the hydrogen inhalation group as compared to the control group. Moreover, the study exhibited that hydrogen gas inhalation is a feasible and safe treatment during PCI and it may also encourage left ventricle reverse remodeling 6 months after ST elevated myocardial infarction (27). Besides these effective and encouraging results in pilot-scale studies, more similar studies and large-scale clinical trials are required to administer hydrogen inhalation therapy for cardiovascular diseases." Source

Hydrogen Inhalation Therapy Saves Lives and Improves Outcomes for
Out-of-Hospital Cardiac Arrest Patients

As the study was terminated prematurely because the COVID-19 pandemic led to a drastic increase in the demand for ventilators and a chronic staff shortage that hampered patientenrollment, the increase in participants with good neurological outcomes following post-OHCA H2 inhalation in a selected population of patients was not statistically significant.
However, the secondary outcomes suggest that H2 inhalation may increase 90-day survival from 61% to 85%. Further, 90-day survival with no neurological deficits increased from 21% to 46%. H2 has been recognized as safe for the human body, and no side effects attributable to H2 were observed in this clinical trial. This treatment is expected to save the lives of many patients when implemented in clinical settings. The results of this study were published in eClinicalMedicine on March 17, 2023 (JST) Source

Results and Significance of a Study
Patients with cardiogenic OHCA who regained spontaneous circulation but remained comatose were included in this trial. They were admitted to the ICU and underwent standard targeted temperature management, with one group (the H2 group) inhaling 2% hydrogenated oxygen for 18 hours while the other group (the control group) received no H 2(See Fig. 1). Their 90-day neurological outcomes were evaluated by two independent neurologists. A total of 73 patients were eligible for the study (39 in the H2 group and 34 in the control group). Unfortunately, the study had to be terminated due to COVID-19, which caused a strain on emergency medical care. Therefore, it was inconclusive as to whether the H2 inhalation therapy was effective. Nevertheless, the fully intact survival rate after 90 days increased from 21% in the control group to 46% in the H2 group, and the survival rate increased from 61% to 85%. These differences were statistically
significant, and no apparent side effects were associated with H2 inhalation in this clinical trial. Source

"Is hydrogen inhalation therapy safe for humans?

As hydrogen is an inert gas, it does not react with other molecules in normal mammalian physiological conditions. However, many research studies have also used a wide range of hydrogen gas concentrations and found them safe. As the use of hydrogen gas inhalation therapy is a concern for humans, a study was carried out to determine the safe dose of hydrogen gas in healthy individuals to determine its clinical efficacy. They administered 2.4% hydrogen gas in individuals and observed no significant clinical adverse effects, suggesting it is a safe treatment for a number of diseases, including cardiac arrest (28). Moreover, it may help researchers and clinical experts to devise safe hydrogen gas concentrations for curing diseases. Besides being an effective treatment strategy, the low cost of hydrogen gas can help reduce the economic burden of disease."

Conclusions

Hydrogen has great potential in the regulation of oxidative stress, inflammation, energy metabolism of organelles, and programmed cell death. Many animal experiments and clinical trials have established the protective effects of hydrogen on many organs and systems. Source from Hydrogen: A Novel Option in Human Disease Treatment

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