Clinical Use and Treatment Mechanism of Molecular Hydrogen in the Treatment of Various Kidney Diseases including Diabetic Kidney Disease.

As diabetes rates surge globally, there is a corresponding rise in the number of patients suffering from diabetic kidney disease (DKD), a common complication of diabetes. DKD is a significant contributor to chronic kidney disease, often leading to end-stage renal failure. However, the effectiveness of current medical treatments for DKD leaves much to be desired. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. Recent studies have demonstrated that H2 not only possesses antioxidant properties but also exhibits anti-inflammatory effects, regulates cell lethality, and modulates signal transduction. Consequently, it is now being utilized in clinical applications. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Hence, we undertook a comprehensive review of the literature focusing on animal models and human clinical trials where H2 demonstrated effectiveness against a variety of renal diseases. The collective evidence from this literature review, along with our previous findings, suggests that H2 may have therapeutic benefits for patients with DKD by enhancing mitochondrial function. To substantiate these findings, future large-scale clinical studies are needed.

The overlooked benefits of hydrogen-producing bacteria.

Intestinal bacteria can be classified into "beneficial bacteria" and "harmful bacteria." However, it is difficult to explain the mechanisms that make "beneficial bacteria" truly beneficial to human health. This issue can be addressed by focusing on hydrogen-producing bacteria in the intestines. Although it is widely known that molecular hydrogen can react with hydroxyl radicals, generated in the mitochondria, to protect cells from oxidative stress, the beneficial effects of hydrogen are not fully pervasive because it is not generally thought to be metabolized in vivo. In recent years, it has become clear that there is a close relationship between the amount of hydrogen produced by intestinal bacteria and various diseases, and this report discusses this relationship.

Guidelines for the selection of hydrogen gas inhalers based on hydrogen explosion accidents.

Despite the fact that we have reported on the dangers of the explosion of hydrogen gas inhalers, hydrogen gas inhalers with explosive hazards are, as a matter of fact, still being sold today. In this study, we investigated past reports of hydrogen gas inhaler explosion accidents to clarify the causes of these explosion incidents. As a result of this investigation, we found that the central cause was the leakage of hydrogen gas inside the hydrogen gas inhaler. Although it is said that the explosive concentration of hydrogen is between 10% and 75%, and that the gas does not explode above 75% due to the lack of oxygen, we confirmed through a series of ignition experiments that explosions can occur even in hydrogen gas inhalers that produce 100% hydrogen gas. Some manufacturers of such highly concentrated hydrogen gas inhalers claim that the high concentration and purity of hydrogen is safe and that there is no risk of explosion. We believe that manufacturing or selling such products that pose a risk of explosion or detonation is a violation of social justice. This paper presents ideas for selecting safe hydrogen gas inhalers based on a survey of past accident cases.

Conventional drug acts as a "rifle gun" while hydrogen as a "machine gun".

Most of the drugs used in modern medical treatments are symptomatic treatments and are far from being a cure for the diseases. The adverse effects are unavoidable in the drugs in modern medical treatments. Molecular hydrogen (H2) has a remarkable therapeutic effect on various diseases, and many clinical studies have reported that H2 has no adverse effects. Therefore, H2 is a novel medical gas that is outside the concept of modern medical treatment. H2, unlike drugs, works on the root of many diseases by scavenging the two kinds of strong reactive oxygen species, hydroxyl radical (·OH) and peroxynitrite (ONOO-). Since the H2 alleviates the root of diseases and can treat many diseases at the same time, the medical application of H2 may be called "machine gun therapy." In this review, we demonstrated that the root of many diseases is based on ·OH-induced oxidative stress in the mitochondria, and at the same time, the root of chronic inflammation is also attributed to ·OH.

Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction. There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism. The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired. Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species. Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue. Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects. Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.

Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression.

While many antitumor drugs have yielded unsatisfactory therapeutic results, drugs are one of the most prevalent therapeutic measures for the treatment of cancer. The development of cancer largely results from mutations in nuclear DNA, as well as from those in mitochondrial DNA (mtDNA). Molecular hydrogen (H2), an inert molecule, can scavenge hydroxyl radicals (·OH), which are known to be the strongest oxidizing reactive oxygen species (ROS) in the body that causes these DNA mutations. It has been reported that H2 has no side effects, unlike conventional antitumor drugs, and that it is effective against many diseases caused by oxidative stress and chronic inflammation. Recently, there has been an increasing number of papers on the efficacy of H2 against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H2 as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulation of gene expression.

Molecular Hydrogen as a Novel Protective Agent against Pre-Symptomatic Diseases.

Mibyou, or pre-symptomatic diseases, refers to state of health in which a disease is slowly developing within the body yet the symptoms are not apparent. Common examples of mibyou in modern medicine include inflammatory diseases that are caused by chronic inflammation. It is known that chronic inflammation is triggered by the uncontrolled release of proinflammatory cytokines by neutrophils and macrophages in the innate immune system. In a recent study, it was shown that molecular hydrogen (H2) has the ability to treat chronic inflammation by eliminating hydroxyl radicals (·OH), a mitochondrial reactive oxygen species (ROS). In doing so, H2 suppresses oxidative stress, which is implicated in several mechanisms at the root of chronic inflammation, including the activation of NLRP3 inflammasomes. This review explains these mechanisms by which H2 can suppress chronic inflammation and studies its applications as a protective agent against different inflammatory diseases in their pre-symptomatic state. While mibyou cannot be detected nor treated by modern medicine, H2 is able to suppress the pathogenesis of pre-symptomatic diseases, and thus exhibits prospects as a novel protective agent.

Molecular Hydrogen as a Potential Clinically Applicable Radioprotective Agent.

Although ionizing radiation (radiation) is commonly used for medical diagnosis and cancer treatment, radiation-induced damages cannot be avoided. Such damages can be classified into direct and indirect damages, caused by the direct absorption of radiation energy into DNA and by free radicals, such as hydroxyl radicals (•OH), generated in the process of water radiolysis. More specifically, radiation damage concerns not only direct damages to DNA, but also secondary damages to non-DNA targets, because low-dose radiation damage is mainly caused by these indirect effects. Molecular hydrogen (H2) has the potential to be a radioprotective agent because it can selectively scavenge •OH, a reactive oxygen species with strong oxidizing power. Animal experiments and clinical trials have reported that H2 exhibits a highly safe radioprotective effect. This paper reviews previously reported radioprotective effects of H2 and discusses the mechanisms of H2, not only as an antioxidant, but also in intracellular responses including anti-inflammation, anti-apoptosis, and the regulation of gene expression. In doing so, we demonstrate the prospects of H2 as a novel and clinically applicable radioprotective agent.

Potential Therapeutic Applications of Hydrogen in Chronic Inflammatory Diseases: Possible Inhibiting Role on Mitochondrial Stress.

Mitochondria are the largest source of reactive oxygen species (ROS) and are intracellular organelles that produce large amounts of the most potent hydroxyl radical (·OH). Molecular hydrogen (H2) can selectively eliminate ·OH generated inside of the mitochondria. Inflammation is induced by the release of proinflammatory cytokines produced by macrophages and neutrophils. However, an uncontrolled or exaggerated response often occurs, resulting in severe inflammation that can lead to acute or chronic inflammatory diseases. Recent studies have reported that ROS activate NLRP3 inflammasomes, and that this stimulation triggers the production of proinflammatory cytokines. It has been shown in literature that H2 can be based on the mechanisms that inhibit mitochondrial ROS. However, the ability for H2 to inhibit NLRP3 inflammasome activation via mitochondrial oxidation is poorly understood. In this review, we hypothesize a possible mechanism by which H2 inhibits mitochondrial oxidation. Medical applications of H2 may solve the problem of many chronic inflammation-based diseases, including coronavirus disease 2019 (COVID-19).

A "philosophical molecule," hydrogen may overcome senescence and intractable diseases.

It has been revealed that the cause of senescence and diseases is associated with the reactive oxygen species "hydroxyl radicals" (·OH). Senescence and diseases may be overcome as long as we can scavenge •OH mostly produced in mitochondria. It is one and only one "molecular hydrogen" (H2) that can both penetrate into the mitochondria and scavenge the •OH. The H2 in the body can function in disease prevention and recovery. H2 gas is explosive so that a safe hydrogen inhaler has to be developed for home use. We would like to advocate the great use of H2.