ArticlePDF AvailableLiterature Review

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

Authors:
  • MiZ Co. Ltd., Japan, Kanagawa

Abstract

It has been revealed that the cause of senescence and diseases is associated with the reactive oxygen species “hydroxyl radicals” (·OH). Se-nescence 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.
© 2020 Medical Gas Research | Published by Wolters Kluwer - Medknow 47
REVIEW
INTRODUCTION
Although modern medicine has evolved so far with stalling
rapidly in the 21st century, large walls hinder the development
of medicine. There are many diseases which cannot be cured
or healed by treatment based on “element reductionism.” The
element reductionism is associated with one treatment. Many
diseases are caused not by single factor abnormalities but by
multiple factors with various mechanisms. These multiple
factors may not have been elucidated in modern medicine.
However, we have recently developed how we can break
through these challenges. A key solution lies in using molecular
hydrogen (H2).
From a scientic standpoint, all activities of the molecules
can be called the exchange of electrons: “oxidation” and
“reduction.” From the viewpoint of the longevity of the
youth, oxidation means “senescence” while reduction does
“rejuvenation.” Life activity begins after the birth, and
immediately the oxidation proceeds. It means that “electrons
are deprived” to be oxidized. H2, supplying electrons, can
be said that the reducing agent “rejuvenated material.”
Senescence and diseases can be interpreted as oxidative
phenomenon, rejuvenation and recovery as reductive one.
The substance with oxidizing maximizes the phenomenon. In
this paper, we propose the possibility that H2 will overcome
the senescence and intractable diseases from the viewpoint of
mitochondrial oxidation and reduction.
REACTIVE OXYGEN SPECIES AND MITOCHONDRIA
What is the most potent oxidizing one? It is hydroxyl radicals
(•OH). About 90% of reactive oxygen species (ROS) are
generated in the mitochondria in the cells.1 The •OH have
been generated in large quantities almost all within the
mitochondria. Mitochondria are the organs that create the
energy ATP that is necessary for our life activities.
Mitochondrial functions can be compared to the boiler
of a steam locomotive. In the past, the term “boiler” as a
word for locomotive originated from the fact that the boiler
occupied most of the body of the locomotive. In the same way,
mitochondria are energy generating organs for life activities
that must be necessary for life. Locomotives run with fuel,
but in that case a large amount of soot, imperfect combustion
substance is generated. When energy conversion is performed,
the combustion efciency is not perfect without exception. In
the mitochondria, when converting the incorporated material
into energy, about a few percent of the imperfect combustion
substance are produced. The imperfect combustion materials
are ROS. There are a variety of ROS that can be used usefully.
If they are not necessary for life, metabolic system to scavenge
by the use of enzymes has been constructed. However, in the
mitochondria of the generated ROS, there is only •OH that
cannot be reduced by any means. The •OH is generated in
the mitochondria, and can cause oxidation, senescence and
diseases. Because •OH has the strongest oxidizing power,
and reacts with nucleic acids (DNA), lipids and proteins that
make up our bodies and destroy them. This vandalism is an
oxidative reaction. We do not know how to handle with •OH.
Antioxidants except H2 are not very effective especially
because of the impossibility into the cell and mitochondria. We
should scavenge the •OH that produces in the mitochondria.
Is there any substance that can scavenge it? It is H2 that can
solve the vandalism of •OH.
DEVELOPMENT OF THE eQUIPMENT TO DELIVER H2 TO
OUR BODY
We have reported that drinking of H2 water produced in our
electrolytic cell released a pioneering study to inhibit oxidative
disorders in the liver of rats in 2005.2 This is the rst hydrogen
medicine paper in Japan. Two years later, a series of papers
A “philosophical molecule, hydrogen may overcome
senescence and intractable diseases
Shin-ichi Hirano1, *, Yusuke Ichikawa1, Ryosuke Kurokawa1, Yoshiyasu Takefuji2, Fumitake Satoh1
1 MiZ Company Limited, Kamakura, Japan
2 Faculty of Environment and Information Studies, Keio University, Fujisawa, Japan
*Correspondence to: Shin-ichi Hirano, DVM, PhD, s_hirano@e-miz.co.jp.
orcid: 0000-0002-8610-8922 (Shin-ichi Hirano)
It has been revealed that the cause of senescence and diseases is associated with the reactive oxygen species “hydroxyl radicals” (·OH). Se-
nescence 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.
Key words: Google; Amazon; Facebook; Apple; hydroxyl radicals; mitochondria; molecular hydrogen; oxidation; reactive oxygen species;
reduction; rejuvenation; senescence
doi: 10.4103/2045-9912.279983
How to cite this article: Hirano S, Ichikawa Y, Kurokawa R, Takefuji Y, Satoh F. A “philosophical molecule,” hydrogen may overcome se-
nescence and intractable diseases. Med Gas Res. 2020;10(1):47-49.
Abstract
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Hirano et al. / Med Gas Res
Medical Gas Research ¦ March ¦ Volume 10 ¦ Issue 1
48
www.medgasres.com
on H2 began to emerge from other research institutes.3 We
have reported the equipment to deliver H2 to the living body.4,5
H2 is capable to pass through all materials, because H2 is
the smallest molecule. Only H2 can pass through the cell
membrane and also pass the mitochondrial membrane, while
the other antioxidants cannot do that to scavenge the •OH. H2
has been reported to react with two kinds of strong ROS,3,6 i.e.,
•OH and peroxynitrite (ONOO-).7 However, it is reported that
H2 reacts with ONOO- somewhat.3 The reactivity of H2 with
•OH is high and quick. As observed from the production of
H2 in the body (gut),8,9 it is completely harmless for the body.
H2 does not interfere with the metabolic system. Rather, H2
can scavenge the waste, •OH in soot that has occurred in the
metabolic reaction, harmless and non-toxic. In conclusion, it
is only H2 that can penetrate into the mitochondria and can
also scavenge •OH (Figure 1). Thereby, the H2 in the body
can function in disease prevention and recovery.10-26 There is
a possibility of longevity of youth.
GAFA AND PUBLIC ORGANIZATION IN THE US
There are many diseases which we cannot treat well. The
massive fund-raising of Google, Amazon, Facebook and Apple
(GAFA) is continuing to discover the cure for those diseases.
Apple CEO Tim Cook said that in the future, if anybody asks
what Apple’s greatest contribution to humankind is “health”
will be his answer.27
The wasteful medical treatment is rampant in the modern
therapy. The medical expense increase of the nation is
spurred. As a solution, there is a “Choosing Wisely” in the
United States. This is a public organization in Philadelphia of
United States, the United States Internal Medicine Specialist
Certication Organization Foundation (ABIM Foundation)
becomes the epicenter, bundling the medical Society of the
United States, to announce a wasteful medical treatment. For
example, United States Clinical Oncology Society, United
States gastroenterological Society, United States Psychiatric
Society, United States Cardiology Association, United States
Obstetrics and Gynecology Society, United States Pediatrics
Association, etc., the world’s first medical Association
has presented themselves with “the medical act that seems
unnecessary.”
How should we overcome various problems including
medical problems and social problems? As mentioned in this
paper, we would like to propose a safe H2 medical use with
no adverse effects. H2 may be able to solve various problems
by combining with modern treatment or alone use in the
future. This proposal does not deny the modern medicine
indiscriminately. Especially in acute diseases, the modern
medical treatments are very effective certainly. However,
there are diseases due to chronic diseases and complex factors
that cannot be covered by modern medicine. Up to now there
are more than 600 papers regarding the use of H2, including
about 50 clinical trials papers. The use of H2 is indispensable
in the future, and we would like to advocate the promotion of
hydrogen medicine.
Acknowledgements
The authors are grateful to Ms. Yoko Satoh and Mr. Masatsugu Saitou
of MiZ Company Limited, and Dr. Goh Matsuo for their excellent
advices in writing this manuscript.
Author contributions
SH, YT and FS designed and wrote the manuscript. YI and RK sup-
ported this study by giving advice and revised the manuscript. All
authors read and approved the nal manuscript.
Conflicts of interest
The authors have no conicts of interests to declare.
Financial support
None.
Copyright license agreement
The Copyright License Agreement has been signed by all authors
before publication.
Plagiarism check
Checked twice by iThenticate.
Peer review
Externally peer reviewed.
Open access statement
This is an open access journal, and articles are distributed under
Figure 1: “Molecular hydrogen” (H2) is the only molecule that can both enter the mitochondria and scavenge the hydroxyl radicals.
Note: Inhalation gas was prepared by mixing of H2 gas and air, where the H2 gas was produced by the electrolysis of water, and the concentration was controlled under
the detonation limit of the mixture of H2 gas and air (below 10% H2 concentration in the apparatus “Jobs-α").·OH: Hydroxyl radicals; PTSD: posttraumatic stress disorder.
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Medical Gas Research ¦ March ¦ Volume 10 ¦ Issue 1 49
Hirano et al. / Med Gas Res www.medgasres.com
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build upon the work non-commercially, as long as appropriate credit
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... These papers have led to global research on the medical applications of H 2 . We recently showed that although H 2 is an inactive substance, compared to other antioxidants, it is the only molecule with mitochondrial permeability and an ability to reduce •OH, which is promising for future medical applications [9,10]. Selective •OH scavengers may have potential medical applications as radioprotective agents. ...
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Molecular hydrogen (H2) is clinically administered; however, in some hospitals, H2 is given to patients without consideration of its safe use. In the present study, we prepared convenient and safe devices for the drinking of super-saturated H2 water, for intravenous drip infusion of H2-rich saline, and for the inhalation of H2 gas. In order to provide useful information for researchers using these devices, the changes in H2 concentration were studied. Our experimental results should contribute to the advance of non-clinical and clinical research in H2 medicine.
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Background: Mortality of hemorrhagic shock primarily depends on whether or not the patients can endure the loss of circulating volume until radical treatment is applied. We investigated whether hydrogen (H2) gas inhalation would influence the tolerance to hemorrhagic shock and improve survival. Methods: Hemorrhagic shock was achieved by withdrawing blood until the mean arterial blood pressure reached 30-35 mm Hg. After 60 minutes of shock, the rats were resuscitated with a volume of normal saline equal to four times the volume of shed blood. The rats were assigned to either the H2 gas (1.3% H2, 26% O2, 72.7% N2)-treated group or the control gas (26% O2, 74% N2)-treated group. Inhalation of the specified gas mixture began at the initiation of blood withdrawal and continued for 2 hours after fluid resuscitation. Results: The survival rate at 6 hours after fluid resuscitation was 80% in H2 gas-treated rats and 30% in control gas-treated rats (p < 0.05). The volume of blood that was removed through a catheter to induce shock was significantly larger in the H2 gas-treated rats than in the control rats. Despite losing more blood, the increase in serum potassium levels was suppressed in the H2 gas-treated rats after 60 minutes of shock. Fluid resuscitation completely restored blood pressure in the H2 gas-treated rats, whereas it failed to fully restore the blood pressure in the control gas-treated rats. At 2 hours after fluid resuscitation, blood pressure remained in the normal range and metabolic acidosis was well compensated in the H2 gas-treated rats, whereas we observed decreased blood pressure and uncompensated metabolic acidosis and hyperkalemia in the surviving control gas-treated rats. Conclusions: H2 gas inhalation delays the progression to irreversible shock. Clinically, H2 gas inhalation is expected to stabilize the subject until curative treatment can be performed, thereby increasing the probability of survival after hemorrhagic shock.
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Background: The present study aimed at investigating the effect of a novel antioxidant, hydrogen (H2) gas, on the severity of contrast-induced acute kidney injury (CIAKI) in a rat model. Methods: CIAKI was induced in rats by intravenous injection of a contrast medium, Ioversol, in addition to reagents inhibiting prostaglandin and nitric oxide synthesis. During the injection of these reagents, the rats inhaled H2 gas or control gas. Results: One day after the injection, serum levels of urea nitrogen were significantly lower in H2 gas-inhaling CIAKI rats (17.6 ± 2.3 mg/dl) than those in control gas-treated CIAKI rats (36.0 ± 7.3 mg/dl), although they both were elevated as compared to untreated rats (14.9 ± 0.9 mg/dl). Consistently, creatinine clearance in H2 gas-treated CIAKI rats was higher than that in control gas-treated counterparts. Renal histological analysis revealed that the formation of proteinaceous casts and tubular necrosis was improved by H2 gas inhalation. Mechanistic analyses showed that inhalation of H2 gas significantly reduced renal cell apoptosis, expression of cleaved caspase 3, and expression of an oxidative stress marker, 8-hydroxydeoxyguanosine, in injured kidneys. Conclusion: Results suggest that H2 gas inhalation is effective in ameliorating the severity of CIAKI in rats by reducing renal cell apoptosis and oxidative stress. © 2015 S. Karger AG, Basel.