HYDROGEN – AT THE CORE OF LIFE

It was first suggested with humour in Nature (1996) as a natural antioxidant and selective scavenger of oxygen free radicals to treat oxidative stress. More recently, it has been broadly indicated that molecular Hydrogen exerts its biological effects in two major ways. The first one is scavenging free radicals, and the other is modulating specific gene expression or signalling pathways, both in animals and plants. Molecular Hydrogen has been demonstrated to induce change in gene expression leading to anti-oxidative, anti-inflammatory, and anti-apoptotic responses in all organisms tested without any detrimental side effects. Thus, molecular Hydrogen enables the organism to reduce and withstand stress longer and better while thriving.

However, the latest discovery takes this even further and indicates that it is at the core of multicellular life that is positively affected. Molecular hydrogen could be donating electrons in the Q chamber of complex I to the ubiquinone, thereby shortening the electron transfer chain in complex I. Consequently, the production of superoxide radicals by this complex decreases while the proton pump activity is maintained. Molecular hydrogen, both the protons and electrons, supplemented to the mitochondria and complex I, ultimately results in a proton gradient increase, and the increased proton gradient generated will result in an increased production of ATP.

The mitochondrion is the main source of ATP (adenosine triphosphate) and is an essential organelle of plants, animals and fungi that divide independently from the cells, and have their own genome. Their primary function is to provide energy to the cell in the form of ATP using oxygen by a process called cellular respiration. In addition, mitochondria are also involved in other critical tasks, such as signalling, maintaining control of the cell cycle, cell growth, cellular differentiation, and even cell death. There are an estimated 37.2 trillion cells in the body, and each cell contains between 2 and 2500 mitochondria, each possessing a 17000 ATP assembly line. It is estimated that there are about 10 million billion (10,000 trillion) mitochondria in an adult human, for example!

Molecular hydrogen supplementation can increase mitochondrial ATP production by more than 50% while decreasing the production of superoxide by the first respiratory complex. The ability to increase the production of ATP while reducing the production of reactive oxygen species, thus reducing the need to repair the damage they cause, represents an advancement in biology that could not be more relevant in today’s world with peer-reviewed scientific documents now running into the thousands. Taken collectively, they clearly identify that hydrogen deficiency in biological organisms, costs the world well over 100 trillion dollars in lost income every year. It underpins the health potential and lifespan of all things, and ultimately our entire biosphere (including its climate) as we know it.

The enormous potential that Molecular Hydrogen and Oxygen supplementation has identified to affect and determine outcomes for includes:

• Mitochondrial Function
• The increased production of ATP
• Oxidative Stress and its management
• Immune Cell Recovery
• Inflammation and inflammatory Response
• NF-kB Protein Complex

At this level, the vast majority of life all works the same way, and it is in the mitochondrion where we find the critical function of life independent of species.

Mitochondrial Function

The mitochondrion is an essential organelle of plants, animals and fungi that divide independently from the cells, and have their own genome. Their primary function is to provide energy to the cell in the form of ATP (adenosine triphosphate) using oxygen by a process called cellular respiration. In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signalling, cellular differentiation, maintaining control of the cell cycle, and cell death. Cellular respiration is a catabolic pathway that breaks down glucose and other molecules to produce ATP ultimately. The stages of cellular respiration include glycolysis, pyruvate oxidation, the citric acid or Krebs cycle, and oxidative phosphorylation that uses oxygen as a terminal electron acceptor. However, the process is very complex and sensitive and is at the origin of the accidental production of reactive oxygen species. Thus, the mitochondrion is also the centre of oxidative stress where the most potent free radical, the hydroxyl radical, is produced.

It has been shown that Hydrogen gas could scavenge the hydroxyl radical in live cells resulting in a decrease of oxidative stress in vivo, furthermore, it is demonstrated that H2 supplementation suppressed superoxide production by complex I. It is proposed that H2 could donate electrons in the Q chamber which identifies that Complex I could be using H2 directly to enable the pumping of protons from the matrix to the intermembrane space, increasing the potential ATP production without using substrate originating from the degradation of glucose, with suggestion that an increase of more than 50% in ATP production can be achieved in the presence of H2 compared to control.

Oxidative Stress

Oxidative Stress refers to elevated intracellular levels of Reactive Oxygen Species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress results from an imbalance of ROS and antioxidants in a living organism, such as alpha-lipoic acid, glutathione and hydrogen. Oxidative stress occurs naturally as the result of the normal function of the organism but can also be potentiated by environmental and pathological pressures while also playing a direct role in the ageing process. Reactive oxygen species are molecules that “want” to capture electrons from others to stabilise themselves. Because they are highly reactive, they will steal electrons from any source close to them, such as proteins and DNA, which damages the stability and function of the donating molecule. The primary cellular source of ROS is the mitochondria. In response to this, antioxidants are molecules that can donate electrons without becoming reactive themselves. Antioxidants stop the oxidation pathway by “reducing” the oxidant, and preventing damage.

One such powerful antioxidant that can passively diffuse through the living body (or plant) at great speed is molecular Hydrogen. Furthermore, organisms produce the enzymes Superoxide Dismutase (SOD) and Catalase, which catalyse the safe conversion of superoxide into molecular oxygen and oxygen peroxide. At the same time, the catalase converts hydrogen peroxide into water and molecular oxygen. Interestingly, exposure to hydrogen increases the activity of both enzymes significantly, further potentiating the antioxidant system.

Inflammation

Inflammation is a generic response of body tissue following damage to cells or the detection of potential damaging effectors. Both infectious and non-infectious agents, as well as cellular injury, can activate an inflammatory response. The response is generic because it doesn’t distinguish between the possible causes. The inflammatory response removes harmful stimuli and initiates the healing process while involving immune and circulatory systems. However, it is a balancing act that can go awry. Molecular Hydrogen supplementation acts against inflammation in two synergistic ways. The first is associated with oxidative stress, which can initiate or sustain an inflammatory response. Since Molecular Hydrogen is a powerful antioxidant, it suppresses the oxidative stress signal and reduces the risk of unnecessarily triggering or over sustaining an inflammatory response. And second, all pathways to inflammation pass through the activation of the NF-kB pathway. Molecular hydrogen dampens the NF-kB pathway, directly avoiding a highly detrimental runaway inflammatory response.

NF-kB

NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation and bacterial or viral antigens. It also plays a crucial role in regulating the immune response to infection. Thus, incorrect regulation of NF-κB is linked to many challenges such as inflammatory and autoimmune responses, sepsis, viral infection, and improper immune development. Although the inflammatory response is essential, it can become self-sustaining and become a problem as inflammation causes oxidative stress, and oxidative stress causes inflammation.

Immune Cells

Long-lasting immune challenges result in abnormally high exhaustion rates of immune cells that ultimately lead to their death. Recently, it has been demonstrated that immune cell exhaustion was caused by mitochondrial dysfunction associated with increased reactive oxygen species, such as the hydroxyl radical and superoxide. Immune cell exhaustion is linked to a decrease in mitophagy and an accumulation of dysfunctional depolarised mitochondria. Yet again, we see that supplementation with molecular hydrogen maintains or helps restore the mitochondrial inner membrane polarisation by enabling proton pumping in complex I while decreasing ROS production by the same complex and increasing ATP production. Furthermore, molecular hydrogen supplementation promotes the expression of superoxide dismutase and catalase, further reducing the ROS level and upregulating the PINK1/parkin pathway that enables mitophagy.

The Beneficial Action of Molecular Hydrogen

Since 2007, around 2,000 research papers have demonstrated that Molecular Hydrogen has both anti-oxidant and anti-inflammatory effects throughout a broad range of biological applications and species. Molecular Hydrogen acts as a powerful antioxidant in biological systems both directly and indirectly. Directly by scavenging some Reactive Oxygen Species, and indirectly by boosting natural antioxidant systems. Molecular Hydrogen dampens the NF-kB pathway in normal cells, helping to bring about healing by decreasing inflammation. Hydrogen atoms generally represent 62% of all the atoms in terrestrial bodies. That’s more than 3 out of every 5.

• Molecular Hydrogen improves the normal functioning of the mitochondria.
• Molecular Hydrogen is nature’s own potent anti-oxidant.
• Molecular Hydrogen manages oxidative stress.
• Molecular Hydrogen acts as an anti-inflammatory.
• Molecular Hydrogen decreases proinflammatory cytokines.
• Molecular Hydrogen regulates the action of the NF-kB transcription factor.
• Reactivation of exhausted immune cells

Our entire planet awaits the biological benefit potential of molecular hydrogen and Oxygen supplementation on what will be a grand scale. In poultry, fish, animals, etc… Molecular Hydrogen has been shown to significantly improve mitochondrial function, ATP production, the immune response, decrease oxidative stress, reduce and manage inflammation, considerably improve growth rate, and enhance disease resistance capabilities.

Hydrogen supplementation can improve livestock health, growth rate, and feed conversion ratio such as poultry. A 10-15% increase in weight can be achieved along with an improvement in meat quality while decreasing stimulant and biotic intervention. In aquatic species, increased yields of 30-40% are seen as growth rates rise and mortality decreases. In plants, treatment with hydrogen-enriched water increases yield, salt and heavy metal resilience, flowering potential and fruit set. An increase in H2 in the rhizosphere led to beneficial impacts for subsequent plant growth resulting in a 15–48% biomass increase in plants and termed a hydrogen fertilisation effect. It represents a low-cost solution to improve the nutritional content and enhance production under abiotic stresses, such as drought and salinity, throughout all agricultural endeavours.

We believe that the biological relevance of Molecular Hydrogen represents the single most important technology on the planet today. The progression towards this technology is inevitable, and in these very challenging times, the need is pressing and relevant for all governments the world over.

Hydrogen and oxygen have been intrinsically involved with the evolution of life in both prokaryotes and eukaryotes (e.g. hydrogenases, hydrogenosomes, mitochondria, etc.), and we are at the leading edge of a new understanding of biology. A common theme has already emerged: the supplementation of Molecular Hydrogen into biological systems has a complementary beneficial effect on the entire system. As you can see, there is a vast range of options and potentials that could benefit us all in both the long and short term.

Regardless of what we do or do not do, hydrogen will still be at the core of life itself, and no matter what path any of us take, hydrogen, by count, will remain the single most significant piece of any biological puzzle. From little things – big things come.

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