It is now possible to virtually eliminate cow methane emissions by manipulating the type of water they drink and the feed they have access to.

Changing the environment of the Rumen, changes what can live there.

Research suggests that elevating the dissolved concentration of molecular hydrogen to 100µM (0.2 ppm) or more, will thermodynamically inhibit methanogenesis.

This suggests that an easy delivery mechanism would be for the animal to drink hydrogen (and oxygen) saturated water.

 

If cows were to drink Hydrogen nanobubble-infused water, it is expected that it should suppress all rumen methane production.

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The World Hydrogen 2022 Summit and Exhibition will take place on the 9th to 11th of May 2022 in Rotterdam Ahoy, Netherlands. The event is the largest gathering of hydrogen-related stakeholders and a great opportunity to learn about the latest advancements in this growing industry. 

The three-day Summit will feature 90 global leaders driving the Hydrogen industry forward. In addition, running parallel to the Summit Sessions, the H2 Tech Series offers attendees a unique opportunity to hear directly from global hydrogen experts presenting their company’s latest technologies and solutions. 

Hydrogen Technologies will be represented by our Hydrogen Technologies EU’s head of Research and Development, Medical devices and healthcare applications, Mr. Mario van den Bree.  

Hydrogen Technologies are a socially responsible engineering solutions company applying the groundbreaking science of supplementing molecular hydrogen and oxygen to living organisms for greater health and vitality. Our products are used for a range of applications, including agriculture, aquaculture, water enrichment, bathing, drinking as well as hydroponics, to name only a few. 

To find out more about Hydrogen Technologies, head to Booth B27 on the 9th and 10th of May at the World Hydrogen 2022 Summit and Exhibition in Rotterdam Ahoy, Netherlands. We’ll have several of the Hydrogen Technologies products on display, including: 

• Moleculizer 810 
• Hydro-qube “QB5” 
• Hydro-qube “QB-10” 
• With Cart and Accessory systems 

Don’t forget to catch Mr. Mario van den Bree’s presentation at the H2Tech Series at 5pm on Tuesday the 10th where he will identify several of the globally significant applications where Hydrogen Biology relevance actually changes the game and significantly benefits. 

Hydrogen Biology based technologies represent the future of health. We look forward to seeing you there! 

Helpful links: 

https://www.world-hydrogen-summit.com/speakers/mario-van-den-bree/ 

https://www.world-hydrogen-summit.com/registration/ 

The post Hydrogen Technologies at the World Hydrogen 2022 Summit and Exhibition first appeared on Hydrogen Technologies.

In keeping with the analogy of electricity production, ATP can be produced by various means, one of which is solar. ATP is produced in plants using solar energy in an organelle called chloroplast, while another cell organelle the mitochondria, provides the baseload ATP production in plants, animals, and fungi. Other processes in the cell can produce ATP and provide peak load power, the main ones being the phosphocreatine system for extremely fast supply of ATP in the very short term (much like a battery system), and glycolysis for a quick (if inefficient), production of ATP like a gas-fired power station. In this analogy the mitochondria are the nuclear central that provide the baseload and takes longer to adapt. In all cases, ATP is formed by adding a phosphate group to a molecule of Adenosine Diphosphate (ADP).

To illustrate the importance of ATP in cell physiology, let’s examine for example its function for insulin release. Insulin is produced by pancreatic Beta-cells and stored for future use in vesicles ready to be released in the bloodstream. Insulin promotes cellular glucose uptake, particularly in muscle and adipocytes (fat-storing cells), helping to maintain an optimum glucose level in the bloodstream. While insulin promotes glucose uptake, glucagon produced by the pancreatic alpha-cell promotes its release in the bloodstream. The Pancreatic Beta-cell secretes insulin into the bloodstream in response to glucose, a process that has everything to do with the relative level of mitochondrial ATP vs its precursor ADP in the cell. In the cellular membrane of the beta-cell, two channels are key to the secretion of insulin, one is the voltage-dependent Calcium channel which is closed at the normal beta-cell resting potential, and the second is an ATP sensitive potassium channel. This channel allows the exit of potassium from the beta cell, maintaining the proper resting potential. While ADP (the precursor of ATP), promotes its opening, ATP promotes its closing, and thus a change in membrane potential ad consequently the calcium channel’s opening. The entry of Calcium in the cell will trigger the fusion of the insulin vesicles with the cell membrane, and thus the release of insulin into the bloodstream.

So how is the level of glucose in the bloodstream sensed? As the glucose concentration in the blood increases (e.g. after a meal), the amount of glucose that enters the cell increases. Glucose is converted to pyruvate and is then transported to the mitochondria, which results in an increased ATP production by the mitochondria (Figure 2). The increased production of ATP translates into a rising concentration of ATP in the cell, coupled with a decrease in the concentration of ADP (ADP is consumed when producing ATP), which will close the ATP-sensitive potassium channel, inducing depolarisation of the cell membrane. This depolarisation enables the opening of the voltage-dependent calcium channel, enabling calcium to enter the cell. This in turn, causes the fusion of the insulin-containing vesicle with the cell membrane and the release of insulin into the bloodstream.

In the example above (figure 1), potassium exits the cell because there is always more potassium inside the cell than outside the cell, however in the case of calcium, the calcium concentration in the cytoplasm is maintained low compared with the outside concentration, thus the opening of calcium channel will always trigger an entry of calcium into the cell. Once again, ATP is necessary to maintain the normal relative potassium, sodium, and calcium concentration inside and outside of the cell. In pretty much all cell type’s membranes, there exists a sodium-potassium pump powered by ATP. Three sodium ions are exported for every ATP molecule that the pump uses, and two potassium ions are imported into the cell. These pumps ensure that the extracellular concentration of sodium is always higher outside the cell, whereas the concentration of potassium is always higher inside the cell. Calcium is a critical modulator of enzymatic activities, thus its concentration inside the cell is highly regulated, especially in the cell cytoplasm. Therefore, an ATP dependent calcium pump is found in the cell membrane and will pump one calcium outside the cell for every ATP it consumes. The regulation of Calcium concentration in the cell is essential, and thus, additional mechanisms exist for its control, however, they are still reliant on there being enough ATP available to facilitate it.

The availability of ATP for protein folding is another example, as it is not only the protein amino-acid sequence that determines properties or activity but also its 3D structure that defines it. In any organism, each gene codes for one or more proteins, and to build proteins, each cell needs to transcript DNA to RNA, and then read (translate) the RNA to build the protein sequences. The young protein then needs to be properly folded to acquire proper function. Protein folding is a very complex process, but it is dependent on ATP, and if there is not enough ATP present, the protein is likely to be misfolded. The misfolding of protein can affect the recognition of self by the immune system as well as cellular function itself. However, terminally misfolded proteins are generally directed to recycling by protease before they leave the reticulum endoplasmic and thus, mechanisms exist within the cell to avoid undesirable consequences even though they are not fool proof.

ATP as an energy source also enables muscle contraction and relaxation, it enables a heart to beat, and the reabsorption of important metabolites by a kidney. As a signalling molecule, it is used as a neurotransmitter by some neurons, but it is also one of the building blocks of RNA, and the precursor of dATP (deoxyadenosine triphosphate), a building block of DNA. Although we have tried to use familiar examples to highlight the importance and relevance of ATP in biology, it is species indifferent and virtually all life works the same way. The primary function of mitochondria is to convert chemical energy into a biological energy, to be used by every cell throughout the entire body, regardless of species. The ability to produce more ATP or less, is dependent on a great many things however, it is directly related to the efficient functioning of the mitochondria.

Hydrogen is a major constituent of any life form and represents more than three of every five atoms in animal species, and just under half of all the atoms in plants. Hydrogen, both its protons and electrons, appears to not only enable, but also optimise energy production by mitochondria and chloroplast. The significance of hydrogen in biology cannot be underestimated as it is part of the very first step in mitochondrial function as well as the last, be it part of a proton pump, the transfer of electrons, and the completion of redox balance and homeostasis.

There are an estimated 37.2 trillion cells in the body and each cell contains between 2 and 2500 mitochondria each possessing 17,000 ATP assembly line. Thus, it is estimated that there are about 10 million billion (10,000 trillion) mitochondria in an adult human for example! The oxidative phosphorylation of one molecule of glucose consumed by the cell results in the production of 32 ATP by the mitochondrion.

Molecular hydrogen supplementation has the ability to increase mitochondrial ATP production by more than 50% while decreasing the production of superoxide by the first respiratory complex, thus increasing cell energy availability while decreasing harmful reactive oxygen species. The ability to increase the production of ATP while reducing the production of reactive oxygen species and reducing the need to repair the damage they cause, represents an advancement in biological strength and health that could not be more relevant in today’s world.

Very recently it was demonstrated that H₂ supplementation suppressed superoxide production¹ by complex I, its main producer. Furthermore, Ishihara et al. suggested that H₂ donated electrons directly in the Q chamber of complex I¹, consequently making 2 more H+ available also. Two main mechanisms are possible, but given that Hydrogen evolution (the production of H₂ from two protons) by complex I in plants have recently been demonstrated², the most likely mechanism is that complex I acts as an oxygen insensitive hydrogenase capable of both using Hydrogen to reduce ubiquinone to ubiquinol, and to accept electrons from ubiquinol and evolve Hydrogen gas from two protons. Regardless of how H₂ participates in the respiratory chain, it is demonstrated that H₂ supplementation translates into more than a 50% per min increase in ATP production by the mitochondria³, as well as the significant reduction of superoxide at the same site. It is also known that H₂ supplementation upregulates superoxide dismutase and catalase. This taken together with the significant reduction of superoxide production in the matrix by complex I, represents enormous biological benefit to the mitochondria. Furthermore, the ATP increase appears to be partially a least, to be uncoupled from nutrient intake. An increase in ATP production by the mitochondria following H₂ supplementation, means that cells can divert the nutrients not used to produce energy, into the production of the building blocks of the cells. This further explains why crops supplemented with hydrogen can invest more energy into growth and production as well as the increased rate of wound repair and recovery from exhaustion and injury in animal species.

Peer-reviewed scientific documents now run into the thousands. Taken collectively they clearly identify that the deficiency of hydrogen, and consequently ATP, in biological organisms costs the world well over 100 trillion dollars in unnecessary expenses or lost income every single year. It underpins the health potential and lifespan of all things, ultimately and consequentially our entire biosphere (including its climate) as we know it. From a scientific viewpoint, it is only now that we are beginning to realise the importance of molecular hydrogen in biology and its tremendous benefit. From little things, big things come, and it is from the smallest atom that comes a planet of life.

References:

1.      Ishihara, G., Kawamoto, K., Komori, N. & Ishibashi, T. Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential. Biochem Biophys Res Commun 522, 965-970 (2020).

2.      Xin Zhang et al. Mitochondria in higher plants possess H2 evolving activity which is closely related to complex I.

3.      Gvozdjáková, A. et al. A new insight into the molecular hydrogen effect on coenzyme Q and mitochondrial function of rats. Canadian Journal of Physiology and Pharmacology 98, 29-34 (2020).

The post ATP first appeared on Hydrogen Technologies.

Jim Wilson – Director – Founder

Adenosine triphosphate (ATP) is often described as the energy currency of life, and every cell needs to produce it to sustain its normal function. ATP is mainly formed into two cell compartments the cytoplasm periphery adjacent to the cell membrane and the mitochondria generally situated closer to the nucleus and the reticulum endoplasmic. While peripherical ATP production uses aerobic glycolysis and provides a fast response to rapid change in ATP demand, the mitochondria provide a large amount of ATP and is less sensitive to quick changes of demand. They can be described as satisfying the base-load demand¹. Interestingly manipulation of peripherical ATP demand, for example, by inhibition of Na+/K+ membrane pump, translates into a decrease in glycolysis, while manipulation macromolecule synthesis translates into changes in respiration rate and thus changes in ATP by the mitochondria¹.

The Respiration Chain:

The mitochondrion is a cell organelle enclosed by a double membrane – an outer membrane and an inner membrane – separated by the intermembrane space. It is on the inner membrane surrounding the DNA containing matrix that are localised the respiratory complexes responsible for ATP production. The respiratory chain comprises five protein complexes, Complex I, II, III, IV and V (Figure 1). The general purpose of the respiratory chain is to pump protons (H⁺) from the matrix to the intermembrane space, resulting in a larger concentration of H⁺ (Hydrogen ions) in the intermembrane space than in the matrix, so in creating a chemical and an electrical gradient. The creation of this gradient will provide the energy necessary for the synthesis of ATP by the ATP synthetase (complex V) following the terminal electron acceptor role of Oxygen in complex IV. The re-entry in the matrix of 3-4 moles of H⁺ at complex V, converts into the production of one mole of ATP. The motrice force necessary to pump protons across the membrane is provided by electron transfer (figure 1).

Complex I:

Complex I is an NADH : ubiquinone oxidoreductase, and is one of the largest membrane-bound enzymes in the cell. Complex I contains 44 subunits in mammals², including 14 core subunits enabling its catalytic activities and conserved from bacteria to humans^3,4. Complex I catalyse NADH oxidation to NAD+ on the matrix side, capturing 2 electrons that are going to be transferred toward the membrane domain along a  Flavin Mononucleotide (FMN) located near the site of NADH oxidation and a chain of iron-sulfur clusters up to the N2 cluster from which the electrons are going to be donated to the Ubiquinone-10 (Q10 or Q) in the Q chamber, thus reducing the lipophilic Ubiquinone to Ubiquinol (QH2). QH2 will transport the electron across the inner membrane and donate them to complex III. The reduction of Ubiquinone to ubiquinol provides the energy necessary to transport four protons (Hydrogen ions) across the complex I membrane domain⁵. It is of note that NAD+ is reactivated to NADH via Beta oxidation of fatty acids and the tricarboxylic acid cycle taking place in the mitochondrial matrix.

Complex I is able to leak electrons at two sites ⁶ and transfer them to Oxygen forming superoxide ions (O^.-) during the transfer of electrons from the NADH oxidase to the N2 cluster. The superoxide produced is found in the matrix, which can be converted in the matrix to hydrogen peroxide via a manganese superoxide dismutase (MnSOD). Complex I is the main source of ROS (reactive oxygen species) in the respiratory chain. If the production of superoxide is not balanced out by the activity of MnSOD, superoxide can deactivate complex I⁷. Superoxide is also the primary source of the very destructive Hydroxyl radical.

Complex II:

Complex II is a Succinate : ubiquinone oxidoreductase, and is composed of 4 subunits. The two largest subunits function as succinate dehydrogenase, oxidising succinate to fumarate. The two electrons freed are transferred to a covalently bound FAD (Flavin adenine dinucleotide)⁸ reducing it to FADH2, from there the electrons are transferred to be ultimately donated to ubiquinone Q reducing it to ubiquinol. Complex II is not a major leakage site but may produce some superoxide on the matrix side of the intermembrane. Complexe II does not pump H⁺.

Complex III:

Complex III is a Ubiquinol cytochrome c reductase, and is a symmetrical dimer that contains 11 subunits each in mammals. Complex III receive successively two ubiquinol in the Q₀ chamber each time, transferring one electron to cytochrome c that will transfer them again to complex IV, and one electron to its Q_i site where ubiquinone is reduced to ubiquinol in a process called the Q cycle. So, one Q cycle sees the oxidation of two ubiquinol to ubiquinone at site Q₀, the reduction of cytochrome c and the reduction of one ubiquinone to ubiquinol Q_i. The transfer of electrons provides the energy necessary to transfert 4 H⁺ (4 x Hydrogen ions) to the intermembrane space (two of which are pumped from the matrix). Complex III can produce superoxide at each Q site resulting in superoxide release both in the intermembrane space where a copper-zinc superoxide dismutase (CuZnSOD), converts it to hydrogen peroxide. At the same time, the MnSOD in the matrix serves the same purpose⁶.

Complex IV:

Complex IV is a Cytochrome c oxidase, and is composed in mammals of 13 subunits. It transfers electrons from cytochrome c to the terminal electron acceptor O2 (Oxygen gas) to generate H2O, pumping four H+ (4 x Hydrogen ions) from the matrix to the intermembrane space. It is in this complex that Oxygen plays its role in the creation of ATP and mitochondrial function as the terminal electron acceptor at the end of the electron transport chain following the pumping of 12 hydrogen ions.

The ATP Synthase:

The ATP synthase sometimes called Complex V, is a mitochondrial enzyme localized in the inner membrane adjacent to the respiratory complexes. It catalyzes the synthesis of ATP from ADP and phosphate, using the energy derived from the re-entry flux of protons (H+) in the matrix from the intermembrane space. Thus, the respiratory chain enabled accumulation of H+ (Hydrogen ions) in the intermembrane space is the power that enables ATP synthesis in the mitochondria. The energy needed to pump H+ from the mitochondrial matrix to the intermembrane space is naturally derived from the metabolism of nutrients that we consume, such as the tricarboxylic acid cycle (also called the Kreb cycle), and the Beta oxidation of fatty acids or glutaminolysis. It is therefore directly associated with both the food and toxins ingested on a daily basis, that will determine the availability of the required cellular and mitochondrial ingredients, that enables an increase or decrease of ATP production.

Ultimately, the more H⁺ that are pumped into the intermembrane space, and the greater the difference with the H⁺ concentration in the matrix, the more ATP that can be produced by the ATP synthase and in consequence, the more ATP that is available to sustain cellular processes, and of course, life itself. Generally speaking, the less ATP produced, the less resilient an organism can be.

The Action of Molecular Hydrogen (H2) Supplementation on the Respiratory Chain:

Very recently it was demonstrated that H2 supplementation suppressed superoxide production⁹ by complex I, its main producer. Furthermore, Ishihara et al. suggested that H2 donated electrons directly in the Q chamber of complex I⁹, consequently making 2 x H+ available also. Two main mechanisms are possible, but given that Hydrogen evolution (the production of H2 from two protons) by complex I in plants have recently been discovered¹⁰, the most likely mechanism is that complex I acts as an oxygen insensitive hydrogenase capable of both using Hydrogen to reduce ubiquinone to ubiquinol, and to accept electrons from ubiquinol and evolve Hydrogen gas from two protons.

Regardless of how H2 participates in the respiratory chain, it is demonstrated that H2 supplementation translates into more than a 50% per min increase in ATP production by the mitochondria¹¹, as well as the significant reduction of superoxide at the same site. The significant reduction of superoxide production in the matrix by complex I, represents enormous biological benefit to the mitochondria. Furthermore, the ATP increase appears partially a least, to be uncoupled from nutrient intake. An increase in ATP production by the mitochondria following H2 supplementation, means that cells can divert the nutrients not used to produce energy, into the production of the building blocks of the cells.

Refences:

1.      Epstein, T., Xu, L., Gillies, R. J. & Gatenby, R. A. Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane. Cancer Metab 2, 7 (2014).

2.      Rodenburg, R. J. Mitochondrial complex I-linked disease. Biochim Biophys Acta 1857, 938-945 (2016).

3.      Bridges, H. R. et al. Structure of inhibitor-bound mammalian complex I. Nat Commun 11, 5261 (2020).

4.      Zhu, J., Vinothkumar, K. R. & Hirst, J. Structure of mammalian respiratory complex I. Nature 536, 354-358 (2016).

5.      Zhang, X. C. & Li, B. Towards understanding the mechanisms of proton pumps in Complex-I of the respiratory chain. Biophysics Reports 5, 219-234 (2019).

6.      Zhao, R. Z., Jiang, S., Zhang, L. & Yu, Z. B. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int J Mol Med 44, 3-15 (2019).

7.      Indo, H. P. et al. A mitochondrial superoxide theory for oxidative stress diseases and aging. J Clin Biochem Nutr 56, 1-7 (2015).

8.      Dourado, D. F. A. R., Swart, M. & Carvalho, A. T. P. Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron-Transport Chain for the Conversion of FADH₂ into FAD. Chemistry 24, 5246-5252 (2018).

9.      Ishihara, G., Kawamoto, K., Komori, N. & Ishibashi, T. Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential. Biochem Biophys Res Commun 522, 965-970 (2020).

10.    Zhang, X. et al. Hydrogen evolution and absorption phenomena in plasma membrane of higher plants. (2020).

11.    Gvozdjáková, A. et al. A new insight into the molecular hydrogen effect on coenzyme Q and mitochondrial function of rats. Canadian Journal of Physiology and Pharmacology 98, 29-34 (2020).

The post How ATP is Produced in the Mitochondria and the Benefit of Molecular Hydrogen first appeared on Hydrogen Technologies.

Jim Wilson – Director – Founder

Hydrogen is a major constituent of any life form and represents more than three of every five atoms in animal species, and just under half of all the atoms in plants. Hydrogen, both its protons and electrons, appears to not only enable, but also optimise energy production by the mitochondria. The significance of Hydr-Oxygen in biology cannot be underestimated as it is part of the very first step in mitochondrial function as well as the last, be it part of a proton pump, the transfer of electrons, and the completion of redox balance and homeostasis.

While the global hydrogen focus seems to be around energy production to power our transport and service needs, we believe the big story is its relevance to biology and its role in all living things. The total value of the hydrogen energy sector (an estimated 8 trillion dollars) pales compared to the 100 trillion dollars plus estimate when considering the relevance associated with the hydrogen biology sector. The significance and diversity of this must not be underestimated. The use of hydrogen and oxygen supplementation will define improvements in food production and health for the next hundred years.

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.

Please contact us, we would love to hear your thoughts.

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