THE FIRST AND THE GREATEST

With the advent of the Big Bang and the cooling of the universe in the succeeding millionths of a second, high-energy subatomic particles began to stabilize as they cooled down and the first element was formed from this stabilization. Hydrogen, a simple proton with a single electron orbiting around it, became the building block for all the proceeding natural elements in this great big factory of atomic manufacturing. 14 billion years later, the expanding universe still employs the first and greatest building block in its constructive processes. Hydrogen makes up 73% of the visible or observable universe with its first fusion product, Helium, making the other 25%. Everything else from carbon to iron to nitrogen to oxygen, all of us with our planets essentially make up just 2%.

From this history lesson, it is clear to see what mother nature thought of as the first and greatest tool to breathe life into the universe. Perhaps we should follow suit with our bodies don’t you think? Because of its simple structure and myriad of chemical functions, as we will briefly see later, hydrogen serves as the perfect first step to constructing, well, anything organic. Think about it, every other atom you can think of is essentially a different combination of the same base hydrogen configuration. Even the neutrons are essentially a proton and electrons combined into one neutral particle.

For the human body that also means something. Every element in the human body can be theoretically traced back to the hydrogen configuration that our universe was born with and so, it makes perfect sense that hydrogen must have some truly unique and interesting features that make it an amazing bio-chemical booster for the body.

Before we dive into the different forms and ways hydrogen can benefit the human body on our way to becoming something more, a brief lesson in biological chemistry to fine-tune your thinking as to how exactly we can claim hydrogen to be a biological booster for the body.

OXIDATION AND REDUCTION

Forgive the overly science section here but it is important to understand some of the jargon that helps explain why we think hydrogen is the future of healthcare. If any of those boring and dry high school chemistry lessons are lurking around in some corner of the brain, you may recognize these two words: Oxidation and Reduction.

Chemically speaking, Oxidation is defined as a reaction in which any of the following three things occur to an atom:

1. A gain of an Oxygen atom
2. A loss of a Hydrogen atom
3. A loss of an electron pair

When you think about oxidation, one very easy example may come to mind. Rust. Just as any machine part or any item made of iron is left at the mercy of climatic elements, it starts turning a brick red color. That color is of rust and that coating is the result of oxidation of the surface of the iron into Iron Oxide. Similarly, when you cut a piece of fruit and it lays there with its flesh exposed and starts turning brown. Yes, oxidation of the surface of the flesh gives it that color. Oxidation is the basic process by which human respiration occurs and is one of the main reasons we need such a regular supply of oxygen from the air.

The opposite of chemical oxidation is Reduction. It is defined as a chemical reaction in which an atom undergoes any of the following three changes:

1. A loss of an Oxygen atom
2. A gain of a Hydrogen atom
3. A gain of an electron pair

Notice how the requirements of Oxidation and Reduction are exactly opposite to each other. Reduction is often seen alongside oxidation. They occur together so frequently that a blanket term of Redox Reaction is used to describe them both.

Let’s go back to our oxidation examples from before. We discussed the oxidation of iron, of fruit and in our bodies. At the same time you may notice that the added oxygen atoms came from the oxygen molecules in the air. So while all the above was being oxidized, the Oxygen gas in the air itself was being reduced. It’s a redox reaction.

A more streamlined example of reduction is one of extracting metallic iron from its ore. Reduction is employed there to extract the metallic iron by stripping hematite of its oxygen.

Redox reactions are one of the most common reactions in nature, because they so frequently occur together. Even in biological organisms such as ourselves, the millions upon millions of chemical reactions occurring in our body every single day consist largely of redox reactions. Be it by the loss or gain of oxygen, or as we shall see later, the shifting bonds of hydrogen, this concept of redox reactions forms the cornerstone of this chapter.

So what may redox reactions look like inside human bodies? Let’s have a look.

OXIDATIVE STRESS AND AGEING

The human body is a remarkable piece of organic machinery. Partially self-sustaining with an intricate system of regulatory reactions and an equally information dense DNA to boot, the micro-environment of human physiology is not that different from organic chemistry.

Being the carbon based life-forms we are, the human body is composed largely of three elements, namely Carbon, Oxygen and Hydrogen, with little bits of Nitrogen, Phosphorus, Sulphur, Iron here and there. Our entire workings are coded into our DNA and that same DNA also governs how our bodies grow and age with time.

Ageing is a process we all are aware of. From our birth we begin growing in size and intelligence and with time we reach a pinnacle of maximum bodily growth and fitness. For most of us this ‘Prime’ lasts from ages 25 to 40. After that begins the slow descent into old age and our eventual demise. Biologically, all this is translated to the rate and quality of chemical reactions in our body and how our DNA is expressed as time passes.

As we age, our body’s tightly regulated internal systems begin to develop a certain laxness and our energy profile goes from being predominantly anabolic to predominantly catabolic. What this looks like on the sub-cellular scale is the steady increase in the production of certain molecules and reaction products that can lend harm to our cellular structures. We’ll take a brief look into some of those harmful products that can be targeted by the novel hydrogen therapies we recommend.

1. Reactive Oxygen Species
   With literally millions of chemical reactions happening inside the body every day, it makes sense that not all of those reactions will be perfect. Some of them can include harmful “free radicals” such as a single charged oxygen atom, called a reactive oxygen species or ROS. Because of its strong charge, ROS are notorious for stripping electrons away from nearby molecules, achieving stability for themselves whilst making their victim molecules unstable. You can probably extrapolate how that plays out on a cellular scale.
   ROS are generated in our body daily, and their level increases under conditions of physical stress like exercise and disease. Not all ROS are bad though. A certain tiny number of them are useful intermediaries in enzymatic reactions and are even used as chemical signals. The problem arises when there are too many of them floating around to destabilize other organic molecules such as cell membrane components or critical cellular machinery, leading to cell death. Further extrapolation reveals the greater rate of cell death as compared to cell division is what is essentially behind the ageing process.
2. Advanced Glycation End-products
   Advanced Glycation End-products or AGEs are complex lipid and protein molecules that have become coupled with sugars or ‘glycated’ if you will. AGEs have come into light as we have entered the age of fast food and processed goods. They are implicated in the disease processes of various conditions such as Diabetes, Hypertension, Obesity and other Metabolic Syndromes.
   AGEs enhance the oxidative stress on the body systems and additionally they also enhance production of ROS, augmenting cellular damage. Human DNA comes with its own set of antioxidative genes that are normally employed to counter oxidative stress. However, AGEs also attenuate the expression of these genes, limiting the natural antioxidative response the body can exhibit. All of these synergistic effects increase the ageing process and make us prone to the abovementioned lifestyle diseases.
3. Pro-inflammatory cytokines
   Our bodies are remarkable in the level of preparedness they come with preloaded into our DNA to combat environmental and internal insults to our systems. One such line of defense is the level of anti-inflammatory cytokines. These are biologically active molecules and enzymes that provide anti-inflammatory effects by activating our immune system and neutralizing inflammation-causing organisms and processes.

Anti-inflammatory cytokines are themselves counteracted by pro-inflammatory cytokines (that have a role in promoting the inflammation process in the earlier stages of disease in order to contain the damage and seal the causative agents by calling in white blood cells to the area) and for the most part they are in equilibrium throughout our earlier years. Once past our prime or under physical stress, the level of pro-inflammatory cytokines begins to rise. As a result we begin to see a steady increase in our propensity towards diseases and weakness. Chronic inflammatory states like Inflammatory Bowel Disease and Bronchitis are some examples of the long term harmful effects of increased pro-inflammatory cytokines.

1. Genomic Instability
   Let’s face it. We weren’t built to live forever and to have perfect cell replication every single time like our friend the Immortal Jellyfish (Turritopsis dohrnii) or Wolverine or Deadpool. Our DNA, though having a very cool half life of 500 years, is still fallible at the hands of years and years of environmental exposure. From Asbestos exposure to alcohol consumption to Cosmic Rays from deep space to just regular repeated cell division, the human genome accumulates tiny mutations and replication errors in its code.
   On average, scientists estimate that our DNA accumulates about 1.14 spontaneous mutations per cell division during hematopoiesis (blood cell generation from stem cells). Coupled with the average 2 trillion cells dying and being replaced every single day, the spontaneous mutation rate can get very very scary.
   While, fortunately, most of these spontaneous mutations are harmless, a handful can be worrisome for the stability of our genome, and the more exposure to potential mutagens from the environment, the higher this worrisome handful can become.

Many more factors are responsible for ageing and increase in physical stress on the body and this subject is constantly undergoing new breakthroughs and research. The abovementioned 4 are highlighted because the beneficial effects of Hydrogen therapy target these processes. Now that we know what can go wrong, let’s focus on how we can protect ourselves from it with Hydrogen therapy.

HOW CAN HYDROGEN HELP

Hydrogen as we have discussed so far is one of the first stable atoms in the universe and due to its unique structure, it possesses some amazing qualities that render it excellent potential to be used as a therapeutic tool against ageing and disease. The recently increased fascination with hydrogen therapy is seen in the discipline of sports medicine with athletes considering the use of therapeutic hydrogen modalities to aid them in their goal of ultimate fitness. So how can hydrogen help with all the problems we so painstakingly discussed before? Let’s dive in.

Hydrogen being a very light molecule allows it to safely traverse human bio membranes and while our brains may immediately think of hydrogen as flammable, it’s fortunate for us that hydrogen gas is a relatively inert molecule and does not react with oxygen or nitrogen at room or body temperature. It ignites only above 527 Celsius temperature and the therapeutic concentration employed for medical purposes is usually nowhere near the concentration at which the gas can explode (above 4% vol/vol).

These properties of hydrogen allow it a few remarkable roles within the confines of our biological systems, and this is where all the above knowledge on biochemistry will come in handy. While still under research, some of the discovered roles hydrogen can perform at the cellular level include but are not limited to:

• ROS Hunter
  Of all the different reactive oxygen species that can be formed in a chemical reaction, the Hydroxyl free radical (denoted as ⦁OH) is often found in areas of oxidative stress and this radical is hunted down in a hydrogen rich medium. This leads to decreased levels of oxidative stress and inflammation in cells, allowing a longer healthier cell life. We also talked about how some ROS are utilized by the body as intercellular signaling apparatus, and it has been seen that hydrogen only scavenges the hydroxyl radicals and not the oxygen or nitrous radicals. This selective hunting is what makes hydrogen a potentially revolutionary anti-oxidant.
• AGE and Cytokine Inhibitor
  Remember the Advanced Glycation End-products and the Pro-inflammatory cytokines we talked about? Hydrogen plays a role in counteracting the effects of AGE-induced cell death and also acts on the DNA, specifically at the Bcl-2 and Bax genes to reduce the synthesis of ROS. Furthermore, hydrogen can also inhibit the actions of pro-inflammatory cytokines, mainly the Monocyte Chemoattractant Protein-1 (MCP-1), Interleukin 4 and Interleukin 6. This results in attenuation of the inflammatory response and is currently under study for use in the infamous Cytokine Storm of COVID-19.
• Genome Protector
  Tying it in with its effect on ROS synthesis, researches have shown hydrogen to confer a protective effect in the human genome by shielding it from ⦁OH induced ionizing radiation damage. Its protective effects from Cosmic rays in the hopes of providing extra protection during high altitude craft operations is also under exploration.
  Furthermore, a study on bone marrow cells showed that hydrogen therapy increased the replicative lifespans of bone marrow cells in vitro, with decreased rates of mutations all while preserving its genetic expression and function.
• Cerebral Guardian
  In rat models that were given localized brain ischemia followed by administration of hydrogen gas, scientists found that not only did hydrogen reduce the initial brain injury from ischemia-reperfusion, but also markedly retarded the progression of said brain injury as compared to rats who did not receive any hydrogen.
  Hydrogen’s effects on the brain have also been studied with reference to neurodegenerative diseases like Parkinson’s Disease. Oxidative stress due to mitochondrial dysfunction in dopamine producing neurons inside the brain is essentially what causes the features of Parkinson’s disease and hydrogen conferred a therapeutic advantage by suppressing that oxidative stress, decreasing the progression of the disease. This action is now being studied as a potential option to prevent Parkinson’s disease in those with predisposition.
• Improvement in Metabolic Syndromes
  We mentioned how redox reactions and the increased rate of free radical generation was at the core of many metabolic diseases like Diabetes, Heart disease and Obesity. Hydrogen’s effects in these conditions have been studied and it was found that intermediate to long term use of hydrogen rich fluids not only helped in controlling body lipid proportions and weight gain but also increased the metabolic expenditure of fats and sugars by the body by augmenting the process at the genetic level, thereby offering itself as a potential therapy for management of Obesity, Diabetes and reduction in risks of heart disease.
• Anti-Allergy
  While not as extensively studied as some of the above mentioned effects, hydrogen is also theorized to not only suppress free radical generation but also inhibit the immediate and intermediate types of allergic responses by attenuating the signaling machinery that powers this response.

MODALITIES OF HYDROGEN THERAPY

In the quest to further improve mankind’s chances of survival and progress in an increasingly physically competitive world, different methods or modalities of hydrogen therapy have been devised to aid the body in its attempts to repair itself better and stronger for the future. Some of the currently existing modalities include but are not limited to:

Hydrogen Gas

The simplest method of all. Hydrogen gas inhalation is quickly gaining popularity among the research circuits for its easy operability. Because it is very light in its atomic mass, it has a very rapid diffusion time across our bio membranes, and because of its relative inertness in its molecular gaseous form, hydrogen is also a very safe modality to inhale. It does not damage the cell membranes that it crosses, does not interfere with oxygen diffusion in the lungs and has a very good safety profile i.e. it does not show toxic effects even at relatively high concentrations as opposed to other medical gases like Nitrous Oxide and Exogenous Carbon Monoxide or even Oxygen gas itself. Being light and safe also gives it a very quick action time and hydrogen gas shows promising potential to be used in states of acute oxidative stress such as heart attacks and stroke syndromes for rapid reversal of ischemia ridden tissues.

Hydrogen Saline

Normal Saline (0.9% Sodium Chloride solution) is an indispensable fluid in the medical sphere. Used for management of low blood pressure states as well as acute blood loss in the trauma bays or fluid losses due to persistent vomiting or diarrhea, Saline is the go-to fluid whenever doctors need fluid resuscitation in any patient. With the addition of hydrogen in it, the story gets more interesting. Similar to the effects of inhalation, Hydrogen Saline infusion directly into the blood is also a quick way of getting hydrogen into the system. For many conditions such as heart attacks, strokes and other acute oxidative stress states, time is of the essence. So, as an equally effective alternative to hydrogen gas inhalation, hydrogen saline is a good candidate to have in hospital emergencies.

Hydrogen-rich Water

Although regular water already has 2 hydrogen atoms in it per water molecule, hydrogen rich water is being investigated as an even better solution as opposed to just regular water in body states that require anti-inflammatory and antioxidant effects, such as during strenuous exercise or in endurance sports. Hydrogen water is essentially water with additional hydrogen, and occasionally additional minerals pumped in, and is popular among scientists interested in the body’s physiology during sporting activities and thus, long term use of hydrogen water poses to be the next great hit in the energy drink market due to its efficient properties of enhancing stamina, increasing overall energy levels, and attenuating the effect of fatigue on the overall body.

Hydrogen Baths

Just as hydrogen water is a popular ingestion therapy for reversing the effects of physical stress on the body, hydrogen baths are also an alternative and quite interesting method especially to manage body fat. Bathing in hydrogen rich water allows the hydrogen to permeate the skin through pores and it therefore is able to directly target subcutaneous and visceral fat. As we saw above hydrogen increases the utilization of fat and thus, hydrogen baths may very well be an easier method of weight management than, say diet and exercise.

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