Overview
Hydrogen is the most abundant element in our universe — it’s in our water, air, food, and bodies.
An isotope is a different form of an element with the same atomic number (protons) but with a different amount of neutrons, resulting in a different atomic mass and physical properties.
Heavy Hydrogen (‘2H’ or ‘Deuterium) is a stable Hydrogen isotope — Hydrogen with an extra Neutron, making it twice as heavy and twice the size. 2x in size and mass is a massive difference in isotope chemistry, physics, and biology.
Heavy Hydrogen (we’ll refer to it as 2H for the remainder of this Whitepaper) is also naturally occurring — it makes up about 0.015% of all the Hydrogen in our Universe.
But, because there are so many hydrogen atoms in the body, this amounts to a significant amount of 2H in the body – the concentration of 2H in our bodies/blood is larger than the concentration in nature. At approximately 12–14 mmol/L, 2H is present in the bloodstream 2–4x more than glucose, 3x more than potassium, 6x more than calcium, and 10x more than magnesium — molecules that play a significant role in biological functioning, especially when the concentration is altered.
Due to the high concentration of Hydrogen and its involvement in millions of biochemical reactions in the body, altering the ratio of the isotope 2H to regular Hydrogen has proven to have effects on cellular functioning and addressing the root cause of disease.
There’s a growing body of research demonstrating that utilizing an optimal ratio of 2H to H in the body, and periodically lowering this ratio, is a fundamental component of maintaining optimal cellular function, and the cascading downstream health effects from it.
The purpose of this Whitepaper is to examine:
- Do we currently have too much 2H in our bodies?
- If so, which bodily functions could that disrupt? Through which mechanisms of action?
- The research that has been done on the effects of lowering 2H in the body
- Hypotheses for further research
- Protocols and Human3’s plan to pioneer the space of lowering 2H in the body with low 2H Water
Brief History
The existence of 2H was discovered in 1932 by scientists at Columbia University.
Since that time, scientists have been researching the effects of 2H on living organisms, by adding or removing quantities of it and seeing its effects. Over the years, compelling evidence has emerged that lowering the concentration of 2H in organisms can have profound health effects, and vice versa — increasing 2H levels can be extremely damaging to living organisms, accelerating aging and disease.
Current research estimates the optimal ratio of 2H levels in the body to be between 120–130ppm (parts per million). Most people are around 150ppm, a 20% higher level than optimal.
We intake 2H from our food, air, and water.
Tap water and almost all bottled waters have been tested to be at 150ppm. To have an effect on reducing 2H levels, water needs to be below 130ppm. The only natural water in the world that’s been tested close to that — 133pm — is in the Hunza Valley, home of the largest population of centenarians in the world. (More on that later).
Carbohydrates and protein tend to be around 150ppm. Fats have been tested to be 118ppm — an optimal level. In addition, fats are broken down by the metabolic process in the body, it produces metabolic water for the body to use, that has 0 2H. Because of this two-fold effect, an increase in fat consumption is a key aspect of 2H-reduction and understanding how we got here.
Why our are 2H levels “too high” now?
Cells have a natural mechanism to remove excess levels of 2H and maintain an optimal ratio of 2H to H within the cell.
However, some key factors over the past century have increased our 2H intake and compromised the body’s ability to remove excess 2H levels:
- An increased amount of carbohydrates in the diet, and lower amount of fat
- As noted before, carbohydrates are a high 2H food. This coupled with the reduction in fat consumption, a low 2H food that has a two-fold effect on reducing 2H in the body through metabolic water production, has increased the standard load of 2H in the body.
- Increased amount of water consumption
- Drinking loads of water as a means to be healthy is a recent phenomenon, largely driven by marketing campaigns from bottled water companies. There’s no sound biochemical evidence for drinking 3–4L of water per day. The narrative has been to stay hydrated, and not tolerate any degree of thirst. From an evolutionary perspective, this doesn’t make sense — our paleolithic ancestors didn’t sip from water bottles all day.
- The issue is two-fold:
- We’re overloading our bodies with 150ppm water, increasing the 2H concentration
- Chronic ‘overhydrating’ decreases Anti Diurhetic Hormone (ADH) in the body. This decrease leads us to produce less of the metabolic low-2H water mentioned previously.
- Gut Biome
- The microorganisms in the gut reduce 2H in the body by breaking it down from our food and using it as a food source to grow. Lack of diversity in gut bacteria or a change in balance of beneficial gut bacteria due to Glyphosates, Antibiotics, mono crops on nutrient-devoid soil, or an altered soil microbiome has modified our gut bacteria’s ability to reduce 2H naturally
- Lack of sunlight
The Biochemistry
Most therapeutics aim to address health issues from the molecular level.
Modifying 2H is a novel therapeutic intervention because it’s approaching from a sub-molecular level — how cellular function is altered when there’s changes in mass and size of atoms.
This key shift is the main reason why it’s such a promising intervention for addressing the root cause of disease and aging.
Addressing the Root Cause: Sub-Molecular
3 key reasons Low-2H Water is a promising therapeutic for addressing the root causes of disease and aging:
- It addresses cellular functioning at the atomic level
- It doesn’t introduce any new molecules to the body
- No contraindications → an effective adjunct therapeutic
Research
Much of the research on the biochemical effects of excess 2H in the body has come from two prominent Hungarian researchers:
Dr Gabor Somlyai, a molecular biologist and researcher who has been researching low 2H (‘Deuterium Depletion’) protocols and its effect on Cancer for 30 years. His book — Defeating Cancer!: The Biological Effect of Deuterium Depletion is an essential read on the topic, written in 2003.
Dr. Laszlo Boros — a biochemist, professor at UCLA, and researcher who has done considerable research on the topic of the biochemical reactions in the body that are affected by 2H.
In distilling the research of Boros, Somlyai, and others, there’s 3 fundamental mechanisms of action causing issues when we have too much 2H in our bodies:
1. Mitochondrial Disfunction
It damages mitochondrial nanomotors and slows the Electron Transport Chain, reducing the production of ATP (cellular energy).
There are 30 trillion cells in the human body that make up our muscles, organs, nervous system, skin, systems. Each of these cells has about 1,000 mitochondria, an organelle within the cell that produces energy for the cell to do what it needs to do.
Each of these mitochondria has 320,000 ‘nano-motors’ spinning at 3,000rpm to produce ATP — the molecule of energy that cells use. Hydrogen passes through these nanomotors to make them spin, which produces ATP.
When there’s too much 2H in the body, it attempts to take the place of regular Hydrogen in these nanomotors (this will be a recurring theme). The problem is that it’s twice as heavy.
Boros lays out that when you substitute a particle that’s 2x the weight into one of these nanomotors, it slows down the functioning by an order of magnitude or even breaks the nanomotor, damaging the mitochondria’s ability to produce ATP — the energy needed for the cell to function properly.
To get the total amount of mitochondrial nanomotors: 30 trillion cells x 1,000 mitochondria per cell x 320,000 nano-motors = 1.12x10^22 nanomotors in a 70kg human body. These nanomotors functioning properly are essential to health.
When you surpass a threshold of mitochondrial disfunction (60–80%), it leads to cellular disfunction, which can then manifest as disease.
It’s also theorized that it’s likely to slow down the electron transport in the Electron Transport Chain in the mitochondria, and cause upstream accumulation and leakage of electrons, leading to increased free radical generation.
2. Disruptions in Molecule Shape, Function, and Bonds
It goes where Hydrogen is supposed to, altering the shape, disrupting the function, and slowing the reaction rate of molecules by an order of magnitude.
2H’s physical size (2x that of Hydrogen) means it significantly alters the shape of molecules that its apart of. It also strengthens Hydrogen bonds, which slows biochemical reaction rates. Both significantly alter the function of molecules in the body.
This is most important in DNA — it means it can cause errors in epigenetic expression and replication:
- When 2H goes into the deoxyribose sugar backbone moiety that forms the double helix in DNA, there are changes in the shape of the DNA. This effect how the DNA is read and expressed (epigenetic shifts).
- “The addition of a deuterium atom into the newly formed DNA increases the size and hydrogen (1H; P+) bond strength in DNA by about 8 to15 times or, about one magnitude as deuterium’s nucleus (2H; P+N) is twice the size and weight of hydrogen. If this happens more frequently, the cell will end up with additional DNA in the cytoplasm or nucleus or both. A normal human cell wraps all newly synthesized DNA in 46 chromosomes before dividing. If there is too much DNA, the cell will produce additional chromosomes to wrap it all up neatly. This is called aneuploidy or cancer. For example, a pancreatic cancer cell (MIA PaCa) will have 52 chromosomes, a metastatic lung cancer cell 61 (H441). This is why we call deuterium an oncoisotope.”
It’s theorized that it can affect many enzymatic processes as well.
3. 2H is a Growth Factor for Cells, Causing Tumorous Growths
In his landmark paper, Naturally occurring deuterium is essential for the normal growth rate of cells, Dr. Gabor Somlyai established the fundamental role of lowering 2H as a regulator of cell proliferation.
“It is known that the binding site for protons to be transported by plasma membrane H+-ATPase of yeast does not accept deuterons with the same ease as H’ or perhaps not at all [5]. It is therefore reasonable to assume that when the cell eliminates the H+ to govern the pH, by activating the Na’lH’ antiport system [7,8,11] the D/H ratio increases in the intracellular space. We suggest that the cell cycle regulating system is somehow able to recognize the changes in the D/H ratio and when this ratio reaches a certain threshold this will trigger the molecular mechanism which causes the cell to enter the S phase. Our assumption provides explanations for the following observations: (i) the growth of animal cells in tissue culture in deuterium-depleted water slows down because the water with low D content extends the time necessary for the cell to reach the threshold of D/H; (ii) the yeast ATPase gene might behave as an oncogene in mammalian cells [9] because the specific elimination of H’ from the cell generates the high D/H ratio required for cell proliferation; (iii) the absence of Na’/H’ antiport activity precludes cell growth at neutral and acidic pH [16] because cells are not able to increase the intracellular D concentration; (iv) the artificial increase of pH, is not sufficient to stimulate proliferation [12] because it does not modify the internal D/H ratio; (v) a slight increase in the D concentration in the external space stimulates growth because it makes it easier for the cells to elevate the intracellular D concentration up to the threshold.”
Tumor cells need a high D/H ratio in order to divide, evade apoptosis (cell suicide), and continue multiplying. Numerous studies in vitro have shown low-2H water to be able to induce apoptosis in cells.
A healthy cell has a normal method of keeping the 2H/H ratio balanced — it produces low-2H water in its mitochondria. Tumorous cells’ mitochondria are damaged, so they’re not producing metabolic low-2H water — the resulting higher D/H ratio helps them continue to divide.
When you lower 2H in the body, you’re starving the tumorous cells of the high 2H/H ratio needed to continue to divide. Healthy cells are able to adapt to this lower level in the body (and it may even be a form of mitohormesis). Tumorous cells can not, or take much longer to adapt — inducing cell necrosis.
Health Implications
Cancer
Tumorous cells need 2H in order to grow and replicate. Periodically starving them of the 2H they need can trigger their necrosis.
When the 2H/H ratio is left unchecked, cells will continue to grow.
Lowering 2H is an extremely promising therapeutic and annual prophylactic to trigger tumorous cell necrosis.
Aging & DNA
Excess 2H in the body may accelerate aging by disrupting both DNA replication and epigenetic expression.
2H may disrupt DNA replication — how:
- Molecules in DNA bind to one another via hydrogen bonds to create base pairs; DNA has 3 billion bases
- 1 2H bond instead of Hydrogen for every 300 base pairs = 10 million 2H atoms in the genome taking position of protium
- This added mass can distort the precise and optimal shape of DNA — potentially creating errors in transcription
“The addition of a 2H atom into the newly formed DNA increases the size and hydrogen (1H; P+) bond strength in DNA by about 8 to 15 times or, about one magnitude as deuterium’s nucleus (2H; P+N) is twice the size and weight of hydrogen. If this happens more frequently, the cell will end up with additional DNA in the cytoplasm or nucleus, or both. A normal human cell wraps all newly synthesized DNA in 46 chromosomes before dividing. If there is too much DNA, the cell will produce additional chromosomes to wrap it all up neatly. This is called aneuploidy or cancer. For example, a pancreatic cancer cell (MIA PaCa) will have 52 chromosomes, a metastatic lung cancer cell 61 (H441). This is why we call deuterium an oncoisotope.
2H may disrupt genetic expression (epigenetics)
- When 2H populates the deoxyribose sugar backbone moiety that forms the double helix in DNA, there are shape changes that alter the expression of genetic material without small nuclear polymorphism (SNPs) or epigenetic events. Genome transformation that can alter epigenetic expression of genes.
As David Sinclair has succintly put, aging is in and of itself a disease. It’s the key factor in developing other diseases — meaning when we address aging through epigenetic expression and DNA repair, we’re simultaneously addressing a wide array of age-related disease.
Athletic Performance + Physical Energy
The body’s tissues need ATP in order to perform. When the mitochondria aren’t able to produce the same amount of ATP, physical energy available for the tissues is reduced. By reducing the load on nanomotors, the body is able to produce more ATP. In a human study, it ATP levels in the blood increased over 200% while drinking low-2H water (see: Key Studies section).
Obesity / Metabolic Health
Mitochondrial functioning is a key factor in Metabolic Diseases:
- Obesity
- Heart Disease
- Diabetes
By ‘lowering the load’ on the mitochondria, lowering 2H levels effectively allows the cells to return to its more optimal metabolic state. By not adding in any new compounds, low-2H is an essential part of the toolkit for addressing mitochondrial health and metabolic disease.
Vitamin D Metabolism
Vitamin D is essential for all bodily processes. Excess 2H may inhibit the conversion of cholestrol to Vitamin D in the body, causing low Vitamin D levels.
When 2H substitutes for H on the cholestrol molecule, the carbon-2H bond is 7 times more difficult to break than carbon‑H bonds. This prevents the non-enzymatic conversion of cholestrol to Vitamin D. This can cause low levels of Vitamin D.
To Be Studied
These are the main and obvious implications of 2H’s impact on Human Health. All of the above, and the biochemical bases, are factors that can have implications for:
- Neurodegeneration
- Metabolic dysfunction is observed in neurodegenerative diseases
- Mental Health
- Rat study showed similar improvement to stress-induced Depression as SSRI Citalopram
- Autoimmune Disorders
- Anti-inflammatory and anti-viral cytokine production increased in study
Key Studies
More studies and research needs to be conducted, but there’s a significant amount of compelling evidence to immediately introduce low 2H water as a non-invasive prophylactic for cancer and other metabolic disease, as well as a tool to optimize health and wellness.
There’s:
- No known side effects or contraindications, even with long-term consumption
- No new molecules entering the body
- Published papers explaining the biochemical mechanisms of action
- In vitro studies
- Mice studies
- Observational and experimental data
- Anecdotal clinical reports and individual case studies
- Retrospective studies on efficacy for Median Survival Time in prostate, pancreatic, lung, and breast cancer
- Phase II, randomized, double-blind clinical study on prostate cancer
- Phase II clinical study on pre-diabetic or diabetic patients showing improvement in glucose and insulin sensitivity
- Approval for use as a pharmaceutical product for pets in Hungary to treat cancer
High Level Study Takeaways
- Cancer: Retrospective study found 3x — 7x increase in Median Survival Time in 2,222 cancer patients treated with low-2H water
- Cancer: Random Double Blind Phase II Clinical Trial found increase in MST + lifespan extension in prostate cancer patients
- Athletic Performance: Improved Athletic Performance 21% (RDI) — 29% (OI)
- Athletic Performance: Improved ATP levels in blood 238%
- DNA: Cells given TNF-Alpha and DDW showed a 29.5% decrease in single-strand DNA breaks from the Control, suggesting an activation of DSB DNA repair.
- Aging: Significantly increased some markers of redox imbalance in blood components (superoxide anion-radical production, catalase, and glutathione peroxidase activities), suggesting mitohormesis. Mitohormesis has increasingly been studied as a therapeutic for aging.
- Depression: Ameliorated stress-induced depressive-like changes in mice, similar to Citalopram SSRI
- Diabetes: Stimulated GLUT4 Translocation in diabetic mice — a key enzyme in the role of blood sugar levels
- Immune system: Antiviral cytokine IFN‑γ increased 37.5% (p<0.01) and Anti-inflammatory IL-10 increased 36% (p<0.05)
Further Research
Some intriguing areas of focus for further research:
Aging & Disease Prevention
In his work, David Sinclair has outlined important epigenetic factors to address aging as a disease — a disease that causes all other disease through ex-differentiation.
If we can both decrease DNA damage AND increase activity of the longevity genes, we stand to address issues in the genome and epigenome that result in aging.
The first area of research to explore is determining whether lowering 2H in the body to an optimal range (from 150ppm to 125–130ppm) has an effect on these epigenetic factors. After that, we will explore its effects on inflammation, blood glucose levels, mental health disorders, and athletic performance.
Epigenome
Does lowering 2H levels in the body impact:
- NAD levels
- Reduction in DNA damage (DNA Methylation, ‘Biological Age’)
- Activity of the longevity gene pathways: Sirtuins, mTOR, AMPK
- ‘Mitohormesis’ in the cell (slight stress for adaptation)
Other Key Biomarkers
- C‑Reactive Protein (Inflammation)
- Vitamin D (Testing body’s ability to convert cholestrol to Vitamin D)
- TNF-Alpha
Blood Glucose
- Does lowering 2H levels improve blood glucose levels in people with Diabetes?
- Does lowering 2H levels blunt blood sugar spikes (using CGM i.e. Levels)?
Depression
- Does lowering 2H levels have an impact on neurotransmitter production?
- Does lowering 2H levels show a double-blind impact on Depression, Bipolar, or Anxiety?
Athletic Performance
- Does lowering 2H levels improve strength, endurance, recovery (inflammation)?
Conclusion
The human body is so intricately balanced at the atomic level — a scale that’s challenging for us to deeply comprehend.
Modifying the fundamental components of cell biology, without adding any new compounds to the body, is a breakthrough for preventative health.
The aim is to make this simple nutraceutical technology ubiquitous and cost-effective, so that preventative health and a simple means to push the needle on longevity is accessible to all.
The Hunza Valley in Pakistan is a living case study of how 2H can impact health/longevity.
In this region resides the largest population of centenarians on Earth, where it’s been reported that people live to 110+ years old.
The Hunza people drink water from the Ultar Glacier. We’ve tested this water and found it to be ~20% lower in 2H (133ppm) than most other (RO/Tap/Spring) water we drink in other parts of the world. Hunza is unique in that despite being at a high altitude, the rainfall is very minimal, meaning high 2H rain water doesn’t dilute the low 2H water from the glacier.
It’s the only place where centenarian claims have been both not purported by fraud, and has a scientific explanation with the water being tested.