Key Takeaways

• Light Water, a form of water that removes ~20% of Heavy Hydrogen (2H) isotopes, has proven to be an effective therapeutic for Cancer, especially in conjunction with standard of care

• Research is showing it to be a promising therapeutic for preventative health, slowing Aging/DNA Damage, improving Athletic Performance and Energy levels, relieving biological aspects of stress-induced Depression, and improving markers of Metabolic Disease such as Obesity.

• We have too much 2H in our bodies partly because of increase in water consumption and carbohydrate consumption over the past century.

• It has no known contraindications or side effects from long term consumption; unlike supplements or drugs, it introduces no new compounds to the body.

• Not a ‘water fad’ -- Alkaline water has 0 studies backing its claims. Light Water has dozens.

• Currently sells for $10/Liter due to expensive production methods. Human3 has pioneered a low-cost production method that will retail at ~$3/Liter.

I. 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 our plan to pioneer the space of lowering 2H in the body with low 2H Water

II. 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. **Add studies

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:

1. 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.

2. 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.

3. 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

4. Lack of sunlight

#2 seems to be the key factor — it explains why someone following a Ketogenic diet, getting loads of sunlight, and eating organic foods that are nutrient-dense and probiotic-rich may still have a 2H level in the body above 140ppm. The healthiest among us are simply drinking too much 150ppm water.

III. 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:

1. 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.

2. 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, we find 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.

Further Reading

• Biological effects of deuteronation: ATP synthase as an example

• Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle

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.

IV. Implications on Human Health

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

• 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.

Study showing the DNA repair effects of low-2H water (in vitro) detailed in Key Studies section.

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

• Skin & Gut Health

  • Skin-condition causing yeast and bacteria need high 2H levels to propagate

V. 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.

Currently:

• 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)

https://lighto2.notion.site/All-Study-Summaries-5b1538380bf6422db4591b498639afd7

VI. Protocols

Light O2 Water

Light O2 Water (working title) combines two technologies to create a formula that has a profound impact on the human body in the short and long-term: 120ppm 2H Heavy Hydrogen, and 30ppm of O2, dissolved oxygen.

• 120ppm (20% reduction) of 2H brings the body’s 2H levels down to an optimal level over 3-4 weeks

• 30ppm of dissolved O2 oxygen gives an immediate burst of mental clarity and physical energy as oxygen enters the cells minutes after drinking

Protocols

With modifying 2H levels in the body, the goal is not to get it as low as possible. In fact, this can be detrimental.

The goal is to modify 2H levels in order to illicit beneficial change within the cells.

Depending on the goals and state of the individual, there are protocols to follow.

Preventative Health (Drink for 3 months per year)

Goal

• Annual ‘cleanup’ of damaged/diseased cells to prevent unwanted cellular growths

Mechanism

• By substantially dropping the 2H levels in the body, diseased cells are starved of the 2H needed to grow, and can not adapt. This triggers cell necrosis of damaged/diseased cells, preventing unwanted growths in the body.

Optimization + Longevity + Prevention

Goal

• Decrease 2H load in body to 125pmm year-round

• Oxygenate cells all day for performance

• Annual ‘cleanup’ of damaged/diseased cells to prevent unwanted cellular growths

Protocol

• 120ppm 2H for 9 months

• 85ppm 2H for 3 months

Mechanisms

• Max Oxygenation of Cells

• Improved ATP production

• Decreased DNA Damage

• Increased Cellular Hormesis

• Annual Cell Necrosis

Chronic Illness / Cancer

Goal

• Kill off diseased cells with stepwise solution over 6-9 months

• Oxygenate cells

Protocol

• 105ppm for 2 months

• 95ppm for 2 months

• 85ppm for 2 months

• 75ppm for 2 months

→ Then go into Longevity + Prevention protocol

VII. Further Research & Plan Forward

Few studies have been conducted on dissolved oxygen O2, as the technology is something we’re pioneering. What’s known is that it’s safe, and has a beneficial effect on the human body.

We plan to fund and pursue further research in the fields of Epigenetics, Aging, Metabolic Disease, and Wellness, using our combination of low-2H and high-O2.

Below are our initial focuses:

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 the blood sugar spikes (using Levels)?

Depression

Rat Study: Does lowering 2H levels have an impact on neurotransmitter production?

Clinical Study: 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)?

VIII. 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.

Our 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.

With proper education, we aim to bring the benefits of the Hunza valley’s atomic elixir to the rest of the world.

Cannabidiol, commonly known as CBD, has infiltrated the mainstream over the past decade, and its beneficial effects on the human body are now widely known.

Cannabinoids like CBD interact with the human body through the endocannabinoid system and noncannabinoid receptors, modulating brain functions like sleep and stress responses.

The purpose of this whitepaper is two-fold:

1. Explain the scientific mechanisms for the effectiveness of both standard CBD and Instant Hemp™, a nanotech CBD with particles 100x smaller than other CBD tinctures.

2. Explore how CBD affects the nervous system and other biological systems, and how nanoparticles from Instant Hemp™ can vastly improve the effectiveness and time it takes to feel these benefits.

Instant Hemp™ was designed for those that aim to substantively feel the subjective benefits of CBD – quickly:

• Creatives

• Biohackers seeking to optimize their sleep quality (falling asleep, staying asleep longer, and increasing Deep/REM sleep).

• Psychedelic explorers

• Athletes

• Working professionals

Top use cases As reported by users from from beta testing.

1. Deep Sleep + REM sleep optimization

2. Falling back asleep in the middle of the night

3. Creative work – accessing divergent creative thinking

4. Socializing – a social lubricant that acts as an alternative to alcohol

5. Facilitating a soft landing from a psychedelic session

6. Recalibrating the nervous system from stressful events

7. Downshifting from an action-packed day into evening

The Poor Bioavailability of CBD

A supplement can only have an effect if the body can absorb it.

Bioavailability—the rate and degree at which a substance enters the bloodstream—is crucial to creating CBD products that deliver proven benefits.

The bioavailability of CBD depends on several factors, including the method of consumption. If an individual receives CBD directly into the bloodstream (for example, via an intravenous bolus injection), bioavailability is, by definition, 100%. This means that CBD will exert its full effect.

Other methods, such as oral capsules, are less effective.

After oral administration, the amount of CBD that reaches the bloodstream depends on:

1. The particle's size

2. Ability to dissolve in water (hydrophilicity)

3. Ability to dissolve in oil (lipophilicity).

To apply its medicinal effect, CBD particles must be sufficiently hydrophilic to dissolve in body fluids at the site of absorption (e.g., under your tongue or in the gastrointestinal tract), but also sufficiently lipophilic to pass through cell membranes (made of two layers of lipid molecules).

Most CBD tinctures on the market are oil-based, lipophilic solutions.

Bioavailability from a regular oil-based capsule formulation of CBD was estimated to be as low as 6% due to poor ability to dissolve in water and significant hepatic first-pass metabolism.

Hepatic first-pass metabolism is a phenomenon of drug metabolism whereby the concentration of the active ingredient (in this case, CBD) is greatly reduced before it reaches systemic circulation.

In addition, standard CBD particles don’t get absorbed in the gut easily.

All these characteristics drastically reduce the bioavailability and therapeutic effects of CBD. So - theoretically, if you consume 150 mg of standard oil-based CBD, only 6% of it (9 mg) will arrive in your bloodstream to produce an active effect. This means that you may need a very large quantity of CBD to have a therapeutic effect.

CBD at the Nanoscale

Nanotechnology deals with dimensions less than 100 nanometers, which is 1,000 times smaller than the width of human hair.

We've applied the science of nanotechnology to improve the effectiveness of CBD 5-fold.

Breaking down CBD into nanoparticles accomplishes two things:

• Increases solubility in water

• increases surface-area-to-volume ratio.

Increased solubility in water allows the particles to absorb under your tongue and along the gastrointestinal tract, allowing them to reach the bloodstream.

The increased surface area in contact with the body's tissues greatly improves absorption.

The tiny particle size of the molecules allows them to effortlessly fit between the spaces in your cells, including the mucous layer in the mouth, and the gastrointestinal lining of the gut. Standard large CBD particles are unable to fit through the mucous layer.

Instant Hemp™ effectiveness

Instant Hemp is taken sublingually. Its tiny particle size and ability to dissolve in water allow it to be absorbed through the mucous membrane in the mouth.

This gets the CBD to the bloodstream in minutes, avoiding the problems associated with digestion and first-pass metabolism. Ultimately, this produces a substantially higher concentration of CBD in the bloodstream.

Recent studies with nanoformulations have demonstrated this effect.

Atsmon and colleagues compared the bioavailability of Sativex® (an oromucosal spray with approximately equal doses of THC and CBD) to a CBD/THC nanoemulsion in healthy male volunteers. The authors reported several advantages of the CBD/THC nanoemulsion over Sativex®, including a faster rate of absorption and improved bioavailability.

Another study with healthy volunteers reported an improved absorption of a CBD/THC nanoemulsion containing piperine (an absorption enhancer) compared to Sativex®.

How does CBD reach the brain?

The central nervous system needs a highly controlled microenvironment to maintain proper neuronal functioning, and the blood-brain barrier (BBB) provides this function. It prevents neurotoxic molecules, blood cells, and pathogens from entering the brain.

At the same time, the BBB regulates the transport of molecules into and out of the central nervous system. This mechanism helps maintain the tightly controlled chemical composition of the neuronal milieu.

In the capillaries forming the BBB, endothelial cells are wedged extremely close to each other, forming so-called tight junctions. The tight gap allows only tiny particles, fat-soluble molecules, and some gases to pass through the capillary wall to enter the brain tissue.

Once CBD is absorbed into the bloodstream, it quickly crosses the BBB and accesses the central nervous system, as reviewed by Calapai and colleagues (2020).

The main advantage of Instant Hemp™ is the increased bioavailability compared with regular-sized particles of CBD. Its small particle size allows more CBD particles to reach the brain, faster.

CBD & the nervous system

Once in the brain, CBD affects the central nervous system by engaging different targets and acting through multiple molecular mechanisms.

A well-accepted set of targets include cannabinoid, opioid, and serotonin 5-HT1A receptors, the last one being closely related to its effects on mental health.

Parasympathetic Activity

Studies have also shown that CBD directs the brain to activate the parasympathetic nervous system, which induces a state of calm. This is evident by an increase in heart rate variability induced by CBD. The greater heart rate variability (the variance in time between the beats of your heart), the more ready your body is to respond to various physiological and environmental stimuli, including stress.

GABA

CBD also increases brain GABA levels in neurotypical individuals. GABA is a neurotransmitter that helps to decrease the activity of neurons in the brain, which can reduce anxiety, promote feelings of relaxation and well-being. By increasing GABA levels in the brain, it is possible to promote sleep and improve sleep quality.

Adenosine

CBD alsoand boosts adenosine signaling, another mechanism that has beneficial effects in the context of sleep disturbances. Adenosine is known as ‘sleep pressure’ – an increase in adenosine drives the desire to fall asleep.

Furthermore, CBD modifies the activity of ion channels and enhances the activation of G protein-regulated receptors.

Mental health, anxiety, and stress

Several studies have shown CBD’s effect on anxiety, stress, and mental health:

• A study conducted by Crippa and colleagues (2019) showed that healthy male subjects given oral CBD before a simulated public speaking test induced anxiolytic effects

• A study conducted by Crippa and colleagues revealed that 400mg of CBD decreased neuronal activity in the limbic and paralimbic areas of the brain. The limbic and paralimbic brain areas comprise of a collective of structures involved in processing emotion and memory. The study suggests that the anti-anxiety effects of CBD are exerted through modulating the limbic and paralimbic areas of the brain.

• A study by Masataka et al. showed that relative to placebo, 300mg/day of CBD for four weeks significantly reduced anxiety of participants with social anxiety and avoidant personality disorder

• retrospective clinical trial that included any type of anxiety disorder, found that a dose of CBD (25 to 75 mg/day) was also effective for reducing anxiety

• a 2022 review article reported that CBD had a positive effect against stress and its manifestations of fear, anxiety, depressive behaviors, or burnout.

• a study with frontline healthcare workers during the COVID-19 pandemic reported that the anxiolytic effects of repeated CBD administration (300mg /day for 28 days) were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world.

It's important to note that most of these studies used standard oil-based CBD formula, meaning its bioavailability was likely closer to 6%.

CBD protects against the adverse psychological effects of THC

Although many recreational users of Cannabis will never face serious or permanent health deficits, it can still cause undesirable psychological side effects, including cognitive impairment, anxiety, paranoia, and an increased risk of developing chronic psychosis and addiction, especially with the daily use of Cannabis that is high in THC.

As reported by Andrew Huberman’s review of the literature on his Huberman Lab Podcast, other potential downsides of chronic Cannabis use are:

• Changes in vocal effort, intensity, pronunciation of words, intonation, and anunciation.

• Lowered libido.

• Lowered testosterone.

• Impaired sperm motility.

• Anxiety or depression when not under the influence of Cannabis.

Several studies have reported that CBD can reduce the anxiety and psychosis-like effects that are seen after THC administration.

CBD attenuates the emotional and reward processing impairments associated with a single high dose of THC, as reviewed by Freeman et al. (2019). Although significant variability was reported in the effects of CBD and THC between studies and across individuals within studies, this review article suggests that CBD may weaken the effects of THC on emotion and reward processing.

The mechanisms by which CBD mitigates the side effects of THC have not been fully identified. A study with healthy volunteers showed that THC strongly disrupts striato-cortical networks, a well-integrated regulatory circuit that links the cortical and subcortical brain regions involved in cognition, attentional control, and motivation. The study also found that and the co-administration of CBD counteracts this effect.

In addition, preclinical evidence suggests that CBD prevents THC-induced behavioral and neural abnormalities by blocking its ability to overstimulate the ERK pathway in the hippocampus. Notably, the effects of THC on ERK in the hippocampus and their consequences on gene expression may be involved in the motivational aspects related to THC, including the rewarding effects.

CBD & Sleep Quality

Theorized mechanisms of why CBD tends to anecdotally enhance sleep architecture include increased adenosine and GABA signaling, reduced core body temperature (a tenet of deep restorative sleep), and reduced anxiety.

The increased productivity in studies of CBD actions is likely to accelerate and will provide essential neurobiological information about the mechanisms involved in the actions of CBD in sleep.

Most studies on the effects of cannabinoids in sleep have focused on purified THC or THC/CBD preparations. For example, experience to date with Sativex® in many Phase I-III studies demonstrates marked improvement in subjective sleep parameters in patients with various pain conditions, including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain and rheumatoid arthritis, with no evidence of tolerance to the drug action and an acceptable adverse event profile.

A study conducted by Nicholson and colleagues (2004) reported mixed effects of combined THC and CBD, with THC generally increasing sedation and a low dose of CBD (15mg) having opposing, wake-enhancing effects. In fact, the administration of CBD has been shown to have differential effects on sleep based on dose. While low-dose CBD has a stimulating effect, high-dose CBD has a sedating effect. In a study among individuals with insomnia, administration of 160 mg/day of CBD increased total sleep time and decreased the frequency of arousals during the night, while low-dose CBD has been associated with increased wakefulness, as mentioned above.

A retrospective case series at a psychiatric clinic measured sleep and anxiety scores in 72 adults treated with CBD (25 mg/day to 175 mg/day). Anxiety scores decreased within the first month of CBD administration in 79.2% of patients and remained decreased for the duration of the study. Sleep scores improved within the first month in 66.7% of patients but fluctuated over time. Importantly, CBD was well tolerated in all but three patients.

Recent observations have suggested that CBD might represent an alternative treatment for REM sleep behavior disorder, which is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behavior during dreaming.

In a case series reported by Chagas and colleagues (2014), four patients treated with CBD had a prompt and substantial reduction in the frequency of REM sleep behavior disorder-related events without side effects. Likewise, a clinical study enrolling 33 patients with REM sleep behavior disorder and Parkinson's disease reported that CBD (300mg administered orally for 12 weeks) significantly improved the average sleep satisfaction from the 4th to 8th week of treatment compared to the placebo group.

Although further controlled research into the physiological effects of CBD is necessary, these studies suggest that a low dose of CBD could help manage excessive daytime sleepiness, while some cannabis formulations support sustained sleep improvement.

Key Takeaways

CBD is proving promising as a therapeutic for:

• Reducing anxiety, stress, and fear

• Improving Sleep Quality (through boosting GABA, Adenosine)

• Activating the parasympathetic nervous system

• Protecting against the adverse psychological effects of THC

Most standard CBD tinctures are poorly bioavailable, meaning you need to take megadoses to reach therapeutic effect, and wait 45-60 minutes to feel an effect.

Instant Hemp utilizes CBD nanoparticles for:

• Rapid effect in the bloodstream

• Increased bioavailability

• Lower dose needed for therapeutic effect

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For a higher-level short summary, check out our Heavy Hydrogen One Pager.

Key Takeaways:

• Light Water, a form of water that removes ~20% of Heavy Hydrogen (2H) isotopes, has proven to be an effective therapeutic for Cancer, especially in conjunction with standard of care

• Research is showing it to be a promising therapeutic for preventative health, slowing Aging/DNA Damage, improving Athletic Performance and Energy levels, relieving biological aspects of stress-induced Depression, and improving markers of Metabolic Disease such as Obesity.

• We have too much 2H in our bodies partly because of increase in water consumption and carbohydrate consumption over the past century.

• It has no known contraindications or side effects from long term consumption; unlike supplements or drugs, it introduces no new compounds to the body.

• Not a ‘water fad’ -- Alkaline water has 0 studies backing its claims. Light Water has dozens.

• Currently sells for $6/Liter due to expensive production methods. We’ve pioneered a low-cost production method that will retail at ~$3/Liter.

• Join Us: seeking a Co-Founder/COO & Seed Round Investors

Heavy Hydrogen — An 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 post) 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.

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.

Because 2H is double the weight and size of regular Hydrogen, excess levels of it cause issues in the human body:

• Its molecular weight disrupts the electron transport chain and ATP synthase nanomotors, leading to a reduction in ATP production and mitochondrial disfunction. ATP is the gasoline your cells use to function. Without ATP, you’d die within seconds.

• Its size modifies the shape of DNA, and strengthens its hydrogen bonds, causing potential errors in replication and epigenetic expression

• It’s a growth factor for cells, causing tumorous growths when there’s excess

The effect of these issues on human health is most relevant for: Cancer, Aging/Longevity, Energy, Mental Wellness, Obesity, and Athletic Performance.

Why are our 2H levels “too high” now?

Why is this a problem now, and not before? Why do we have more 2H in our bodies now than in the past?

Some key factors over the past century have increased our 2H intake and compromised the body’s ability to remove excess 2H levels:

1. An increased amount of carbohydrates in the diet + lower amount of fat

   - 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.

2. 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 basis for drinking 3-4L of water per day. The narrative that’s been created over the past 50 years 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. Our bodies are designed to make metabolic water from fat sources, and go periods of time enduring thirst.

• The issue is two-fold:

  • We’re overloading our bodies with high 2H (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.

1. 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

2. Lack of sunlight

#2 appears to be the key factor — it explains why someone following a Ketogenic diet, getting loads of sunlight, and eating organic foods that are nutrient-dense and probiotic-rich likely still has a 2H level in the body above 140ppm (130ppm is optimal). The healthiest among us are simply drinking too much 150ppm water.

Change at the Atomic Level

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.

3 key reasons Light 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

For a deep dive on the Biochemistry, check out our 2H Whitepaper.

Key Studies

More studies and research needs to be conducted, but there’s a significant amount of compelling evidence to immediately introduce Light 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, peer-reviewed papers explaining the biochemical mechanisms of action, in vitro studies, mice studies, anecdotal clinical reports, retrospective studies, a phase II randomized double blind clinical study, and approval for use as a pharmaceutical product for pets in Hungary for 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)

For a deep dive on all key studies, view 2H Whitepaper.

Protocols

Because 2H is a naturally occurring isotope - and not a toxin - it’s important to simply modify the levels in the body, rather than attempt to get them as low as possible.

Below are suggested protocols, depending on goals.

Preventative Health

Goal**:** Annual ‘cleanup’ of damaged/diseased cells to prevent unwanted cellular growths

Protocol: 120ppm Water 3 months per year

Mechanism:

• By substantially dropping the 2H levels in the body, diseased cells are starved of the 2H needed to grow, and can not adapt. This triggers cell necrosis of damaged/diseased cells, preventing unwanted growths in the body.

Wellness & Longevity

Goals:

• Decrease 2H load in body to 125pmm year-round

• Annual cleanup of damaged/diseased cells to prevent unwanted cellular growth

• Healthspan + Longevity Effects

Protocol:

• 120ppm 9 months/year → 85ppm 3 months/year

Mechanisms:

• Improved ATP production

• Decreased DNA Damage

• Increased Cellular Hormesis

• Annual Cell Necrosis

Chronic Illness

Goal: Decrease 2H load in body to 105ppm for 3-6 months → follow a protocol above

Protocol: 105ppm 6 months → Preventative or Wellness/Longevity Protocol

Mechanism:

• Restore function to dysfunctional cell mitochondria, to address root cause of chronic illness

Oncology

Goal: Kill off diseased cells with step-down solution

Protocol: 105ppm for 2 months → 95ppm for 2 months → 85ppm for 2 months → 75ppm for 2 months → Prevention or Wellness/Longevity Protocol

Conclusion

We plan to fund and pursue further research in the fields of Epigenetics, Aging, Metabolic Disease, and Wellness.

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.

Our 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 on Earth where centenarian claims have been both not purported by fraud, and has a scientific explanation for a potential cause with the tested water.

With proper education, we aim to bring the benefits of the Hunza valley’s atomic elixir to the rest of the world.

Join Us

We’re on track to launch in Q1 2024. Ways to get involved below -- email ali@human3.co.

Co-Founder/COO

Seeking a COO to join the founding team, with experience in managing supply chain & day to day ops of a CPG brand.

Investors

Raising a Pre-Seed round to build our production facility and launch the brand. We’re looking to align with strategic investors in the Longevity, Wellness, or CPG space.