The Ultimate Guides

The Ultimate Guide to Deuterium Depletion

The Ultimate Guide to Deuterium Depletion Featured Image

Guide to Deuterium Depletion

Download PDF

 

About the Authors

Kriben Govender

Kriben Govender

Kriben Govender, is a Food Scientist, Registered Nutritionist and Founder of Nourishme Organics, a company specialising in Gut Health and Mitochondrial health-focused products and Allele Microbiome – a provider of cutting edge Metagenomic Stool Testing and Deuterium Testing.

 

Corey Nelson

Corey Nelson

Corey Nelson is a science writer and health coach who focuses on mitochondrial health, as well as the ways our living environments create wellness or disease. Learn more or contact him at CoreyNelson.io

 

Little Girl Drinking Water

Deuterium depletion is a cutting-edge health practice for lowering deuterium levels in your body. It may result in higher energy levels, a faster metabolism, anti-cancer effects, and more.

People use deuterium-depleted water, the ketogenic diet, and other methods you’ll learn about in this article to reduce their deuterium levels.


By the time you finish reading, you’ll have a better understanding of why you might want to deplete deuterium, what to expect from it, and how to design your own deuterium depletion protocol.

 

What is Deuterium?

Deuterium is a stable isotope of hydrogen. Unlike normal hydrogen (also called protium), deuterium has an extra neutron, doubling its atomic mass. For that reason, another name for deuterium is “heavy hydrogen.”

Protium (Element)

The big bang may have created most of the deuterium in the universe  [1] .

As a hydrogen isotope, deuterium can fit in any chemical or physical reaction where a hydrogen atom can fit. That means it’s in your body, in the foods you eat, and in the water you drink.

When deuterium substitutes for protium in a molecule of water (H2O), the result is called deuterium oxide or “heavy water.”

Here’s a key point we will revisit more than once: heavy water has different physical properties than regular water.

Heavy water has a higher melting point (3.82 °C), higher boiling point (101.4 °C), and evaporates more slowly than “light” water without deuterium [2] .

And because of these properties, deuterium levels vary depending on where you are on earth. To learn why, let’s take a quick look at how the water cycle influences the distribution of deuterium.

 

What is Deuterium?

On the surface of the earth, there is about one deuterium atom in ocean water for every 6420 hydrogen atoms on average. In other words, the deuterium concentration for most of our planet’s water is about 150-160 parts per million (ppm) or 0.000156%.

However, higher elevation and distance from the equator both reduce the heavy water concentration because of how the water cycle changes deuterium levels [3] .

In other words, deuterium levels are usually lower farther from the ocean or where it’s cold. These differences occur because of the different melting point and evaporation rate of heavy water compared to normal water.

Illustration of Deuterium Depletion origin

Therefore, the deuterium content of water you drink and the foods you eat also vary depending on their origin [5] .

Now that you know what deuterium is, it’s time to learn about deuterium and life.

 

What is Deuterium Depletion?

A kid drinking water

Deuterium depletion is any method of lowering deuterium levels.

Humans, animals, plants, and other living creatures can deplete deuterium naturally when they are young and healthy.

Unlike the 150-160 parts per million (ppm) levels found in ocean water, many organisms maintain levels as low as 100 ppm in their tissues by depleting deuterium [6] .

Healthy cells, mitochondria (the “powerhouses of the cell”), and gut flora tend to excrete deuterium on their own. You can eliminate some of your excess deuterium by simply breathing, sweating, urinating, and evacuating solid waste [7] .

Additionally, living organisms respond to variations in deuterium.

For example, E. coli bacteria grow faster in a mildly deuterium-enriched environment [8] .

Your body may use deuterium strategically in some tissues to reduce damage to cells, and some researchers think early life on earth evolved thanks to this effect of deuterium [9] .

On the other hand, high levels of deuterium are toxic to living organisms [10] .

Studies of cells and plants show that deuterium depletion can slow cell growth, while deuterium enrichment can speed up fast-growing cells [10] .

Therefore, while deuterium may be useful for development and normal cell growth, too much deuterium can also encourage cancer cell growth and cause cellular damage [6] .

It appears that life has evolved to make use of deuterium, but also to keep it sequestered or contained when necessary.

Growing plants tend to store excess deuterium in their fruits, sugars, or leaves [11] .

And a study of fruit flies also found that given the choice, they choose lower deuterium levels in drinking water [12}.

However, in some cases these depletion, containment, or avoidance mechanisms don’t work properly.

For example, aging may impair deuterium depletion ] [7] [13] .

In other cases, the dietary or environmental deuterium levels are too high to deplete naturally.

 

Deuterium and Evolutionary Biology

As recently as 11,700 years ago, deuterium levels on earth may have been over 30% lower.

Why? Because that’s when the most recent ice age ended.

A view of an huge ice

Ice core evidence suggests that during ice ages, colder temperatures and more ice and snow can remove deuterium from water [3] .

In other words, deuterium levels in water and food were probably a lot lower during large stretches of our ancestors’ evolution.

And the deuterium content of modern, highly processed foods that contain grains, sugar, or corn is higher still [14] .

It appears elevated deuterium levels may cause higher rates of obesity, cancer, and cardiovascular disease, which is consistent with increased rates of those diseases in modern people  [15] [16] [17]

The deuterium hypothesis would also fit with evidence suggesting that lower-deuterium diets like the paleo diet and the ketogenic diet have anti-inflammatory properties and can help people with cancer, epilepsy, and type 2 diabetes  [18] [19] [20] [21] [22] .

To better understand why this might be the case, let’s focus on what deuterium does at the microscopic level-- and even smaller at the subatomic level.

 

Deuterium Substitution in Molecules

Deuterium can fit anywhere in a molecule or reaction that hydrogen can fit. That means excess deuterium gets used during the synthesis of hormones, fats, enzymes, and cells.

And the abnormal properties of heavy water and deuterium can cause problems when your body uses deuterium in place of regular hydrogen.

In addition to higher boiling and melting points, heavy water has 25% greater viscosity than regular water. It also has a five-fold lower ionization constant, meaning that it donates and receives electrons more slowly than normal water [2] .

For those reasons, deuterium incorporation reduces the stability of phospholipids, a key part of cell membranes [23] .

It’s likely that other types of deuterated hormones and lipids (fats) behave abnormally, too. Basically, higher deuterium concentrations could disrupt normal functioning of biological molecules.

 

The Kinetic Isotope Effect

When it comes to living organisms, the biggest distinction between hydrogen and deuterium occurs due to the kinetic isotope effect.

Simply put, deuterium slows down chemical reactions when substituted in place of hydrogen.

Because it’s twice as heavy as hydrogen, a simple reaction with deuterium is usually seven- to ten-fold slower compared to the same reaction with regular hydrogen [2] .

And the kinetic isotope effect has big implications for living things.

Many biological processes including DNA replication, DNA repair, and cytochrome P450 enzymatic reactions work on rapid timescales that are sensitive to the kinetic isotope effect [24] [25] [26] [27] .

Basically, deuterium can interfere with your body’s normal functioning by slowing down chemical reactions.

Mathematical models suggest that the kinetic isotope effect can cause system-wide metabolic changes [28] .

In other words, slowing down a single reaction can have a “butterfly effect” elsewhere in your body and cause major disruptions.

Not only that, in other studies, deuterium slows the speed of reactions drastically--30- to 800-fold--by preventing a process called quantum tunneling [29] [30] [31] [32] .

Now that we’ve established the basics of how deuterium can affect your body, it’s time to take a closer look at the potential health benefits of depletion.

 

5 Health Benefits of Deuterium Depletion

#1: Less Fatigue, More Energy

Photo of a fatigue man

 

Deuterium depletion has the potential to reverse fatigue and increase your energy levels.

Your mitochondria, which you may know as the “powerhouses of the cells,” provide your entire body with energy.

Deuterium slows down energy production, interferes with mitochondrial function, and increases the production of damaging free radicals [33] .

And over time, elevated deuterium levels could also lead to mitochondrial damage.

Here’s why that’s a problem: damaged mitochondria and insufficient energy production can contribute to fatigue [35] .

Research findings in people with chronic fatigue syndrome (CFS) confirm that impaired mitochondrial function is associated with fatigue [36] [37] [38] .

That’s why some researchers think depleting deuterium could be a key step to reducing fatigue.

So far, one animal study has shown that deuterium depleted water (DDW) can increase energy production in mitochondria [24] .

Bottom line: there’s excellent evidence that fatigue is a mitochondrial problem and good reason to suggest deuterium depletion can help fatigue.

 

#2: Faster, Healthier Metabolism

Depleting deuterium may boost your energy production and repair your mitochondria, and could be an excellent way to lose unwanted body fat and maintain a healthy weight.

Keep in mind that high deuterium levels damage your mitochondria.

As it turns out, with unhealthy mitochondria, you’ll have fat-burning difficulties, sugar cravings, and increased fat storage [39] .

A thriving colony of mitochondria is also vital for healthy carbohydrate metabolism and preventing diabetes [40] .

And according to a 2017 animal study, deuterium-depleted water can increase glucose transporter expression and aid glucose uptake, which could also prevent or aid diabetes [41] .

The takeaway: people who have trouble losing weight, struggle with sugar addictions, or have metabolic problems like type 2 diabetes may benefit from depleting deuterium.

 

#3: Better Mood and Brain Function

Of all your organs, your brain uses the most energy relative to its mass [42] . As a result, it’s incredibly dense with energy-producing mitochondria [43] .

Image of a scientist

Scientists think mitochondrial dysfunction may be responsible for numerous brain-related issues like psychiatric symptoms, migraine headaches, chronic traumatic encephalopathy (CTE), and even Alzheimer’s disease [43] [44] [45] [46] .

But even if you don’t have any brain health issues, the colony of mitochondria in your brain still influences your mental function, cognition, and memory.

According to the authors of a 2014 scientific paper,

“The brain appears most vulnerable to mitochondrial defects, suggesting that neurons are particularly sensitive to bioenergetic fluctuations, and consequently, that mitochondria regulate fundamental aspects of brain function” [47]

Therefore, it’s no surprise that depleting deuterium to enhance the function of brain mitochondria could boost your mood, prevent brain-based diseases, and increase your mental acuity.

A 2014 animal study also found that deuterium-depleted water improved the animals’ long-term memory [48] .

Not only that, deuterium depletion may enhance the production of neurotransmitters in your brain.

According to the authors of a 2015 study, the deuterium-depleted water they provided to mice seemed to mimic the effects of antidepressant drugs [49] .

 

#4: Anti-Cancer Effects

Deuterium depletion is a promising experimental cancer therapy. Relative to other possible health benefits of depletion, the anti-cancer effects of deuterium depletion are supported by the strongest clinical evidence.

Rather than a primary cancer treatment method, researchers mostly use it as an adjuvant therapy along with standard of care treatments [50] .

Researchers in the field of deuterium depletion have documented dramatically increased survival times across multiple studies in the following types of cancer:

 

Here’s how the benefits probably work:

  • Deuterium depletion may decrease DNA damage and single-strand breakage associated with cancerous mutations [52] .
  • Depletion therapies may induce oxidative stress in cancer cells by reversing the deuterium gradient in mitochondria and moving protons from the mitochondrial matrix to the intermembrane space [53] .
  • The Warburg metabolism (anaerobic glycolysis) of many cancer cells is associated with deuterium accumulation, but deuterium depletion may reverse this effect by promoting healthier metabolism and “recycling” of cancer cells [34] .
  • Deuterated lipids (fats) increase inflammatory and pro-cancer lipoxygenase metabolism, while deuterium depletion reverses it [54] [55] .

Essentially, deuterium depletion may be a non-invasive way to prevent cancer, slow its growth, or even reverse it.

And if you don’t have cancer, there’s also a good chance that deuterium depletion can reduce your cancer risk.

 

#5: Improved Cardiovascular Health

Your heart is dense with mitochondria, containing an astounding 35% mitochondria by weight [56] .

Deuterium depletion may improve cardiovascular health and heart function by helping your mitochondria work better [52] [57] .

And as you’ll recall from earlier, deuterium can reduce the stability of phospholipids and may disrupt their function [23] .

Some evidence shows that phospholipid alteration in the heart is linked to heart disease [58] .

Therefore, deuterium depletion may also benefit your heart health by maintaining the orderly configuration of phospholipids.

 

The 7 Best Methods to Deplete Deuterium

#1: Diet for Deuterium Depletion

Diet food for Deuterium Depletion

Your diet is a major factor behind your body’s deuterium levels.

A low-carb, whole food-based-diet that’s high in fats, green vegetables, and animal products can lower your deuterium levels [59] .

On the other hand, a diet high in sugar, starches, or processed foods can raise deuterium levels in your body [59] .

The guiding principle behind a deuterium depletion diet is simple: eat foods low in deuterium and mostly avoid high-deuterium foods.

As you may have noticed, the low deuterium foods mentioned above have plenty of overlap with diets like the keto diet, paleo diet, and carnivore diet. (It’s probably no coincidence that these low deuterium diets may help prevent or treat conditions like obesity, diabetes, cancer, epilepsy and heart disease. [21] [60] [61] )

Deuterium Content of Foods

Here’s a sampling of the deuterium content of food, courtesy of Preventa:

  • Wheat flour: 150 ppm
  • Beet sugar: 146 ppm
  • Corn: 145 ppm
  • Potato: 143 ppm
  • Oat: 141 ppm
  • Pork meat: 138 ppm
  • Beef meat: 138 ppm
  • Spinach: 136 ppm
  • Peanut butter: 131 ppm
  • Olive oil: 130 ppm
  • Butter: 124 ppm
  • Beef fat: 121 ppm
  • Lard: 116 ppm (also confirmed by Basov, et al. (2014))

However, you don’t need to know the precise deuterium content of every food to make wise decisions.

Here’s what you do need to consider:

  • Ingredients
  • Processing or preparation
  • Location

As you can tell from the first list, ingredients make a significant difference

For the most part carbs, sugars, and starches have a higher deuterium content--naturally. Grass-fed animal products, fats, and leafy greens are the opposite.

Processing and preparation affect deuterium content too.

For one thing, refined flour, sugar, or other plant products have more deuterium because the manufacturing process removes the low-deuterium plant matter.

Another reason is because of evaporation. Many food preparation methods involve some form of heating (like boiling or dehydration) that results in evaporation, which concentrates deuterium in food.

 

DEUTERIUM CONTENT OF WATER SAMPLES*

Good Sources of Water
* Deuterium content of food and water samples courtesy of Dr Gabor Somlyai, Dr Lazlo Boros and Allele Microbiome

At home, you can keep the deuterium content of foods lower by trapping steam and moisture during cooking or boiling.

Finally, as with water, altitude and latitude affect the deuterium content of plants and other foods.

That means, for example, that if you live far from the equator, you probably shouldn’t eat imported foods from equatorial countries--particularly in winter. (There’s also an evolutionary argument for eating locally and seasonally, since global food transportation is a relatively recent invention.)

 

#2: Deuterium-Depleted Water (DDW)

Deuterium-depleted water is exactly what it sounds like: water with reduced deuterium content [5] [62] .

Different scientists define DDW differently, but statistically speaking, naturally-occurring water under 140 parts per million (ppm) is very rare and mainly occurs in the polar regions.

However, water with much lower deuterium content is commercially available. Using a process called fractional distillation that takes advantage of the boiling point differences between light water and heavy water, manufacturers produce water with deuterium content from 5-125 ppm.

DDW vs. Deuterium Depleted Diet

Compared to diet, commercial DDW is more effective in the short term for lowering your deuterium levels. Food and water are the main sources of deuterium in your body, but commercial DDW has much lower deuterium levels than natural deuterium-depleted foods, making it the faster method.

And unlike most other methods, DDW doesn’t rely on your body’s natural depletion mechanisms. Therefore, it’s a good choice for people with cancer or who have trouble achieving healthy deuterium levels by other means.

Whereas low-deuterium diets deplete deuterium from the inside out, drinking DDW lowers deuterium in cells and mitochondria through a process called isotopic shock [63] .

The lower the deuterium concentration of DDW, the faster it depletes your body levels, but the more it costs.

 

How to Use Deuterium Depleted Water

Many people use 25-105 ppm deuterium depleted water as their sole method of hydration for 4-16 weeks. This type of DDW protocol typically costs between $200 USD and $3000 USD.

The most common way is to use DDW to achieve a target deuterium level in your body, then maintain the reduced deuterium level through a low-deuterium diet and other methods.

Young woman looking at the camera

For maintenance, wellness purposes, and to potentially slow down aging, some people use water with 125-136 ppm long-term. You can achieve this concentration by diluting DDW or by using naturally deuterium-depleted glacial spring water.

Remember the water cycle illustration earlier? Deuterium levels are lower away from the equator, at high altitudes, and where it’s cold.

Low D is an affordable, naturally deuterium-depleted glacial spring water from Canada.

You don’t need to mix, measure, or titrate your dosage. Just drink Low D like you would regular water. It’s an ideal way to try out deuterium depletion, follow up a medical DDW protocol for maintenance, or pair up with other inexpensive methods.

Not only that, but you can also mix Low D with 25 ppm DDW for a cleaner deuterium-depleted drinking experience.

Deuterium Depleted Water Dilution Chart

Use the chart below to obtain the proper ratio of Low D to DDW when mixing. The calculations provide 2 liters of water, which is plenty to meet most people’s daily water needs and still deplete deuterium economically.

Deuterium Depleted Water Dilution Chart

 

#3: Fasting and Dry Fasting

Regular fasting can deplete deuterium by shifting your body’s metabolism towards fat-burning.

When you burn fat (whether stored or eaten recently), your mitochondria make 1.1 kilograms of water for every 1000 grams of fat you burn [64] . This “metabolic water” is deuterium-depleted, typically to approximately 115 ppm.

And similar to the keto diet, fasting can help treat obesity, cancer, and type 2 diabetes [65] [66] [67] . These benefits may be due, at least in part, to deuterium depletion.

Dry fasting is similar to fasting but along with avoiding food, you don’t drink any water, either.

A 2013 study found that a five-day dry fast was safe for ten healthy adults. That small study doesn’t prove it’s safe for everyone, but it does prove that dry fasting isn’t reckless [68] .

In fact, metabolic water production could help explain why dry fasting appears to be safe. Also, note that you don’t necessarily need to dry fast for five days in a row!

When it comes to deuterium depletion, the logic behind dry fasting is sound. By temporarily avoiding water along with food, you’re eliminating the two main sources of deuterium, which can accelerate depletion as your body runs on stored fat.

Fasting and the other practices you’ll learn about in a moment are unlikely to dramatically reduce deuterium by themselves. Nonetheless, they work well combined with other methods or to maintain low deuterium levels.

 

#4: Infrared Light and Sunlight

Infrared light (IR) boosts your energy production by supercharging your mitochondria [69] .

You can obtain infrared light from light therapy devices or from sunlight, which is approximately 49.4% infrared light [70] .

As a result of the increased energy production, your mitochondria also make extra metabolic water, which is deuterium-depleted [71] .

It’s worth noting that some researchers have an alternative theory for how IR aids your mitochondria [72] [73] .

They think that infrared might work by reducing the viscosity of the water surrounding mitochondria to increase energy production [76] .

If correct, the reduced water viscosity from IR would also mimic the benefits of deuterium depletion due to the fact that deuterium can increase water viscosity [75] .

Last but not least, infrared light, sunlight, and sauna heat all increase your sweating. Sweating is one of your body’s natural deuterium depletion mechanisms, so that’s good news for reducing your levels, too [76] .

 

#5: Cold Exposure

Exposing your body to cold increases your metabolic rate through non-shivering thermogenesis, which generates heat by dissipating protons [77] .

Proton dissipation during heat production is favorable to deuterium depletion.

It also increases levels of brown adipose tissue, a special type of fat with the ability to dissipate protons to create even more heat [78] .

Cold exposure works well for deuterium depletion, but with one caveat. Some people’s bodies can adapt to cold better than others [79] .

Most likely, if your ancestors lived far from the equator, you’ll get better results with cold exposure and cold adaptation.

 

#6: Exercise

Man exercising

Exercise depletes your deuterium levels by increasing your deuterium-depleted metabolic water production and making you sweat [80] .

Aerobic exercise under 65% VO2 max (maximum oxygen volume) is the best form of exercise to boost your metabolic water production because it burns the most fat [81] .

Pairing aerobic exercise with fasting or the keto diet allows you to attain fat oxidation levels of 1.5 grams of fat or more per minute [81] . Put differently, that’s 99 milliliters of 115 ppm deuterium-depleted metabolic water per hour.

 

#7: Breathing Clean Air

Breathing clean air isn’t enough to reduce deuterium levels alone, but air pollution can make it harder to deplete deuterium.

Air contaminants found in buildings, roadways, and agricultural applications can increase the risk of obesity, diabetes, and mitochondrial damage as well as make weight loss difficult [82] [83] [84] [85] .

And low blood oxygen levels from pollution may increase reliance on sugar, cause insulin resistance, and result in the loss of mitochondria [86] [87] [88] .

Remember that when your body relies on carbs and can’t burn fat effectively, the result is higher deuterium levels [14] .

Essentially, you need clean air for optimal mitochondrial function and to maintain healthy deuterium levels. Along with ensuring you breathe clean air, you can also enhance mitochondrial function (and thus deuterium depletion) by breathing slowly to get plenty of oxygen.

Slow breathing at six breaths per minute increases oxygen saturation in your blood, which may help reduce your deuterium levels [89] .

 

Conclusion

The majority of deuterium depletion methods are fantastic for your health, even before taking deuterium into account.

Everyone can benefit from practices like a whole food diet, fasting, sunlight, exercise, and breathing clean air.

Using DDW is the fastest way to deplete deuterium, but also the most expensive. Most people don’t use DDW long-term.

As a less expensive alternative for long-term health and wellness, Low D is the only commercially available, natural spring water that’s deuterium depleted.

Don’t forget that food and drinking water are the main sources of deuterium in your body. That means if you’re keto but still drinking water that has the usual 150-155 ppm deuterium content, your depletion results won’t be as good.

NourishMe Organics tests Low D to ensure it has:

  • 136 ppm or lower deuterium-to-hydrogen ratio
  • No heavy metals or arsenic
  • No chlorine
  • No fluoride
  • No glyphosate (Roundup)
  • Alkaline pH (7.2)

 

Natural deuterium-depleted glacial spring water is a more economical choice than DDW for wellness purposes, trying out deuterium depletion for the first time, or to get more mileage out of a deuterium-depleted diet (especially paired with other methods like infrared, cold, and exercise).

Want to try Low D? Click here to buy it from Nourishme Organics while supplies last. Low D is also the perfect choice to dilute 25 ppm DDW for a cleaner DDW experience. In case you missed it, check out the easy-to-use DDW dilution chart.

Image credits: Dirk Hünniger, Daniel Dawson

 

 

References:

1. Matteucci, F. The cosmic origin of deuterium. Nature 405, 1009–1010 (2000)

2. Evans BR1, Shah R2. Development of approaches for deuterium incorporation in plants. Methods Enzymol. 2015;565:213-43.

3. P. Yiou, F. Vimeux, and J. Jouzel, Ice-age variability from the Vostok deuterium and deuterium excess records, JOURNAL OF GEOPHYSICAL RESEARCH, VOL. 106, NO. D23, PAGES 31,875-31,884, DECEMBER 16, 2001

4. Dawson, Daniel, Stable hydrogen isotope ratios of individual hydrocarbons in sediments and petroleum, 2006

5. Bowen, G.J., Winter, D.A., Spero, H.J., Zierenberg, R.A., Reeder, M.D., Cerling, T.E. and Ehleringer, J.R. (2005), Stable hydrogen and oxygen isotope ratios of bottled waters of the world. Rapid Commun. Mass Spectrom., 19: 3442-3450.

6. Somlyai, Gabor et.al Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion, 2010, Orvosi Hetilap

7. Lysenko OB, Radchuk VV, Zabulonov YL, Shatilo VB, Demihov VV, et al. (2016) Biogenic Chemical Elements Isotope Ratios in Living Organism as a New Potential Indicator of Physiological State. J Phys Chem Biophys 6: 218.

8. Xie X, Zubarev RA. Effects of low-level deuterium enrichment on bacterial growth. PLoS One. 2014;9(7):e102071. Published 2014 Jul 17.

9. Piero Sestili, Maurizio Brigotti, Cinzia Calcabrini, et al., “Deuterium Incorporation Protects Cells from Oxidative Damage,” Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 6528106, 13 pages, 2019.

10. Xie X, Zubarev RA. On the Effect of Planetary Stable Isotope Compositions on Growth and Survival of Terrestrial Organisms. PLoS One. 2017;12(1):e0169296. Published 2017 Jan 4.

11. Dunbar, J et al, Oxygen and Hydrogen Isotopes in Fruit and Vegetable Juices, Plant Physiol. (1983) 72, 725-727

12. Maria, Isabel & Franco, Maribel & Turin, Luca & Mershin, Andreas & Skoulakis, Efthimios. (2011). Molecular vibration-sensing component in Drosophila melanogaster olfaction. Proceedings of the National Academy of Sciences. 108. 3797-3802. 10.1073/pnas.1012293108.

13. Kirsanow et al,(2011), Oxygen and hydrogen isotopes in rodent tissues: Impact of diet, water and ontogeny, Palaeogeography, Palaeoclimatology, Palaeoecology, Volume 310, Issues 1–2, 15 September 2011, Pages 9-16

14. Boros LG, D’Agostino DP, Katz HE, Roth JP, Meuillet EJ, Somlyai G. Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle. Med Hypotheses. 2016;87:69–74. doi:10.1016/j.mehy.2015.11.016

15. Hruby A, Hu FB. The Epidemiology of Obesity: A Big Picture. Pharmacoeconomics. 2015;33(7):673–689. doi:10.1007/s40273-014-0243-x

16. Hallberg et al, (2002), Journal of Australian College of Nutritional & Environmental Medicine Vol. 21 No. 1; April 2002: pages 3-8

17. Dalen et al (2014), The epidemic of the 20(th) century: coronary heart disease, Am J Med. 2014 Sep;127(9):807-12. doi: 10.1016/j.amjmed.2014.04.015. Epub 2014 May 5.

18. Kristine A Whalen, Suzanne Judd, Marjorie L McCullough, W Dana Flanders, Terryl J Hartman, Roberd M Bostick, Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with All-Cause and Cause-Specific Mortality in Adults, The Journal of Nutrition, Volume 147, Issue 4, April 2017, Pages 612–620, https://doi.org/10.3945/jn.116.241919

19. Tan-Shalaby J. Ketogenic Diets and Cancer: Emerging Evidence. Fed Pract. 2017;34(Suppl 1):37S–42S.

20. Martin et al (2016), Ketogenic diet and other dietary treatments for epilepsy, Cochrane Database Syst Rev. 2016 Feb 9;2:CD001903. doi: 10.1002/14651858.CD001903.pub3.

21. Klonoff DC. The beneficial effects of a Paleolithic diet on type 2 diabetes and other risk factors for cardiovascular disease. J Diabetes Sci Technol. 2009;3(6):1229–1232. Published 2009 Nov 1. doi:10.1177/193229680900300601

22. Westman et al, (2018), Implementing a low-carbohydrate, ketogenic diet to manage type 2 diabetes mellitus, Expert Rev Endocrinol Metab. 2018 Sep;13(5):263-272. doi: 10.1080/17446651.2018.1523713.

23. Deborah Guard-Friar, Chang Hwei Chen, and Adam S. Engle, 1985, Deuterium isotope effect on the stability of molecules: phospholipids, The Journal of Physical Chemistry, 89 (9), 1810-1813, DOI: 10.1021/ j100255a054

24. Maffeo, C., Chou, H.‐Y. and Aksimentiev, A. (2019), Molecular Mechanisms of DNA Replication and Repair Machinery: Insights from Microscopic Simulations. Adv. Theory Simul., 2: 1800191. doi:10.1002/ adts.201800191

25. Werner, R. Marshall & Stivers, James. (2000). Kinetic Isotope Effect Studies of the Reaction Catalyzed by Uracil DNA Glycosylase: Evidence for an Oxocarbenium Ion−Uracil Anion Intermediate †. Biochemistry. 39. 14054-64. 10.1021/bi0018178.

26. Frederick P. Guengerich, Chapter Nine - Kinetic Deuterium Isotope Effects in Cytochrome P450 Reactions,Methods in Enzymology, Academic Press,Volume 596, 2017, Pages 217-238,

27. Berezhkovskii AM, Szabo A, Rotbart T, Urbakh M, Kolomeisky AB. Dependence of the Enzymatic Velocity on the Substrate Dissociation Rate. J Phys Chem B. 2017;121(15):3437–3442. doi:10.1021/acs.jpcb.6b09055

28. Millard, P., Portais, J. & Mendes, P. Impact of kinetic isotope effects in isotopic studies of metabolic systems. BMC Syst Biol 9, 64 (2015) doi:10.1186/s12918-015-0213-8

29. Lamberson CR, Xu L, Muchalski H, et al. Unusual kinetic isotope effects of deuterium reinforced polyunsaturated fatty acids in tocopherol-mediated free radical chain oxidations. J Am Chem Soc. 2014;136(3):838–841. doi:10.1021/ja410569g

30. Syroeshkin, Anton & Pleteneva, Tatiana & Uspenskaya, Elena & Zlatskiy, Igor & Antipova, Nadine & Grebennikova, Tatiana & Levitskaya, Olga. (2018). D/H control of chemical kinetics in water solutions under low deuterium concentrations. Chemical Engineering Journal. 10.1016/j.cej.2018.08.213.

31. Ranaghan K.E. (2013) Quantum Effects/Tunneling. In: Roberts G.C.K. (eds) Encyclopedia of Biophysics. Springer, Berlin, Heidelberg

32. Drechsel‐Grau, C. and Marx, D. (2014), Exceptional Isotopic‐Substitution Effect: Breakdown of Collective Proton Tunneling in Hexagonal Ice due to Partial Deuteration. Angew. Chem. Int. Ed., 53: 10937-10940. doi:10.1002/anie.201405989

33. Olgun A. Biological effects of deuteronation: ATP synthase as an example. Theor Biol Med Model. 2007;4:9. Published 2007 Feb 22. doi:10.1186/1742-4682-4-9

34. Boros, Laszlo. (2016). Biological Nanomechanics: ATP Synthesis and Deuterium Depletion. 10.13140/ RG.2.2.31944.72961.

35. Wallace DC. A mitochondrial bioenergetic etiology of disease. J Clin Invest. 2013;123(4):1405–1412. doi:10.1172/JCI61398

36. Naviaux RK, Naviaux JC, Li K, et al. Metabolic features of chronic fatigue syndrome [published correction appears in Proc Natl Acad Sci U S A. 2017 May 2;114(18):E3749] . Proc Natl Acad Sci U S A. 2016;113(37):E5472–E5480. doi:10.1073/pnas.1607571113

37. Wawrzyniak NR, Joseph AM, Levin DG, et al. Idiopathic chronic fatigue in older adults is linked to impaired mitochondrial content and biogenesis signaling in skeletal muscle. Oncotarget. 2016;7(33):52695–52709. doi:10.18632/oncotarget.10685

38. Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P. Cellular bioenergetics is impaired in patients with chronic fatigue syndrome [published correction appears in PLoS One. 2018 Feb 8;13(2):e0192817] . PLoS One. 2017;12(10):e0186802. Published 2017 Oct 24. doi:10.1371/journal. pone.0186802

39. Serra D, Mera P, Malandrino MI, Mir JF, Herrero L. Mitochondrial fatty acid oxidation in obesity. Antioxid Redox Signal. 2013;19(3):269–284. doi:10.1089/ars.2012.4875

40. Rogge, M. M. (2009). The Role of Impaired Mitochondrial Lipid Oxidation in Obesity. Biological Research For Nursing, 10(4), 356–373. https://doi.org/10.1177/1099800408329408

41. Yavari K, Gholamali M, Yazdian F. The Biological Effects of Deuterium Depleted Water: A Possible Tool in Diabetes Therapy. Electronic J Biol, 13:4

42. Raichle ME, Gusnard DA. Appraising the brain’s energy budget. Proc Natl Acad Sci U S A. 2002;99(16):10237–10239. doi:10.1073/pnas.172399499

43. Rezin, G.T., Amboni, G., Zugno, A.I. et al. Neurochem Res (2009) 34: 1021. https://doi.org/10.1007/s11064008-9865-8

44. William R. Yorns, H. Huntley Hardison, Mitochondrial Dysfunction in Migraine, Seminars in Pediatric Neurology,Volume 20, Issue 3,2013, Pages 188-193

45. Turner RC, Lucke-Wold BP, Robson MJ, Lee JM, Bailes JE. Alzheimer’s disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities. Brain Inj. 2016;30(11):1279–1292. doi:10.1 080/02699052.2016.1193631

46. Mulchandani, H. (2010). “Mitochondria and Brain Disease.” Inquiries Journal/Student Pulse, 2(03). Retrieved from http://www.inquiriesjournal.com/a?id=195

47. Mitochondria impact brain function and cognition, Martin Picard, Bruce S. McEwen Proceedings of the National Academy of Sciences Jan 2014, 111 (1) 7-8; DOI:10.1073/pnas.1321881111

48. Cristian Mladin, Alin Ciobica, Radu Lefter, Alexandru Popescu, Walther Bild, Deuterium-depleted water has stimulating effects on long-term memory in rats, Neuroscience Letters, Volume 583, 2014, Pages 154-158

49. Tatyana Strekalova, Matthew Evans, Anton Chernopiatko, Yvonne Couch, João Costa-Nunes, Raymond Cespuglio, Lesley Chesson, Julie Vignisse, Harry W. Steinbusch, Daniel C. Anthony, Igor Pomytkin, KlausPeter Lesch, Deuterium content of water increases depression susceptibility: The potential role of a serotoninrelated mechanism, Behavioural Brain Research,Volume 277, 2015,Pages 237-244

50. Mirica, Roxana. (2010). Deuterium- Depleted water in cancer therapy. Environmental Engineering and Management Journal. 9. 1543-1545. 10.30638/eemj.2010.210.

51. Gyöngyi Z, Budán F, Szabó I, et al. Deuterium depleted water effects on survival of lung cancer patients and expression of Kras, Bcl2, and Myc genes in mouse lung. Nutr Cancer. 2013;65(2):240–246. doi:10.1080/0 1635581.2013.756533

52. Krempels K, Somlyai I, Gyöngyi Z, Ember I, Balog K, Abonyi O, Somlyai G. A retrospective study of survival in breast cancer patients undergoing deuterium depletion in addition to conventional therapies Journal of Cancer Research & Therapy, Volume 1, Issue 8, October 2013, Pages 194 – 200, ISSN 2052-4994, http:// dx.doi.org/10.14312/2052-4994.2013-29

53. Anticancer effect of deuterium depleted water - redox disbalance leads to oxidative Stress, Xuepei Zhang, Massimiliano Gaetani, Alexey Chernobrovkin, Roman A. Zubarev, Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17 165 Stockholm, Sweden

54. Lipidomics reveals physiological isotope effects during the enzymatic oxygenation of polyunsaturated fatty acids ex vivo. Aaron R. Navratil, Mikhail S. Shchepinov, and Edward A. Dennis, The FASEB Journal 2018 32:1_supplement, 658.1-658.1

55. Pidgeon, G.P., Lysaght, J., Krishnamoorthy, S. et al. Cancer Metastasis Rev (2007) 26: 503. https://doi. org/10.1007/s10555-007-9098-3

56. Park SY, Gifford JR, Andtbacka RH, et al. Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?. Am J Physiol Heart Circ Physiol. 2014;307(3):H346–H352. doi:10.1152/ ajpheart.00227.2014

57. Dimitry A. Chistiakov, Tatiana P. Shkurat, Alexandra A. Melnichenko, Andrey V. Grechko & Alexander N. Orekhov (2018) The role of mitochondrial dysfunction in cardiovascular disease: a brief review, Annals of Medicine, 50:2, 121-127, DOI: 10.1080/07853890.2017.1417631

58. Cell biology of cardiac mitochondrial phospholipids, Grant M Hatch Biochemistry and Cell Biology, 2004, 82:99-112, https://doi.org/10.1139/o03-074

59. László G. Boros, T. Que Collins, Gábor Somlyai, What to eat or what not to eat—that is still the question, Neuro-Oncology, Volume 19, Issue 4, 1 April 2017, Pages 595–596, https://doi.org/10.1093/neuonc/now284

60. Kosinski C, Jornayvaz FR. Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies. Nutrients. 2017;9(5):517. Published 2017 May 19. doi:10.3390/nu9050517

61. Weber DD, Aminazdeh-Gohari S, Kofler B. Ketogenic diet in cancer therapy. Aging (Albany NY). 2018;10(2):164–165. doi:10.18632/aging.101382

62. Basov A, Fedulova L, Baryshev M, Dzhimak S. Deuterium-Depleted Water Influence on the Isotope 2H/1H Regulation in Body and Individual Adaptation. Nutrients. 2019;11(8):1903. Published 2019 Aug 15. doi:10.3390/ nu11081903

63. Basov, A.; Fedulova, L.; Baryshev, M.; Dzhimak, S. Deuterium-Depleted Water Influence on the Isotope 2H/1H Regulation in Body and Individual Adaptation. Nutrients 2019, 11, 1903.

64. MELLANBY, K. Metabolic Water and Desiccation. Nature 150, 21 (1942) doi:10.1038/150021a0

65. Stockman MC, Thomas D, Burke J, Apovian CM. Intermittent Fasting: Is the Wait Worth the Weight?. Curr Obes Rep. 2018;7(2):172–185. doi:10.1007/s13679-018-0308-9

66. de Groot S, Pijl H, van der Hoeven JJM, Kroep JR. Effects of short-term fasting on cancer treatment. J Exp Clin Cancer Res. 2019;38(1):209. Published 2019 May 22. doi:10.1186/s13046-019-1189-9

67. Furmli S, Elmasry R, Ramos M, et alTherapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulinCase Reports 2018;2018:bcr-2017-221854.

68. Papagiannopoulos I, A, Sideris V, I, Boschmann M, Koutsoni O, S, Dotsika E, N: Anthropometric, Hemodynamic, Metabolic, and Renal Responses during 5 Days of Food and Water Deprivation. Forsch Komplementmed 2013;20:427-433. doi: 10.1159/000357718

69. Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys. 2017;4(3):337–361. doi:10.3934/biophy.2017.3.337

70. Dr. James H. Gibson, Senior Research Scientist, Director, USDA UVB Monitoring Program, Natural Resource Ecology Laboratory, Colorado State University

71. Lina Salomonsson, Gisela Brändén, Peter Brzezinski, Deuterium isotope effect of proton pumping in cytochrome c oxidase, Biochimica et Biophysica Acta (BBA) - Bioenergetics, Volume 1777, Issue 4, 2008, Pages 343-350

72. Sommer AP. Mitochondrial cytochrome c oxidase is not the primary acceptor for near infrared light-it is mitochondrial bound water: the principles of low-level light therapy. Ann Transl Med. 2019;7(Suppl 1):S13. doi:10.21037/atm.2019.01.43

73. Paula L.V. Lima, Claudia V. Pereira, Nadee Nissanka, Tania Arguello, Giulio Gavini, Carlos Magno da Costa Maranduba, Francisca Diaz, Carlos T. Moraes,

74. Photobiomodulation enhancement of cell proliferation at 660 nm does not require cytochrome c oxidase, Journal of Photochemistry and Photobiology B: Biology, Volume 194, 2019, Pages 71-75

75. Goncharuk VV, Kavitskaya AA, Romanyukina IY, Loboda OA. Revealing water’s secrets: deuterium depleted water. Chem Cent J. 2013;7(1):103. Published 2013 Jun 17. doi:10.1186/1752-153X-7-103

76. Siniak et al (2006), Fractionation of hydrogen stable isotopes in the human body, Aviakosm Ekolog Med. 2006 Sep-Oct;40(5):38-41.

77. Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

78. Wijers SLJ, Schrauwen P, Saris WHM, van Marken Lichtenbelt WD (2008) Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis. PLOS ONE 3(3): e1777. https://doi.org/10.1371/journal.pone.0001777

79. Nishimura T, Watanuki S. Relationship between mitochondrial haplogroup and seasonal changes of physiological responses to cold. J Physiol Anthropol. 2014;33(1):27. Published 2014 Sep 3. doi:10.1186/18806805-33-27

80. Effects of endurance exercise on metabolic water production and plasma volume J. M. Pivarnik, E. M. Leeds, and J. E. Wilkerson Journal of Applied Physiology 1984 56:3, 613-618

81. Purdom T, Kravitz L, Dokladny K, Mermier C. Understanding the factors that effect maximal fat oxidation. J Int Soc Sports Nutr. 2018;15:3. Published 2018 Jan 12. doi:10.1186/s12970-018-0207-1

82. Ambient Air Pollution and Type 2 Diabetes: Do the Metabolic Effects of Air Pollution Start Early in Life? Sung Kyun Park, Diabetes Jul 2017, 66 (7) 1755-1757; DOI: 10.2337/dbi17-0012

83. de Bont J, Casas M, Barrera-Gómez J, et al. Ambient air pollution and overweight and obesity in schoolaged children in Barcelona, Spain. Environ Int. 2019;125:58–64. doi:10.1016/j.envint.2019.01.048

84. Carrie V. Breton, Ashley Y. Song, Jialin Xiao, Su-Jeong Kim, Hemal H. Mehta, Junxiang Wan, Kelvin Yen, Constantinos Sioutas, Fred Lurmann, Shanyan Xue, Todd E. Morgan, Junfeng Zhang, Pinchas Cohen, Effects of air pollution on mitochondrial function, mitochondrial DNA methylation, and mitochondrial peptide expression, Mitochondrion,Volume 46, 2019, Pages 22-29

85. Lee DH. Can Air Pollution Biologically Hinder Efforts to Lose Body Weight?. Diabetes Metab J. 2018;42(4):282–284. doi:10.4093/dmj.2018.0139

86. Dawn L. DeMeo , Antonella Zanobetti , Augusto A. Litonjua , Brent A. Coull , Joel Schwartz , and Diane R. Gold, (2004), Ambient Air Pollution and Oxygen Saturation, American Journal of Respiratory and Critical Care Medicine, https://doi.org/10.1164/rccm.200402-244OC

87. Foti et al, (2017), Linking Hypoxia to Obesity, Frontiers in Endocrinology DOI=10.3389/fendo.2017.00034

88. Lukyanova Ludmila D., Kirova Yulia I. (2015), Mitochondria-controlled signaling mechanisms of brain protection in hypoxia, Frontiers in Neuroscience DOI=10.3389/fnins.2015.00320

89. Marc A. Russo, Danielle M. Santarelli, Dean O’Rourke, Breathe 2017 13: 298-309; DOI: 10.1183/20734735.009817

Guide to Deuterium Depletion