Branka D. NAJDOVSKA 

Nathan Bryan is an American biochemist, professor, entrepreneur, and author, internationally known and recognized for his more than two decades of work and research in the field of nitric oxide and its impact on human health. Prof. Dr. Brian has a PhD in molecular and cellular physiology (and a BA in biochemistry), is the founder and CEO of several companies that commercialize his scientific discoveries. He has taught at several top American universities, and has also collaborated with Ferid Murad (Nobel Prize winner for research on the role of nitric oxide), at the invitation of the Nobel laureate.  

Prof. Dr. Bryan is one of the first scientists to describe nitrite and nitrate as essential nutrients for optimal cardiovascular health. His research into the endocrine function of nitric oxide and ways to safely increase its production has been the impetus for numerous publicly published clinical studies and technologies. 

There are dozens of issued patents (US and international) related to the biochemistry of nitric oxide, as well as production technologies in this field. He has published numerous scientific papers, with cited publications supporting his expertise, and his book "The secret of nitric oxide - Bringing nitric oxide to life" has been adapted for a wider audience, thus experiencing great global popularity.  

In short, Prof. Dr. Bryan's work advances the idea that nitric oxide is a key molecule for heart health, circulation, and aging, and that its production in the body can be supported through lifestyle, nutrients, and specialized technologies. 

What motivated you to dedicate yourself specifically to nitric oxide research?  

-I was first introduced to the science of nitric oxide when I was a first year student at Louisiana State University School of Medicine.  I was working on a Ph.D. in Molecular and Cellular Physiology.  The Nobel Prize has just been awarded to three U.S. Scientists for their discoveries of nitric oxide as a signaling molecule in the cardiovascular system.  I had the great privilege of meeting Dr. Lou Ignarro and learn of his research that led to his Nobel Prize.  He encouraged me to continue in this field as there was still a lot to learn and understand.  He said to me if someone can figure out how to safely and effectively deliver nitric oxide, it would change the world.  That was sufficient motivation for me to dedicate my entire career to this line of research. 

Why is nitric oxide so important for cardiovascular health?  

-Nitric oxide controls the regulation of blood flow and oxygen delivery to every cell in the body.  It keeps the blood vessels clean and clear, maintain normal blood pressure and inhibits vascular inflammation, the primary drivers of cardiovascular disease. We now understand that the functional loss of nitric oxide production is the earliest event in the onset and progression of cardiovascular disease, which remains the number one killer of both men and women worldwide.  If we can maintain adequate and sufficient nitric oxide production, we can prevent cardiovascular disease.  It is the Holy Grail in Cardiovascular medicine. 

What do you consider your most significant scientific discovery to date?   

-My most significant discovery is the development of a solid dose form of nitric oxide gas.  Nitric oxide is a gas that is naturally produced in the body and then is gone in less than one second.  Based on this physical chemistry, the only way it could be delivered therapeutically is through inhalation nitric oxide therapy in the hospital.  My objective was to figure out how we could deliver bioactive and therapeutic doses of nitric oxide in a shelf stable product that could be taken by anyone outside a hospital setting.  

I have discovered ways to produce nitric oxide through several form factors including an orally disintegrating table that produces therapeutic amounts of nitric oxide over 5-6 minutes.  I have developed a fermented beet powder that produces nitric oxide gas when dissolved in water.  I also have a topical nitric oxide dual chamber technology that produces nitric oxide when two components are mixed together.  All of these form factors produce nitric oxide gas.  If your body has lost the ability to produce nitric oxide naturally, my products can provide it for you.  

How has the understanding of nitrates and nitrites changed in the last two decades? 

-We have made remarkable progress in correcting the record on nitrates and nitrites over the past few decades.  Nitrite and nitrate were once vilified as toxic, unwanted food additives that potentially caused cancer.  Today we know they are indispensable nutrients that are required for optimal nitric oxide production.  My paper published in the American Journal of Clinical Nutrition back in 2009 initiated a reassessment of their value.  I then edited a book Nitrite and Nitrate in Human Health and Disease in 2011 with Joe Loscalzo, M.D., Ph.D., Chair of Medicine at Harvard Medical School that furthered our understanding of nitrite and nitrate.  Today we have companies selling products proclaiming they are enriched in nitrate.  What was once feared and avoided is now sought out.  That is what we call scientific progress and innovation. 

What is the connection between nitric oxide (NO) deficiency and chronic disease?  

-It is now well established that the loss of nitric oxide is what leads to all chronic disease.  When we look at the hallmarks of all chronic disease, there are always 4 common denominators: low blood flow (hypoxia or ischemia), inflammation, oxidative stress and immune dysfunction.  It is the loss of nitric oxide that causes all of those.  Nitric oxide maintains normal blood flow and circulation.  It inhibits inflammation.  Nitric oxide prevents oxidative stress and corrects immune dysfunction.  It is the signal that controls every aspect of optimal cardiovascular health.  When we lose that signal, it leads to a rapid onset and progression of chronic disease. 

Can improving NO signaling prevent heart attacks and strokes?  

-Absolutely. Heart attacks and strokes occur when plaque becomes unstable and then ruptures in the coronary arteries and cerebral arteries respectively.  The thrombus then blocks downstream blood vessels shutting off blood supply to certain regions of the heart and brain.  Nitric oxide not only stabilizes existing plaque, preventing its rupture, but it actually prevents the original plaque formation.  As long as we have sufficient nitric oxide production in the lining of the blood vessels, plaque cannot and does not accumulate or deposit in the lining of the blood vessels.  It keeps blood vessels clean, clear and maintain normal vascular reactivity. 

What does clinical research show about the role of NO in aging?   

-NO is the ultimate anti-aging molecule.  When we look at molecular and cellular aspects of aging, there are three primary objective mechanisms.  Those three are the length of our telomeres (the ends of our chromosomes), the work of our own stem cells and the function of our mitochondria (the energy producing organelles of the cells).  Nitric oxide is the molecule that activates an enzyme called telomerase that prevents our telomeres from shortening.  Shorter telomeres, shorter life.  Longer telomeres, longer life.  Without nitric oxide our telomeres get shorter.  Nitric oxide is the signal that tells our own stem cells to mobilize, differentiate to repair and replace dysfunctional cells.

Aging is when our cells no longer work properly, partly due to insufficient stem cells in circulation to replace dysfunctional cells.  Without nitric oxide, we do not mobilize stem cells for repair.  Cells then become dysfunctional and disease sets in.  The third is the function of our mitochondria.  Every age related chronic disease is associated with lower numbers or mitochondria per cell and what mitochondria are present are not efficient at producing cellular energy.  Nitric oxide induces mitochondrial biogenesis leading to more mitochondria per cell and nitric oxide enhances the function of the mitochondria making them generate more energy more efficiently.  Everything we know about aging and longevity is dependent upon adequate and sufficient nitric oxide production. 

Do NO therapies have potential in treating Alzheimer's disease?   

-Without a doubt.  Alzheimers disease is a condition of chronic nitric oxide deficiency.  Alzheimers disease is now recognized as a vascular and metabolic disease. Prior to Alzheimers, it is referred to as vascular dementia.  Brain scans reveal that many parts of the brain are not getting sufficient blood flow or perfusion.  This creates focal ischemia where some regions are not getting enough blood supply and the brain begins to atrophy.  Alzheimers has also been termed diabetes type 3, referring to the insulin resistance in the brain.  

We published in 2013 that nitric oxide is required for insulin signaling.  Without nitric oxide production, the cell becomes resistant to insulin and unable to bring glucose into the cell.  Brain cells primarily utilize glucose as their primary energy source.  If brain cells cannot get glucose into each cell, the cell cannot do its job and proteins can misfold.  

These misfolded proteins are referred to as Tau tangles and amyloid plaques, seen in Alzheimers patients.  Nitric oxide is the molecule that dilates blood vessels and improves blood flow throughout the brain and it is also the molecule that allows insulin to signal and get glucose into each cell.  When the body has lost the ability to produce sufficient nitric oxide, it creates an environment that eventually leads to Alzheimer's disease.  We are confident that restoring nitric oxide through drug therapy will completely prevent, treat, cure, reverse and eradicate the disease. 

How much does diet affect the body's natural production of nitric oxide?  

-We estimate that the proper diet and lifestyle can contribute as much as 50% of the total body nitric oxide production.  However, the proper diet can only work if the right oral bacteria are present and the stomach makes sufficient stomach acid.  Without good oral bacteria and stomach acid production diet will have zero effect on nitric oxide production.  You could eat a perfect diet but if you use fluoride toothpaste, antiseptic mouthwash and/or take an antacid, you will get no nitric oxide benefit from diet.  This is a huge problem since most toothpaste contain fluoride, many people use antiseptic mouthwash every day.  In the U.S., two out of three people use mouthwash daily.  Nearly 50% of the global population are using antacids, either by prescription or an over-the-counter antacid.  Diet is important but only if the person has the right mechanisms working to utilize diet to produce nitric oxide.   

Which foods are most important for healthy NO levels?   

-When we consider that nitrate is the primary nutrient used to make nitric oxide in the human body, we find that dark green leafy vegetables are typically the highest in nitrate.  However, this is dependent upon how the foods are grown, the soil conditions, the amount of sunlight, the addition of nitrogen-based fertilizers and time of harvest.  Nitrate levels in vegetables can vary by 50-fold based on geography.  Therefore, it is nearly impossible to predict which foods can provide adequate nitric oxide support.  As discussed above, foods will provide no benefit in people using fluoride, mouthwash or antacids. 

Is modern lifestyle reducing nitric oxide production?   

-Yes, indeed.  Now that we understand how the human body produces nitric oxide, we are beginning to understand what leads to a loss of its natural production.  A sedentary lifestyle leads to nitric oxide deficiency.  Smoking completely disrupts nitric oxide production.  Consuming a diet high in sugar and simple carbohydrates completely shuts down nitric oxide production and leads to insulin resistance and metabolic disease.  Fluoride toothpaste, antiseptic mouthwash, overuse of antibiotics cause microbial dysbiosis, leading to a loss of nitric oxide production.  We have also been conditioned to avoid sunlight. Sunlight activates and stimulates nitric oxide release.  Cholesterol lowering medications can lead to nitric oxide deficiency.  Unfortunately, this is the modern lifestyle of many people and we must make changes to prevent the loss of nitric oxide production. 

What do you think about NO supplements?  

-Most of the nitric oxide supplements sold on the market provide no nitric oxide benefit. Companies who sell and market these products do not understand the complex biochemistry and physiology of nitric oxide.  So how can they develop products to address the deficiencies?  The simple answer is they cannot because they do not understand.  Many of the companies are really good at marketing but very poor at science.  Many companies now are trying to convince consumers that beets are nitric oxide.  Beets are not nitric oxide.  We have to maintain the integrity of the science of nitric oxide with product technology that actually works.  That is why I created a line of nitric oxide supplements and nutritional products based on real science that actually provide a source of nitric oxide gas and fix the reason people are nitric oxide deficient.  My line of supplements are under the N1o1 brand of product. 

How do you see the future of personalized medicine related to NO?  

-The future of medicine is dependent on safe and effective nitric oxide product technology and drug therapy.  There is not a single disease indication where nitric oxide at the right dose, right time in the right patient would not provide benefit.  The challenge is to determine how much nitric oxide and how often is required for each disease indication.  That will make it personalized medicine. 

Which diseases could benefit most from new NO therapies?   

-The most obvious are cardiovascular disease, the number one killer of men and women, and Alzheimers disease.  My company Bryan Therapeutics, Inc has drugs for heart disease and Alzheimers currently in development and in clinical trial.  The fact that cardiovascular disease remains the number one killer is simply unacceptable given that nitric oxide addresses the root cause of cardiovascular disease and Alzheimers disease. 

What is your lab or company researching next?  

-We are developing consumer products that restore nitric oxide production.  We recently launched a nitric oxide friendly toothpaste to help restore the normal oral microbiome to enhance nitric oxide production.   We are working on a mouthrinse that can enhance nitric oxide production rather than destroy it.  We have our drugs going through the US Food and Drug Administration for drug approval.  We have a drug for heart disease, Alzheimers and a topical drug for diabetic ulcers and non-healing wounds.   

What is the most common misconception about nitrates and nitric oxide by the public?   

-The public still buys meat products that say no added nitrite or nitrate because they think they cause cancer.  Nitrite and nitrate are naturally produced in the human body and are important nutrients that most people are deficient.  We must continue to educate and inform and communicate the latest science on nitrite and nitrate so consumer can make educated and informed decisions. 

What is your most important piece of advice for people who want better long-term health?  

-People need to do an 18 hour daily fast, get at least 8 hours of sleep per night, exercise regularly and eat a balanced diet in moderation with high protein, good quality fats and limited carbohydrates while avoiding sugar.  This lifestyle will ensure adequate nitric oxide production and a good long quality of life free of disease. 

What would you recommend to young scientists who want a career in biomedicine?   

-Find a line of research where many important unanswered questions remain.  See what everyone else has seen but think what others have not thought.  Do not let your colleagues and peers criticism discourage you.  New discoveries are often met with ridicule, criticism and opposition.  Each experiment, each new observation and data tells a story, even if you get the answer you do not expect. 

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