Nitric Oxide: Heart Disease, Diabetes, Immune Function and What You Need to Know About This Critical Compound
Hello, I am Julie Donaldson and I am a clinical nutritionist with functional medicine training. I specialize in restoring balance in complex, chronic and acute health conditions. I welcome you to peruse other articles that may be of interest to you in your health investigation!
Since working with Julie I have discovered several things that I would not have figured out on my own or with any conventional doctor. I have a nutrition degree and work in food retailing, but I still didn’t understand how important the Metabolic Typing® was to my recovery. I have also come to learn that heavy metals and viral load may be at the root of my challenges.
- Doug, Austin, Texas
Nitric oxide (NO) deficiency is a major factor in virtually all disease processes. Because it is critical to circulation and microcirculation, either preventing or healing a disease requires adequate levels of nitric oxide. it is truly a key component for maintaining holistic health. Oral health, gut health, and cardiovascular health are all dependent upon an adequate level of nitric oxide.
200,000,00 Americans are using mouthwash and/or PPIs (proton pump inhibitors) daily, knocking out their bodies’ ability to turn dietary nitrates into nitric oxide in the body. Mouthwash kills healthy bacteria as well as harmful ones in the mouth, and the oral biome is the first step in the process to reduce plant-based nitrates into nitrites and then into nitric oxide. Without healthy bacteria to act upon nitrates, the process is halted. PPIs reduce hydrochloric acid (HCL) in the stomach, a 2nd critical compound required for this conversion. PPIs are also associated with increased cardiovascular events, very possibly because of their impact upon nitric oxide production.
There are also over 200,000,000 Americans using antibiotics in a given year, another factor impacting both the oral and gut microbiomes required for NO production. Additionally, NO drops about 10-15% per decade of life, clearly contributing to yet another level of declining vitality in older people. Do we really need to accept the inevitable decline with age, or can we live in the brilliance of science, knowledge, and opportunity to assure all living people to have ongoing vitality? In this article, we’ll look at some of the most prevalent diseases of our time and their requirements of adequate stores of nitric oxide.
What Is Nitric Oxide?
Nitric oxide, known as endotheoium-derived relaxing factor (EDRF), is a compound biosynthesized endogenously from L-arginine, oxygen and NADPH by various nitric oxide synthase (NOS) enzymes. Reduction of inorganic nitrate may also serve to make nitric oxide. The endotheoium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, thus resulting in vasodilation and increased blood flow.
Blood flow to tissues is actually more important in most circumstances than how much oxygen is carried by hemoglobin. The respiratory cycle is actually a three-gas system inclusive of oxygen, nitric oxide and carbon dioxide.
Nitric oxide production occurs when nitric oxide synthase is “coupled” with L-arginine, iron and BH4 in its enzyme complex. Uncoupling of these compounds results in failed production of nitric oxide.
Nitric Oxide and Diabetes
We know that diabetes carries with it increased vascular wall oxidative stress, as well as increased advanced glycosylation end products (damage to proteins and lipids resulting in oxidative stress and tissue damage). Along with hyperinsulinemia, these effects down-regulate eNOS, or endothelial nitric oxide synthase. This is the nitric oxide located specifically in the inner lining of blood vessels. With lower eNOS comes lower bioavailability in the vascular system and then a higher risk of cardiovascular disease. People who suffer from diabetes are up to four times as likely to develop cardiovascular disease, the #1 killer from disease in the United States. Diabetes is the #7 cause of mortality in the US. Together, this is a deadly combination. People with diabetes most typically die of vascular complications, not blood sugar episodes. In those 65 years and older, 75% will die of vascular complications.
Clearly, the prevention of diabetes requires attention to healthy nutritional and lifestyle habits. But there are certainly people who have more complications than this who succumb to the disease. We know that weight, blood pressure and toxicity all matter in one’s risk for developing diabetes. But how often is the immune system discussed as part of this equation? and how often do we hear about nitric oxide as part of this equation?
In order for there to be binding and uptake of glucose, there must be signaling from NO to Glucose transporter type 4 (GLUT 4), a protein encoded, in humans, by the SLC2A4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle. Through NO signaling, cysteine (protein) residues on the outside of cells go through post modification to allow GLUT 4 to bind to and enhance glucose uptake through the cell membrane. This is key…diabetes medications are bypassing this NO signaling. This makes management of diabetes through current medications extremely difficult.
Nitric Oxide, the Immune System and Cardiovascular Disease
''The discovery of NO and its function is one of the most important in the history of cardiovascular medicine.'‘Dr. Valentin Fuster 1998 President of American Heart Association
Nitric oxide is required to maintain healthy blood pressure and healthy blood flow into and out of the heart. The earliest beginnings of cardiovascular disease (CVD) come with the excesses and adhering of immune cells in the endothelium of the blood vessels. T cells, neutrophils, platelets and monocytes collect in response to inflammation and immune threats, and when unable to reach resolution become amassed in the endothelium. Monocytes will then migrate out of the lining and contribute to oxidative stress leading to modified LDL cholesterol and cell plaque formation. These initiate the development of atherosclerosis.
As part of comprehensive blood testing at True Nature, immune markers and CVD-related markers such as homocysteine are routinely checked and can provide insights into current function and possible risks.
Notably also with current global concerns is that nitric oxide can block the replication of dangerous viruses.
Nitric Oxide, Genetic Mutations and Toxicity
Approximately 50-55% of us have genetic methylation defects and accompanying toxicity concerns that will alter the normal course of nitric oxide production.
In its normal state, nitric oxide synthase (NOS) converts the amino acid L-arginine to nitric oxide (NO), with L-citrulline as a by-product. Oxygen and nicotinamide adenine dinucleotide phosphate are substrates in this reaction, as is tetrahydrobiopterin (BH4).
This pathway via L-arginine is negatively impacted, however, in the presence of heavy metals, oxidative stress, pollution, and medications like antacids. Rather than producing nitric oxide, NOS generates superoxide. An activated MTHFR mutation also contributes to this alteration in the standard process, and depletes BH4. MTHFR is not only important for the formation of 5-MTHF (and thus the methionine cycle) but also for the regeneration of BH4. Without adequate BH4, the L-arginine conversion is impaired through uncoupling. (Note: it is important to test for activated mutations biochemically when possible. The simple presence of a genetic mutation in one’s genetic profile is not proof of current activation. Activation can result in both over and under-methylation patterns. Each requires its own strategy., but both involve low availability of cofactors such as B vitamins, zinc, selenium, choline, etc.)
These factors contribute to the lowering of circulation and microcirculation with lower levels of nitric oxide. With this also comes the potential to experience neuropathy with pressure on the nerves, reduced stores of and reduced absorption of vitamin B12. NO has neuroprotective actions with Brain Derived Neurotrophic Factor (BDNF).
Other Potential Expressions and Symptoms of Depleted Nitric Oxide
While we will not delve into every possible disease or symptomatic expression of low nitric oxide here, a few others are worth mentioning:
regulation of inflammatory response
sleep dysregulation
cognitive impairment and/or decline
exercise performance/endurance
stem cell differentiation and regeneration
regulation of inflammatory response
erectile dysfunction, vasodilation/innervation of erectile tissue
cognitive decline
compromised neurotransmission
It is posited by many who have researched nitric oxide and its impacts for decades that its depletion may be fundamental in almost any disease process, no matter where in the body.
Lifestyle and Solutions
First and foremost, as in everything I educate about at True Nature, the appropriateness and individuality of your nutrition and lifestyle are foundational to all healing. Without proper energy regulation with nutrient balance and without a healthy gut/microbiome, everything will begin to suffer. As you’ve read here, NO production begins in the mouth with a healthy biome and salivary concentration of nitrates. From there, we need adequate HCL in the stomach and balanced methylation to complete the process. At True Nature, a personalized nutrition approach called Metabolic Typing ® is the beginning point of all healing. It is required to optimize the production of ATP (our body’s fuel) and all homeostatic mechanisms. With imbalances in pH, electrolytes, blood pressure, blood sugar and body temperature, all metabolic systems can be negatively impacted.
Get tested!! Not just your nitric oxide level, but your overall blood chemistry, toxic burden, and methylation function. I recommend everyone test twice annually for these things, no matter what. It’s the path of prevention and staying ahead of any developing problems.
It has now been studied and shown that moderate sun exposure supports nitric oxide production as well as vitamin D synthesis. We have become a culture of indoor activity and excessive sun screening. While vitamin D and nitric oxide supplementation may be necessary under certain circumstances, getting those moments unfiltered in the sun will give us what nature always intended in a healthy, balanced way. The link above also provides access to a healthy sunscreen which will allow UV support without burning.
Utilizing nitric oxide supplements may be key. Fortunately, there are affordable test strips which measure NO in the saliva. When deficient or low, supplementation is key. I have carefully researched products with the best tolerance and highest efficacy and recommend based upon my findings.
The inclusion of nitrate rich foods in the diet can help, especially in between supplements. Beware, however, that we cannot rely on predictable levels. The chart below shows the wide variation in levels in different areas of the country, based upon soil content.
As always, proper direction and guidance of a complex health picture is advised. Be sure you receive annual physicals with your physician and be sure to work in conjunction with a top-notch functional practitioner to support non-medical practices in your life. Contact me at Julie@truenaturehealthconsulting.com. We provide holistic telehealth services.