Connecting The Dots Between Nitric Oxide and True Gut Health
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!
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Until the late 1980’s, it was unknown that nitric oxide plays a central role in the physiology of many human body systems. The multitude of cellular actions requiring nitric oxide and its synthesis are currently an area of great scientific discovery, with new information arriving in the research on a regular basis. This article will focus on the significant impacts of nitric oxide (NO) upon gut health, which, as we know is a driver of overall holistic health.
From the Mouth Down…
There is the old saying “The fish rots from the head down” - and this old saying applies to the health (or lack thereof) of the oral biome extending down through the gut biome. As much as 45% of the biomes of the mouth and gut are overlapping on a constant basis, so as we swallow saliva and as we chew and swallow food, the oral biome is impacting that of the gut and vice versa. As we consider the impacts of nitric oxide on the health of the digestive mucosa and digestive tract, we begin with attention to the mouth.
We often think that digestive health is as simple as eating good food. We may not know what good food is for us individually, and we often don’t understand how many pieces need to line up in order to be able to digest good food. Nitric oxide and its supportive compounds fit into the missing pieces of the digestion puzzle.
Nitric oxide is the compound used by our blood cells to impact digestion, circulation, neurotransmission and many other functions. It must be produced from the reduction of nitrates to nitrites. There are two ways the body makes nitric oxide:
Through the consumption and metabolism of inorganic nitrate found in green leafy vegetables and some root vegetables. When we consume nitrate-containing foods, our saliva becomes rich in nitrite from special bacterial action. Then as we swallow our saliva, nitric oxide is produced in the stomach, provided there is adequate stomach acid (HCL). For this pathway to work, people must consume sufficient nitrates in their diet (300-400mg daily), must have healthy oral bacteria and must have sufficient stomach acid production.
Through an enzymatic reaction using L-arginine and the enzyme nitric oxide synthase (NOS). This enzyme is found throughout the body, but primarily in the cells that line all blood vessels (endothelial cells). L-arginine is a semi-essential amino acid, meaning that your body makes it through normal metabolism in the urea cycle. It is also found in many proteins we eat. Unless you have an inborn error in metabolism (which is extremely rare), your body will always make enough L-arginine to produce NO. The reaction to convert L-arginine to nitric oxide is complex and requires multiple co-factors and substrates.
Our tongues contain specialty bacteria whose purpose is to reduce nitrates to nitrites, hence they are called nitrate-reducing bacteria. Nitrates, both in the form of supplements and foods, increase nitrate-reducing bacteria on the tongue and decrease levels of bacteria that are associated with poor oral health. Nitrate supplementation aids in reduction and prevention of bacterial dysbiosis, while increasing the beneficial, healthy bacteria and decreasing levels of disease-associated bacteria.
So, what goes wrong in the process to be able to produce nitric oxide, beginning in the mouth? As part of the aging process, the NOS enzyme becomes dysfunctional and no longer converts L-arginine to nitric oxide. This is termed endothelial dysfunction. (Read more about endothelial damage/dysfunction here.) Also as part of the aging process, we produce less HCL in the stomach. Other interfering factors are the use of oral antiseptics (mouthwash) which kill healthy bacteria along with bad ones. Another very important consideration is the SAD (Standard American Diet), which does not include healthy, raw fresh foods that contain beneficial bacteria for the mouth. What I call “dead” food cannot deliver these critical living organisms that support our immune health beginning with oral digestion. We must attend to our individual nutritional needs through Metabolic Typing ®, utilizing proper balances and ideal foods for ourselves to attain this piece of healthy personalized nutrition and digestion.
Moving Down Into the Esophagus
The esophagus is also part of the microbiome and mucosal barrier. Its health, or lack thereof, also depends upon healthy bacteria and mucosal integrity. As our chewed food begins the transit down into the stomach, a healthy esophagus allows smooth movement. When your mouth forces fluid or chewed food into your throat, your brain begins the process of swallowing. You use your voluntary nervous system to start a swallow. Your involuntary nervous system takes over your swallowing once the liquid or food enters the top of your esophagus.
Stretching from food or liquid stimulates the smooth muscles that make up the walls of your esophagus. This stimulates a dense network of nerves inside your muscles. These nerves, known as intrinsic nerves, start a coordinated muscle action called peristalsis. Peristalsis squeezes your esophageal muscles from top to bottom. This pushes food and liquid along. If you could see peristalsis, it would look like a wave passing down your esophagus.
To keep food and liquids moving in the right direction, your digestive tract has special muscles along its course called sphincters. Sphincters act like one-way valves. They relax to let food and liquid pass into your stomach and then tighten to prevent backflow, also known as reflux.
Research has shown that nitric oxide is involved in the proper relaxation of the esophagus via cholinergic nerves in the lower section that are responsive to its actions. We can understand from these findings that GERD (gastroesophageal reflux disease) can be associated with low nitric oxide.
Next Step, The Stomach
As your food reaches your stomach, adequate stomach acid (HCL) is required to break it down for successful digestion. In the United States, there are over 100 million prescriptions written every year for proton pump inhibitors (which reduce stomach acid). This is usually the “solution” for GERD, and in conjunction with a failure to look behind the curtain for possible NO deficiency. Many of these antacid drugs can also now be sourced over the counter, with considerable self misdiagnosis and misuse of a product. It is estimated that there could be another 100 million Americans consuming these antacids who are not accounted for in the reporting of prescription drug statistics.
The Rhythm of the Small Intestine
The small intestine receives food broken down in the stomach. It is then responsible for 90% of our food assimilation through simple and facilitated diffusion as well as active transport. It too is part of the long pathway down from the mouth through the colon that makes up successful digestion.
Nitric oxide activates the smooth rhythm of the small intestines. In the small intestines, there is a propulsive, contracting motor pattern that moves food downward into the colon. This becomes clustered by the enteric nervous system into a minute rhythm that is dependent upon nitric oxide. In the clinical study referenced here, when cluster formation was inhibited by failure of NO synthesis to occur, function was fully restored in a highly rhythmic fashion with a constant level of nitric oxide. Studies are needed, but this may have associations and ramifications for the widespread incidence of SIBO.
The Large Intestine, Final and Crucial Stop
Your large intestine is a crucial final stop for your food and waste material. Not only does the colon finish the steps of delivering nutrients to all of your body systems via the blood, but it must complete critical detoxification tasks as well, all of which are dependent upon healthy bacteria. Surpassing those for antacids, even more prescriptions for antibiotics are written annually without careful attention to the restoration of the microbiome after their use. Antibiotics kill all of our bacteria, not just the bad ones. When our microbiomes are wiped out with antibiotics, we are left with open receptor sites that are very vulnerable to accumulations of bad bacteria and fungi. The use of antibiotics has long been linked to intestinal disorders, leaky gut syndrome, and even mental illness, including anxiety, depression, brain fog, and severe fatigue. Dietary and/or supplemental nitrates have a supportive role to play during antibiotic treatment. Nitrates taken during antibiotic therapy reduce gastric mucosal inflammation and prevent inflammatory processes that result in increased intestinal epithelial permeability.
Having a healthy mucosal barrier is our first line of defense against pathogenic bacteria. It is a critical protective layer that balances good and harmful bacteria. NO Is one of the most important signal mediators for mucous secretion. It also increases mucosal blood flow, increases mucous production and thickness, modulates the mucosal immune response and can even repair damage to the intestinal tract. Nitrates may act as a substrate for the existing microbial communities, allowing them to thrive and prevent dysbiosis.
The GI tract’s mucosal barrier is continuously exposed to potentially damaging substances and toxins that can compromise its integrity. As the colon receives waste material and bile from the small intestine for removal, dangerous accumulations of toxins can damage this precious barrier. As NO increases blood flow, this acts to dilute toxic substances and neutralize them in conjunction with methylation processes. Read more specifically about the role of NO with methylation here.
Numerous studies indicate that adequate nitric oxide plays a key role in preventing and/or treating inflammatory bowel diseases. During inflammatory events, there is increased expression of myeloperoxidase, which is involved in the body’s antimicrobial immune response. As part of this response, reactive oxygen species (ROS) are increased. While ROS have important biological function, they can cause irreversible damage to DNA as they oxidize and modify cellular components, preventing them from performing their original functions. Whether ROS will act as harmful or protective signaling factors depends upon the balance between ROS production and their disposal at the right time and place. Nitric oxide also supports a healthy inflammatory response in the GI tract by decreasing myeloperoxidase activity in gastric mucosa, thereby preventing this risk of harmful ROS activity.
All the Positive Benefits of NO Visualized
Nitric oxide benefits
What a myriad of beneficial impacts we can see here! Nitric oxide INHIBITS the following potentially negative responses in the GI defense systems:
mast cell activation
excess neutrophils and macrophages
cytokine release
oxidative stress
all the while providing STIMULATION of these positive responses:
mucous secretion
formation of new blood vessels and fibroblasts (wound healing)
dilation of vasculature
So, What To Do?
Gut health is paramount in our overall immune health. And immune health is paramount on our cardiovascular health. The dots connecting nitric oxide to all of them are truly life-sustaining.
We finish with the question of what to do…what to eat, what to take, how to get that all-important nitric oxide level up.
Going back to the two possible ways to increase nitric oxide, we realize there is never a condition where people are deficient in L-arginine. We eat it in the form of proteins and the body produces it endogenously. Therefore taking a L-arginine product will not lead to any improvement in NO production, especially in patients that have endothelial dysfunction. In people that are nitric oxide deficient, the NOS enzyme doesn’t work. Furthermore, clinical trials have demonstrated that giving L-arginine can make things worse.
That leaves us with increasing nitric oxide through consumption of nitrate-rich foods and/or through the use of high quality supplements. As stated earlier, it takes at least 300 mg of nitrates in the diet to produce adequate nitric oxide. This amounts to 1-2 cups daily of the foods highest in nitrates - spinach, beets, arugula, cabbage and celery are at the top of the list. Some of these foods must be avoided for those needing to limit oxalates in their diets, thus creating a challenge to reach optimal intake levels. High quality supplements which initiate the nitrate-nitrite pathway must then be utilized. Often, a combination of the two can work quite nicely.
In order to utilize the nutrients appropriately, we must investigate and attend to oral health as well as the overall health of the stomach and digestive tract. Long-term or acute immune responses must be evaluated for the potential to cause endothelial dysfunction. All aspects of the cooperative nature of one’s body systems with digestion and assimilation are addressed at True Nature Health Consulting, along with appropriate personalized nutrition and therapeutic practices. Contact me for more information at Julie@truenaturehealthconsulting.com. We provide holistic telehealth services.