Nitric Oxide and the Oral-Systemic Connection: Why the Mouth Matters More Than We Think

The mouth plays an important role in systemic health through oral function, microbial activity, and biochemical pathways.

What if one of the most important contributors to cardiovascular health, circulation, and oxygen delivery begins in the mouth?

For decades, dentistry and medicine have recognized that oral health is closely connected to systemic health. Periodontal disease, chronic inflammation, and oral infections have all been investigated for their relationships with cardiovascular disease, diabetes, and other medical conditions.

But there is another connection that deserves greater attention: the relationship between the oral microbiome and nitric oxide production.

In an Airway Circle Thursday Night Live presentation, Dr. Nathan Bryan, a nitric oxide biochemistry researcher with more than 25 years of experience, shared how oral bacteria, dietary nitrate, nasal breathing, and vascular health are connected through one of the body's most important signaling molecules.

Dr. Bryan earned his PhD from Louisiana State University School of Medicine and completed postdoctoral training at Boston University. He later joined the University of Texas Health Science Center, where he worked in a research environment shaped by Nobel Laureate Dr. Ferid Murad, whose work helped establish the importance of nitric oxide in cardiovascular physiology.

As the founder of Bryan Therapeutics, Dr. Bryan also develops nitric oxide-based products and investigates potential therapeutic applications.

His presentation highlighted an important message for dental hygienists, dentists, myofunctional therapists, and airway-focused healthcare professionals: the microorganisms living in the mouth do much more than influence cavities, periodontal disease, and bad breath. Some of them participate in biochemical pathways that help regulate systemic physiology.

What Is Nitric Oxide?

Nitric oxide, commonly abbreviated as NO, is a naturally occurring gas produced throughout the human body.

Although it consists of only one nitrogen atom and one oxygen atom, nitric oxide acts as an important signaling molecule involved in multiple physiological processes.

Its functions include:

• Regulation of blood vessel dilation
• Vascular blood flow and circulation
• Endothelial signaling
• Immune system activity
• Cellular communication
• Mitochondrial function
• Regulation of inflammatory responses
• Pulmonary and respiratory physiology

Nitric oxide gained international recognition in 1998 when the Nobel Prize in Physiology or Medicine was awarded to Robert Furchgott, Louis Ignarro, and Ferid Murad for discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system.

Their research helped change the understanding of how blood vessels relax and how the body regulates circulation.

Today, nitric oxide remains an important area of research in cardiovascular medicine, respiratory physiology, metabolism, and oral-systemic health.

The Relationship Between Nitric Oxide and Blood Flow

One of nitric oxide's best-established functions is its ability to regulate vascular smooth muscle relaxation.

Blood vessels contain smooth muscle that can contract or relax to change vessel diameter.

When nitric oxide is produced by endothelial cells lining blood vessels, it can diffuse into nearby smooth muscle cells.

There, it activates an enzyme called soluble guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP).

This signaling pathway promotes smooth muscle relaxation and vasodilation.

As blood vessels relax, their diameter increases, which can reduce vascular resistance and support blood flow.

This mechanism is fundamental to cardiovascular physiology.

Dr. Bryan emphasized that impaired nitric oxide signaling is associated with endothelial dysfunction, a process involved in several cardiovascular and metabolic disorders.

However, nitric oxide is one component of a complex physiological system. Chronic diseases cannot generally be explained by nitric oxide deficiency alone.

The Oral Microbiome: More Than Bacteria

The human mouth contains a diverse community of microorganisms collectively known as the oral microbiome.

These microorganisms occupy different ecological environments, including the tongue, teeth, gingival tissues, saliva, and oral mucosal surfaces.

Historically, many approaches to oral hygiene focused heavily on eliminating bacteria associated with disease.

Modern microbiome science offers a more nuanced perspective.

Not all oral bacteria are harmful.

Some microorganisms contribute to healthy microbial communities and participate in metabolic processes that humans cannot perform as efficiently without them.

One of the most clinically relevant examples is the role of nitrate-reducing bacteria.

Certain bacteria living on the dorsal surface of the tongue can convert dietary nitrate into nitrite, supporting an alternative pathway for nitric oxide generation.

This makes the oral microbiome an important link between nutrition, oral health, and cardiovascular physiology.

How the Mouth Helps Produce Nitric Oxide

Certain bacteria on the tongue help convert dietary nitrate into nitrite, contributing to nitric oxide-related pathways.

The human body generates nitric oxide through two major biochemical pathways.

The first involves nitric oxide synthase enzymes, which produce nitric oxide from L-arginine.

The second involves the reduction of nitrate to nitrite and subsequently to nitric oxide.

The second pathway is particularly relevant to dentistry because it depends partly on bacteria living in the oral cavity.

The process begins when a person consumes nitrate-containing foods, especially certain vegetables.

Dietary nitrate is absorbed into the bloodstream, and a portion is concentrated in the salivary glands.

As saliva enters the mouth, nitrate becomes available to nitrate-reducing bacteria on the tongue.

These microorganisms convert some of that nitrate into nitrite.

The nitrite is swallowed and may undergo further chemical conversion in the acidic environment of the stomach. Nitrite can also participate in nitric oxide-related reactions elsewhere in the body.

This pathway is commonly referred to as the enterosalivary nitrate–nitrite–nitric oxide pathway.

It provides a clear example of how oral microorganisms participate in systemic physiology.

Why the Tongue Microbiome Matters

The dorsal surface of the tongue is an important habitat for nitrate-reducing bacteria.

During his presentation, Dr. Bryan discussed research examining the relationship between oral microbial communities and blood pressure.

His research group investigated whether differences in the abundance and activity of nitrate-reducing bacteria were associated with differences in cardiovascular measurements.

The findings suggested that some oral bacterial populations may contribute to nitrate metabolism and blood pressure regulation.

This is an important distinction for dental professionals.

The goal of oral hygiene should not be to eliminate every microorganism from the mouth.

Instead, modern preventive care aims to control pathogenic biofilms, prevent oral disease, and preserve a healthy microbial environment.

The challenge is understanding how oral hygiene interventions influence both beneficial and potentially harmful microorganisms.

Can Antiseptic Mouthwash Affect Nitric Oxide Production?

One of the most thought-provoking sections of Dr. Bryan's presentation concerned antiseptic mouthwash.

Certain antimicrobial rinses, particularly chlorhexidine, can reduce the activity of oral nitrate-reducing bacteria.

Because these bacteria contribute to nitrate conversion, disrupting them may interfere with the enterosalivary nitric oxide pathway.

Dr. Bryan discussed studies in which participants used antibacterial mouthwash for several days.

Some studies demonstrated reduced oral nitrate-to-nitrite conversion and modest increases in blood pressure following antimicrobial mouthwash use.

In one randomized crossover study involving treated hypertensive adults, antibacterial mouthwash reduced oral nitrate conversion and was associated with an approximately 2.3 mmHg increase in systolic blood pressure compared with a water control.

Other studies, however, have not demonstrated clinically significant blood pressure changes despite showing reduced bacterial nitrate conversion.

These differences illustrate why findings must be interpreted carefully.

The research does not establish that every mouthwash causes hypertension or that patients should discontinue medically indicated antimicrobial treatment.

Instead, it suggests that the choice, duration, and frequency of antiseptic use may deserve greater consideration within oral-systemic health.

Does This Mean Patients Should Avoid All Mouthwash?

Not necessarily.

Antimicrobial mouthwashes can play an important role in managing selected oral conditions, including gingival inflammation and periodontal disease.

Chlorhexidine, for example, may be useful for short-term treatment when prescribed appropriately.

The clinical question is whether prolonged or unnecessary broad-spectrum antimicrobial use could disrupt beneficial oral microbial functions.

For dental hygienists and dentists, this reinforces the importance of individualized recommendations.

Patients should receive oral hygiene guidance based on their periodontal condition, caries risk, medical history, and treatment goals.

Protecting the oral microbiome should complement, not replace, effective prevention and treatment of oral disease.

Fluoride, Oral Health, and the Microbiome

Dr. Bryan also raised concerns about fluoride-containing dental products and their possible effects on oral microorganisms.

This topic requires careful distinction.

Fluoride has a well-established role in preventing dental caries by supporting enamel remineralization and reducing demineralization.

Fluoride toothpaste remains an evidence-based component of routine preventive dental care.

Although fluoride can influence bacterial metabolism at certain concentrations, current evidence does not establish that properly used fluoride toothpaste causes clinically significant nitric oxide deficiency or systemic cardiovascular disease.

For dental professionals, the priority remains the appropriate use of fluoride according to age, caries risk, and established safety guidelines.

Research into oral microbiome preservation is important, but it does not justify abandoning proven caries-prevention strategies.

Dietary Nitrate and Nitric Oxide Production

Vegetables such as leafy greens and beetroot provide dietary nitrate that participates in nitric oxide metabolism.

Diet is another important contributor to nitric oxide metabolism.

Vegetables such as spinach, arugula, lettuce, celery, and beetroot can provide dietary nitrate.

After ingestion, nitrate enters the circulation and participates in the enterosalivary pathway.

Dr. Bryan discussed how nitrate concentrations can vary substantially depending on growing conditions, soil characteristics, agricultural practices, storage, and vegetable type.

This means two servings of the same vegetable may contain different amounts of nitrate.

However, this variability does not mean vegetables are ineffective or that nitrate-rich foods cannot contribute to cardiovascular health.

A vegetable-rich dietary pattern provides multiple benefits beyond nitrate, including fiber, potassium, vitamins, and other bioactive compounds.

For patients, a balanced diet that includes a variety of vegetables remains a practical and evidence-supported foundation for health.

The Importance of Stomach Acid

The stomach also contributes to nitrate–nitrite–nitric oxide chemistry.

When swallowed nitrite enters the acidic gastric environment, some of it can be converted into nitric oxide and related nitrogen compounds.

Dr. Bryan discussed how medications that suppress stomach acid might alter this pathway.

Proton pump inhibitors, commonly used for gastroesophageal reflux disease and other gastrointestinal conditions, reduce gastric acid production.

Some observational studies have reported associations between long-term PPI use and adverse health outcomes.

However, these associations do not establish that PPIs directly cause cardiovascular disease, Alzheimer's disease, or nitric oxide deficiency in every patient.

These medications provide important benefits for appropriately diagnosed conditions.

Patients should not discontinue prescribed acid-suppressing therapy without consulting their medical provider.

The broader clinical lesson is that medication use, nutrition, gastrointestinal physiology, and oral microbial metabolism may interact in ways that deserve further investigation.

Exercise and Nitric Oxide Signaling

Exercise is one of the most established ways to support vascular health.

During physical activity, changes in blood flow and shear stress stimulate signaling pathways within the vascular endothelium.

These pathways include the activation of endothelial nitric oxide synthase.

Nitric oxide contributes to the vascular response to exercise by helping regulate blood vessel dilation.

Regular physical activity can also support endothelial function, metabolic health, blood pressure regulation, and cardiovascular fitness.

Dr. Bryan emphasized exercise as one practical strategy for supporting healthy nitric oxide biology.

Unlike many emerging nitric oxide-based products, the cardiovascular benefits of regular physical activity are supported by extensive clinical evidence.

Nitric Oxide, Oxygen Delivery, and Cellular Function

Nitric oxide participates in several processes related to oxygen utilization and cellular signaling.

Dr. Bryan discussed its involvement in vascular perfusion, mitochondrial biology, and the regulation of oxygen delivery.

These connections are particularly relevant to tissues with substantial oxygen and energy requirements, including the brain, heart, and skeletal muscles.

Nitric oxide signaling can influence mitochondrial respiration and cellular responses to changing oxygen availability.

However, oxygen transport and delivery involve multiple interacting systems, including ventilation, hemoglobin concentration, cardiac output, blood flow distribution, and tissue oxygen extraction.

Nitric oxide is an important contributor to this physiology, but it is not the sole regulator.

Understanding its role helps clinicians appreciate why vascular health and respiratory function are closely connected.

Nitric Oxide and Inflammation

Another topic explored during the presentation was nitric oxide's relationship with inflammation.

Nitric oxide participates in immune signaling and helps regulate interactions between inflammatory cells and the vascular endothelium.

Its effects are complex and depend on factors such as concentration, location, the enzyme responsible for its production, and the surrounding inflammatory environment.

Under some conditions, nitric oxide supports protective vascular responses.

Under other conditions, excessive or dysregulated nitric oxide production may contribute to inflammatory injury.

This is why nitric oxide should not be described simply as an anti-inflammatory molecule that eliminates all inflammation.

Its biological activity is context-dependent.

For healthcare professionals, the important concept is that nitric oxide signaling intersects with vascular, metabolic, and immune pathways.

Nitric Oxide and Nasal Breathing

Nasal breathing supports respiratory function, while the nasal passages and paranasal sinuses naturally produce nitric oxide.

For the Airway Circle community, one of the most relevant connections is the relationship between nitric oxide and nasal breathing.

The nose and paranasal sinuses naturally produce nitric oxide.

Nasal nitric oxide participates in local respiratory physiology and can be detected in exhaled air.

The paranasal sinuses are an especially important source.

When a person breathes through the nose, nitric oxide-containing air from the nasal passages can enter the lower respiratory tract.

This is one reason nasal physiology deserves attention in airway-focused care.

However, the benefits of nasal breathing extend beyond nitric oxide.

Nasal breathing also helps warm, humidify, and filter inspired air.

Patients with chronic nasal obstruction may need evaluation for allergic rhinitis, structural abnormalities, inflammatory conditions, or other causes of impaired nasal airflow.

Encouraging nasal breathing should always begin with confirming that the nasal airway is sufficiently patent.

Humming and Nitric Oxide: What Does the Research Show?

During the question-and-answer portion of the webinar, the Airway Circle host asked Dr. Bryan about humming and whether it could help increase nitric oxide.

This was a particularly relevant topic for myofunctional therapists and breathing-focused professionals.

Humming has been studied as a method of increasing measured nasal nitric oxide output.

In a small study by Weitzberg and Lundberg, published in 2002, nasal nitric oxide levels increased approximately fifteenfold during humming compared with quiet exhalation.

The investigators proposed that the oscillating airflow generated during humming increased gas exchange between the paranasal sinuses and nasal cavity.

Subsequent research further explored how humming frequency, sinus anatomy, and sinus ostium patency influence this response.

These findings demonstrate an interesting physiological effect.

However, an increase in measured nasal nitric oxide during humming does not automatically establish sustained increases in systemic nitric oxide, improved blood pressure, or treatment of sleep-disordered breathing.

Additional clinical studies are needed to determine whether repeated humming produces meaningful long-term health benefits.

Humming in Myofunctional and Breathing Therapy

Humming can be incorporated into selected breathing exercises because it combines nasal airflow, vocalization, and controlled exhalation.

For some patients, it may serve as a useful way to increase awareness of nasal breathing and regulate the pace of exhalation.

Dr. Bryan discussed how the nasal nitric oxide response may vary depending on individual anatomy and physiology.

This is important because not every patient will demonstrate the same response.

For myofunctional therapists, humming is best understood as a potentially useful breathing exercise rather than a proven treatment for nitric oxide deficiency.

The broader therapeutic goal remains comfortable nasal breathing, appropriate respiratory coordination, and individualized functional improvement.

Nitric Oxide-Based Supplements and Therapies

Dr. Bryan also discussed the development of nitric oxide-related nutritional products, lozenges, and experimental therapies.

His work focuses on creating products intended to deliver nitric oxide or support nitric oxide-related signaling pathways.

He raised concerns about the variability of products marketed for nitric oxide support, including formulations containing beetroot powder, L-arginine, or L-citrulline.

An important issue is that products marketed under the same general category may contain different ingredients and doses.

However, the effectiveness of one formulation cannot be assumed from the biological importance of nitric oxide itself.

Clinical claims require appropriately designed studies evaluating the specific product, dose, safety profile, and intended indication.

Dr. Bryan disclosed commercial interests in nitric oxide technologies during his presentation.

For clinicians, it is important to separate established nitric oxide physiology from preliminary research, individual case reports, and commercial product claims.

Experimental Applications in Wound Healing and Chronic Disease

Dr. Bryan shared several case examples involving nitric oxide-based approaches to wound healing and cardiovascular conditions.

These included a pediatric patient with a rare metabolic disorder and severe hypertension, as well as complex wound-healing cases.

He also discussed ongoing efforts to develop nitric oxide-based treatments for neurological conditions, cardiovascular disease, and non-healing wounds.

These examples illustrate areas of active therapeutic investigation.

However, individual case reports cannot establish that nitric oxide products alone caused the observed improvements, particularly when multiple medical and surgical treatments were involved.

Experimental therapies should not be presented as established cures for Alzheimer's disease, diabetes, cardiovascular disease, or other chronic conditions.

Their clinical role must be determined through appropriate safety testing and controlled research.

Why Dental Professionals Should Pay Attention

The oral microbiome's contribution to nitrate metabolism gives dental professionals another reason to participate in conversations about systemic health.

Dental hygienists and dentists frequently see patients who may be living with hypertension, diabetes, cardiovascular disease, sleep-disordered breathing, or other chronic conditions.

They also routinely evaluate the oral environment and recommend products that influence oral microbial communities.

This creates opportunities for collaboration between dentistry and medicine.

Dental professionals can support patients by:

• Maintaining effective periodontal and caries prevention
• Recognizing oral inflammation and infection
• Considering the appropriate duration of antiseptic therapies
• Educating patients about the oral microbiome
• Encouraging balanced nutrition and healthy lifestyle behaviors
• Screening for relevant systemic conditions
• Coordinating care with medical providers

The oral-systemic connection is not limited to periodontal pathogens entering the bloodstream.

It also includes the beneficial metabolic activities of healthy microbial communities.

Clinical Questions for Healthcare Professionals

When considering the relationship between nitric oxide and oral-systemic health, clinicians may ask:

• Does the patient have chronic oral inflammation or periodontal disease?
• Is the patient using antiseptic mouthwash regularly?
• Is antimicrobial therapy clinically indicated?
• Does the patient have cardiovascular risk factors or hypertension?
• Is the patient consuming a balanced diet that includes vegetables?
• Does the patient breathe comfortably through the nose?
• Is there chronic nasal obstruction?
• Does the patient demonstrate mouth breathing or sleep-related breathing concerns?
• Would the patient benefit from medical evaluation or coordinated care?
• Are claims about a recommended product supported by appropriate clinical studies?
• Could breathing education or myofunctional therapy help address an identified functional problem?

These questions encourage clinicians to consider both oral disease prevention and the broader physiological roles of the oral environment.

Key Takeaways for Healthcare Professionals

Nitric oxide is an important signaling molecule involved in vascular regulation, circulation, immune signaling, and respiratory physiology.

The body produces nitric oxide through enzymatic pathways and through the nitrate–nitrite–nitric oxide pathway.

Certain oral bacteria contribute to nitrate metabolism, creating an important connection between the tongue microbiome and systemic physiology.

Research indicates that some antiseptic mouthwashes can reduce oral nitrate conversion, although their effects on blood pressure vary across studies.

Preserving a healthy oral microbiome is important, but it should not come at the expense of proven dental treatments or appropriate antimicrobial therapy.

Fluoride toothpaste remains an evidence-based strategy for preventing dental caries.

A vegetable-rich diet and regular physical activity support cardiovascular health and nitric oxide-related physiology.

The nasal passages and paranasal sinuses are important sources of nitric oxide.

Humming can temporarily increase measured nasal nitric oxide output, but its long-term therapeutic benefits require further research.

Nitric oxide products and experimental treatments should be evaluated according to their specific clinical evidence rather than broad biochemical claims.

Interdisciplinary collaboration between dental and medical professionals is essential for advancing oral-systemic healthcare.

The Airway Circle Perspective

At Airway Circle, we believe the mouth is an important part of the broader physiological system.

Dr. Nathan Bryan's presentation reminds us that oral health involves more than teeth, gums, and occlusion.

The tongue, saliva, oral microbiome, nasal airway, and surrounding tissues participate in processes that extend beyond the oral cavity.

For myofunctional therapists and airway-focused providers, this opens an important conversation about how nasal breathing, oral function, microbiome health, and systemic physiology intersect.

It also reinforces the importance of evidence-informed care.

As new research emerges, clinicians must remain curious while distinguishing established science from developing hypotheses.

The goal is not to replace conventional dental or medical care.

It is to integrate new knowledge into more comprehensive, collaborative patient care.

Final Thoughts

Nitric oxide offers a fascinating example of the connection between oral and systemic health.

A molecule produced throughout the body is influenced, in part, by microorganisms living on the tongue.

The foods we eat, the oral environment we maintain, and the way we breathe all interact with biological pathways that extend far beyond the mouth.

For dental hygienists, dentists, myofunctional therapists, and other healthcare professionals, this changes how we think about the oral cavity.

It is not simply the beginning of the digestive tract or a collection of teeth and supporting tissues.

It is also an active microbial and physiological environment that contributes to broader health.

As nitric oxide research continues to develop, the most valuable clinical approach will combine scientific curiosity, careful interpretation of evidence, and interdisciplinary collaboration.

The oral-systemic connection is not just about how disease in the mouth may affect the body. It is also about how healthy oral function and microbial activity participate in normal physiology.

Need Guidance With Airway, Nasal Breathing, or Myofunctional Therapy?

Understanding the relationship between breathing, oral function, sleep, tongue posture, and airway health can help patients and families make more informed decisions.

Whether care involves myofunctional therapy, nasal breathing support, ENT evaluation, airway-focused dentistry, orthodontics, sleep assessment, or collaboration with medical specialists, the goal is to understand the underlying concerns and determine the most appropriate next steps.

With the right guidance, patients can work toward improved oral function, healthier breathing patterns, and better quality of life.