by Nathan S. Bryan, PhD

Oral health is absolutely essential for systemic health. The notion that oral bacteria may contribute to disease in other parts of the body has been discussed since at least the end of the 19th century. William Hunter in 1900 first described “oral sepsis” as a cause of human disease.¹ This started a wave of research into the role of oral health and the development of systemic disease. Today we certainly have an appreciation for the oral systemic link that describes how poor oral hygiene leads to an increased risk of conditions such as cardiovascular diseases, diabetes, respiratory disorders, osteoporosis, and even adverse pregnancy outcomes. There are known bacterial pathogens that have been shown to contribute to periodontal disease and gingivitis. Rightfully so, these pathogens are often times targeted by dentists in patients that have known oral pathogens. Use of stringent antiseptics such as chlorhexidine has been used in dental medicine since the 1970s. Data have shown that the use of chlorhexidine can reduce gingival plaque by killing oral bacteria thereby improving the progression of periodontal disease.² However, there is always collateral damage due to the complete destruction of the human oral microbiome. These antiseptics kill the pathogens, but they also destroy the non-pathogenic commensal bacteria. Science now reveals this may cause more harm than good.

Human Oral Microbiome – Bacterial Nitrate Reduction

The human microbiome is made up of hundreds of different bacterial species, which outnumber our human cells ten to one and provide functions that are essential for our survival. There exists a human nitrogen cycle which is now well elucidated that provides a source of bioactive nitric oxide through the activity of specific oral bacteria. This pathway, termed the entero-salivary nitrate-nitrite-nitric oxide pathway, can positively contribute nitric oxide based signaling throughout the human host.^3,4 It is now recognized that the oral commensal bacteria provide an important metabolic function in human physiology by contributing a nitric oxide synthase (NOS)-independent source of NO. Human nitrate reduction requires the presence of oral nitrate-reducing bacteria as mammalian cells cannot effectively reduce this anion. The two-electron reduction of nitrate forms nitrite in the saliva and then when we swallow our own saliva, in the acid environment of the stomach, nitric oxide is produced. The nitric oxide that is produced in the acid stomach enhances gastric mucosal blood flow,⁵ protects from gastric ulcerations from chronic non-steroidal anti-inflammatory drugs (NSAIDS)⁶ and from ulcer causing bacteria Helicobacter pylori.⁷ Obviously, this pathway serves as a critical and fundamental source of nitric oxide. The process of bacterial nitrate reduction to nitrite and nitric oxide is illustrated below. Nitric oxide derived from nitrite is known to regulate blood pressure, improve insulin signaling, and inhibit inflammation.^8-10 Without the right oral bacteria present and without stomach acid production, this pathway cannot be effective at producing nitric oxide and providing any benefit to the human host.

An increase in blood pressure puts you at an increased risk for heart disease and stroke, which are leading causes of death in the United States and worldwide. Two out of every three Americans has an unsafe elevation in blood pressure. Despite aggressive treatment with medications, sometimes multiple medications, only about half of those medicated have managed blood pressure. The Systolic Blood Pressure Intervention Trial (SPRINT) showed that among adults with hypertension but without diabetes, lowering systolic blood pressure to a target goal of less than 120 mm Hg, as compared with the standard goal of less than 140 mm Hg, resulted in significantly lower rates of fatal and nonfatal cardiovascular events and death from any cause.¹¹ Because blood pressure remains elevated in ≈50% of all treated hypertensive patients despite polypharmacy,^12,13 perhaps focusing on a healthy oral microbiome that can provide a source of nitric oxide may provide additional blood pressure lowering effects.

The presence or absence of select and specific bacteria may determine steady state blood pressure levels.¹⁴

Eradication of Nitrate Reducing Bacteria Eliminates Health Benefits of Nitrate-based Diets and Interventions

In various animal models and in humans, dietary nitrate supplementation has shown numerous beneficial effects, including a reduction in blood pressure, protection against ischemia-reperfusion damage, restoration of NO homeostasis with associated cardioprotection, increased vascular regeneration after chronic ischemia, and a reversal of vascular dysfunction in the elderly.^15-18 However, all of these effects were reduced or completely abolished when the oral microbiota were abolished with an antiseptic mouthwash.^15,19 Plasma and salivary nitrite levels are abolished after a dietary nitrate load in healthy subjects taking an antiseptic mouthwash.²⁰ It has been reported that dietary nitrate reduces blood pressure in healthy volunteers,^21,22 and that the effects are abolished after rinsing with oral antiseptic mouthwash.²³ Both strong and weak antibacterial agents suppress the rise in plasma nitrite observed following the consumption of a high nitrate diet and stronger antiseptics can influence the blood pressure response during low-intensity exercise.²⁴ Additionally, it was recently shown that in the absence of any dietary modifications, a seven-day period of antiseptic mouthwash treatment to disrupt the oral microbiota reduced both oral and plasma nitrite levels in healthy human volunteers, and was associated with a sustained increase in both systolic and diastolic blood pressure.²³ Oral nitrite exerts antihypertensive effects in the presence of antiseptic mouthwash that disrupts the enterosalivary circulation and reduction of nitrate.²⁵ Altogether, these studies firmly establish the role for oral nitrate-reducing bacteria in making a physiologically relevant contribution to host nitrite and thus NO levels, with measureable physiological effects. It appears that providing nitrite can overcome the absence of microbial nitrate reduction.

Eradication of oral bacteria through anti-septic mouthwash or over-use of antibiotics causes blood pressure to increase. Allowing recolonization of nitrate and nitrite reducing bacteria can normalize blood pressure. Management of systemic hypertension through maintenance of the oral microbiome is a completely new paradigm in cardiovascular medicine. In some cases, using mouthwash for only one week caused a more than 25 mmHg increase in blood pressure. The results and implications from this study are life changing. For the first time, we may have an explanation for the hypertension epidemic and why prescription drugs don’t always work to reduce blood pressure. This study demonstrates that we have missed the target and have focused on the wrong scientific pathways for answers.

Cardiovascular disease remains the number one killer of men and women worldwide. Every year approximately 610,000 people die from cardiovascular related events in the US alone. That’s one out of every 4 deaths. High blood pressure is the number one modifiable risk factor for the development of cardiovascular disease. Two out of three people in the US have an elevation in blood pressure.26 This is over 200,000,000 people. For every 1 mmHg increase in blood pressure starting at 110 mmHg in systolic blood pressure, this increases your risk of heart disease by 1%. So, if your systolic pressure or top number is 140, you have increased your chance of heart disease by 30%. According to the American Heart Association, only about half of the people who take blood pressure medicine have their blood pressure normalized and many of these people are taking 2-4 different prescription medications.

The microbiome has been a major story in science and medicine for the past 20 years. We now know that many diseases are caused by dysbiosis or disruption of good bacterial communities in the body. However, most of these studies and information comes from studying our gut bacteria. We have only recently begun to focus on oral bacteria. We have known for decades the importance of oral bacteria. Poor oral hygiene, people with periodontitis and gingivitis have an increased risk of dying from heart disease. In fact, oral bacteria have been found in the plaque of arteries of people who have died of heart attack. This led dentists and other health care practitioners to recommend using antiseptic mouthwash to kill the oral bacteria. The use of fluoride toothpaste has increased. Recommendations to use antiseptic mouthwash were pushed by dentists and consumer product makers. Over prescribing antibiotics began to occur. All of these now common practices have now caused a serious problem. We know that along with the bad bacteria, there are good bacteria that are necessary for normal human metabolism. Killing the bad bacteria leads to the collateral damage and killing of the good bacteria. The consequences may be more damaging than we ever imagined.

We now know that many diseases are caused by dysbiosis or disruption of good bacterial communities in the body

We need nitrate reducing bacteria in the mouth in order to utilize the nitrate we get from eating green leafy vegetables in our diet. Without these bacteria, we do not get the cardiovascular benefits of eating a healthy diet.²⁷ The nitrate reducing bacteria generate nitrite and nitric oxide which are both cardioprotective, reduce blood pressure, and maintain normal cardiovascular function. At least 50% of our daily nitric oxide production comes from our diet and oral bacteria. Loss of nitric oxide production is the first step in the onset and development of cardiovascular disease. Therefore, anything that disrupts or interrupts nitric oxide puts our body at risk for hypertension and cardiovascular disease.²⁸

This is our problem today. Every single day, over 200,000,000 Americans get up and use an antiseptic mouthwash. Most people are using a fluorinated toothpaste. Fluoride is a stringent antiseptic that kills most oral bacteria. There are over 250,000,000 million prescriptions written every year for antibiotics. Are these practices causing unintended problems with oral dysbiosis and a lack of nitric oxide production? It is time to re-evaluate our daily practices. The risks of using antiseptic mouthwash far outweigh the benefits. Doctors are too eager to prescribe antibiotics even for prophylactic reasons rather than let our own immune system do its job.

If you use mouthwash or use fluorinated toothpaste, then this completely eliminates the nitric oxide producing effects of eating a plant-based diet.²⁰ Using antiseptic mouthwash can actually prevent the cardioprotective benefits of exercise.²⁹ As we try to live longer and better lives, many of us try to eat better, including more green leafy vegetables, and try to get exercise. However, if we use mouthwash or any oral antiseptic, we lose the benefits of our diet and of our exercise regimen.

What is becoming increasingly clear is how critical and important nitric oxide is for our health and well-being. There is a clear and beneficial role of oral nitrate reducing bacteria to produce nitric oxide inside our bodies. Getting rid of these bacteria disrupts nitric oxide production and therefore disrupts every function in the body that is dependent upon nitric oxide. This includes maintaining normal blood pressure, maintaining normal sexual function, cognition, memory, reducing inflammation, and making sure every cell in our body gets the oxygen and nutrients it needs to survive and do its job.

It is important to remember to do the good things that are proven to improve nitric oxide production such as moderate physical exercise, eating a balanced diet enriched in green leafy nitrate rich vegetables, and deep breathing. Perhaps just as or more important, we must stop doing the things that disrupt our body’s ability to produce nitric oxide and this includes using antiseptic mouthwash, overusing antibiotics as well as antacids. The human body is much smarter than we are. If we give the body what it needs, it heals itself. If we remove the barriers that disrupt how the body works, it begins to heal itself.

I think sometimes we have become too sophisticated in our daily practices. There is nothing more important to your health and well-being than making sure your body can produce nitric oxide. We should get out of our own way and let the body do what it is designed to do. Heal thyself. The good news is that you do not have to rely on your physician to get you started. You can actually take control of your own health. Start improving your nitric oxide production today. There are a few simple steps:

• If you use antiseptic mouthwash or fluoride toothpaste, you must stop. Mouthwash and fluoride kill essential bacteria in the mouth responsible for production of nitric oxide.
• If you use antacids, you should consult with your physician to wean off. Antacids shut down nitric oxide production and increase your risk of heart attack and stroke by 40%.
• Avoid sugary foods, gummies, and chews that disrupt the oral microbiome.
• Eat more green leafy vegetables and less processed food.
• Get at least 20-30 minutes of physical activity per day.
• Take a nitric oxide supplement to restore normal levels.

These simple steps will have a profound impact on your personal health. I have witnessed this over the past 20 years. Consult with your dentist or find a dentist that understands the importance of a healthy and diverse oral microbiome. Advancements in dental medicine are dependent upon continuous research and new discoveries. Once we learn and understand new mechanisms, we must integrate those into clinical practice. This is innovation and improvement in patient care.