Nitric oxide gas is an exploding frontier in medicine. Celeste McGovern looks at how supplemental NO could revolutionize the treatment of everything from heart disease and dementia to diabetic wounds
A 99-year-old woman was discovered unconscious at her home in Caldwell, Texas, and taken to hospital by ambulance. Her breathing was extremely shallow, her heartbeat was irregular and her blood pressure was dangerously low.
She didn’t respond to oxygen, and her doctors had little hope for recovery. A “Do not resuscitate” order was placed on her file.
Her grandson, a physician, visited her and saw there wasn’t much more that could be done, but he decided to try something unconventional. He pulled a little white lozenge from his pocket and crushed it into a powder, which he gently placed in her mouth with a bit of water. Then he walked away.
About 20 minutes later, a nurse came running to find him. His grandmother had woken up and was alert and talking. Her heart rate had returned to normal, her blood pressure was stable and her breathing had improved. She recovered—and lived to see her 100th birthday.
What was in this lozenge that resuscitated the old woman and took her from death’s door to life in a matter of minutes?
It turns out it was nitric oxide (NO), a tiny molecule of gas made of a single atom of oxygen and a single atom of nitrogen. Discovered only in the 1970s and known primarily as an industrial gas and environmental pollutant, nitric oxide has since enjoyed a dramatic perspective shift in science and medicine.
It was hailed as Molecule of the Year in 1992. Then it brought three doctors the 1998 Nobel Prize in Physiology or Medicine for their groundbreaking research showing that nitric oxide acts as a signaling molecule in the body, particularly in the cardiovascular system.
This was a landmark discovery because it revealed how nitric oxide helps relax and widen blood vessels, regulating blood pressure and improving circulation, oxygen delivery and overall cardiovascular health. It laid the foundation for revolutionary drugs like nitroglycerin for angina and heart failure and opened new avenues for treating heart disease, stroke and other vascular disorders.
Today, research into nitric oxide’s health functions has exploded, with more than 200,000 published studies in the medical literature. Nitric oxide has changed the way scientists understand cell communication and vascular health.
Beyond its role in relaxing blood vessels to allow for increased blood flow to tissues, nitric oxide is now recognized as a master regulator of vascular tone, immune response, neurotransmission and cellular energy. It supports energy levels, endurance and cognitive function.
“Imagine a single molecule that can dramatically improve your health,” says biochemist Dr Nathan Bryan, one of the foremost experts in the world on molecular medicine, including nitric oxide biochemistry.
According to Bryan, author of The Secret of Nitric Oxide: Bringing the Science to Life (Brick Tower Press, 2025), “NO sends crucial signals within every cell, tissue and organ of your body.”
This molecule protects vital organs like the heart, brain and kidneys. It keeps arteries supple and clear, preventing blood clots that can lead to heart attacks and strokes, and lowers harmful triglyceride levels. It also reduces the risk of diabetes and its serious complications—such as slow-healing wounds, amputations, vision loss and kidney failure.
But its benefits don’t stop there. Nitric oxide supports brain health, potentially slowing the cognitive decline that occurs in dementia and Alzheimer’s disease.
It alleviates joint pain and swelling in arthritis, reverses erectile dysfunction, calms inflammation in asthma, guards against osteoporosis and helps regulate immune responses in autoimmune diseases. Its antimicrobial action helps fight off infections and cancer, and it even plays a role in protecting the skin from sunburn.
Cardiovascular health. Perhaps the best-known function of nitric oxide is its role in vasodilation. By relaxing the inner muscles of the blood vessels, NO increases blood flow and reduces blood pressure.
Recent case studies suggest that supplemental nitric oxide (especially via lozenges or skin-delivered systems) may rapidly stabilize cardiac and vascular function in emergency situations—rebalancing heart rhythms, normalizing blood pressure and restoring blood flow to compromised organs.
A double-blind, placebo-controlled crossover study involving 30 unmedicated hypertensive patients showed that a single dose of an NO-generating lozenge reduced systolic and diastolic blood pressures by 4 mmHg and 5 mmHg, respectively, within 20 minutes. They fell by 6 mmHg each after 60 minutes. The study also noted improvements in blood vessel function within hours of the dose.1
In another 30-day randomized controlled trial at the California Medical Institute, prehypertensive adults who took NO lozenges saw a big drop in their resting blood pressure—from an average of 138/84 mmHg to 126/78 mmHg. They also showed improved physical endurance, as measured by the six-minute walk test, and reported better quality of life.2
Wound healing. Nitric oxide plays several important roles in helping wounds heal. It helps grow new blood vessels (a process called angiogenesis), encourages the body to make collagen (which gives skin and connective tissues strength and structure), fights off harmful bacteria and helps control inflammation.
All these actions are key to repairing damaged tissue. Early results of using nitric oxide serums on surgical wounds and chronic ulcers show they may speed up healing—especially in people with poor circulation, diabetes or weakened immune systems. This could become a promising new treatment for hard-to-heal wounds, without side effects.
In one clinical study, 25 patients with various skin injuries—including surgical wounds, diabetic ulcers and burns—were treated with a nitric oxide–generating topical serum. The outcomes were striking:
Across the board, doctors noted faster healing, reduced swelling and less bruising, with no side effects.3
Cognitive function. Nitric oxide acts as a neurotransmitter in the brain, influencing processes related to learning and memory. It supports synaptic plasticity, which is essential for cognitive function. Studies suggest that maintaining adequate nitric oxide levels may help protect against age-related cognitive decline.4
Immune system support. Nitric oxide contributes to the body’s defense mechanisms by fighting microbes. It aids immune cells in combating pathogens and plays a role in regulating inflammation.5 This function is particularly important for middle-aged people, as immune efficiency can decline with age.
Sexual dysfunction. Erectile dysfunction, which used to be considered a lifestyle condition, often precedes heart disease and is now considered an early marker of it. In both men and women, sexual dysfunction is a canary for poor blood flow to the sexual organs.
“If you have erectile dysfunction, you are NO deficient,” says Bryan. “It’s important to take corrective steps to restore your nitric oxide production.”
Enhanced exercise performance. For middle-aged adults aiming to maintain physical fitness, nitric oxide can be beneficial. It enhances oxygen and nutrient delivery to muscles during exercise, improving endurance and reducing fatigue. Research indicates that nitrate-rich supplements, like beetroot juice, can improve exercise performance in various athletic activities.6
At high altitudes, oxygen levels are reduced, triggering hypoxic stress that can impair physical performance and cognitive function. Nitric oxide helps optimize oxygen delivery by increasing blood flow and enhancing mitochondrial efficiency.
Bryan recounts how he helped a group of US Navy SEALs who often had to fly quickly from their base at 3,000 feet to high-altitude missions at 10,000–12,000 feet. The rapid change in altitude often made them sick—headaches, nausea, fatigue—classic signs of altitude sickness.
He gave them his nitric oxide–generating lozenges, which they took during their helicopter ride, and the results were striking: They arrived alert, focused and ready for rappelling into combat zones without the usual symptoms. The lozenges appeared to help their bodies use oxygen more efficiently at high altitudes.
It’s real-world evidence of NO’s potential as a performance enhancer and altitude acclimation tool. The molecule is finding popularity among athletes, climbers and emergency responders operating in thin air.
Young, healthy bodies produce nitric oxide all day long, on demand. Yet it vanishes within a second of being produced. As we age—or when we are ill or our nitric oxide production is blocked (see more on this below)—we make less and less of this precious, fragile vanishing gas.
“A lack or deficiency of nitric oxide is basically at the root of most chronic diseases, including cardiovascular disease, which is the leading killer of women and men worldwide,” says Bryan. NO deficiency is at the heart of high blood pressure, poor circulation, slow healing and virtually all age-related chronic disease, he adds.
It seems impossible that one tiny molecule could be responsible for so many actions, but nitric oxide works in four crucial ways in the body:
Most diseases are characterized by inflammation, oxidation, immune system misbehavior or lack of blood flow, which brings nutrients and oxygen to tissues.
“Nitric oxide basically gets to the root cause of all chronic diseases,” says Bryan. “This means there really is no disease or drug indication for which nitric oxide at the right dose would not provide therapeutic benefit.”
His thoughts echo those of Louis Ignarro, the 1998 Nobel laureate for his nitric oxide discoveries, who said, “There may be no disease process where this miracle molecule does not have a protective role.”
How do we get it, then? There are two pathways for NO production in the human body.
The first is a complex, enzyme-dependent process known as the endothelial pathway because it occurs in the endothelium, a thin layer of cells lining blood vessels. This production pathway is triggered by shear pressure, the friction that blood cells exert on endothelium as they rush through the vessels, and by actions like exercise.
However, endothelial NO production inevitably wanes as we age. Even people with normal blood sugar and blood pressure have plummeting endothelial nitric oxide production as they age. “The older you are, the lower your nitric oxide,” says Bryan. “We lose 10–12 percent of our endothelial-produced nitric oxide every decade.”
This means that by age 40, we’ve lost about 50 percent of our endothelial nitric oxide.
NO production also wanes under high oxidative stress or with diabetes or high blood pressure. We now understand that a lack of nitric oxide production and signaling is responsible for the onset and progression of cardiovascular disease and many other age-related diseases.
There is a well-established vicious cycle involving diabetes, hypertension and endothelial nitric oxide production. High blood glucose (hyperglycemia) and high blood pressure (hypertension) cause oxidative stress and promote inflammation leading to endothelial cell damage.
This in turn, inhibits the enzyme needed for NO production in the blood vessels, and NO production plummets. Since nitric oxide is essential for vasodilation, preventing platelets from clumping and preventing atherosclerosis, the drop leads to more trouble:
Impaired blood flow and vascular tone contribute to more insulin resistance, progressively higher blood pressure (from stiffened, poorly dilated vessels), and atherosclerosis and its complications.
And the negative feedback loop continues, worsening the conditions and leading eventually to cardiovascular disease, stroke and kidney failure.
More than half of Americans and almost half of UK adults report using antacid medications for heartburn and gastroesophageal reflux disease (GERD). These include over-the-counter medicines and prescription proton pump inhibitors (PPIs) like omeprazole.
Because they damage the epithelium of blood vessels7 and lower the acidity in the stomach, PPIs can interfere with the body’s production of nitric oxide, and this may explain the resulting higher risk of heart attack,8 dementia9 and systemic autoimmune disease.10
“Turning down stomach acid is a very bad idea,” says Bryan.
Eating healthily, eliminating mouthwash (see below) and stopping antacid medication alone will go a long way toward restoring the body’s nitric oxide production.
Eat nitrate-rich foods. Fortunately, our bodies have a built-in backup system for producing NO, especially important because it’s so vital to our health. This alternate route is known as the nitrate–nitrite–NO pathway.
Unlike the primary pathway that depends on an enzyme (eNOS) in the endothelium, this one relies on nitrate from food. Nitrate is converted to nitrite and then to nitric oxide.11
The dietary pathway becomes even more important as we age or develop conditions like cardiovascular disease, in which the body’s ability to produce NO through the endothelial pathway declines.
So yes—your mother was right when she told you to eat your greens. Leafy vegetables like spinach, kale and arugula (rocket) as well as beets (beetroot), celery and other nitrate-rich foods, deliver the raw material (nitrate) we need for this process (see below).
Here’s how it works:
What can go wrong? For this pathway to work well, a few things need to be in place:
According to Dr Bryan, we need at least 300 mg of dietary nitrate per meal to support optimal nitric oxide levels—especially for maintaining healthy blood pressure and circulation. Yet most of us consume only 150 mg per day or less on a typical Western diet, leading to widespread nitric oxide deficiency as we age.
These are some nitrate-rich foods to focus on:
Exercise. Exercise is one of the best natural ways to boost nitric oxide in the body, which helps keep your blood vessels healthy and your blood pressure in check. When you move—especially during activities like walking, running or cycling—your blood flows faster, which signals your body to make more nitric oxide.
This helps relax and widen your blood vessels, improving circulation. Regular exercise also helps your body make more nitric oxide synthase, the enzyme needed to produce NO, and increases levels of helpful compounds like nitrate and nitrite in your blood.
Breathe through your nose. The paranasal sinuses are key sites of nitric oxide production. When you breathe through your nose, NO is released into the nasal passages and travels into the lungs, where it helps dilate blood vessels to improve oxygen delivery, open the airways, and fight off bacteria, viruses and fungi.
Studies show that nasal breathing significantly increases the body’s production and use of nitric oxide compared to mouth breathing, which bypasses this process and reduces NO availability.12
Avoid sugar. Sugar—particularly in the form of refined sugars and high-glycemic carbohydrates—can impair NO production through several mechanisms:
Get more sunlight. Moderate exposure to sunlight can boost nitric oxide levels. Ultraviolet rays stimulate the release of nitric oxide from skin stores into the bloodstream, aiding in blood pressure regulation.
Take supplements. What’s remarkable is that even when the body loses its ability to make nitric oxide, it still responds to the gas when it’s provided as a supplement. That’s why lozenges, skin creams and other nitric oxide–releasing treatments are now being explored as powerful tools to restore balance in the body.
Nitric oxide may be a small molecule, but it’s making a big impact on how we understand and treat disease. Whether it’s helping a centenarian come back from the brink, healing chronic wounds or protecting elite soldiers in extreme conditions, nitric oxide is showing up as a key ingredient in health and healing.
In essence, NO acts as a biochemical “switchboard” modulating numerous physiological processes across nearly every system in the body.
The growing body of evidence—from published clinical studies to dramatic case reports—positions nitric oxide as a cornerstone of future treatment. As science continues to uncover its many roles in the body, nitric oxide could become one of the most versatile and valuable tools in modern medicine.
Rather than asking whether nitric oxide works, the better question may now be how many conditions it can help us prevent or treat.
About 200 million people in the US and 17 million in the UK regularly swish with a mouthwash or dental rinse. It may sound like a good idea to keep your mouth fresh, but researchers have noted a connection between mouthwash use and hypertension for years.
A 2024 review of data from 55 studies reported that mouthwash could increase the risk of developing high blood pressure and diabetes by 85% and 55% respectively.1
One 2019 study of a small group found that just one week of swishing with chlorhexidine mouthwash twice a day was enough to raise systolic blood pressure.2
Now there’s an explanation for the connection: antiseptic mouthwash blasts the nitrate-processing bacteria in the mouth, significantly reducing the conversion to NO.
“People think they’re doing all the right things. They’re exercising and eating their vegetables,” says Dr Nathan Bryan, “but they’re canceling those nitric oxide benefits by using mouthwash.”
Antibiotics also damage the oral microbiome, so take only those you need. Fluoride damages the oral microbiome too, says Bryan, who sells his own fluoride-free, bacteria-boosting toothpaste (n1o1.com).
Numerous clinical trials now show that dietary nitrate can deliver all the key health benefits of vegetables, including these:
In fact, some researchers believe nitrate may be the main reason for the health benefits of vegetables. It’s no coincidence that diets known for promoting heart health—like the Mediterranean diet, DASH diet and traditional Japanese diet—are also some of the richest in dietary nitrates.
Eating more greens is Dr Nathan Bryan’s first recommendation. But when he tested vegetables across the US to determine their nitrate content, he found surprising differences depending on where and how the food was grown.
Celery from California could have as much as 50 times the nitrate content as the same amount of celery grown in New York. This makes it impossible to advise on how much food to eat to get the right amount of nitrate.
Another surprising finding: Organic vegetables and fruits generally have up to 10 times less nitrate because inorganic fertilizers aren’t used to grow them. It’s a tough trade-off, but Bryan suggests looking for conventionally grown produce that hasn’t been treated with pesticides.
However, efforts are underway in the US and the UK to reduce the use of nitrate fertilizers generally because they pollute ecosystems and groundwater. Another option is to eat produce grown with a rich compost and manure, which help to add nitrogen to the soil.
If you search for nitric oxide supplements, you’ll find hundreds that include the amino acid L-arginine or its precursor, L-citrulline. While the body uses these to make nitric oxide, Dr Nathan Bryan warns they may be not only ineffective but potentially harmful.
“Deficiency in L-arginine is extremely rare,” he explains. “It’s found in a wide variety of foods, from meat and seafood to beans. Nitric oxide deficiency is a completely different issue.”
According to Bryan, the real problem is not a lack of arginine but the body’s reduced ability to convert existing arginine into nitric oxide. “It’s like putting gas in a car with a blown engine—it doesn’t fix the problem,” he says.
More concerning, he adds, is clinical evidence showing increased risk in those given L-arginine after a heart attack. One major study found these patients were more likely to die than those who didn’t take the amino acid.1
“Buyer beware,” Bryan cautions.
Dr Nathan Bryan describes one published case in which his nitric oxide lozenges were able to work, even when the body’s nitric oxide production pathway was prevented by inborn disease.
A 15-year-old boy with a rare genetic disorder called argininosuccinic aciduria couldn’t make his own nitric oxide. As a result, he had long suffered from dangerously high blood pressure and kidney problems, and he was in the early stages of heart disease.
Although his doctors had given him several medications, nothing was bringing his blood pressure under control, and it was averaging around 185/110 mmHg. With nothing else in their tool kit, doctors tried a nitric oxide lozenge.
Within just four hours, the teen’s blood pressure dropped dramatically to a safe level of 135/85 mmHg, and it stayed there. After three weeks, his kidney problems disappeared, and five months later, his heart had healed.
This was the first time any treatment had made such a difference for him, according to the report in The American Journal of Human Genetics. It also underscored a crucial insight: Even in severe disease, the body retains its capacity to respond to nitric oxide, though it may lose the ability to produce it.
For information on where to buy nitric oxide supplements and what to look for, see Healthy Shopping: Nitric oxide-boosting supplements.
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