Nitric Oxide: What It Is, How It’s Made, and Why It Matters for Ageing and Health

Nitric oxide (NO) sounds like a complicated chemical but it’s one of the most important molecules your body makes. It helps regulate blood flow, supports healthy blood pressure, boosts exercise performance, helps reduce skin ageing and even links your mouth bacteria to your cardiovascular system.

 The best way to support nitric oxide is through lifestyle, diet, and the bacteria in your mouth.

What is Nitric Oxide (in Everyday Terms)?

Nitric oxide is a tiny molecule that tells your blood vessels to relax and widen  a process known as vasodilation. This makes it easier for blood to flow, which:

• Helps maintain healthy blood pressure
• Improves oxygen delivery to muscles and organs
• Supports overall cardiovascular health because it influences so many systems in the body.

It’s so central that some researchers call nitric oxide a determinant of healthy lifespan and longevity (Poeggeler et al., 2023). MDPI

How Your Body Makes Nitric Oxide

Nitric oxide is produced in two major ways:

1. The L-Arginine Pathway

Inside blood vessel cells, enzymes convert the amino acid L-arginine into nitric oxide. This process depends on the health of the blood vessel lining and the availability of cofactors like antioxidants.

However, in many adults  especially as we age  this system becomes less efficient. This is one reason why arginine supplements often don’t reliably increase nitric oxide levels in humans: the limiting issue isn’t lack of arginine but how the body processes it (e.g., enzyme effectiveness and oxidative stress) (Derella et al., 2024). MDPI

2. The Nitrate–Nitrite–Nitric Oxide Pathway

This pathway depends on diet and your oral microbiome:

1. You eat nitrate rich foods (like beetroot and leafy greens).
2. Nitrates enter your saliva.
3. Oral bacteria turn nitrate into nitrite.
4. Nitrite is swallowed, then converted into nitric oxide in the body.

This pathway is especially important because it bypasses the enzyme steps that often become impaired with age. Human trials now show that dietary nitrate consistently raises nitrite and nitrate levels in saliva and plasma, even if traditional measures of vascular function don’t always change immediately (Derella et al., 2024). MDPI

Your Mouth Isn’t Just for Eating It Helps Make Nitric Oxide

This might be the most surprising part.

The bacteria living on the back of your tongue are essential for turning dietary nitrate into nitrite a critical step toward making nitric oxide. Recent systematic reviews confirm that nitrate exposure alters the oral microbiome in ways that increase beneficial bacterial groups like Neisseria and Rothia while reducing disease-associated bacteria (Morana et al., 2024). PubMed

Nitrate’s effects on the oral microbiome are strong enough that it’s being studied as a prebiotic a dietary component that promotes health-associated microbes. PubMed

Mouthwash Matters

New evidence suggests regular use of over-the-counter mouthwash is associated with lower markers of nitric oxide metabolism and higher markers of inflammation  likely because strong antiseptics kill nitrate reducing bacteria (Frontiers, 2025). Frontiers

This doesn’t mean you should stop brushing, but it does mean you should be mindful of products that obliterate the oral microbiome, especially if cardiovascular or blood pressure health is a priority.

Ageing, the Oral Microbiome, and Blood Pressure

Emerging clinical research shows that how your mouth bacteria respond to dietary nitrate changes with age. In a double-blind trial, older adults experienced reductions in blood pressure after nitrate supplementation, while younger adults did not, and these changes correlated with differences in the oral microbiome (Vanhatalo et al., 2025). ScienceDirect

This suggests:

• Older adults may benefit more from nitrate-rich foods
• The oral microbiome plays a direct role in nitric oxide bioavailability
• Changes in oral bacteria with ageing can influence vascular responses

Supplements: Helpful or Overhyped?

Research on nitric oxide boosting supplements (beetroot juice, nitrates, and precursors) shows mixed results:

• About half of clinical trials report performance or vascular benefits with inorganic nitrate supplementation, especially in clinical populations (e.g., cardiometabolic or pulmonary disease) (Derella et al., 2024). MDPI
• Nitrate appears to both support nitric oxide production and improve markers of oral and systemic health in some trials (Alhulaefi et al., 2024). Cambridge University Press & Assessment

However, not everyone responds the same way, and results are influenced by the oral microbiome, baseline health status, and individual biology.

Ageing, Genetics, and Why Nitric Oxide Doesn’t Work for Everyone

Not everyone gets the same benefits from foods and supplements. One reason is that people’s bodies don’t all process nutrients in the same way.

Some people have a common genetic variation called MTHFR. This doesn’t mean anything is “wrong” it simply means their body is a bit less efficient at using folate (a B vitamin found in leafy greens and other foods).

When folate isn’t processed as efficiently, a substance called homocysteine can slowly build up in the blood.

What Is Homocysteine?

Homocysteine is something everyone’s body makes as part of normal metabolism, especially when we eat protein. At healthy levels, it’s harmless and quickly recycled by the body.

Problems only arise when levels become too high. When that happens, homocysteine can:

• Put extra strain on blood vessels
• Make nitric oxide break down more quickly
• Increase low-grade inflammation in the body

This makes it harder for nitric oxide to do its job even if someone is eating well or taking supplements.

What This Means in Simple Terms

This doesn’t mean someone will get sick or develop disease. It simply means their body may be less forgiving.

Things like:

• Poor diet
• Chronic stress
• Lack of sleep
• Getting older

can have a bigger impact on them than on someone whose system is more efficiently

So, What Works Best? (Practical Tips)

1. Eat Nitrate-Rich Foods Daily

Foods like beetroot, spinach, arugula, and lettuce are excellent sources of dietary nitrate, which fuels nitric oxide production through the oral microbiome pathway.

2. Support Your Oral Microbiome

• Avoid over-use of antibacterial mouthwash
• Use gentle dental care products
• Consider tongue scraping and good oral hygiene that preserves beneficial bacteria

3. Exercise Regularly

Physical activity stimulates nitric oxide release through shear stress on blood vessel walls, a powerful, natural stimulus.

4. Liposomal Supplements as Adjuncts

Nitrate supplements and precursors can be useful in certain populations (e.g., older adults, clinical patients, or people with metabolic dysfunction), but they are not a substitute for diet and lifestyle. Please remember to always consult your Dr before supplementing with any products.  

• Nitric oxide is a central molecule for healthy blood flow and ageing.
• Your mouth bacteria are an active part of how NO is produced.
• Diet impacts nitric oxide not only through nutrients but by shaping your oral microbiome.
• Supplements can help, but individual response varies and lifestyle matters most.
•  

Ageing, Genetics, and Why Nitric Oxide Doesn’t Work for Everyone

Not everyone gets the same benefits from foods or supplements that boost nitric oxide. One reason is that people’s bodies don’t all process nutrients in the same way.

Some people have a common genetic variation called MTHFR. This doesn’t mean anything is “wrong” it simply means their body is a bit less efficient at using folate (a B vitamin found in leafy greens and other foods).

When folate isn’t processed as efficiently, a substance called homocysteine can slowly build up in the blood.

Homocysteine is something everyone’s body makes as part of normal metabolism, especially when we eat protein. At healthy levels, it’s harmless and quickly recycled by the body. Problems only arise when levels become too high.

When homocysteine levels rise, it can:

• Put extra strain on blood vessels
• Interfere with nitric oxide, the molecule that helps blood vessels relax and widen
• Increase low-grade inflammation in the body

Higher homocysteine is known to reduce nitric oxide stability and increase oxidative stress within blood vessels, meaning nitric oxide may break down faster than it can be used effectively (Stühlinger et al., 2001; Förstermann & Münzel, 2022).

This doesn’t mean someone will become sick or develop disease. It simply means their system may be less resilient and more affected by factors like poor diet, chronic stress, lack of sleep, or ageing  all of which are known to further reduce nitric oxide availability (Seals et al., 2011; Townsend et al., 2023).

In simple terms:
Some people can make nitric oxide, but it doesn’t last long enough to do its job properly.

How Can You Check Your Nitric Oxide or Vascular Health?

Nitric oxide itself is difficult to measure directly because it breaks down very quickly. Instead, testing focuses on markers that reflect nitric oxide activity or blood vessel function.

1. Saliva Nitric Oxide Test Strips

Saliva nitric oxide (nitrate/nitrite) strips measure nitrite levels in saliva, which reflect how well the dietary nitrate → nitric oxide pathway is working.

These strips can help indicate:

• Whether your diet is providing enough nitrate
• Whether oral bacteria are converting nitrate effectively
• Changes over time after diet or lifestyle adjustments

They do not diagnose disease and should be viewed as a trend tool, not a medical test. Salivary nitrite is widely used in research as a surrogate marker of nitric oxide bioavailability in the nitrate–nitrite pathway (Lundberg et al., 2023; Morana et al., 2024).

2. Vascular Screening Devices (e.g., Max Pulse)

Devices such as Max Pulse assess arterial stiffness and pulse wave characteristics, which reflect how flexible or stiff blood vessels are.

These devices do not measure nitric oxide directly, but nitric oxide plays a major role in maintaining arterial flexibility. Increased arterial stiffness is a recognized marker of vascular ageing and reduced endothelial function (Townsend et al., 2023).

These tools are best used for:

• Monitoring vascular trends over time
• Supporting lifestyle change decisions

They are not diagnostic devices and do not detect plaque or blockages.

3. Functional or Integrative Medicine Testing

A functional or integrative physician may assess related markers that influence nitric oxide availability, including:

• Homocysteine
• Folate and B-vitamin status
• Markers of inflammation or oxidative stress

This approach focuses on identifying why nitric oxide support may not be working, rather than simply increasing supplements.

4. Clinical or Research-Level Testing

In specialist or research settings, more advanced tests may include:

• Plasma nitrate and nitrite levels
• Flow-mediated dilation (FMD) ultrasound
• Pulse wave velocity (PWV)

These are considered gold-standard measures of endothelial and vascular function but are not routinely used in general practice.

No single test can fully capture nitric oxide health. Patterns over time, combined with diet, movement, oral health, sleep, and stress management, are far more meaningful than any single number.

References:

Förstermann, U., & Münzel, T. (2022). Endothelial nitric oxide synthase in vascular disease: From marvel to menace. European Heart Journal, 43(45), 4090–4104.

Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2023). The nitrate–nitrite–nitric oxide pathway in human physiology and therapeutics. Nature Reviews Cardiology, 20(9), 585–601.

Morana, S. P., Rosier, B. T., Henriquez, F. L., & Burleigh, M. C. (2024). The effects of nitrate on the oral microbiome: A systematic review. Journal of Oral Microbiology, 16, 2322228.

Seals, D. R., Jablonski, K. L., & Donato, A. J. (2011). Aging and vascular endothelial function. Clinical Science, 120(9), 357–375.

Stühlinger, M. C., Oka, R. K., Graf, E. E., Schmolzer, I., Upson, B. M., Kapoor, O., & Cooke, J. P. (2001). Endothelial dysfunction induced by hyperhomocysteinemia. Circulation, 104(21), 2569–2575.

Townsend, R. R., Wilkinson, I. B., Schiffrin, E. L., et al. (2023). Recommendations for improving and standardizing vascular research on arterial stiffness. Hypertension, 80(3), e1–e20.