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All About Nitric Oxide Production

Written by Henry P. Barham, MD, Mohamed A. Taha, MD, Natan Rosenfeld, and Marianne Madsen

“Eat your greens!” Did your mom say that? If so, it’s because she already knew that greens are healthy for your body in many ways. But did you know that one of those ways is a boost to your immune system? Next time you eat your spinach, remember that you’re helping your body fend off COVID-19 and other respiratory infections just by eating things that help you produce nitric oxide. 

 

Nitric oxide (NO), with its anti-inflammatory and immune system-boosting effect, can be utilized via foods containing nitrates, particularly certain types of vegetables. Once these foods are digested, the body converts the nitrates into nitrites, and finally into NO. Exercise can also boost NO production. 

 

It’s important to note, however, that while small amounts of NO are beneficial, larger amounts can have harmful effects on the body. So before reading the below paragraphs about NO, know that a balanced diet with plenty of vegetables paired with regular exercise is the best way to stay healthy and keep your NO levels at optimum levels.

 

The benefits of nitric oxide on immunity

 

NO is a compound that has potent antimicrobial effects. Cells that line the upper airway release NO as an innate immune response in the face of invading pathogens. Bitter products secreted from common pathogens of the respiratory tract are detected by bitter taste receptors (T2Rs) of upper airway epithelial cells and elicit many of these downstream NO responses. NO then diffuses through the mucus overlying these cells into the offending pathogen, where it produces components that are destructive to bacterial structures–DNA, bacterial replication machinery, enzymes, or virulence factors can all be affected by NO. 

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In addition to having a direct antimicrobial effect, NO also speeds up ciliary (the small hairs in your nose) beating frequency so you have a better chance of clearing the pathogen–the movement clears trapped pathogens in the nose and sinuses into the back of your throat, where they can be removed before they take hold and make you sick.

 

Earlier studies have indicated that the ability to release NO in response to pathogens in the respiratory tract has been linked to genetic differences between individuals, specifically the T2Rs genes. This directly correlates with the clinical outcomes in infected patients. A study was able to detect significantly lower levels of NO in patients with chronic rhinosinusitis (chronic inflammation of nose and sinuses) with nasal polyps. Because of their low NO production, these patients had a poorer chance of eliminating the invading pathogens.

 

NO also paves the way for other immune responses to efficiently kill the invading pathogens. For example, a bacterium called P. aeruginosa forms a protective layer around itself called biofilm, to isolate itself from the various immune mechanisms. NO disrupts this biofilm so that other immune defenses have unimpeded access to this bacteria. 

 

In a prior study evaluating the association of NO with SARS-CoV, it was found that NO inhibits the replication of SARS-CoV by two distinct mechanisms. First, NO or its derivatives may cause a reduction in the fusion between the virus and its receptor on the target cell. Second, NO or its derivatives may cause a reduction in viral RNA production in the early steps of viral replication.

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Other benefits of nitric oxide

 

In addition to reducing inflammation and strengthening the immune system, NO has a variety of health benefits including better blood pressure control, increased cognitive function, and reduced heart disease risk. It even helps with erectile dysfunction. 

 

The cardiovascular benefits of NO are due to the fact that NO widens and relaxes the blood vessels, increasing blood flow. For this reason, drugs like Viagra (sildenafil) work by enhancing NO production, dilating arteries in the penis which allows users to achieve and maintain an erection. 

 

NO production is involved in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease as well. Reduced NO production can restrict blood flow to the brain and lead to a decline in cognitive functions. But overproduction of NO can also contribute to the development of such diseases. 

 

Foods that increase nitric oxide production

 

Certain nitrate-rich foods, mainly vegetables, have been shown to generate NO in the body. But other compounds can also stimulate NO production. An amino acid called L-arginine, for instance, leads to the same effect. 

 

Foods high in nitrates include:

  • Spinach
  • Collard greens
  • Cabbage
  • Beets
  • Radishes
  • Celery

 

Processed meats are also high in nitrates. But these should be avoided, as processed meats have been linked to colon cancer (although it’s not clear if their nitrate content is responsible).

 

Foods high in arginine include:

  • Nuts
  • Chocolate
  • Oats
  • Wheat
  • Turkey
  • Dairy products

 

Arginine is also found in various supplements. However, while some studies have shown arginine supplements to be effective at improving symptoms of cardiovascular disease, others have found them to have detrimental effects. It appears that the evidence is mixed, and that it’s likely better to get arginine in moderation from natural food sources rather than take it in the form of a pill. 

 

How can I stimulate nitric oxide production?

 

Remember that too much NO can have harmful effects in the long run. So avoid dietary supplements claiming to boost your NO levels, as they can cause more harm than good. But you can still boost your NO levels naturally by eating plenty of vegetables, enjoying nuts, chocolate, and dairy products in moderation, and working out on a daily basis.

Doctor Profile

Henry P. Barham, MD

Rhinologist

Dr. Barham is a board-certified ear, nose, and throat (ENT) physician who works as a dedicated rhinologist (nose, sinus, allergy, endoscopic sinus, and skull base surgery) at Sinus and Nasal Specialists of Louisiana, LLC. He is also a widely published researcher with over 100 publications and book chapters throughout his career.

Doctor Profile

Mohamed A. Taha, MD

Research Fellow

Dr. Taha is a consultant physician of ear, nose, and throat (ENT) at the Faculty of Medicine - Cairo University, where he got his MD degree in 2019. He is currently a Research Fellow at the Sinus and Nasal Specialists of Louisiana, LLC. Dr. Taha has published many studies in ENT, mainly about COVID-19. His latest publication linking bitter taste receptors to COVID-19 (published in JAMA) showed interesting results.

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