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How does nitrate in food affect FeNO?

We spoke to FeNO expert Professor Kjell Alving about the science behind foods that affect a patient’s level of fractional exhaled nitric oxide (FeNO). There’s more to it than meets the eye, so let’s take a closer look.

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Professor Alving was one of the pioneers of FeNO testing in asthma, and part of the team that discovered its value in the respiratory setting back in the 1990s. As well as developing the technology we use to test FeNO in patients today, experts have looked at the origin and production of nitric oxide (NO) in the body. Getting to grips with a little about the facts helps to explain why patients should be asked to avoid certain foods for a few hours before a test, so only their true FeNO value is revealed.

“There are two major biochemical formation pathways for NO in the airways,” Professor Alving explains.1 “The most important, and what is seen in the airway mucosa in the respiratory epithelium, is so-called enzymatic NO formation, which is dependent upon the expression of an enzyme called inducible NO synthase (iNOS). This is expressed in respiratory epithelial cells that utilise L-arginine and oxygen to form NO.” Healthy individuals have a basal expression of this enzyme, Professor Alving points out, but that expression increases with Type 2 airway inflammation.

“In the respiratory tract, there is also non-enzymatic NO formation, which takes place primarily in the mouth,” says Professor Alving. “In this pathway, nitrate is utilised by facultative anaerobic bacteria on the base of the tongue that has bacterial reductase. These bacteria reduce nitrate to nitrite and, if the biochemical conditions are right – for example, with reducing agents such as ascorbate or if the environment is slightly acidic – nitrite will be further reduced to NO.” Added together, these elements form the basis of an NO source in the mouth and pharynx.

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Now, nitrate is found in certain foodstuffs, most notably green, leafy vegetables, which means that eating this kind of food may increase the source of NO.

“What happens,” notes Professor Alving, “is that after eating a Caesar salad, for example, nitrate will be taken up by the gastrointestinal tract and enter the blood circulation before being taken up by the salivary glands and excreted with saliva into the mouth.” This increases the presence of the substrate for the reduction to nitrite and NO. Interestingly, nasal NO, the testing of which can be used to help diagnose primary ciliary dyskinesia, is not affected by nitrate intake.

Salivary contribution to exhaled nitric oxide

Zetterquist W et al. Salivary contribution to exhaled nitric oxide. European Respiratory Journal. 1999;13(2):327-332

Laboratory salad conditions

Scientists have conducted experiments to demonstrate the process, as Professor Alving goes on to describe. “A group of healthy volunteers ingested a solution of potassium nitrate corresponding to approximately one head of lettuce. Of course, this amount is greater than would normally be ingested when consuming a salad, but to illustrate the point.

“The NO release rate increased, reaching a peak after approximately two hours. This means it’s important to ask patients about their intake of especially green-leaved vegetables before testing FeNO.”

If you’d like to learn more about the science behind FeNO in asthma, you might like this article, which explains why FeNO is higher in asthma patients. Of course, if you’d like to get straight to FeNO testing, you can contact us today for a demo and try NIOX® technology in your own practice.

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References

1. Prof. Kjell Alving. Factors affecting FeNO: confounders vs determinants. Available at; https://www.niox.com/prof-alving-webinar/
2. Zetterquist W et al. Salivary contribution to exhaled nitric oxide. European Respiratory Journal. 1999;13(2):327-33.