Intragastric nitric oxide production in humans: measurements in expelled air.
Open accessAbstract
High values (800-6000 parts per billion) of nitric oxide (NO) in expelled air from the stomach were shown in humans by chemiluminescence technique. These NO values were more than 100 times higher than those found in orally exhaled air. Intragastric NO production is probably non-enzymatic, requiring an acidic environment, as NO in expelled air was reduced by 95% after pretreatment with the proton pump inhibitor omeprazole. Furthermore, large amounts of NO were formed in vitro from lettuce and saliva when placed in hydrogen chloride (pH < 2). In conclusion, large amounts of NO are formed intragastrically in humans and this source of NO may be of importance for the integrity of the gastric mucosa in health and disease. Measurements of NO in expelled air might be of value as a non-invasive method for estimation of gastric acidity.
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Continuous swallowing of nitrite-containing saliva produces various nitrogen oxides, including NO, in the acidic environment of the gastric lumen.
“The continuous swallowing of nitrite-containing saliva (~1.5 liters per day) generates a variety of nitrogen oxides, including NO, in the acidic milieu of the gastric lumen.”
From Nitrate and nitrite in biology, nutrition and therapeutics (2009) · cites this paper as [29]
The discussion under “Nitric Oxide Formation in Vitro” (page not provided) says that swallowed, nitrite-containing saliva can support continuous NO formation in the acidic stomach. It does not report production of a variety of nitrogen oxides, and gives daily saliva production as often exceeding one litre rather than approximately 1.5 litres. (LLM, conf=0.87)
Experimental — accuracy not yet measuredNitric oxide gas is generated in the human stomach at high concentrations, dependent on gastric acidity and involving reduction of salivary-derived nitrite.
“Nitric oxide gas was generated in the human stomach at high concentrations, and this production was dependent on gastric acidity and involved reduction of salivary-derived nitrite.”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [8]
The Abstract reports high NO concentrations in air expelled from the human stomach, and the Discussion reports that omeprazole nearly abolished them, supporting dependence on gastric acidity. The NITRIC OXIDE FORMATION IN VITRO section calls nitrite the probable substrate, but says it may come from swallowed saliva or gastric secretion. The claim presents reduction of salivary-derived nitrite as established rather than a proposed mechanism. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNitric oxide generation in the stomach is greatly enhanced after intake of nitrate.
“Furthermore, nitric oxide generation was greatly enhanced after intake of nitrate.8”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [8]
Nitrite is swallowed and can undergo downstream reactions, including formation of NO and NO-donating species following protonation to HNO2 and secondary nitrosating and nitrating species in the low pH of the stomach, or further reduction by enteric bacterial nitrite reductases.
“Nitrite is then swallowed where it can undergo a diversity of downstream reactions, including formation of NO and NO-donating species following a) protonation to HNO2 and an array of secondary nitrosating and nitrating species in reactions facilitated by the low pH of the stomach[80,83,89–91], or b) further reduction by enteric bacterial nitrite reductases (NiRs)[74].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [90]
Acid-reduction reduces gastric production of NO.
“Additionally, acid-reduction is known to reduce gastric production of NO[76,90,254]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [90]
In humans, nitrite reduction to NO was discovered in expelled air and attributed to non-enzymatic reduction in the stomach.
“In humans, nitrite reduction to NO was discovered in expelled air and attributed to non-enzymatic reduction in the stomach [28].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [28]
Nitrite reduction to NO can occur under anoxic and/or acidic conditions.
“initial studies documented the potential for nitrite reduction to NO under anoxic and / or acidic conditions [1-4].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [4]
Oral ingestion of nitrite into the acidic environment of the stomach produces NO that augments mucus secretion, antibacterial effects of gastric fluids, and ulcer healing.
“Moreover, oral ingestion of nitrite into the acidic environment of the stomach produces NO that augments mucus secretion, antibacterial effects of gastric fluids, and ulcer healing [93–97].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [97]
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Nitrite is an alternative source of NO in vivo
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Generation of NO by probiotic bacteria in the gastrointestinal tract
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Urinary nitrite: more than a marker of infection
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Self-citationDietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia
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Nitrated oleic acid up-regulates PPARγ and attenuates experimental inflammatory bowel disease
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Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function
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Nitric oxide deficiency is a primary driver of hypertension
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Gastrointestinal nitric oxide generation in germ-free and conventional rats
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Self-citation
- Authors
- Lundberg, J. O., Weitzberg, E., Lundberg, J. M., & Alving, K.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Gut
- Publisher
- BMJ
- Published
- 1994-11
- Volume
- 35
- Issue
- 11
- Pages
- 1543-1546
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1375608
- OpenAlex
- W2144413971
- Cited by
- 661
- References
- 17
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 23 · 2023: 16 · 2022: 21 · 2021: 25 · 2020: 24 · 2019: 33 · 2018: 25 · 2017: 35 · 2016: 31 · 2015: 26 · 2014: 36 · 2013: 24 · 2012: 31
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- nitric oxide, gastric acidity, omeprazole, proton pump inhibitors, gastric mucosa, hydrogen chloride, lettuce, saliva
- MeSH terms
- Adult, Air, Asthma, Breath Tests, Gastric Mucosa, Humans, Hydrochloric Acid, Hydrogen-Ion Concentration, Nitric Oxide, Omeprazole, Saliva, Lactuca, In Vitro Techniques
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