The relationship between plasma and salivary NOx
Open accessAbstract
Several studies have shown that fasting plasma nitrite (NO2(-)) is an indicator of endothelial nitric oxide synthase (NOS) activity while plasma nitrate (NO3(-)) or the sum of NO2(-) and NO3(-) (NOx) does not reflect NOS function. Plasma NO2(-) can also be elevated through dietary NO3(-) where the NO3(-) is partially reduced to NO2(-) by oral bacteria and enters the plasma through the digestive system. NO3(-) is taken up from plasma by salivary glands and the cycle repeats itself. Thus, one may propose that salivary NO2(-) is an indicator of plasma NO2(-) and consequently of NO production. Many brands of nitric oxide (NO) saliva test strips have been developed that suggest that their product is indicative of circulatory NO availability. However, data supporting a relationship between salivary and plasma NO2(-) or NO bioavailability are lacking. Here we have measured basal salivary and plasma NO2(-) and NO3(-) to determine if any correlation exists between these in 13 adult volunteers. We found no significant correlation between basal salivary and plasma NO2(-). Also no correlation exists between salivary NO3(-) and plasma NO2(-). However, we did see a correlation between salivary NO3(-) and plasma NO3(-), and between salivary NO2(-) and plasma NO3(-). In a separate study, we compared the efficiency of salivary NO3(-) reduction with the efficacy of increasing plasma NO3(-) and NO2(-) after drinking beet juice, a high NO3(-)-containing beverage, in 10 adult volunteers. No significant correlation was observed between the ex vivo salivary reduction of NO3(-) to NO2(-) and plasma increases in NO3(-) or NO2(-). These results suggest that measures of salivary NO3(-), NO2(-) or NOx are not good indicators of endothelial function. In addition, the efficiency of saliva to reduce NO3(-) to NO2(-)ex-vivo does not demonstrate one's ability to increase plasma NO2(-) following consumption of dietary NO3(-).
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Approximately 25% of total circulating nitrate is actively sequestered into salivary glands and concentrated in saliva up to 20 times that in plasma, in proportion to the dietary load of nitrate.
“In proportion to the dietary load of nitrate, approximately 25% of total circulating nitrate is actively sequestered into salivary glands and concentrated in saliva up to 20 times that in plasma[73,75,82–88].”
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 [87]
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- Authors
- Clodfelter, W. H., Basu, S., Bolden, C., Dos Santos, P. C., King, S. B., & Kim-Shapiro, D. B.
- Affiliations
- Wake Forest University (US)
- Wake Forest University Health Sciences (US)
- Corresponding author
- King, S. Bruce
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 47
- Pages
- 85-90
- ISSN
- 1089-8603 (ISSN-L)
- PMC
- PMC4439285
- OpenAlex
- W2091158022
- Cited by
- 39
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 17 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (HL058091)
- Translational Science Center of Wake Forest University
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- nitrite, nitrate, salivary biomarkers, plasma biomarkers, endothelial nitric oxide synthase, endothelial function, dietary nitrate, beetroot juice, oral bacteria, nitric oxide bioavailability
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Nitrates, Nitrogen Dioxide, Saliva, Young Adult
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