A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load
Abstract
Nitric Oxide (NO) bioavailability is essential for vascular health. Dietary supplementation with inorganic nitrate, which is abundant in vegetables and roots, has been identified as an effective means of increasing vascular NO bioavailability. Recent studies have shown a reduction in resting blood pressures in both normotensive and hypertensive subjects following ingestion of inorganic nitrate. Oral bacteria play a key role in this process and the use of strong antibacterial mouthwash rinses can disable this mechanism. Hence, mouthwash usage, a $1.4 billion market in the US, may potentially be detrimental to cardiovascular health. The purpose of this study was to examine the effects of different strengths of commercially available mouthwash products on salivary and plasma nitrate and nitrite concentrations following 8.4 mmol inorganic nitrate load (beetroot juice). Specifically, we examined the effects of Listerine antiseptic mouthwash, Cepacol antibacterial mouthwash, and Chlorhexidine mouthwash versus control (water). Twelve apparently healthy normotensive males (36 ± 11 yrs) completed four testing visits in a randomized order, separated by one week. Testing consisted of blood pressure (BP), and saliva and venous blood collection at baseline and each hour for 4 h. Following baseline-testing participants consumed 140 ml of beet juice and then 15 min later gargled with 5 mL of assigned mouthwash. Testing and mouthwash rinse was repeated every hour for 4 h. Linear mixed effects models, followed by pairwise comparisons where appropriate, were used to determine the influence of treatment and time on plasma and saliva nitrate and nitrite, and BP. Plasma and salivary nitrate increased above baseline (time effect) for all conditions (p ≤ 0.01). There were time (p ≤ 0.01), treatment (p ≤ 0.01), and interaction (p ≤ 0.05) effects for plasma and salivary nitrite. There was a treatment effect on systolic BP (p ≤ 0.05). Further examination revealed a differentiation of plasma and salivary nitrite concentration between control/antiseptic and antibacterial/chlorhexidine treatments. When examined in this manner there was a reduction in both SBP (p ≤ 0.01) and mean arterial BP (p ≤ 0.05) from the antibacterial/chlorhexidine treatments. These results suggest a potentially differentiating effect of different commercially available mouthwash solutions on plasma and salivary nitrite concentrations and resting blood pressure responses. This raises potential public health related questions on the appropriate widespread usage of different mouthwash formulations.
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Periodontal disease, denture use and antiseptic mouthwashes can disrupt the balance of microbes and reduce nitrite formation, thereby reducing the cardiovascular benefits of dietary nitrate.
“periodontal disease, denture use and antiseptic mouthwashes can disrupt the balance of microbes and reduce nitrite formation, thereby reducing the cardiovascular benefits of dietary nitrate [249,250,251,252].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [251]
In two included studies, more than one mouthwash was tested, resulting in some differences in outcomes.
“In two studies more than one mouthwash was tested (McDonagh et al., 2015; Woessner et al., 2016), resulting in some differences in the outcomes (Table 2).”
From Do Changes in Oral Microbiota Correlate With Plasma Nitrite Response? A Systematic Review (2019) · cites this paper as Woessner et al., 2016
In three included studies, systolic blood pressure was significantly higher in test groups following mouthwashing compared with controls.
“Anyway, only three studies suggested a significant increase of systolic BP following mouthwashing compared with controls.”
From Do Changes in Oral Microbiota Correlate With Plasma Nitrite Response? A Systematic Review (2019) · cites this paper as Woessner et al., 2016
Alterations in oral microbiota could lead to variations in systemic availability of NO.
“Subsequently, it was supposed that such alterations could also lead to variations in the systemic availability of NO (Govoni et al., 2008; Kapil et al., 2013; Woessner et al., 2016).”
From Do Changes in Oral Microbiota Correlate With Plasma Nitrite Response? A Systematic Review (2019) · cites this paper as Woessner et al., 2016
These reactions can beneficially regulate cardio-metabolic function and will be attenuated or abolished by chemical or physical destruction of the oral microbiota.
“These reactions can beneficially regulate cardio-metabolic function and will be attenuated or abolished by chemical or physical destruction of the oral microbiota[60,75,76,97–99].”
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 [99]
Enterosalivary nitrate reduction depends on living oral microbiota for its biologic activity.
“the global dependency of enterosalivary nitrate reduction on living oral microbiota to enact its biologic activity[73,99,109].”
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 [99]
Both salivary nitrate and nitrite concentrations and gingival expression of NO-forming NOS have been found to be increased in periodontal disease, which also tend to increase with disease severity and improve with periodontal treatment.
“Interestingly, both salivary nitrate and nitrite concentrations and gingival expression of NO-forming NOS have been found to be increased in periodontal disease, which also tend to increase with disease severity and improve with periodontal treatment[99,193,291,292].”
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 [99]
One's choice in mouthwash greatly impacts the degree of bacterial nitrate reduction and blood pressure effects.
“evidence suggesting that one’s choice in mouthwash (from the strongest bactericidal formulations with chlorhexidine, to weaker ones such as with triclosan or cetylpyridinium, to the widely available and weakest antiseptic formulations) greatly impacts the degree of bacterial nitrate reduction and blood pressure effects[99,429,434]”
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 [99]
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- Authors
- Woessner, M., Smoliga, J. M., Tarzia, B., Stabler, T., Van Bruggen, M., & Allen, J. D.
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 54
- Pages
- 1-7
- ISSN
- 1089-8603 (ISSN-L)
- OpenAlex
- W2268392914
- Semantic Scholar
- f2450b8dec8252b5c8bf235ae2b610c194159326
- Cited by
- 137
- References
- 43
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 17 · 2023: 15 · 2022: 20 · 2021: 5 · 2020: 9 · 2019: 16 · 2018: 11 · 2017: 20 · 2016: 6
- FWCI
- 12.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Funders
- High Point University
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- nitric oxide bioavailability, dietary nitrate, inorganic nitrate, mouthwash, chlorhexidine, Listerine, antibacterial mouthwash, salivary nitrite, plasma nitrite, plasma nitrate, blood pressure, beetroot juice, oral bacteria, cardiovascular health, hypertension, nitrate loading, resting systolic blood pressure, mean arterial pressure
- MeSH terms
- Fruit and Vegetable Juices, Adult, Anti-Infective Agents, Local, Blood Pressure, Cetylpyridinium, Chlorhexidine, Diet, Drug Combinations, Humans, Male, Middle Aged, Mouthwashes, Nitrates, Nitric Oxide, Nitrites, Salicylates, Saliva, Terpenes, Water, Beta vulgaris
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