{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T19:10:13Z","timestamp":1739387413685,"version":"3.37.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Diversity Scholars Research Program of the Center for Research and Learning at Indiana University Indianapolis"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Antiseptic mouthwash use is widespread due to its oral health benefits. However, its impact on systemic physiological processes, particularly nitric oxide (NO) bioavailability and muscle contractility, is not fully understood. We sought to determine the effects of cetylpyridinium (antibacterial) versus sodium chloride (control) mouthwashes on salivary and breath NO markers and muscle contractile function in healthy young adults. Thirty participants (n\u2009=\u200915\/group) completed a randomized, parallel-arm, blinded trial, comparing the two mouthwashes before and after 7 d of treatment. NO bioavailability was inferred via measurement of salivary nitrate (NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>), nitrite (NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>), and cyclic guanyl monophosphate (cGMP) concentrations and breath NO level. Contractile function of the knee extensor muscles was determined via isokinetic dynamometry. No changes in salivary NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>, or cGMP or in breath NO were observed in response to either treatment. However, cetylpyridinium mouthwash reduced the percentage of NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> in saliva (17\u2009\u00b1\u200910% vs. 25\u2009\u00b1\u200913%; p\u2009=\u20090.0036). Peak torque at velocities of 0\u20136.28 rad\/s was unaffected by mouthwash use. Calculated maximal knee extensor velocity (Vmax) and power (Pmax) were therefore also unchanged. Cetylpyridinium mouthwash reduces the relative abundance of NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> in the oral cavity but does not significantly diminish overall NO bioavailability or impair muscle contractile function in healthy young adults.<\/jats:p>","DOI":"10.1371\/journal.pone.0312961","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:42:04Z","timestamp":1739385724000},"page":"e0312961","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pilot randomized trial of the effect of antibacterial mouthwash on muscle contractile function in healthy young adults"],"prefix":"10.1371","volume":"20","author":[{"given":"Edgar J.","family":"Gallardo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William S.","family":"Zoughaib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahaan","family":"Singhal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard L.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7723-8872","authenticated-orcid":true,"given":"Andrew R.","family":"Coggan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"pone.0312961.ref001","unstructured":"Grand View Research. Oral rinse market size, share & trends analysis report by product (antiseptic mouthwash, natural mouthwash), by indication, by distribution channel, by region, and segment forecasts, 2022 \u2013 2030. 2022. Available from: https:\/\/www.grandviewresearch.com\/industry-analysis\/oral-rinse-market-report\/methodology"},{"issue":"3","key":"pone.0312961.ref002","doi-asserted-by":"crossref","first-page":"313","DOI":"10.17219\/dmp\/91774","article-title":"Self-reported oral status and habits related to oral care in adult Poles: a questionnaire study","volume":"55","author":"R G\u00f3rska","year":"2018","journal-title":"Dent Med Probl"},{"issue":"4","key":"pone.0312961.ref003","first-page":"e2","article-title":"Mouthwash use in general population: results from adult dental health survey in grampian, Scotland","volume":"1","author":"TV Macfarlane","year":"2011","journal-title":"J Oral Maxillofac Res"},{"key":"pone.0312961.ref004","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1111\/adj.12769","article-title":"Oral hygiene behaviours among Australian adults in the national study of adult oral health (NSAOH) 2017\u201318","volume":"65","author":"L Luzzi","year":"2020","journal-title":"Austral Dent J"},{"issue":"7","key":"pone.0312961.ref005","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.3390\/molecules26072001","article-title":"Recent development of active ingredients in mouthwashes and toothpastes for periodontal diseases","volume":"26","author":"M Rajendiran","year":"2021","journal-title":"Molecules"},{"issue":"4","key":"pone.0312961.ref006","doi-asserted-by":"crossref","first-page":"597","DOI":"10.2334\/josnusd.16-0593","article-title":"The effects of essential oil, povidone-iodine, and chlorhexidine mouthwash on salivary nitrate\/nitrite and nitrate-reducing bacteria","volume":"59","author":"T Mitsui","year":"2017","journal-title":"J Oral Sci"},{"key":"pone.0312961.ref007","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fcimb.2019.00039","article-title":"Frequency of tongue cleaning impacts the human tongue microbiome composition and enterosalivary circulation of nitrate","volume":"9","author":"GD Tribble","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0312961.ref008","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.freeradbiomed.2019.05.010","article-title":"Dietary intake of inorganic nitrate in vegetarians and omnivores and its impact on blood pressure, resting metabolic rate and the oral microbiome","volume":"138","author":"A Ashworth","year":"2019","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"pone.0312961.ref009","doi-asserted-by":"crossref","first-page":"5254","DOI":"10.1038\/s41598-020-61912-4","article-title":"Effects of Chlorhexidine mouthwash on the oral microbiome","volume":"10","author":"R Bescos","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0312961.ref010","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.bbrc.2010.02.136","article-title":"NO-synthase independent NO generation in mammals","volume":"396","author":"JO Lundberg","year":"2010","journal-title":"Bioche Biophys Res Commun"},{"issue":"1","key":"pone.0312961.ref011","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1515\/hsz-2019-0349","article-title":"Inorganic nitrite bioactivation and role in physiological signaling and therapeutics","volume":"401","author":"MB Amdahl","year":"2019","journal-title":"Biol Chem"},{"key":"pone.0312961.ref012","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.freeradbiomed.2012.11.013","article-title":"Physiological role for nitrate-reducing oral bacteria in blood pressure control","volume":"55","author":"V Kapil","year":"2013","journal-title":"Free Radic Biol Med"},{"issue":"5","key":"pone.0312961.ref013","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1093\/ajh\/hpu192","article-title":"Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women","volume":"28","author":"CP Bondonno","year":"2015","journal-title":"Am J Hypertens"},{"issue":"9349","key":"pone.0312961.ref014","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/S0140-6736(02)11911-8","article-title":"Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies","volume":"360","author":"Prospective Studies Collaboration","year":"2002","journal-title":"Lancet"},{"issue":"2","key":"pone.0312961.ref015","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/08037051.2019.1680270","article-title":"Over-the-counter mouthwash use, nitric oxide and hypertension risk","volume":"29","author":"K Joshipura","year":"2020","journal-title":"Blood Press"},{"key":"pone.0312961.ref016","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.niox.2017.09.004","article-title":"Over-the-counter mouthwash use and risk of pre-diabetes\/diabetes","volume":"71","author":"KJ Joshipura","year":"2017","journal-title":"Nitric Oxide"},{"key":"pone.0312961.ref017","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.freeradbiomed.2019.07.035","article-title":"Post-exercise hypotension and skeletal muscle oxygenation is regulated by nitrate-reducing activity of oral bacteria","volume":"143","author":"C Cutler","year":"2019","journal-title":"Free Radic Biol Med"},{"issue":"8\u20139","key":"pone.0312961.ref018","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1007\/s000180050359","article-title":"Effects of nitric oxide on the contraction of skeletal muscle","volume":"55","author":"G Mar\u00e9chal","year":"1999","journal-title":"Cell Mol Life Sci"},{"issue":"1","key":"pone.0312961.ref019","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12970-021-00463-z","article-title":"Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis","volume":"18","author":"AR Coggan","year":"2021","journal-title":"J Int Soc Sports Nutr"},{"issue":"4","key":"pone.0312961.ref020","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1249\/JES.0000000000000167","article-title":"Dietary nitrate enhances the contractile properties of human skeletal muscle","volume":"46","author":"AR Coggan","year":"2018","journal-title":"Exerc Sport Sci Rev"},{"key":"pone.0312961.ref021","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1093\/gerona\/glz156","article-title":"A single dose dietary of nitrate increases maximal muscle speed and power in healthy older men and women","volume":"75","author":"AR Coggan","year":"2020","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"5","key":"pone.0312961.ref022","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1161\/CIRCHEARTFAILURE.115.002141","article-title":"Acute dietary nitrate intake improves muscle contractile function in patients with heart failure: a double-blind, placebo-controlled, randomized trial","volume":"8","author":"AR Coggan","year":"2015","journal-title":"Circ Heart Fail"},{"key":"pone.0312961.ref023","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/gerona\/glaa311","article-title":"Dose-response effect of dietary nitrate on muscle contractility and blood pressure in older subjects: a pilot study","volume":"76","author":"EJ Gallardo","year":"2021","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"pone.0312961.ref024","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.niox.2023.05.005","article-title":"Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women","author":"WS Zoughaib","year":"2023","journal-title":"Nitric Oxide"},{"key":"pone.0312961.ref025","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s00421-003-0941-0","article-title":"The relationship between maximal jump-squat power and sprint acceleration in athletes","volume":"91","author":"G Sleivert","year":"2004","journal-title":"Eur J App Physiol"},{"issue":"1","key":"pone.0312961.ref026","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/JES.0b013e31823b5f13","article-title":"Skeletal muscle power: a critical determinant of physical functioning in older adults","volume":"40","author":"KF Reid","year":"2012","journal-title":"Exerc Sport Sci Rev"},{"issue":"6","key":"pone.0312961.ref027","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/j.1600-051X.1994.tb00736.x","article-title":"The magnitude and duration of the effects of some mouthrinse products on salivary bacterial counts","volume":"21","author":"S Jenkins","year":"1994","journal-title":"J Clin Periodontol"},{"key":"pone.0312961.ref028","first-page":"4056708","article-title":"Efficacy of a rinse containing sea salt and lysozyme on biofilm and gingival health in a group of young adults: a pilot study","author":"J Hoover","year":"2017","journal-title":"Int J Dent"},{"key":"pone.0312961.ref029","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1183\/09031936.03.00008603","article-title":"Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers","volume":"21","author":"A Soop","year":"2003","journal-title":"European Respiratory Journal"},{"key":"pone.0312961.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2021.08.002","article-title":"Nitrite in paraffin-stimulated saliva correlates with blood nitrite","volume":"116","author":"S Lumbikananda","year":"2021","journal-title":"Nitric Oxide"},{"key":"pone.0312961.ref031","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF01466270","article-title":"Presence of atrial natriuretic factor and cyclic guanosine monophosphate in saliva. Comparison of plasma and salivary concentrations during a head-down tilt","volume":"65","author":"G Gauquelin","year":"1992","journal-title":"Eur J Appl Physiol"},{"key":"pone.0312961.ref032","volume-title":"Statistical power analysis for the behavioral sciences","author":"J Cohen","year":"1988"},{"key":"pone.0312961.ref033","first-page":"1","article-title":"Resilience of the oral microbiome","volume":"00","author":"WG Wade","year":"2020","journal-title":"Periodontology 2000"},{"issue":"4","key":"pone.0312961.ref034","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1600-051X.1981.tb02040.x","article-title":"Comparison of the in vivo and in vitro antibacterial properties of antiseptic mouthrinses containing chlorhexidine, alexidine, cetyl pyridinium chloride and hexetidine. Relevance to mode of action","volume":"8","author":"WR Roberts","year":"1981","journal-title":"J Clin Periodontol"},{"issue":"2","key":"pone.0312961.ref035","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1600-0722.2011.00812.x","article-title":"Acute and substantive action of antimicrobial toothpastes and mouthrinses on oral biofilm in vitro","volume":"119","author":"MPT Otten","year":"2011","journal-title":"Eur J Oral Sci"},{"issue":"1","key":"pone.0312961.ref036","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1186\/s12903-022-02532-4","article-title":"The antibiofilm activity of selected substances used in oral health prophylaxis","volume":"22","author":"R Dudek-Wicher","year":"2022","journal-title":"BMC Oral Health"},{"key":"pone.0312961.ref037","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2016.01.002","article-title":"A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load","volume":"54","author":"M Woessner","year":"2016","journal-title":"Nitric Oxide"},{"key":"pone.0312961.ref038","doi-asserted-by":"crossref","first-page":"100158","DOI":"10.1016\/j.advnut.2023.100158","article-title":"Dietary nitrate from plant foods: a conditionally essential nutrient for cardiovascular health","volume":"15","author":"AC da C Pinaffi-Langley","year":"2024","journal-title":"Adv Nutr"},{"issue":"8","key":"pone.0312961.ref039","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.nutres.2015.06.001","article-title":"Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients","volume":"35","author":"NS Bryan","year":"2015","journal-title":"Nutr Res"},{"issue":"5","key":"pone.0312961.ref040","doi-asserted-by":"crossref","first-page":"938","DOI":"10.14336\/AD.2017.1207","article-title":"Nitrate and nitrite in health and disease","volume":"9","author":"L Ma","year":"2018","journal-title":"Aging Dis"},{"issue":"12","key":"pone.0312961.ref041","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11095-020-02959-w","article-title":"Simultaneous pharmacokinetic analysis of nitrate and its reduced metabolite, nitrite, following ingestion of inorganic nitrate in a mixed patient population","volume":"37","author":"AR Coggan","year":"2020","journal-title":"Pharm Res"},{"issue":"4","key":"pone.0312961.ref042","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.freeradbiomed.2011.05.032","article-title":"Measurement of in vivo nitric oxide synthesis in humans using stable isotopic methods: a systematic review","volume":"51","author":"M Siervo","year":"2011","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"pone.0312961.ref043","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1006\/bbrc.1995.1541","article-title":"The L-arginine:nitric oxide pathway is the major source of plasma nitrite in fasted humans","volume":"209","author":"P Rhodes","year":"1995","journal-title":"Biochem Biophys Res Commun"},{"issue":"21","key":"pone.0312961.ref044","doi-asserted-by":"crossref","first-page":"11460","DOI":"10.1073\/pnas.93.21.11460","article-title":"Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling","volume":"93","author":"L Castillo","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"pone.0312961.ref045","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.niox.2008.08.003","article-title":"The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash","volume":"19","author":"M Govoni","year":"2008","journal-title":"Nitric Oxide"},{"issue":"14","key":"pone.0312961.ref046","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1055\/s-0035-1554700","article-title":"The effects of chronic nitrate supplementation and the use of strong and weak antibacterial agents on plasma nitrite concentration and exercise blood pressure","volume":"36","author":"STJ McDonagh","year":"2015","journal-title":"Int J Sports Med"},{"key":"pone.0312961.ref047","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.niox.2016.10.003","article-title":"Effects of antiseptic mouthwash on resting metabolic rate: a randomized, double-blind, crossover study","volume":"61","author":"ML Sundqvist","year":"2016","journal-title":"Nitric Oxide"},{"issue":"2","key":"pone.0312961.ref048","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1161\/01.CIR.0000105764.22626.B1","article-title":"Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans","volume":"109","author":"JT Kielstein","year":"2004","journal-title":"Circulation"},{"issue":"5","key":"pone.0312961.ref049","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1007\/s00421-023-05369-z","article-title":"Influence of acute dietary nitrate supplementation timing on nitrate metabolism, central and peripheral blood pressure and exercise tolerance in young men","volume":"124","author":"SN Rowland","year":"2024","journal-title":"Eur J Appl Physiol"},{"issue":"1","key":"pone.0312961.ref050","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1177\/1358836X9900400105","article-title":"L-arginine and nitric oxide-related compounds in plasma: comparison of normal and arginine-free diets in a 24-h crossover study","volume":"4","author":"O Tangphao","year":"1999","journal-title":"Vasc Med"},{"issue":"6","key":"pone.0312961.ref051","doi-asserted-by":"crossref","first-page":"H2720-5","DOI":"10.1152\/ajpheart.2000.279.6.H2720","article-title":"Diurnal variation of flow-mediated vasodilation in healthy premenopausal women","volume":"279","author":"A Ringqvist","year":"2000","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"pone.0312961.ref052","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.3109\/07420520903534492","article-title":"Time-of-day effects on fatigue during a sustained anaerobic test in well-trained cyclists","volume":"26","author":"R Lericollais","year":"2009","journal-title":"Chronobiol Int"},{"issue":"1","key":"pone.0312961.ref053","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1600-0722.2004.00184.x","article-title":"Evaluation of bacterial nitrate reduction in the human oral cavity","volume":"113","author":"JJ Doel","year":"2005","journal-title":"Eur J Oral Sci"},{"key":"pone.0312961.ref054","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.niox.2015.04.003","article-title":"The relationship between plasma and salivary NOx","volume":"47","author":"WH Clodfelter","year":"2015","journal-title":"Nitric Oxide"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312961","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:42:25Z","timestamp":1739385745000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312961"}},"subtitle":[],"editor":[{"given":"Ajaya","family":"Bhattarai","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0312961","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]}}}