Topical prebiotic nitrate: optimizing the ‘hang-time’, source and dose for specific oral or systemic effects
Open accessAbstract
In our opinion, the ‘hang-time’ of nitrate-containing products discussed in the letter by Green and Green is an interesting variable that should be considered when nitrate-based treatment or prevention strategies are designed. However, due to direct nitrate recycling after nitrate intake, products with a long ‘hang-time’ (e.g., chewing gum) may not always have an advantage compared to products with a short ‘hang-time’ (e.g., vegetable juices). We argue that extending the ‘hang-time’ is especially relevant and potentially beneficial for different applications, such as using a low nitrate dose to stimulate the oral effects, reaching oral tissues that may otherwise not be exposed to dietary nitrate (e.g., periodontal pockets), and providing a longer nitrate exposure in individuals with an impaired salivary flow. Apart from the ‘hang-time’, other important variables are the nitrate dose and source (e.g., different salts and vegetable extracts), as well as the desired effect (e.g., an oral effect versus systemic effects). Finally, we believe that the alterations in salivary microbiota observed before and after chewing three nitrate-rich gums over a period of ~5 h, as reported by Green and Green, could be considered beneficial. However, the oral microbiota composition is affected by the circadian rhythm and the effect of gum mastication should be evaluated. These results should thus be confirmed by a placebo-controlled study, where these confounding factors can be accounted for.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The timing of optimal intake may affect the efficiency of oral bacterial nitrate reduction.
“the timing of optimal intake may affect the efficiency of oral bacterial nitrate reduction [106,252,271,292].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [292]
The paper’s Abstract says nitrate-reducing oral bacteria fluctuate over the hours of the day and describes changes in salivary nitrate after intake. These observations make a timing effect plausible, but the paper does not establish that an optimal intake time affects the efficiency of bacterial nitrate reduction. (LLM, conf=0.78)
Experimental — accuracy not yet measuredHighly processed beetroot products may exhibit reduced nitrate stability and diminished physiological impact.
“highly processed beetroot products may exhibit reduced nitrate stability and diminished physiological impact [106,252,271,292].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [292]
The paper’s Fig. 2 passage reports that a nitrate-rich beetroot supplement limited oral acidification but did not affect blood pressure. It does not connect either result to how heavily the product was processed. Searches for beetroot processing, storage, and nitrate stability found no passage addressing whether processing reduces nitrate stability or physiological impact. (LLM, conf=0.71)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Inorganic nitrate is a possible source for systemic generation of nitric oxide
Lundberg, J. O., & Govoni, M. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.04.027 · Cited by 657 · see citing works
The environmental controls that govern the end product of bacterial nitrate respiration
Kraft, B., Tegetmeyer, H. E., Sharma, R., Klotz, M. G., Ferdelman, T. G., Hettich, R. L., Geelhoed, J. S., & Strous, M. (2014) · Science · doi:10.1126/science.1254070 · Cited by 558 · see citing works
The effect of nitrate intake on nitrite formation in human saliva
Tannenbaum, S. R., Weisman, M., & Fett, D. (1976) · Food and Cosmetics Toxicology · doi:10.1016/s0015-6264(76)80006-5 · Cited by 381 · see citing works
Metabolic Effects of Dietary Nitrate in Health and Disease
Lundberg, J. O., Carlström, M., & Weitzberg, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.007 · Cited by 374 · see citing works
The oral microbiome and nitric oxide homoeostasis
Hezel, M., & Weitzberg, E. (2015) · Oral Diseases · doi:10.1111/odi.12157 · Cited by 201 · see citing works
Nitrate as a potential prebiotic for the oral microbiome
Rosier, B. T., Buetas, E., Moya-Gonzalvez, E. M., Artacho, A., & Mira, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-69931-x · Cited by 194 · see citing works
Self-citationThe Importance of Nitrate Reduction for Oral Health
Rosier, B. T., Takahashi, N., Zaura, E., Krom, B. P., MartÍnez-Espinosa, R. M., van Breda, S. G. J., Marsh, P. D., & Mira, A. (2022) · Journal of Dental Research · doi:10.1177/00220345221080982 · Cited by 175 · see citing works
Self-citationRosier, B. T., Moya-Gonzálvez, E. M., Corell-Escuin, P., & Mira, Á. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.555465 · Cited by 142 · see citing works
Self-citationSalivary pH and Glucose after Consuming Various Beverages, Including Sugar-Containing Drinks
Meurman, J. H., Rytömaa, I., Kari, K., Laakso, T., & Murtomaa, H. T. (2009) · Caries Research · doi:10.1159/000261039 · Cited by 105 · see citing works
Nitrite Production from Nitrate and Its Link with Lactate Metabolism in Oral Veillonella spp
Wicaksono, D. P., Washio, J., Abiko, Y., Domon, H., & Takahashi, N. (2020) · Applied and Environmental Microbiology · doi:10.1128/aem.01255-20 · Cited by 85 · see citing works
Dietary nitrate and blood pressure: evolution of a new nutrient?
Ashworth, A., & Bescós, R. (2017) · Nutrition Research Reviews · doi:10.1017/s0954422417000063 · Cited by 65 · see citing works
Potassium is a key signal in host-microbiome dysbiosis in periodontitis
Yost, S. C., Duran-Pinedo, A. E., Krishnan, K., & Frias‐Lopez, J. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006457 · Cited by 60 · see citing works
Mazurel, D., Carda‐Diéguez, M., Langenburg, T., Žiemytė, M., Johnston, W., Martínez, C. P., Albalat, F., Llena, C., Al-Hebshi, N. N., Culshaw, S., et al. (2023) · npj Biofilms and Microbiomes · doi:10.1038/s41522-023-00406-3 · Cited by 59 · see citing works
Self-citationEffects of Nitrate Supplementation on Exercise Performance in Humans: A Narrative Review
Macuh, M., & Knap, B. (2021) · Nutrients · doi:10.3390/nu13093183 · Cited by 53 · see citing works
Shannon, O. M., Allen, J. D., Bescós, R., Burke, L. M., Clifford, T., Easton, C., Gonzalez, J. T., JONES, A. M., Jonvik, K. L., Larsen, F. J., et al. (2022) · Sports Medicine · doi:10.1007/s40279-022-01701-3 · Cited by 51 · see citing works
Rosier, B. T., Carlos, P., García‐Esteban, S., Artacho, A., Galiana, A., & Mira, Á. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.692883 · Cited by 47 · see citing works
Self-citationPharmacokinetic study of amaranth extract in healthy humans: A randomized trial
Subramanian, D., & Gupta, S. (2016) · Nutrition · doi:10.1016/j.nut.2015.12.041 · Cited by 43 · see citing works
Chellappa, S. L., Engen, P. A., Naqib, A. D., Qian, J., Vujovic, N., Rahman, N., Green, S. J., Garaulet, M., Keshavarzian, A., & Scheer, F. A. J. L. (2021) · The FASEB Journal · doi:10.1096/fj.202101153r · Cited by 27 · see citing works
Capper, T. E., Siervo, M., Clifford, T., Taylor, G., Iqbal, W. A., West, D. J., & Stevenson, E. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab354 · Cited by 26 · see citing works
Chellappa, S. L., Engen, P. A., Naqib, A. D., Qian, J., Vujović, N., Rahman, N., Green, S. J., Garaulet, M., Keshavarzian, A., & Scheer, F. A. J. L. (2022) · Kölner Universitäts PublikationsServer (Universität zu Köln) · Cited by 18 · see citing works
Fejes, R., Lutnik, M., Weisshaar, S., Pilat, N., Wagner, K., Stüger, H., Peake, J. M., Woodman, R. J., Croft, K. D., Bondonno, C. P., et al. (2024) · Food & Function · doi:10.1039/d3fo03749e · Cited by 17 · see citing works
Lima, C. V., Tenuta, L. M. A., & Cury, J. A. (2018) · Caries Research · doi:10.1159/000489132 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nitrate: “the source makes the poison”
Bowles, E., Burleigh, M. C., Mira, Á., van Breda, S. G., Weitzberg, E., & Rosier, B. T. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2395488 · Cited by 33 · see citing works
Self-citationRosier, B. T., Hajishengallis, G., Wink, D. A., & Mira, Á. (2025) · Periodontology 2000 · doi:10.1111/prd.70006 · Cited by 11 · see citing works
Self-citationKurhaluk, N., Kołodziejska, R., Buyun, L., Kamiński, P., & Tkaczenko, H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27083461 · Cited by 3 · see citing works
“However, highly processed beetroot products may exhibit reduced nitrate stability and diminished physiological impact [106,252,271,292].”
Adding Nitrate to a Sucrose Rinse Reduces Acidogenicity: An in vivo Study
Silva-Acevedo, C. A., Rosier, B. T., Vargas, C. J., Mira, Á., Tenuta, L. M. A., & Fernández, C. E. (2025) · Caries Research · doi:10.1159/000549489
Self-citationThe role and potential mechanisms of prebiotics in periodontitis treatment: a review
Yu, K.-X., He, D.-W., Fan, L., Wang, L., & Sun, J. (2026) · Journal of Functional Foods · doi:10.1016/j.jff.2026.107221
Vargas, C. J., Rivera, C., Marín, L. M., Durán-Agüero, S., & Fernández, C. E. (2026) · Clinical Oral Investigations · doi:10.1007/s00784-026-06966-w
- Authors
- Rosier, B. T., & Mira, A.
- Affiliations
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (ES)
- Corresponding author
- Rosier, Bob T.
- ORCID
- Rosier, Bob T.
- Venue
- npj Biofilms and Microbiomes
- Published
- 2024-07-18
- Volume
- 10
- Issue
- 1
- Pages
- 58-58
- ISSN
- 2055-5008 (ISSN-L)
- PMC
- PMC11258277
- OpenAlex
- W4400778946
- Cited by
- 6
- References
- 22
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Biofilms and Microbiomes (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministerio de Ciencia, Innovación y Universidades (10.13039.501100011033, 10.13039, .13039/501100011033, 501100011033)
- European Regional Development Fund (10.13039/501100011033, 13039/501100011033, 501100011033)
- Agencia Estatal de Investigación (501100011033, 10.13039/501100011033, 13039, .13039/501100011033, 10.13039)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Dentistry › Periodontics › Dental Health and Care Utilization
- Health Sciences › Dentistry › Periodontics › Oral Health Pathology and Treatment
- Keywords
- dietary nitrate, topical nitrate, chewing gum, nitrate sources, oral microbiota, salivary flow, periodontal pockets, circadian rhythm, nitrate recycling
- MeSH terms
- Fruit and Vegetable Juices, Administration, Topical, Chewing Gum, Humans, Mouth, Nitrates, Saliva, Prebiotics, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review