Nitrate metabolism and periodontal health: The roles of nitric oxide in microbial killing and immunoregulation

BACKGROUND: Dietary nitrate, primarily sourced from vegetables, is reduced by oral bacteria to nitrite and subsequently to nitric oxide (NO), a molecule with antimicrobial and immunoregulatory properties, as well as vasodilatory and other cardiometabolic effects. Studies have shown that nitrate supplementation can lower blood pressure, reduce gingival inflammation, and lead to a shift toward microbial eubiosis in the periodontium. However, a paradox arises: nitrate and nitrite-when produced via NO synthase (NOS) activity during chronic inflammation-can serve as biomarkers of periodontitis. AIM: This narrative review aims to (1) examine the molecular mechanisms underlying the health benefits of NO, particularly those stimulated by nitrate-rich vegetable intake; and (2) explore how chronic inflammation can alter the local environment leading to nitrate and nitrite accumulation. MATERIALS AND METHODS: A targeted literature search was conducted in PubMed and Google Scholar to identify articles related to NO, nitrate metabolism, inflammation, and/or periodontitis. RESULTS: , decomposes into nitrate), contributing to their accumulation. Additionally, oxidative stress promotes NOS uncoupling, converting NOS from a NO-producing to a ROS-producing enzyme. Furthermore, periodontitis is associated with an impaired nitrate-reduction capacity of the oral microbiota, further decreasing NO levels. CLINICAL RELEVANCE: Oxidative stress and reduced NO availability may drive periodontal dysbiosis and contribute to the systemic impact of periodontitis. These disease-related conditions could be mitigated through dietary interventions with nitrate-rich vegetables and adjunctive use of nitrate-reducing probiotics, which warrants further investigation.