Betaine‐, xylitol‐, and extra virgin olive oil–based toothpaste modulates inflammation and oral nitric oxide pathway: Clinical trial in gingivitis

BACKGROUND: Gingivitis is a prevalent and reversible inflammatory condition driven by microbial dysbiosis. Beyond plaque control, interest has grown in oral hygiene formulations capable of modulating inflammation while preserving key microbial functions. Extra virgin olive oil (EVOO), together with xylitol and betaine, has demonstrated clinical benefits in gingivitis; however, its effects on neutrophil-driven tissue inflammation and on the oral nitrate-nitrite pathway have not been previously evaluated. METHODS: This randomized, double-blind clinical trial compared an EVOO-, xylitol-, and betaine-based toothpaste with a placebo formulation and a commercially available anti-gingivitis toothpaste. Participants used the assigned toothpaste three times daily for 4 months. Neutrophil elastase concentrations were measured in gingival crevicular fluid by enzyme-linked immunosorbent assay, and salivary nitrate and nitrite levels were quantified by ion chromatography at baseline and follow-up. RESULTS: A total of 96 patients with gingivitis completed the study. Elastase levels increased over time in both control groups, reaching statistical significance in the commercial control, whereas the test group showed a slight reduction. The difference in elastase change between the test group and the commercial control was statistically significant (p = 0.050). Nitrite-to-nitrate ratio was significantly higher compared with both the placebo and commercial control groups (p = 0.040 and p = 0.006, respectively). CONCLUSION: The toothpaste containing EVOO, xylitol, and betaine maintained stable elastase levels in gingival crevicular fluid and significantly increased the salivary nitrite-to-nitrate ratio after 4 months of use. Compared with the placebo and commercial toothpastes, this formulation demonstrated superior anti-inflammatory effects and enhanced nitrate-to-nitrite reduction, indicating a dual benefit in patients with gingivitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05463484 PLAIN LANGUAGE SUMMARY: A toothpaste containing extra virgin olive oil, xylitol, and betaine reduced gum inflammation and improved nitric oxide-related markers in patients with gingivitis.