MDPI Acta Medica Okayama 2227-9032 13 5 2025 Efficacy of Oral Intake of Hydrogen-Rich Jelly Intake on Gingival Inflammation: A Double-Blind, Placebo-Controlled and Exploratory Randomized Clinical Trial 577 EN Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Takayama Department of Oral Biochemistry, Asahi University School of Dentistry Shinichi Tokuno Graduate School of Health Innovation, Kanagawa University of Human Services Manabu Morita Department of Oral Health, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Initiation and progression of periodontal disease include oxidative stress. Systemic application of antioxidants may provide clinical benefits against periodontal disease including gingivitis. Recently, a jelly containing a high concentration of hydrogen (40 ppm) was developed. We hypothesized that oral intake of this hydrogen-rich jelly may be safe and effective on gingivitis. This clinical trial was designed to investigate the safety and efficacy of oral intake of hydrogen-rich jelly against gingival inflammation. Methods: Participants with gingivitis were instructed to orally ingest 30 g of hydrogen-rich jelly (experimental group) or placebo jelly (control group) three times a day for 14 consecutive days. The primary outcome of this trial was the percentage of bleeding on probing (BOP) sites. Secondary outcomes were oral parameters, serum reactive oxygen metabolites, antioxidant capacity, oxidative index, concentrations of cytokine (interleukin [IL]-1ƒÀ, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha) in gingival crevicular fluid, and adverse events. For all parameters, Mann–Whitney U test was used for comparison between experimental and control groups. Analysis of covariance, controlling for baseline periodontal inflamed surface area, was performed to evaluate the association between the effect of the hydrogen-rich jelly and gingival inflammation. Results: In the experiment and control groups, the percentage of sites with BOP and PISA significantly decreased at the end of the experiment compared to the baseline. However, no significant differences were found between groups (p > 0.05). Conclusions: Administration of hydrogen-rich jelly for 14 days decreased gingival inflammation. However, no significant differences were identified compared to the control group. No potential conflict of interest relevant to this article was reported.