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This randomized clinical trial aimed to evaluate the use of 900\u00a0mg \u03a9\u20103 and 100\u00a0mg ASA for 180 days as adjuncts to NSPT for generalized stage III\u2013IV grade C periodontitis (GCP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients underwent subgingival debridement (SD) associated with \u03a9\u20103+ASA or cellulose placebo and received monthly prophylaxis. Clinical and immunological parameters were compared at baseline, 3, and 6 months after treatment. The daily dose of \u03a9\u20103 consisted of 540\u00a0mg eicosapentaenoic acid (EPA) and 360\u00a0mg docosahexaenoic acid (DHA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010eight patients, 12 males (7 in the SD+\u03a9\u20103+AAS group and 5 in the SD+Placebo group; <jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05), with a mean age of 32.84\u00a0\u00b1\u00a05.47 and 30.42\u00a0\u00b1\u00a05.79 years, respectively (<jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05), were included. Both groups showed significant improvements (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) in all full\u2010mouth parameters. Reductions in the number of pockets, mean probing depth (PD), and clinical attachment level of moderate and deep sites, as well as the number and percentage of residual pockets, were observed (intragroup <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05; intergroup <jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05). However, residual pockets' mean PD decrease (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) was only observed at 6 months in the SD+\u03a9\u20103+ASA group. The concentration of interleukin (IL)\u20101\u03b2 from moderate and deep pockets decreased (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) in both groups. The matrix metalloproteinase (MMP)\u20109 to tissue metalloproteinase inhibitor (TIMP)\u20101 ratio in the SD+Placebo group at 3 months revealed a proinflammatory profile in moderate (intergroup <jats:italic>p<\/jats:italic>\u00a0=\u00a00.006) and deep pockets (intergroup <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>\u03a9\u20103+ASA therapy did not add clinical benefits to the NSPT for generalized stage III\u2013IV GCP, although some immunomodulatory benefits could be observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>The use of omega\u20103 (\u03a9\u20103) and aspirin (ASA) along with subgingival debridement (SD) for root decontamination of periodontal pockets has shown better results in the nonsurgical treatment of gum disease and bone loss compared to SD alone. This investigation aimed to evaluate the use of 900\u00a0mg \u03a9\u20103 and 100\u00a0mg ASA for 180 days as adjuncts to the treatment of patients with gum disease and rapid bone loss rate. Thirty\u2010eight patients underwent SD associated with \u03a9\u20103+ASA or placebo. Clinical and immunological parameters were evaluated at the beginning of the study and 3 and 6 months after. Both groups showed significant improvements. A significant reduction in the number of sites with diseased pockets was observed. The number of residual diseased sites was also significantly reduced, without differences between the groups. However, a significant decrease in the pocket size of the diseased sites was only observed at 6 months in the group that received \u03a9\u20103+ASA. The concentration of interleukin (IL)\u20101\u03b2 (a protein present in the inflammatory process) from diseased sites significantly decreased in both groups. We concluded that the proposed therapy did not add any significant clinical benefits for patients with gum disease and rapid bone loss rate.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.24-0322","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:40:54Z","timestamp":1739511654000},"page":"881-893","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Omega\u20103 and aspirin in the nonsurgical treatment of grade C periodontitis: A randomized clinical trial"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-5472","authenticated-orcid":false,"given":"C\u00e1ssia F.","family":"Araujo","sequence":"first","affiliation":[{"name":"Department of Diagnosis and Surgery Division of Periodontology Institute of Science and Technology S\u00e3o Paulo State University  S\u00e3o Jos\u00e9 dos Campos S\u00e3o Paulo Brazil"},{"name":"Division of Dentistry Faculdade Santo Ant\u00f4nio  Ca\u00e7apava S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-2407","authenticated-orcid":false,"given":"Naira M. 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