Background: Oral mucosal lesions, largely driven by inflammatory mechanisms, cause significant pain and discomfort. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) possess potent anti-inflammatory and wound-healing properties with minimal adverse effects. Objective: This systematic review assessed the effectiveness of omega-3 PUFAs in managing oral mucosal lesions and included a meta-analysis focused on recurrent aphthous stomatitis (RAS). Methods: This PROSPERO-registered review (CRD420250655477) searched PubMed, Scopus, Web of Science, Cochrane, Google Scholar, and manual sources up to March 2025, identifying seven eligible studies. Assessed outcomes included Visual Analog Scale, Ulcer Severity Score, mucositis severity, and quality of life (QoL). Risk of bias was evaluated using the Cochrane ROB-2 tool, and meta-analysis was performed in Review Manager 5.3. Results: Of 162 screened records, seven randomized controlled trials (322 participants) were included qualitatively and three quantitatively. Oral Omega-3 capsules (1000 mg) and topical omega-3 nanoemulgel applied thrice daily for 3–6 months yielded clinical benefits without reported side effects. In RAS, pooled standardized mean differences for pain reduction, ulcer size, and healing duration were –3.31 (95% confidence interval (CI): –24.15 to 17.54; P = 0.76), 1.05 (95% CI: –3.79 to 5.89; P = 0.67), and 3.34 (95% CI: –0.86 to 7.54; P = 0.12), respectively, indicating improvements that were not significantly different. There were improvements in oral mucositis grades, mouth opening, tongue protrusion, cheek flexibility, and overall QoL across these studies. Conclusion: All included studies reported beneficial effects supporting omega-3 PUFAs as a promising adjunctive or standalone therapy for oral mucosal lesions. Robust, high-quality, and large-scale trials are needed to validate their effectiveness.
Amani et al. (Thu,) studied this question.