The effect of Zataria multiflora mouthwash on the severity of chemotherapy-induced oral mucositis: a randomized controlled clinical trial

Oral mucositis is a common and debilitating side effect of chemotherapy, significantly impacting patients’ quality of life. Given the limitations of current treatments and the anti-inflammatory and antimicrobial properties of Zataria multiflora (Shirazi thyme), this study was designed to evaluate the efficacy of a mouthwash containing its extract on the severity of chemotherapy-induced oral mucositis. This randomized, double-blind, placebo-controlled clinical trial was conducted in 2024 on 60 cancer patients undergoing chemotherapy with a 5-fluorouracil-based regimen (a regimen known to frequently induce oral mucositis, making these patients at high risk of developing oral mucositis) at Iranmehr Hospital in Birjand. Patients were randomly assigned to two groups of 30 using block randomization (block size = 8): intervention ( Zataria multiflora mouthwash) and control (placebo). Patients were instructed to gargle 5 ml of the mouthwash three times a day for one minute. The primary outcome was oral mucositis severity assessed using the World Health Organization (WHO) scale and secondary outcome was pain intensity measured by Visual Analogue Scale (VAS) and McGill Pain Questionnaire (MPQ) on days 0, 7, 14, and 21. Data were analyzed using Fisher’s exact test, Mann-Whitney U test, and Friedman’s test. At baseline, 83.3% of the placebo group and 60% of the intervention group had grade 0 mucositis, with no significant difference ( P = 0.125). On day 21, 72% of the placebo group developed mucositis (grades 1–3), while only 13.8% of the intervention group had mucositis (all grade 1), and no grade ≥ 2 mucositis was observed in the intervention group ( P < 0.001). The mean VAS pain score in the intervention group decreased from 2.36 ± 1.00 at baseline to 0.41 ± 0.10 on day 21, while in the placebo group it decreased from 1.76 ± 0.76 to 1.78 ± 1.44 ( P < 0.001). Zataria multiflora mouthwash may reduce the severity of oral mucositis and associated pain in patients undergoing 5‑FU‑based chemotherapy. No significant adverse events were observed. Further multi‑center trials are needed to confirm these findings.