Meta-analysis: Zinc supplements show time-dependent efficacy in preventing oral mucositis after chemoradiotherapy

This meta-analysis evaluated the effect of zinc supplements in preventing chemotherapy- and radiotherapy-related oral mucositis (OM) in cancer patients. Researchers retrieved randomized controlled trials (RCTs) from nine databases, including PubMed, Embase, and Cochrane, from their inception to October 2025. The analysis included 16 RCTs comprising 17 comparison groups and involving approximately 1076 patients. Study quality was assessed using the Cochrane risk of bias tool, and analysis was performed using Stata 16.0 software. Zinc supplementation significantly delayed the onset of OM (mean difference [MD] = 1.37, 95% confidence interval [CI]: 0.78 to 1.95, P < 0.001). Regarding overall OM incidence, zinc significantly reduced the risk at 2 weeks (relative risk [RR] = 0.69) and at 7-9 weeks of treatment (RR = 0.33). For severe OM (grade ≥ 3), zinc exhibited a significant protective effect at both 2 weeks and 5-6 weeks of treatment (RR = 0.26 for both time points). Subgroup analyses revealed key findings related to dose, duration, and administration route. In the early treatment phase (2 weeks), topical zinc demonstrated a beneficial trend in reducing both OM incidence and severity. In the mid-to-late phase (5-6 weeks), oral administration of moderate to high doses (≥ 150 mg/day) was markedly effective in preventing severe OM (RR = 0.07, 95% CI: 0.02 to 0.36), showing superior efficacy compared to topical application. Zinc supplementation also significantly alleviated pain scores at 3 weeks (MD = -1.82) and 6 weeks (MD = -2.02), as well as xerostomia symptoms at 6 weeks (MD = -0.60, 95% CI: -0.81 to -0.40, P < 0.001). The conclusion states zinc supplementation is safe and effective, demonstrating a significant time-dependent, bimodal therapeutic effect. The abstract does not report specific safety data, adverse event rates, or limitations of the included studies.

For many people undergoing chemotherapy or radiation, one of the most difficult side effects is oral mucositis—painful sores and inflammation in the mouth that can make eating, drinking, and even talking a struggle. A new analysis of 16 studies, involving over a thousand patients, looked at whether zinc supplements could help prevent this problem. The findings are promising and show that timing matters a lot. Zinc was found to delay the start of these mouth sores. It also reduced the overall risk of getting them at both 2 weeks and 7-9 weeks into treatment. For severe sores, zinc showed a strong protective effect at 2 weeks and again at 5-6 weeks. The analysis suggests a two-part strategy: using topical zinc early on to help control symptoms, and then switching to an oral dose of at least 150 mg per day in the middle and later stages of treatment to powerfully prevent severe sores. Zinc also helped reduce pain scores at 3 and 6 weeks and eased dry mouth symptoms at 6 weeks. The researchers concluded that zinc is safe and effective, with benefits that change over the course of treatment, offering a way to potentially shield patients from some of the most debilitating mouth-related side effects.