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Time-dependent efficacy of zinc supplements in preventing oral mucositis after chemoradiotherapy: a meta-analysis.

  • 2026-03-24
  • Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 34(4)
    • Jiale Wang
    • Jianyu Hu
    • Yongshi Luo
    • Jinfeng Nie
    • Mangui Deng
    • Zhihong Wang

Study Design

Type
Meta-Analysis
Sample size
n = 1,076
Population
cancer patients
Methods
We retrieved randomized controlled trials (RCTs) on the prevention of OM after chemotherapy and radiotherapy using zinc supplements. These studies were sourced from nine databases... Two researchers independently screened studies and extracted data. The Cochrane risk of bias tool was used to assess the quality of the included studies, and Stata 16.0 software was used for analysis.

Objective

To evaluate the effect of zinc supplements in preventing chemotherapy and radiotherapy-related oral mucositis (OM) in cancer patients.

Methods

We retrieved randomized controlled trials (RCTs) on the prevention of OM after chemotherapy and radiotherapy using zinc supplements. These studies were sourced from nine databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and SinoMed, covering the period from their inception to October 2025. Two researchers independently screened studies and extracted data. The Cochrane risk of bias tool was used to assess the quality of the included studies, and Stata 16.0 software was used for analysis.

Results

A total of 16 randomized controlled trials (RCTs) comprising 17 comparison groups and involving approximately 1076 patients were included. Zinc supplementation significantly delayed the onset of OM (MD = 1.37, 95% CI: 0.78 to 1.95, P < 0.001). Regarding the overall incidence of OM, zinc significantly reduced the risk at both 2 weeks (RR = 0.69) and 7-9 weeks (RR = 0.33) of treatment. 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 dose duration, and administration route effects: (1) In the early phase of treatment (2 weeks), topical zinc demonstrated a beneficial trend in reducing both the incidence and severity of OM; (2) 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; (3) zinc supplementation significantly alleviated pain scores at 3 and 6 weeks of treatment (MD = -1.82 and -2.02, respectively), as well as xerostomia symptoms at 6 weeks (MD = -0.60, 95% CI: -0.81 to -0.40, P < 0.001).

Conclusion

Zinc supplementation is safe and effective, demonstrating a significant time-dependent, bimodal therapeutic effect: it reduces the incidence of OM during the second and the seventh to ninth weeks and significantly decreases the occurrence of severe OM in the second and fifth to sixth weeks. Additionally, zinc supplementation offers certain benefits in alleviating oral pain and xerostomia. A phased intervention strategy is recommended: in the early stage, combine zinc with topical agents to control symptoms, and in the mid-to-late stages, administer oral medium-to-high doses (≥ 150 mg/day) to prevent severe OM, particularly in patients with head and neck tumors.

Research Insights

  • Zinc→Delayed Oral Mucositis Onset

    Zinc supplementation significantly delayed the onset of OM (MD = 1.37, 95% CI: 0.78 to 1.95, P < 0.001).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified in aggregate
  • Zinc→Reduced Incidence of Oral Mucositis

    Regarding the overall incidence of OM, zinc significantly reduced the risk at both 2 weeks (RR = 0.69) and 7-9 weeks (RR = 0.33) of treatment.

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified in aggregate
  • Zinc→Reduced Oral Mucositis Severity

    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).

    Effect
    Beneficial
    Effect size
    Large
    Dose
    not specified in aggregate
  • Zinc→Reduced Pain

    zinc supplementation significantly alleviated pain scores at 3 and 6 weeks of treatment (MD = -1.82 and -2.02, respectively).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified in aggregate
  • Zinc→Reduced Xerostomia

    as well as xerostomia symptoms at 6 weeks (MD = -0.60, 95% CI: -0.81 to -0.40, P < 0.001).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified in aggregate
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