Recurrent Oral Ulcer (ROU) is a common oral mucosal disease with complex etiologies, linked to immune abnormalities, trace element deficiencies, oxidative stress, and other factors. As a zinc supplement, zinc gluconate plays a role in ROU treatment primarily through zinc’s effects on mucosal repair, immune regulation, and oxidative stress. The following analysis covers its mechanism of action, clinical efficacy, and application considerations:

I. Mechanisms of Zinc Gluconate in Anti-Ulcer Action

1. Promoting Mucosal Repair and Cell Proliferation

Zinc serves as a coenzyme for multiple human enzymes (e.g., DNA polymerase, RNA polymerase), directly participating in cell division and nucleic acid synthesis to accelerate proliferation and repair of oral mucosal epithelial cells. Studies show zinc deficiency causes abnormal oral mucosal keratinization, while zinc gluconate supplementation upregulates epidermal growth factor (EGF) and its receptor expression, promoting ulcer wound healing.

2. Regulating Immune Function and Inhibiting Inflammation

Zinc maintains normal T lymphocyte function, regulates the Th1/Th2 cytokine balance (e.g., reducing pro-inflammatory factors IL-6, TNF-α), and minimizes immune-mediated damage in oral ulcers. Additionally, zinc suppresses excessive neutrophil activation, alleviates local inflammatory exudation, and relieves ulcer pain.

3. Antioxidant Stress and Mucosal Cell Protection

As the active center of superoxide dismutase (SOD), zinc scavenges free radicals, reducing oxidative stress damage to mucosal cells. ROU patients often exhibit oxidative-antioxidative imbalance, and zinc gluconate supplementation enhances mucosal tissue antioxidant capacity, decreasing lipid peroxidation.

II. Clinical Efficacy and Research Evidence

1. Shortening Ulcer Healing Time

Multiple clinical controlled trials show oral zinc gluconate (daily dose typically 15–30 mg zinc element) shortens ROU healing time by 2–3 days, with significant differences versus placebo. Efficacy correlates with zinc absorption efficiency—zinc gluconate’s high water solubility and bioavailability facilitate better absorption.

2. Reducing Recurrence Frequency

Long-term zinc gluconate supplementation (3–6 months) decreases ROU recurrence. Studies indicate zinc-deficient ROU patients (serum zinc below normal range) are more responsive, with recurrence intervals extended to 1.5–2 times baseline.

3. Alleviating Pain and Improving Quality of Life

Zinc gluconate relieves ulcer pain by inhibiting inflammatory mediator release and promoting nerve repair. Patient subjective scores (e.g., Visual Analogue Scale VAS) show faster pain relief than conventional symptomatic treatments (e.g., oral ulcer powders).

III. Clinical Application Key Points and Precautions

1. Selection of Suitable Populations

Prioritize ROU patients diagnosed with zinc deficiency (serum zinc <70 μg/dL) or those with comorbid dyspepsia/absorption disorders (e.g., Crohn’s disease).

For non-zinc-deficient ROU, zinc gluconate efficacy may be limited, requiring combination with other therapies (e.g., immunomodulators).

2. Optimization of Dosage and Treatment Course

Adult routine dosage: 15–20 mg zinc element daily (e.g., zinc gluconate tablets, ~5 mg zinc per tablet, 3–4 tablets daily), taken 2–3 times after meals to reduce gastrointestinal irritation.

Treatment course: 1–2 weeks for short-term therapy (ulcer phase); 3+ months for long-term recurrence prevention, with serum zinc monitoring to avoid overdose (adult daily zinc intake upper limit: 40 mg).

3. Combination Therapy Strategies

With B vitamins (e.g., B12, folic acid): Synergistically promotes mucosal metabolism and repair.

With local medications (e.g., mouthwashes, ulcer patches): Systemic zinc supplementation combined with local symptom relief shortens disease course.

4. Adverse Reactions and Contraindications

Common gastrointestinal reactions (e.g., nausea, vomiting); take with meals or reduce dosage in divided doses.

Use caution in renal insufficiency; hyperzincemia may exacerbate kidney burden. Avoid concurrent use with tetracyclines (zinc affects their absorption).

IV. Controversies and Future Research Directions

Current studies on zinc gluconate for ROU remain controversial. Some meta-analyses note significant efficacy variations across populations, possibly due to inconsistent sample sizes and zinc deficiency diagnostic criteria. Future research should focus on:

Establishing precise detection indicators for zinc metabolic abnormalities in ROU patients (e.g., red blood cell zinc, zinc transporter ZnT-1 expression).

Exploring synergistic mechanisms of zinc gluconate combined with probiotics, traditional Chinese medicine, etc., to further enhance efficacy.

Zinc gluconate demonstrates clear mucosal repair and immune-regulatory effects in ROU treatment through zinc supplementation, particularly for zinc-deficient patients. Clinically, individual dosage adjustment and combination therapy strategies should be prioritized to optimize efficacy and reduce adverse reactions. Although its mechanisms require deeper study, zinc gluconate serves as a safe, economical adjuvant therapy with important value in ROU comprehensive management.