Oral zinc sulphate reduces the recurrence rate and provides significant therapeutic effects for viral warts: A systematic review and meta-analysis of randomized controlled trials

Abstract

Zinc plays a crucial role in maintaining immune balance in the human body. Zinc is believed to substantially affect cytokine synthesis and signaling; thus potentially combating viral infections, including Human Papillomavirus infection, through various mechanisms. Several randomized controlled trials (RCTs) have investigated whether oral zinc sulphate can improve viral warts; however, no comprehensive data is currently available. Therefore, we conducted a meta-analysis to evaluate the effectiveness of oral zinc sulphate for the treatment of viral warts. On July 1, 2024, we performed an extensive database search on PubMed, Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov. Initially, 952 studies were identified, and after screening, 7 studies were included in the final analysis. Our findings showed that the total clearance rate of warts was significantly higher in the oral zinc sulphate group than in the control group (risk difference = 0.288; 95% CI = 0.087-0.489; p = 0.005). Subgroup analysis revealed that this therapeutic effect was more pronounced in individuals with low initial plasma zinc levels (risk difference = 0.767; 95% CI = 0.649-0.885; p < 0.001). Additionally, meta-regression showed that rise in zinc ion levels post-treatment were correlated with better treatment outcomes (coefficient = 0.0068; p < 0.001). Furthermore, for patients receiving traditional warts treatment, combining oral zinc sulphate significantly reduced the 6-month recurrence rate (log risk ratio = -1.043; 95% CI = -1.666 - -0.420; p = 0.001). The most common treatment-related side effects were nausea (risk difference = 0.562; 95% CI = 0.088-1.036; p = 0.020) and vomiting (risk difference = 0.205; 95% CI = 0.092-0.317; p < 0.001). Based on this evidence, oral zinc sulphate monotherapy offers notable benefits to those avoiding conventional treatments, and when combined with traditional therapies for viral warts, it can notably reduce recurrence rates over six months.

Fig 1. PRISMA 2020 flowchart for the current meta-analysis.

Fig 2. Summary of quality assessment of studies included in the meta-analysis using Cochrane risk of bias 2 tool.

Fig 3. This is a forest plot comparing the total clearance rate of oral zinc sulphate versus placebo in the treatment of viral warts.

Patients taking oral zinc sulphate had significantly greater total clearance rate of warts. The studies are listed in alphabetical order. CI, confidence interval.

Fig 4. This is the result of sensitivity analysis by using the one-study removal method.

All analyses showed statistically significant effects of oral zinc sulphate in treating viral warts. The studies are listed in alphabetical order. CI, confidence interval.

Fig 5. This is a forest plot of a subgroup analysis based on patients’ initial plasma zinc ion concentration.

The analysis shows that patients with lower initial plasma zinc ion levels have more effective treatment for viral warts when taking zinc sulphate. The studies are listed in alphabetical order. CI, confidence interval.

Fig 6. This is a forest plot from a subgroup analysis based on whether patients combined traditional therapies.

The analysis indicates that zinc sulphate alone is more effective for treating viral warts compared to combined treatments. However, this might be due to traditional therapies masking the effects of zinc sulphate in the combined treatment group. The studies are listed in alphabetical order. CI, confidence interval.

Fig 7. Meta-regression of risk difference on mean difference of plasma zinc ion concentration (mg/day) in all experimental groups.

The coefficient was 0.0068 with a p value < 0.001.

Fig 8. Meta-regression of risk difference on disease duration (months).

The coefficient was 0.0233 with a p value was 0.0001.

Fig 9. This is a forest plot comparing the relapse rates within six months for patients treated with oral zinc sulphate combined with traditional therapy versus traditional therapy alone.

The results show that the group receiving zinc sulphate had significantly lower relapse rates. The studies are listed in alphabetical order. CI, confidence interval.