Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage

Abstract

Objective: To compare the efficacy of zinc acetate lozenges with zinc gluconate lozenges in common cold treatment and to examine the dose-dependency of the effect.

Design: Meta-analysis.

Setting: Placebo-controlled zinc lozenge trials, in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on common cold duration was calculated by using inverse-variance random-effects method.

Participants: Seven randomised trials with 575 participants with naturally acquired common colds.

Main outcome measure: Duration of the common cold.

Results: The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192-207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: -29 to + 32).

Conclusions: Properly composed zinc gluconate lozenges may be as effective as zinc acetate lozenges. There is no evidence that zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the common cold. Common cold patients may be encouraged to try zinc lozenges for treating their colds. The optimal lozenge composition and dosage scheme need to be investigated further.

Keywords: common cold; randomised controlled trials; respiratory tract infections; therapeutic equivalency.

Figure 1.

Effect of high-dose zinc lozenges on the duration of the common cold. Trials with zinc acetate are separated from trials with zinc gluconate. The duration of symptoms was transformed to the relative scale, thus the duration in the respective placebo group was given the value of 100%. The estimate of effect over all seven trials indicates a 33% (95% CI: 21% to 45%) reduction in common cold duration. The high level of heterogeneity among all the seven trials (I²= 77%; p = 0.0003) is explained by the Turner trial. If the Turner trial is excluded, there is no significant heterogeneity over the remaining six trials (I²= 39%; p = 0.15), see Supplementary file 2. In the forest plots on the right hand side, the vertical line indicates the placebo level. The horizontal lines indicate the 95% CI for the zinc effect and the square in the middle of the horizontal line indicates the point estimate of the effect in the particular trial. The diamond shapes indicate the pooled effects and their 95% CI.

Figure 2.

Effect of dosage on the zinc lozenge efficacy on the duration of the common cold. Seven randomised trials are shown in which >75 mg/day of elemental zinc was administered per day. The observed effect in each study is indicated by the square in the middle of the vertical line, and the vertical line indicates the accuracy of the measurement as the 95% CI. The thick horizontal line indicates the pooled effect of the seven trials that were included and the thick vertical line denotes the 95% CI for the pooled effect; on average 33% (95% CI 21% to 45%) shorter colds in the zinc groups. Zinc acetate studies are indicated by filled squares and zinc gluconate studies by open squares.

Figure 3.

The dose of zinc per lozenge and the number of lozenges per day in the seven trials that were included in the analysis. Zinc acetate lozenges are indicated by filled squares and zinc gluconate lozenges by open squares. The Mossad et al. and the Turner trials both had 13.3 mg zinc per lozenge and six lozenges per day.