Cochrane review on zinc for the common cold (2024) misled readers

What is it about?

Over a dozen placebo-controlled trials on zinc lozenges and the common cold have been carried out with varying results, with the composition of the lozenges and the dose of zinc effectively explaining the variation. In seven RCTs, zinc acetate and zinc gluconate lozenges containing >75 mg/day of elemental zinc shortened common cold duration on average by 33%. A Cochrane review by Nault et al. (2024) analyzed the published trials; however, there were numerous errors in the Cochrane review. First, Nault et al. Calculated the average treatment effect in days, but that is a poor measure for the effect of common cold treatments. It has been shown that the relative scale (percentage effect) much better captures the treatment effect on the duration of illness. Second, the authors write in the Methods section that “We undertook meta-analyses only where meaningful, that is, if the treatments, participants, and the underlying clinical question(s) were similar enough for pooling to make sense”. However, Analysis 9.1 includes both zinc lozenge trials and nasal zinc administration trials, although they are not similar treatments. Furthermore, one of the included zinc lozenge trials administered 190 mg/day zinc whereas one nasal zinc trial administered just 0.046 mg/day. Pooling two trials with a 4,300-fold difference in the dose is not meaningful. Third, the Cochrane authors do not justify their exclusion of the Mossad et al. (1996) trial from Analysis 9.1, even though it was a placebo-controlled RCT. The Cochrane authors include this trial in several other comparisons, indicating that they had no concerns with the methodology. Fourth, one of the zinc lozenge trials included in the calculation of the 2.37-day estimate was carried out with children. There can be differences in the size of the effect between adults and children and therefore they should be analyzed separately.

Featured Image

Photo by Thought Catalog on Unsplash

Photo by Thought Catalog on Unsplash

Why is it important?

The common cold is the leading cause of acute morbidity and visits to physicians in high-income countries, and it is a major cause of absenteeism from work and school. In one analysis, the economic burden of the common cold was comparable to hypertension and stroke. Therefore it is particularly worrying that the conclusions of the Cochrane review on zinc for the common cold (2024) are based on flawed statistical analyses.

Perspectives