Zinc and the common cold

Zinc lozenges (frequently zinc acetate or zinc gluconate) have been proposed as a treatment for the common cold. The biological mechanism of the effect is not clear, but the benefit of zinc lozenges seems to be caused by local effects in the oropharynx region, since nasal administration of zinc has also shortened the duration of colds.

Research to date has not been conclusive, but has suggested that zinc tablets might lessen the symptoms of a cold while causing possible side-effects such as nausea. The benefits of zinc as a cold treatment, if any, have been described as "very minor".

Background
Zinc has been known for many years to have an effect on cold viruses in the laboratory.

Research into the effect of zinc lozenges on colds between 1984 and 2009 produced a wide range of differing results. It has been hypothesized that these differences were due in part to differences in the lozenges' constituents, mainly the amount of the active ingredient, ionic zinc (iZn). For example, the amount of ionic zinc ranged from 0 to 100%, depending upon the lozenge ingredients in the trials. More recently, the evidence from trials has been reviewed to try and assess the evidence of zinc's effectiveness as a cold cure but the results, while suggestive of a positive effect, have not been conclusive, since no consideration was given to the amount of the active ingredient (iZn) in the lozenges.

Safety
In some studies zinc lozenges caused acute adverse effects, such as bad taste, but none of the studies reported long term harm. Furthermore, many of the adverse effects, in particular regarding taste, may be caused by the specific lozenge composition and probably do not reflect the effects of zinc ions themselves. For example, zinc gluconate with dextrose or sugar becomes extremely vile in taste several weeks after manufacture, while zinc acetate dihydrate in a 1:100 mixture with dextrose by weight is permanently pleasant tasting. The most recent trial on zinc acetate found no significant differences between the zinc and placebo groups in the recorded adverse effects with a 92 mg daily dose of zinc.

According to WebMD, there have been several cases of people using zinc nasal sprays and suffering a loss of sense of smell; for this reason the US Food and Drug Administration has issued a warning that people should not use nasal sprays containing zinc.

Placebo effect
Farr and Gwaltney proposed that the apparent benefit of zinc lozenges in the Eby trial might have been caused by the placebo effect since the lozenge tasted bad. However, Farr and Gwaltney did not provide any evidence indicating that bad taste per se could shorten the duration of colds.

In the most recent trial on zinc acetate lozenges, the occurrence of bad taste did not differ between the zinc and placebo groups, and therefore bad taste cannot explain the significant effect on common cold duration. Lozenge composition and zinc ion availability seem more reasonable explanations for the substantial heterogeneity in the study findings, rather than the bad taste of lozenges in some studies.

Effectiveness
According to WebMD, studies carried out on zinc treatments for colds have produced mixed results. They say that experts are agreed that any benefit zinc brings is "very minor".

Several reviews of zinc and the common cold have been published. A Cochrane Collaboration review suggested in 2011 that it could bring about a modest reduction in the length of symptoms, but was not conclusive; a subsequent 2012 review attempted to gain more certainty and again suggested symptoms may be shortened, but that there may be side-effects such as nausea. All reviews to date have suffered from the variability of the studies which have been assessed; future large-scale randomized trials are necessary to determine whether the benefits from zinc treatment for colds outweigh the disadvantages.

A 2012 systematic review suggested that "zinc formulations may shorten the duration of symptoms of the common cold", but that further research was needed and that possible adverse effects needed to be studied.

A 2011 Cochrane Collaboration review (subsequently updated) found zinc lozenges or syrup beneficial to people with colds who were otherwise healthy but, for lack of evidence, cautioned against its use for people who might be unduly troubled by cold symptoms, such as people with asthma. The authors recommended further research for a more conclusive assessment.

The only review to consider the effects of the amount of the active ingredient, ionic zinc (iZn), showed that results varied in a direct relationship to the amount of iZn in the lozenges and total daily intake of iZn. Those studies that had zero or little iZn showed no results or even worsened results. Studies that used lozenges releasing large amounts of iZn showed strongly beneficial results.

Potential biological mechanisms
Evidence-based medicine focuses primary on the effect of interventions on clinically relevant outcomes in controlled trials. Nevertheless, the potential biological mechanisms are of interest. In laboratory studies, zinc inhibited the replication of respiratory viruses and enhanced the effect of  interferon. Non-immune mechanisms have also been proposed to explain the effect of zinc lozenges on the common cold.