Efficacy Endpoints: Reduction of cold symptoms at 7 days
Harm Endpoints: Adverse medication events
Narrative: The term “common cold” is no misnomer—it affects the average adult 2-4 times annually and the average child up to 10 times annually. We spend almost $3 billion on OTC medications and approximately $400 million on prescription drugs every year for symptom relief. In-vitro studies suggest zinc possesses antiviral properties.
The Cochrane review summarized here included 13 trails with a total of 966 participants, showing a statistically significant symptom benefit affecting roughly 19% more people taking zinc than those taking placebo. This benefit seemed to accrue only for those taking the drug within 24 hours of the onset of their cold symptoms and occurred without accompanying major adverse effects, though with some minor effects including bad taste, dry mouth, and nausea.
Caveats: This Cochrane review suggests zinc can reduce the duration of symptoms in the common cold when initiated very early. The treatment effect is modest, however, and there are important caveats that limit applicability.
We are concerned about the adequacy of blinding in some studies, as biologically active zinc is not tasteless, is astringent, and only some trials performed a placebo matching trial to determine if the placebo was indistinguishable from zinc. In addition, as noted by the Cochrane authors, the studies are heterogeneous, especially regarding zinc preparation. Some preparations (zinc acetate) seem to be associated with a consistent benefit, while others are not. This is of particular note because of suggestions in some literature that the effect of zinc may be dependent upon the dose of positively charged zinc ions at physiologic pH and not the total amount of zinc in the preparation.1, 2. Zinc acetate and zinc gluconate are chemically unstable, releasing a large amount of zinc ions in aqueous solutions at physiologic pH 1, 3, 8, whereas other formulations do not.4 Also, it has been suggested that adding a strong zinc-binding ligand, like citric acid (in some studied formulations and found in many popular over the counter brands), may reduce and even eliminate desired effects.6, 8
Zicam, for instance, a well known zinc product of both zinc acetate and zinc gluconate, is unrepresented in the randomized trials reviewed here, allowing no applicable conclusion to be drawn for the many consumers who use or consider using this product.
Also of note is the presence of seemingly strong trends in existing, under-powered literature that should be addressed by future studies. For instance, zinc treatment seems to be more effective if given within 24 hours of symptom onset (one study, 73 pts),5 administered to adults rather than children (small subgroup analysis) 7, and when strongest formulations at higher doses are used.2, 3, 4, 7
Overall, there appears to be a potentially promising benefit-to-risk ratio with zinc as treatment for the common cold. However, a large, randomized, adequately blinded high quality trial using an appropriate zinc preparation has, in our opinion, the potential to trump and thus replace these data. This leads us to choose a ‘Yellow’ (meaning data are inadequate or unclear) designation for this intervention unless or until more data are available.
Author: Eric Steinberg, DO and Joseph Habboushe, MD
Published/Updated: April 17, 2015
The title bar is color-coded with our overall recommendation.
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