We believe that Mossad and colleagues' study of zinc therapy for colds [1] is flawed by the same bias that affected the original study by Eby and colleagues [2]. As previously discussed, placebos can have powerful supratentorial effects [3, 4]. The worse the taste and aftertaste, the stronger this effect may be. As did Mossad and associates, Eby and coworkers claimed that the placebo lozenges were identical in appearance and that the participants were well blinded; however, significantly more adverse effects occurred with zinc in both studies. Both studies used a relatively tasteless calcium lactate placebo for zinc gluconate, one of the most unpleasant tasting and difficult to blind compounds we have encountered in three decades of research on the common cold. Both studies allowed participants to stop taking zinc if they said they were well. Neither group of investigators reported doing formal studies with adequate statistical power in advance to assure comparability of zinc and placebo lozenges.

The hypothesis that zinc could cure common colds if used as a lozenge lacks biological plausibility. Zinc ions have only modest nonselective inhibitory effects for rhinovirus replication in vitro [5]. Speculation that zinc ions in saliva could affect viral infection in the nose ignores anatomic relations and the physiology of respiratory secretions. Lozenges containing gentian violet do not stain the adenoid region, much less the nasal mucosa. Gastrointestinal absorption and hematogenous distribution to the nose could be postulated, but our study [4] documented significant increases in serum zinc levels without effect on symptoms or objective measures of rhinovirus colds, including duration of viral replication, weights of nasal mucus, and numbers of facial tissues used.

We agree with Mossad and colleagues that confirmatory studies should be done before zinc is accepted as a legitimate treatment for the common cold. Such studies should require a placebo that has similar taste, aftertaste, and gastrointestinal side effects, and therapy should be continued for a predetermined period without early discontinuation.