We do not agree with Farr and colleagues that the placebo used in our study resulted in biased results favoring beneficial treatment effects of the zinc lozenges. Patients receiving zinc lozenges who reported no side effects of the medication before the end of the study reported a duration of symptoms similar to that in persons with side effects. The number of placebo and zinc recipients who believed that their medication had helped alleviate their cold symptoms did not significantly differ. No clear pattern of movement was seen regarding a patient's guesses about which medication he or she was receiving during the study. Patients guessed their group assignment from among seven choices: 1) certainly placebo, 2) probably placebo, 3) possibly placebo, 4) do not know, 5) certainly active, 6) probably active, or 7) possibly active. When the zinc and placebo groups were divided into these seven subgroups, the mean and median durations of symptoms of the zinc recipients in each subgroup were always shorter than those of the placebo recipients in the same subgroup. The study nurse saw the patients within 1 day of their reported cure, and she observed no cold symptoms. These facts, as outlined in our paper, support our beliefs that blinding appears to have been maintained during the study and that the beneficial effects of zinc gluconate lozenges are real and not due to a faulty placebo.

We do not believe that the suggestion to continue treatment for an arbitrary period, even when patients are totally asymptomatic, is clinically reasonable or helpful to the study design. We also disagree with Farr and colleagues' statement questioning the biological plausibility of the hypothesis that zinc could cure common colds if used as a lozenge. Possible mechanisms of the beneficial effects of zinc noted in the medical literature include inhibition of viral capsid formation, induction of interferon, blocking the binding of rhinovirus to respiratory epithelium, stabilization of cell membranes, and an antiprostaglandin effect [1-5]. To the best of our knowledge, Farr and colleagues' implied suggestion that the transport of gentian violet is identical to that of zinc ions has not been studied.

In answer to Dr. Shumate's comments, we do not have data on the use of vitamin and mineral supplementation among our study participants. We agree that widespread subclinical zinc deficiency is an unlikely explanation of the efficacy of zinc if a large percentage of the population takes zinc supplements. Farr and colleagues describe their study that documented significant increases in serum zinc levels when zinc gluconate lozenges were used but that did not show a therapeutic effect in the treatment of experimentally induced rhinovirus colds. This finding makes the correction of a subclinical zinc deficiency a less likely explanation for the efficacy of zinc lozenges in treating the common cold.