Since 1984, at least 10 studies have evaluated the benefits of zinc for the treatment of the common cold. Some of the published results have shown no benefit, while others have found significant reductions in severity or duration of cold symptoms with the use of zinc. Both sets of studies have been criticized on the basis of size, inadequate blinding, use of poorly matched placebos or zinc formulation. Results from a recent study suggested that the main determinant of zinc's efficacy is its ability to deliver zinc ions to the oral mucous membranes and, thus, zinc acetate should be the most effective formulation. Based on this theory, Turner and Cetnarowski performed a study using an experimental rhinovirus cold model to determine the efficacy of zinc as a therapeutic agent in the treatment of symptoms of the common cold.

Subjects enrolled were between 18 and 65 years of age and in good health. They had to be susceptible to the study virus as evidenced by having a serum neutralizing antibody titer of 1:4 or less. The challenge virus was rhinovirus type 39, and it was administered to the subjects as drops in two inocula of 250 μL per nostril given 15 minutes apart. Subjects were then isolated in hotel rooms for the next five days. Beginning at 12 hours post-inoculation, they were asked to assess the severity of seven symptoms: sneezing, rhinorrhea, nasal obstruction, sore throat, cough, headache and hoarseness. Each symptom was given a score from zero to 4. If their total score was at least 3 at 24 hours or at 48 hours, they were randomized to receive two different dosages of zinc acetate lozenges (5 or 11.5 mg), zinc gluconate lozenges or placebo lozenges. After randomization, the subjects continued to record their severity scores at 12-hour intervals. Use of the zinc or placebo product was continued for at least three days or until the symptom scores were 1 or less for two consecutive days. All zinc or placebo therapy was stopped by day 14.

Of the 413 persons enrolled in the study, 273 met symptom criteria for randomization. There were no significant differences in age, sex, race or symptom scores at entry into the study. The median duration of illness was 2.5 days in patients in the zinc gluconate group compared with 3.5 days in the placebo group, and 3.5 and 3.25 days in patients receiving 5 mg and 11.5 mg of zinc acetate, respectively. None of the three preparations of zinc lozenges had an effect on the severity of symptoms during the first three days of treatment compared with placebo.

The subjects also underwent measurement of interleukin-8 in nasal secretions, which is an indicator of disease severity. There were no significant differences in concentrations of interleukin-8 on day zero compared with days 3,4 and 5 in any of the subjects. Finally, rhinovirus was isolated from the nasal secretions of approximately 70 percent of the patients in all four treatment groups on at least one of the five study days, suggesting that zinc had no effect on viral replication in these patients.

Based on this study, the authors conclude that zinc gluconate has a modest benefit on the duration of symptoms of the common cold, but zinc acetate has no benefit. Collectively, with all three zinc formulations studied, there was no effect on the severity of symptoms compared with use of placebo.

editor's note: The authors published additional data within this study on 281 subjects with “naturally” acquired colds. The design of this study was essentially the same as that of the experimental cold group. The mean symptom scores were higher in these patients, so they were self-perceived as “sicker” at the onset of treatment. However, in this trial, none of the three zinc treatments decreased the duration or severity of cold symptoms. Despite this strong evidence that zinc offers little benefit in the treatment of viral respiratory infections, I believe our patients will continue to use many of the zinc-containing cold products that are available over-the-counter.—j.t.k.