Am Fam Physician. 2001 Feb 15;63(4):751-752.
Effective treatment of the common cold has been elusive. Trials of treatment with zinc lozenges have yielded conflicting results. The in vitro inhibition of viral replication secondary to prevention of viral capsid protein formation in rhinovirus by zinc is one postulated mechanism for zinc's usefulness in the treatment of the common cold. Another theory is that zinc inhibits viral binding with intra-cellular adhesion molecule 1, thus preventing entry into the cells. Prasad and associates looked at the duration of cold symptoms in zinc-treated and placebo-treated participants.
Plasma zinc and proinflammatory cytokine levels were measured initially and at the end of cold symptoms in both groups. Forty-eight participants who had cold symptoms for 24 hours or less with at least two of 10 classic cold symptoms were enrolled in the study. Patients were randomized into treatment (one lozenge containing 12.8 mg zinc dissolved in the mouth every two to three hours while awake) or placebo (a similar lozenge without zinc administered in the same manner). Participants recorded symptoms and their severity in a daily log. Plasma samples were obtained for zinc assay and quantitation of three proinflammatory cytokines. Normal levels of proinflammatory cytokines and zinc were evaluated in 17 healthy volunteers who had no cold symptoms. Side effects of treatment were recorded by each participant at the end of the study.
The average duration of cold symptoms was 4.5 days in the zinc recipients and 8.1 days in the placebo recipients. The average severity of symptoms score in the zinc group was one half that of the score in the placebo group. The only adverse effects more frequent in the zinc group were mouth dryness and constipation. Among the proinflammatory cytokine levels, only soluble interleukin-1 receptor antagonist and neopterin were increased in participants with common cold compared with healthy control subjects. No statistically significant differences were found in any proinflammatory cytokine level in the zinc group compared with the placebo group.
The authors conclude that treatment with zinc acetate lozenges (at a dosage level of approximately 80 mg of elemental zinc daily) was associated with a decrease in the average duration and severity of the symptoms of common cold. Levels of proinflammatory cytokines decreased, although not in a statistically significant manner. If a patient does not show clear evidence of improvement after three days of zinc treatment, other respiratory tract disorders or allergy should be investigated and treated. Zinc therapy should be limited to a short period because of the increased incidence of copper deficiency if lozenges are taken indiscriminately for six to eight weeks.
In an accompanying editorial, Desbiens points out the problem of imperfect blinding causing bias in this study's results. He indicated that the author could have adjusted the analysis to see if maximal response occurred among patients who thought they were taking zinc who actually were taking zinc. Or the analysis could have been done using only participants who did not know whether they were taking zinc or placebo, but this would have decreased the power of this already small study. He concludes that the value of zinc in persons with common cold symptoms remains unestablished because of blinding problems in comparing oral zinc preparations with placebo.
Prasad AS, et al. Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. Ann Intern Med. August 15, 2000;133:245–52, and Desbiens NA. Lessons learned from attempts to establish the blind in placebo-controlled trials of zinc for the common cold. Ann Intern Med August 15, 2000;133:302–3.
Copyright © 2001 by the American Academy of Family Physicians.
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