Objective: To test the hypothesis that major variations in daily zinc ion availability (ZIA) between lozenge formulations caused greatly differing results and to describe the biologically closed electric circuit between the mouth and nose. Data Sources: Data sources included clinical and in vitro reports, zinc speciation computations, and unpublished data from the original researchers and manufacturers. Data Extraction: Data were extracted to determine the composition and usage of lozenges and resultant changes in common cold duration. Lozenge ZIA values were determined from Zn2+ ion concentrations and oral contact time. Data Synthesis: Data synthesis disclosed that lozenges releasing Zn2+ ions at physiologic pH (positive ZIA values) shortened the duration of colds. Conversely, lozenges that released negatively charged zinc complexes (ZnLN−) at physiologic pH (negative ZIA values) lengthened the duration of colds. ZIA 100 lozenges reduced the duration of colds by 7 days. ZIA 0 lozenges had no effect. ZIA −55 lozenges lengthened the duration of colds by 4.4 days. Conclusions: The hypothesis is valid that major variations in ZIA from different zinc lozenge formulations used in clinical trials caused greatly differing results. A linear dose-response relationship exists between ZIA values of zinc lozenges and changes in duration of common colds. In agreement with in vitro activity, Zn2+ ions from lozenges inhibit replication of rhinoviruses, induce interferon release, and stabilize cell membranes in common cold treatment. Linearity in dose-response shows efficacy against common cold duration from clinically untested lozenges to be predictable on the basis of readily determined ZIA values of experimental lozenges.
