There were 77 volunteers (39 zinc, 38 placebo) in total. Twenty-eight zinc-treated patients and 27 placebo-treated patients returned report forms. Twenty-four of 28 zinc-treated patients and 23 of the placebo-treated patients had colds for 3 days or less before starting treatment. Of these patients, eight zinc-treated patients and six placebo-treated patients dropped out of the study. Two (12 percent) of the zinc-treated patients became asymptomatic on the first day, but no placebo-treated patients became well on the first day. No statistical significance between the differences between groups after one day (P = 0.23, exact binomial) was observed (see Figure 9). After the first day of study, no difference in rate of recovery between the two groups throughout the remainder of the study occurred, and plots for the two groups have essentially the same slope and are parallel. No further evidence of reduction in duration for the zinc group outside of the two patients who became asymptomatic on the first day occurred. By the end of the 7-day study, statistical significance of difference (P = 0.57, by chi square) was even less than at day 1.

The failure of zinc orotate lozenges appears to be attributable to the choice of zinc orotate. Zinc orotate is an insoluble compound of zinc at oral pH having a stability constant of log K1 = 6.42 at 25°C.(19) Consequently, zinc orotate releases no Zn²⁺ ions at oral or tissue pH. Lozenges were also insoluble to a significant extent. Although most dissolved in 40 minutes, complete dissolution took more than 3 hours for some patients. Lozenges were not particularly pleasant to use, because of the absence of a flavored, sweet carrier and the long time required for dissolution. No salivary protein precipitate in expectorated saliva was detected, directly suggesting absence of Zn²⁺ ions. Saliva generation averaged 18 ml. The average pH of intra-oral dissolution/expectorations was 7.0. Compliance seemed adequate.

Figure 9. Effect of ZIA 0 zinc orotate and placebo lozenges and zinc gluconate nasal spray.

Stronger nasal sprays could not be used as they caused intense, long lasting nasal pain. Patients reported zinc nasal spray was helpful as a short-lived decongestant. Perhaps this action is similar to decongestant action produced by various zinc nasal sprays used commercially from 1900 to 1966 in Europe, Australia and the United States, and as recently demonstrated by Derek Bryce-Smith with zinc sulfate (see Chapters 2 and 3). Because no Zn²⁺ ions were released from lozenges at pH 7.4, ZIA was 0.