Of the 49, 24 were judged to have improved. Of these 24, 11 (46 percent) received zinc aspartate lozenges and 13 (54 percent) received placebo. Of 25 patients judged as having not improved on at least four criteria, 16 (42 percent) received zinc aspartate and 22 (58 percent) received placebo.

Using less stringent criteria, based only on investigators' impression of improvement from patient report forms, 25 additional patients were evaluated. Of these 25, 15 (60 percent) judged improved received zinc, and 40 percent did not.

Figure 10. Effect of ZIA 0 zinc aspartate and placebo lozenges.

Greatly confounding this analysis, was the inclusion of 150 mg calcium ascorbate, 100 mg bee propolis, 25 mg slippery elm, 1000 IU vitamin A palmitate, 2 sugars, 2 stearates, Duratex, and 3 spray-dried flavor oils to both the zinc aspartate and placebo lozenges.(23) Failure of the study was attributed primarily to the use of zinc aspartate, a pleasant-tasting, non-astringent zinc compound having a first stability constant near log K₁ = 5.9 at 37°C.(24) The conditional first stability constant at pH 6.8 is log K₁ = 2.9 because of the protonated ammonium group.(25)

Berthon and Germonneau found in vitro that zinc aspartate concentration needed to be raised 1000 times over its normal levels to be more efficient than Zn²⁺ ion alone to favor zinc-mediated histamine diffusion into tissues.(24)

No salivary protein precipitate in expectorated saliva (18 ml saliva) was observed, suggesting the absence of Zn²⁺ ions. The average pH of zinc-laden saliva was 7.0. Oral dissolution time was 14 minutes. Failure of the study is primarily attributed to the use of zinc aspartate with its high molecular stability.

Of the many possible detrimental solid-state reactions between zinc aspartate and lozenge additives, reactions with calcium ascorbate is possible. Zinc ascorbate samples we tested were essentially insoluble. Stability constant data show essentially no Zn²⁺ ions were present. ZIA was essentially zero.