Zinc ions inhibit the replication of rhinoviruses in vitro and induce the production of interferon and the replication of T-cells. Moreover, zinc ions are also astringents and, therefore, fix proteins and stabilize cell membranes. They also reduce local inflammation, edema, exudation, and the production of mucous and other secretions in tissues containing goblet and other secretory cells, thereby causing affected areas to dry and heal faster. Thus, it had been expected that local treatment with zinc compounds would have led to a reduction in symptoms of the common cold, but the results of several trials yielded disparate results. For example, when zinc gluconate was given in a pleasant-tasting, fructose-based lozenge, the duration of experimentally induced rhinovirus-2 colds was shortened by an average of seven days; however, when zinc acetate lozenges were given, they actually prolonged the symptoms. In an attempt to explain this, Eby re-analysed the data obtained from eight similar, double-blind, placebo-controlled clinical trials of various zinc lozenges and was able to establish a clear dose response between the zinc ion availability (ZIA) at physiological pH (7.4) in the different treatments and the reduction in cold symptoms. (See Table.)

Positively charged zinc ions corresponded with benefit, whereas negatively charged zinc species didn’t and actually prolonged the misery. Eby also postulated that the failure to show any benefit of zinc in some of the trials was due to attempts to mask the bitter taste of zinc gluconate, or present it in an acidic base which effervesced on contact with saliva. Zinc acetate lozenges appear a more acceptable choice, as is attested by their popularity in the United States, and the author urges more carefully controlled trials of them since these are of international importance.

Table

Data from similar double-blind, placebo-controlled, clinical trials of various zinc lozenges

Effect on

Bioavaliability Charge at duration of

Author of zinc (%) pH 7.4 cold symptoms

Eby et al. 1984 100 2+,1+,0 7 day reduction

Al-Nakib et al. 1987 44 2+,1+,0 4.8 day reduction

Smith et al. 1989 25 2+,1+,0 1.6 day reduction

Weisman et al. 1990 13.4 2+,1+,0 no effect

Eby. 1994 0 0 no effect

Eby. 1994 0 0 no effect

Farr et al. 1987 0 0, N- 1 day increase

Douglas et al. 1987 0 0, N- 4.4 day increase

Godfrey et al. 1992 0 0, N- 1.3 day increase

COMMENT BY J. PETER DONNELLY, PhD

Apparently, zinc compounds have been used as nasal decongestants for more than 90 years. (They also remain a popular ingredient of creams for diaper rash.) However, only in the last decade there has been any interest in exploring their potential in reducing the symptoms of the common cold. Although not a major threat to health, the common cold condemns millions of people every year to weeks of abject misery, increases the risk of pneumonia in the elderly, and causes huge economic losses. Thus, if by simply sucking some lozenges the duration of symptoms can be reduced by even a few days, the benefit could be enormous. Eby has produced some pretty convincing evidence that this is the case, since the reduction in cold symptoms (Y) correlated almost perfectly with the ZIA (X) (r = 3D 0.96) and could be predicted from it by the simple straight line equation (Y = 3D 0.077 * X- 0.16). Thus, use of the zinc acetate lozenges, which yield a ZIA of 100%, would be expected to reduce the symptoms by 0.077*100-0.16 days or 7.54 days, providing a clear hypothesis for testing under strict trial conditions.

However, despite Eby’s plea and the obvious benefit that would result, he does not seem to feel confident that another properly conducted clinical trial will be done. Therefore, he proposes a simple test to help the consumer discern which of the commercially available lozenges is likely to worksimply taste them. If they effervesce or have a bitter taste, reject them. Those that induce a dry sensationan indication of astringencyare the ones to opt for. However, the market for cold remedies cannot be anything other than extremely lucrative judging by the plethora of products proferred by all manner of vendors ranging from gas stations to pharmacies.

So, with such a clear hypothesis to test, there has to be an incentive at least for the manufacturers of the lozenges with the highest ZIAs to finance a proper clinical trial which, even if it only showed half the benefit anticipated, could only serve to boost their share of the market and show the sort of healthy return on investment that would satisfy even the most demanding of investors.

Which of the following is correct?

a. The efficacy of zinc in the treatment of the common cold appears to be positively related to the amount of unionized form available.

b. Acidification of zinc preparations is associated with a more favorable therapeutic effect in the common cold.

c. Zinc tablets or lozenges that have a bitter taste rather than a dry, astringent taste are most likely to be beneficial.

d. Enhancement of zinc ion availability is associated with a more favorable therapeutic effect in the common cold.