Zinc lozenges reduced the duration of common cold symptoms
ACP J Club. 1996 Nov-Dec;125:72. doi:10.7326/ACPJC-1996-125-3-072
Mossad SB, Macknin ML, Medendorp SV, Mason P. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. Ann Intern Med. 1996 Jul 15;125:81-8.
To determine whether zinc gluconate lozenges received during the first day of a cold are effective and safe for reducing common cold symptoms.
Randomized, double-blind, placebo-controlled trial.
An outpatient department of a U.S. tertiary care hospital.
100 Cleveland Clinic staff members (mean age 38 y, 81% women, 76% white) who had cold symptoms for ≥ 2 symptoms (cough, headache, hoarseness, muscle ache, nasal drainage or congestion, scratchy or sore throat, or fever) and were not pregnant or immune deficient.
4.4-g, hard-candy lozenges that were composed of sucrose, corn syrup, glycine, lemon and lime oils, and either zinc gluconate trihydrate, 13.3 mg, or placebo. 50 adults were assigned to zinc lozenges and 50 to placebo lozenges. Lozenges were to be taken every 2 hours until symptoms were gone. Acetaminophen was allowed; other medications were discouraged.
Main outcome measures
Self-reported symptoms recorded daily for up to 18 days, amount of medication and lozenges used, and days to resolution of symptoms.
Analysis was by intention to treat. The median time to resolution of all symptoms was 4.4 days in the zinc group compared with 7.6 days in the placebo group (P < 0.001). The difference in time to resolution of all but 1 mild symptom showed similar results (3.7 vs 7.5 d, P < 0.001). Patients in the zinc group had fewer days with throat symptoms, coughing, headaches, hoarseness, nasal congestion, or nasal drainage (P ≤ 0.04 for all comparisons). The groups did not differ for other cold symptoms or use of acetaminophen. More patients in the zinc group reported nausea (P = 0.02) and found the taste of the lozenges to be unpleasant (P < 0.001). The groups did not differ for other adverse effects (vomiting, abdominal pain, diarrhea, constipation, mouth irritation, or dry mouth).
Zinc gluconate lozenges given to adults within 24 hours of the onset of cold symptoms reduced the duration of symptoms but tasted unpleasant and caused nausea.
Sources of funding: The Cleveland Clinic Foundation; Quigley Corporation (lozenges); McNeil (acetaminophen); Becton Dickinson (thermometers).
For article reprint: Dr. M.L. Macknin, Department of Pediatrics and Adolescent Medicine, A 120, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. FAX 216-444-0266.
A cure for the common cold is not yet at hand, but these 2 randomized controlled trials indicate that some relief is available. Mossad and colleagues showed that, if started within 24 hours of onset, zinc gluconate lozenges can shorten the duration of cold symptoms, whereas Hayden and colleagues found that ipratropium nasal spray can reduce rhinorrhea. The patients enrolled in each of these studies were similar to patients with viral upper respiratory tract infections commonly seen in medical practice. The ipratropium study excluded patients with fever (body temperature > 39 °C), allergies, asthma, or bronchitis; the zinc study excluded only patients who were pregnant or had known immune deficiency. Each study used a placebo group, and the ipratropium study used a "no treatment" group as well. The metallic taste of zinc could have made blinding difficult. However, Mossad and colleagues showed that only about half the patients correctly guessed whether they were taking zinc lozenges or placebo, and the participants in the zinc group did not stop treatment prematurely because of side effects. Hayden and colleagues also used objective measures of rhinorrhea (weight of nasal discharge). In each study, the patients who received active treatment had baseline characteristics that were similar to those of the patients who received placebo, compliance was good, follow-up was nearly complete, and patients were appropriately analyzed in the group to which they were assigned (i.e., intention-to-treat analysis). Thus, the studies rate high marks for basic research methods.
In the ipratropium study, patients had cold symptoms and at least moderate rhinorrhea for ≤ 36 hours; therefore, the conclusions of the study are applicable to patients in the rhinorrheal stage of a cold. Ipratropium nasal spray reduced rhinorrhea and sneezing but not nasal congestion. It would have been helpful if Hayden and colleagues had specifically asked the patients about other common cold symptoms, such as malaise, sore throat, and coughing. Because malaise and sore throat usually precede rhinorrhea, the global improvement that Hayden and colleagues described probably refers primarily to reduced rhinorrhea.
The adverse effects of anticholinergic medications are well known, and Hayden and colleagues were remiss for not asking study participants about the specific expected side effects of ipratropium nasal spray. It is likely that they underestimated the prevalence of the adverse effects of ipratropium because they simply recorded them as they were spontaneously reported. On the other hand, Mossad and colleagues used both an open-ended question and categorical responses to identify the specific side effects of the zinc lozenges. Not surprisingly, patients reported more side effects when asked specifically about adverse effects of the zinc lozenges than when asked to respond to an open-ended question.
Compared with the placebo group, patients using this particular zinc gluconate-glycine complex had fewer days with cough, headaches, hoarseness, throat symptoms, nasal congestion, and nasal drainage. Previous clinical trials of zinc lozenges in the treatment of the common cold have shown conflicting results, which may be partly attributable to the different formulations and doses used in the various studies. One other study (1) that used the same formulation showed similar results, but it would be more convincing to see the results replicated in other settings.
The benefits of zinc lozenges and ipratropium nasal spray are clinically important but are tempered by their adverse effects (unpleasant taste and nausea with zinc lozenges and nasal drying with ipratropium nasal spray). We do not know what the economic and epidemiologic effects of these treatments will be. Will they reduce work and school absenteeism or complications of colds? Will they affect transmission of cold viruses?
Ipratropium nasal inhalers for treating cold symptoms are now available by prescription at local pharmacies in the United States. 1 of 2 local health-food stores that I called stocked the zinc gluconate lozenges.
What do we tell our patients? If asked, I will tell mine that one particular formulation of zinc lozenges (but perhaps not other preparations) reduced the duration of colds by nearly half when they were started within 24 hours of the onset of symptoms; 5 lozenges should be dissolved in the mouth daily until symptoms resolve. To reduce the sneezing and rhinorrhea associated with the common cold, ipratropium nasal spray can be used, but patients should be told to titrate the number of sprays to prevent excessive nasal drying.
Peter S. Millard, MD, PhD
Eastern Maine Medical CenterBangor, Maine, USA