Zinc Acetate Lozenges May Improve the Recovery Rate of Common Cold Patients: An Individual Patient Data Meta-Analysis
MD Harri Hemilä, James T Fitzgerald, Edward J Petrus, Ananda Prasad
Open Forum Infectious Diseases, doi:10.1093/ofid/ofx059
Background. A previous meta-analysis of 3 zinc acetate lozenge trials estimated that colds were on average 40% shorter for the zinc groups. However, the duration of colds is a time outcome, and survival analysis may be a more informative approach. The objective of this individual patient data (IPD) meta-analysis was to estimate the effect of zinc acetate lozenges on the rate of recovery from colds. Methods. We analyzed IPD for 3 randomized placebo-controlled trials in which 80-92 mg/day of elemental zinc were administered as zinc acetate lozenges to 199 common cold patients. We used mixed-effects Cox regression to estimate the effect of zinc. Results. Patients administered zinc lozenges recovered faster by rate ratio 3.1 (95% confidence interval, 2.1-4.7). The effect was not modified by age, sex, race, allergy, smoking, or baseline common cold severity. On the 5th day, 70% of the zinc patients had recovered compared with 27% of the placebo patients. Accordingly, 2.6 times more patients were cured in the zinc group. The difference also corresponds to the number needed to treat of 2.3 on the 5th day. None of the studies observed serious adverse effects of zinc. Conclusions. The 3-fold increase in the rate of recovery from the common cold is a clinically important effect. The optimal formulation of zinc lozenges and an ideal frequency of their administration should be examined. Given the evidence of efficacy, common cold patients may be instructed to try zinc acetate lozenges within 24 hours of onset of symptoms. Keywords. common cold; meta-analysis; randomized controlled trials; respiratory tract infections; zinc acetate.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Authors contributions. A. P., J. T. F., and E. J. P. organized the 3 trials and collected the data that were analyzed in this study. H. H. planned and carried out this meta-analysis and wrote a draft manuscript. A. P., J. T. F., and E. J. P. participated in the revision of the manuscript. Financial support. This research received no grant from any funding agency in the public, commercial or not-for-profit sectors. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
Ala, Walker, Ashkan, Wilson's disease, Lancet
Bamford, Gessert, Haller, Randomized, double-blind trial of 220 mg zinc sulfate twice daily in the treatment of rosacea, Int J Dermatol
Brewer, Askari, Wilson's disease: clinical management and therapy, J Hepatol
Core, R Project for Statistical Computing
Czerwinski, Clark, Serafetinides, Safety and efficacy of zinc sulfate in geriatric patients, Clin Pharmacol Ther
Debray, Moons, Van Valkenhoef, Get real in individual participant data (IPD) meta-analysis: a review of the methodology, Res Synth Methods
Eby, Davis, Halcomb, Reduction in duration of common cold by zinc gluconate lozenges in a double-blind study, Antimicrob Agents Chemother
Eby, Elimination of efficacy by additives in zinc acetate lozenges for common colds, Clin Infect Dis
Eby, Zinc lozenges as cure for the common cold-a review and hypothesis, Med Hypotheses
Eby, Zinc lozenges: cold cure or candy? Solution chemistry determinations, Biosci Rep
Farr, Gwaltney, The problems of taste in placebo matching: an evaluation of zinc gluconate for the common cold, J Chronic Dis
Godfrey, Sloane, Smith, Zinc gluconate and the common cold: a controlled clinical study, J Int Med Res
Godfrey, Zinc for the common cold, Antimicrob Agents Chemother
Greaves, Skillen, Effects of long-continued ingestion of zinc sulphate in patients with venous leg ulceration, Lancet
Hadwan, Almashhedy, Alsalman, Oral zinc supplementation restores high molecular weight seminal zinc binding protein to normal value in Iraqi infertile men, BMC Urol
Hallböök, Laner, Serum-zinc and healing of venous leg ulcers, Lancet
Hemilä, Chalker, The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: a meta-analysis, BMC Fam Pract
Hemilä, Concerns about unattributed copying of text and data, and about numerous other problems in the Cochrane review "Zinc for the Common Cold
Hemilä, Petrus, Fitzgerald, Prasad, Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis, Br J Clin Pharmacol
Hemilä, Zinc lozenges may shorten the duration of colds: a systematic review, Open Respir Med J
Hoogenraad, Zinc treatment of Wilson's disease, J Lab Clin Med
Marcellini, Ciommo, Callea, Treatment of Wilson's disease with zinc from the time of diagnosis in pediatric patients: a single-hospital, 10-year follow-up study, J Lab Clin Med
Mossad, Macknin, Medendorp, Mason, Zinc gluconate lozenges for treating the common cold: a randomized, double-blind, placebo-controlled study, Ann Intern Med
Petrus, Lawson, Bucci, Blum, Randomized, double-masked, placebo-controlled clinical study of the effectiveness of zinc acetate lozenges on common cold symptoms in allergy-tested subjects, Curr Ther Res
Prasad, Beck, Bao, Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate, J Infect Dis
Prasad, Fitzgerald, Bao, Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate: a randomized, double-blind, placebo-controlled trial, Ann Intern Med
Serjeant, Galloway, Gueri, Oral zinc sulphate in sickle-cell ulcers, Lancet
Singh, Das, WITHDRAWN: Zinc for the common cold, Cochrane Database Syst Rev
Singh, Das, Zinc for the common cold, Cochrane Database Syst Rev
Stewart, Altman, Askie, Statistical analysis of individual participant data meta-analyses: a comparison of methods and recommendations for practice, PLoS One
