Articles
15 August 2000

Duration of Symptoms and Plasma Cytokine Levels in Patients with the Common Cold Treated with Zinc Acetate: A Randomized, Double-Blind, Placebo-Controlled Trial

Publication: Annals of Internal Medicine
Volume 133, Number 4

Abstract

Background:

Adults and children in the United States get two to six colds per year. Evidence that zinc is effective therapy for colds is inconsistent.

Objective:

To test the efficacy of zinc acetate lozenges in reducing the duration of symptoms of the common cold.

Design:

Randomized, double-blind, placebo-controlled trial.

Setting:

Detroit Medical Center, Detroit, Michigan.

Patients:

50 ambulatory volunteers recruited within 24 hours of developing symptoms of the common cold.

Intervention:

Participants took one lozenge containing 12.8 mg of zinc acetate or placebo every 2 to 3 hours while awake as long as they had cold symptoms.

Measurements:

Subjective symptom scores for sore throat, nasal discharge, nasal congestion, sneezing, cough, scratchy throat, hoarseness, muscle ache, fever, and headache were recorded daily for 12 days. Plasma zinc and proinflammatory cytokine levels were measured on day 1 and after participants were well.

Results:

Forty-eight participants completed the study (25 in the zinc group and 23 in the placebo group). Compared with the placebo group, the zinc group had shorter mean overall duration of cold symptoms (4.5 vs. 8.1 days), cough (3.1 [95% CI, 2.1 to 4.1] vs. 6.3 [CI, 4.9 to 7.7] days), and nasal discharge (4.1 [CI, 3.3 to 4.9] vs. 5.8 [CI, 4.3 to 7.3] days) and decreased total severity scores for all symptoms (P < 0.002, test for treatment × time interaction). Mean changes in soluble interleukin-1 receptor antagonist level differed nonsignificantly between the zinc group and the placebo group (difference between changes, −89.4 pg/mL [CI, −243.6 to −64.8 pg/mL]).

Conclusion:

Administration of zinc lozenges was associated with reduced duration and severity of cold symptoms, especially cough. Improvement in clinical symptoms with zinc treatment may be related to a decrease in proinflammatory cytokine levels; however, in this study, the observed differences between changes in cytokine levels in zinc and placebo recipients were not significant.

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References

1.
Dingle JHBadger GFJordan WS Jr. Illness in the Home: Study of 25,000 illnesses in a Group of Cleveland Families. Cleveland: Pr of Case Western Reserve Univ; 1964.
2.
Gwaltney JM JrHendley JOSimon GJordan WS Jr. Rhinovirus infections in an industrial population. I. The occurrence of illness. N Engl J Med. 1966;275:1261-8.
3.
Couch RB. The common cold: control? J Infect Dis. 1984;150:167-73.
4.
Eby GADavis DRHalcomb WW. Reduction in duration of common cold by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother. 1984;25:20-4.
5.
Al-Nakib WHiggins PGBarrow IBatstone GTyrrell DA. Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges. J Antimicrob Chemother. 1987;20:893-901.
6.
Godfrey JCConant Sloane BSmith DSTurco JHMercer NGodfrey NH. Zinc gluconate and the common cold: a controlled clinical study. J Int Med Res. 1992;20:234-46.
7.
Mossad SBMacknin MLMedendorp SVMason P. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. Ann Intern Med. 1996;125:81-8.
8.
Petrus EJLawson KABucci LRBlum K. Randomized, double-masked, placebo-controlled clinical study of the effectiveness of zinc acetate lozenges on common cold symptoms in allergy-tested subjects. Current Therapeutic Research. 1998;59:595-606.
9.
Farr BMConner EMBetts RFOleske JMinnefor AGwaltney JM Jr. Two randomized, controlled trials of zinc gluconate lozenge therapy of experimentally induced rhinovirus cold. Antimicrob Agents Chemother. 1987;31:1183-7.
10.
Douglas RMMiles HBMoore BWRyan PPinnock CB. Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infection of Australian adults. Antimicrob Agents Chemother. 1987;31:1263-5.
11.
Smith DSHelzner ECNuttall CE JrCollins MRofman BAGinsberg Det al . Failure of zinc gluconate in treatment of acute upper respiratory tract infections. Antimicrob Agents Chemother. 1989;33:646-8.
12.
Weismann EJakobsen JPWeismann JEHammer UMNyholm SMHansen Bet al . Zinc gluconate lozenges for common cold. A double-blind clinical trial. Dan Med Bull. 1990;37:279-81.
13.
Macknin MLPiedmonte MCalendine CJanosky JWald E. Zinc gluconate lozenges for treating common cold in children. JAMA. 1998;279:1962-7.
14.
Eby GA. Linearity in dose-response from zinc lozenges in treatment of common colds. The Journal of Pharmacy Technology. 1995;11:110-22.
15.
Korant BDButterworth BE. Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides. J Virol. 1976;18:298-306.
16.
Moffat AS. Going back to the future with small synthetic compounds. Science. 1993;260:910-2.
17.
Novick SGGodfrey JCGodfrey NJWilder HR. How does zinc modify the common cold? Clinical observations and implications regarding mechanism of action. Med Hypotheses. 1996;46:295-302.
18.
Begg CCho MEastwood SHorton RMoher DOlkin Iet al . Improving the quality of reporting of randomized, controlled trials. The CONSORT statement. JAMA. 1996;276:637-9.
19.
Prasad AS. Biochemistry of Zinc. New York: Plenum; 1993:279-9.
20.
Hatch BBerthon G. Metal ion-FTS nonapeptide interactions. A quantitative study of zinc(II)-nonapeptide complexes (thymulin) under physiological conditions and assessment of their biological significance. Inorganica Chimica Acta. 1987;136:165-71.
21.
Farr BMHyden FGGwaltney J Jr. Zinc gluconate lozenges for treating the common cold [Letter]. Ann Intern Med. 1997;126:738.
22.
Davidoff F. Where's the bias? [Letter]. Ann Intern Med. 1998;128:75.
23.
Jackson JLPeterson CLesho E. A meta-analysis of zinc salts lozenges and the common cold. Arch Intern Med. 1997;157:2373-6.
24.
Geist FCBateman JAHayden FG. In vitro activity of zinc salts against human rhinoviruses. Antimicrob Agents Chemother. 1987;31:622-4.
25.
Catania AAiraghi LMotta PManfredi MGAnnoni GPettenati Cet al . Cytokine antagonists in aged subjects and their relation withcellular immunity. J Gerontol A Biol Sci Med Sci. 1997;52:B93-7.
26.
Fuchs DHansen AReibnegger DWerner ERDierich MPWachter Het al . Neopterin as a marker for activated cell-mediated immunity: application in HIV infection. Immunol Today. 1988;9:150-5.
27.
Catania AManfredi MGAiraghi LCeriani GGandino ALipton JMet al . Cytokine antagonists in infections and inflammatory disorders. Ann N Y Acad Sci. 1994;741:149-61.
28.
Arend WP. Interleukin 1 receptor antagonist. A new member of interleukin 1 family. J Clin Invest. 1991;88:1445-51.
29.
Koch AEKunkel SLStrieter RM. Cytokines in rheumatoid arthritis. J Invest Med. 1995;43:28-38.
30.
Bui LMDressendorfer RHKeen CLSummary JJDubick MA. Zinc status and interleukin-1 β-induced alterations in mineral metabolism in rats. Proc Soc Exp Biol Med. 1994;206:438-44.
31.
Wahl SMWong HMcCartney-Francis N. Role of growth factors in inflammation and repair. J Cell Biochem. 1989;40:193-9.
32.
Pitkaranta AHayden FG. What's new with common colds? Pathogenesis and diagnosis. Infections in Medicine. 1998;15:50-9.
33.
Noah TLHenderson FWWortman IADevlin RBHandy JKoren HSet al . Nasal cytokine production in viral acute upper respiratory infections of childhood. J Infect Dis. 1995;171:584-92.
34.
Stockl JVetr HMajic OZlabinger GKuechler EKnapp W. Human major group rhinoviruses downmodulate the accessory function of monocytes by inducing IL-10. J Clin Invest. 1999;104:957-65.
35.
Beck FWPrasad ASKaplan JFitzgerald JTBrewer GJ. Changes in cytokines production and T cell subpopulations in experimentally induced zinc-deficient humans. Am J Physiol. 1997;272:E1002-7.
36.
Turner RBWecker MTPohl GWitek TJMcNally ESt George Ret al . Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial. JAMA. 1999;281:1797-804.
37.
Prasad AS. Biochemistry of Zinc. New York: Plenum; 1993:259-78.

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 133Number 415 August 2000
Pages: 245 - 252

History

Published online: 15 August 2000
Published in issue: 15 August 2000

Keywords

Authors

Affiliations

Ananda S. Prasad, MD, PhD
From Wayne State University School of Medicine, Detroit, Michigan; and University of Michigan Medical School, Ann Arbor, Michigan.
James T. Fitzgerald, PhD
From Wayne State University School of Medicine, Detroit, Michigan; and University of Michigan Medical School, Ann Arbor, Michigan.
Bin Bao, MD, PhD
From Wayne State University School of Medicine, Detroit, Michigan; and University of Michigan Medical School, Ann Arbor, Michigan.
Frances W.J. Beck, PhD
From Wayne State University School of Medicine, Detroit, Michigan; and University of Michigan Medical School, Ann Arbor, Michigan.
Pranatharthi H. Chandrasekar, MD
From Wayne State University School of Medicine, Detroit, Michigan; and University of Michigan Medical School, Ann Arbor, Michigan.
Acknowledgments: The authors thank Diane Snell, Karen Mirisola, James Nowak, and Sally Bates for technical and secretarial assistance.
Grant Support: In part by an unrestricted fund from the George and Patsy Eby Research Foundation.
Corresponding Author: Ananda S. Prasad, MD, PhD, Department of Medicine, Division of Hematology-Oncology, Wayne State University, University Health Center 5-C, 4201 St. Antoine, Detroit, MI 48201.
Current Author Addresses: Drs. Prasad, Bao, and Beck: Department of Medicine, Division of Hematology-Oncology, Wayne State University, University Health Center, 5-C, 4201 St. Antoine, Detroit, MI 48201.
Dr. Fitzgerald: Department of Medical Education, University of Michigan, G-1100 Towsley Center 0201, Ann Arbor, MI 40109-0201.
Dr. Chandrasekar: Division of Infectious Diseases, Department of Medicine, Wayne State University, Harper Hospital, 4-Yellow Center, 3990 John R., Detroit, MI 48201.
Author Contributions: Conception and design: A.S. Prasad, P.H. Chandrasekar.
Analysis and interpretation of the data: A.S. Prasad, J.T. Fitzgerald, B. Bao, F.W.J. Beck.
Drafting of the article: A.S. Prasad, J.T. Fitzgerald.
Critical revision of the article for important intellectual content: A.S. Prasad.
Final approval of the article: A.S. Prasad, P.H. Chandrasekar.
Provision of study materials or patients: A.S. Prasad, P.H. Chandrasekar.
Statistical expertise: J.T. Fitzgerald.
Obtaining of funding: A.S. Prasad.
Administrative, technical, or logistic support: A.S. Prasad, F.W.J. Beck.
Collection and assembly of data: J.T. Fitzgerald, B. Bao, F.W.J. Beck.

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Ananda S. Prasad, James T. Fitzgerald, Bin Bao, et al. 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.2000;133:245-252. [Epub 15 August 2000]. doi:10.7326/0003-4819-133-4-200008150-00006

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