Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial.Abstract Effective treatments for the common cold have been difficult to develop because so many different types of virus are responsible for this condition. Oral zinc has been studied as a possible means of preventing or alleviating symptoms, with mixed results. We studied a new approach to zinc therapy--an over-the-counter nasal gel formulation (Zicam)--to independently evaluate its efficacy as a treatment for the common cold. Our study was conducted at four sites over a 5-month period. The study group consisted of 213 patients with recent-onset ([less than or equal to]24 hr) cold symptoms; 108 patients received zinc therapy, and 105 received placebo. Symptom charts were used to track the duration and severity of each patient's symptoms. At study's end, the duration of symptoms was 2.3 days ([+ or -]0.9) in the zinc group and 9.0 days ([+ or -]2.5) in the control group--a statistically significant difference (p[less than]0.05). These results provide evidence that zinc nasal gel is effective in shortening the duratio n of common cold symptoms when taken within 24 hours of their onset. Introduction The common cold is caused by a viral infection viral infection, n an infection by a pathogenic virus. A virus acts on the cell nucleus, taking over the genetic material within the nucleus and replicating itself. in the nose. [1] Its symptoms, which vary in severity, include sneezing To verbally tell somebody about a new and interesting Web site. See viral marketing. , rhinorrhea, nasal congestion nasal congestion ENT Difficulty in nasal breathing, due to an ↑ vascular thickness of nasal mucosa. See Nasal stuffiness. , sore and/or scratchy throat, cough, hoarseness, and mild general symptoms such as headache, fever, and body aches. [1,2] Of the more than 100 different cold viruses, the most important are rhinoviruses. [3] The lack of effective treatments for the common cold is of concern because adults contract an average of approximately three colds each year, and children experience twice as many. [2] The number of work days lost to cold-related illness is substantial. [4] The use of zinc formulations for the treatment of common cold symptoms has been receiving increasing attention in the medical literature as well as in the lay press. Some studies in humans have shown that zinc lozenges were effective in shortening the duration of common cold symptoms in adults. [5-7] There have also been some negative reports concerning the use of zinc lozenges, but these findings appear to be related to the use of formulations that did not allow the release of ionized i·on·ize tr. & intr.v. i·on·ized, i·on·iz·ing, i·on·iz·es To convert or be converted totally or partially into ions. i zinc into the oral cavity oral cavity n. The part of the mouth behind the teeth and gums that is bounded above by the hard and soft palates and below by the tongue and the mucous membrane connecting it with the inner part of the mandible. . [8,9] It has been shown that ionized zinc has direct antirhinoviral activity, [10,11] protects cells from damage by viral toxins, [12] and might inhibit the rhinovirus' ability to attach to enter, and infect human nasal cells. [13] Recently, a new approach to zinc therapy--an over-the-counter nasal gel formulation (Zicam)--was the subject of a preliminary study (C.B. Hensley, PhD, and R. Davidson, PhD, unpublished data, 1999). That study demonstrated that the direct application of the nasal gel containing 33 mmol/L of ionic zinc within 24 hours of the onset of common cold symptoms significantly shortened the duration of those symptoms. The researchers hypothesized that the delivery of ionic zinc directly to the site of infection should be more effective than oral delivery. The goal of our study was to attempt to reproduce those results and independently assess the effect of zinc nasal gel on the duration of common cold symptoms. Materials and methods Our methodology was similar to that used by Mossad et al in their clinical evaluation clinical evaluation Medtalk An evaluation of whether a Pt has symptoms of a disease, is responding to treatment, or is having adverse reactions to therapy of zinc lozenges in l996. [7] Subjects were recruited at four sites in the Los Angeles area. The study population consisted of 213 subjects; they were randomly assigned to receive either zinc nasal gel (n = 108) or placebo (n = 105). Only subjects whose cold symptoms had been manifest for 24 hours Adv. 1. for 24 hours - without stopping; "she worked around the clock" around the clock, round the clock or less were enrolled in the study. Subjects were required to have had at least three of the following symptoms: cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat Sore Throat Definition Sore throat, also called pharyngitis, is a painful inflammation of the mucous membranes lining the pharynx. It is a symptom of many conditions, but most often is associated with colds or influenza. , or sneezing. All participants provided informed consent upon enrollment. Exclusion criteria were pregnancy, an immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). state, a duration of common cold symptoms beyond 24 hours, and the use of certain medications. Both gels were dispensed in a double-blind fashion in metered doses of 120 [micro]l in applicators supplied by Botanical Laboratories (Ferndale, Wash.). Subjects were instructed to spray one dose into each nostril nostril /nos·tril/ (nos´tril) either of the nares. nos·tril n. A naris. nostril either of the two apertures (nares) of the nose that lead into the nasal cavity. every 4 hours (9 a.m., 1 p.m., 5 p.m., and 9 p.m.) for as long as they experienced symptoms. Participants were instructed not to take any other cold remedies or any drugs that might affect symptom scores. The zinc nasal gel consisted of zinc gluconate in an emulsion of benzalkonium chloride, glycerin glycerin /glyc·er·in/ (-in) a clear, colorless, syrupy liquid used as a laxative, an osmotic diuretic to reduce intraocular pressure, a demulcent in cough preparations, and a humectant and solvent for drugs. Cf. glycerol. , hydroxyethylcellulose, sodium chloride, and sodium hydroxide; its pH level was 7.2. The compositio n of the placebo gel was identical except that it did not contain zinc. Patients were provided with a diary to document the severity of their symptoms. Twice each day (at 9a.m. and 9p.m.), patients graded each of nine symptoms on a scale of 0 (absent) to 3 (severe). The total daily symptom scores were added together, and the mean and standard deviations were calculated for each patient. The primary endpoint was the complete resolution of symptoms, which was determined when the total symptom score fell to zero. Subjects were asked to return to their study site within 24 hours of symptom resolution for verification and followup. Results The duration of each patient's cold was defined as the number of days from study entry to the complete resolution of symptoms. The zinc nasal gel had a significant effect in shortening their duration (figure 1). The mean resolution time was 2.3 days ([+ or -]0.9) for the zinc patients and 9.0 days ([+ or -]2.5) for the controls (figure 2). The difference was statistically significant (p[less than]0.05). Subjects had also been provided a list of five potential side effects (nausea, bad taste reactions, odor, dizziness, and drowsiness) and asked during the study and again at the end of the study whether they had experienced these or any others. While none of the subjects reported any of these five side effects, 45 zinc patients (42%) and 39 controls (37%) did report that they had experienced a slight tingling tin·gle v. tin·gled, tin·gling, tin·gles v.intr. 1. To have a prickling, stinging sensation, as from cold, a sharp slap, or excitement: tingled all over with joy. or burning sensation. Discussion The 75% difference in the duration of symptoms in our study is consistent with the 85% reduction reported by C.B. Hensley, PhD, and R. Davidson, PhD (unpublished data, 1999). Although zinc nasal gel's precise mechanism of action has yet to be elucidated, data suggest that ionic zinc has a direct effect on the ability of rhinovirus rhinovirus Any of a group of picornaviruses capable of causing common colds in humans. The virus is thought to be transmitted to the upper respiratory tract by airborne droplets. to infect and/or reinfect Re`in`fect´ v. t. 1. To infect again. the nasal epithelium. [10,11] Zinc ions form complexes with rhinovirus coat proteins. This interaction causes an irreversible alteration in the coat proteins and interferes with the assembly mechanism of the virus particles. [11] In addition, Novick et al reported that ionized zinc can directly inhibit the rhinovirus' ability to attach to, enter, and infect human nasal cells. [13] The crystalographically modeled surface features of human rhinovirus-14 provide binding sites for approximately 360 zinc ions. The binding of ionic zinc is stabilized by histidine histidine (hĭs`tĭdēn), organic compound, one of the 22 α-amino acids commonly found in animal proteins. Only the l-stereoisomer appears in mammalian protein. , methionine methionine (mĕthī`ənēn), organic compound, one of the 20 amino acids commonly found in animal proteins. Only the L-stereoisomer appears in mammalian protein. , tyrosine, and carboxyl/carboxylate groups that line the rhinovirus-14 surface canyons. I t has been proposed that this interaction blocks the rhinovirus' ability to dock with intercellular adhesion molecule Intercellular adhesion molecules are members a family of cell adhesion molecules. They include the following:
In conclusion, our results support the findings of the previous study on the effectiveness of zinc nasal gel. Further research is needed to understand the interaction of ionic zinc and rhinoviruses, as well as the extent of susceptibility of other viruses to this treatment. From the Center of Integrative Medicine, Tarzana, Calif. References (1.) Gwaltney JM Jr. The common cold. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed. New York: Churchill Livingstone, 1995:561-6. (2.) Gwaltney JM Jr., Hendley JO, Simon G, Jordan WS Jr. Rhinovirus infections in an industrial population. I. The occurrence of illness. N Engl I Med 1966;275:1261-8. (3.) Gwaltney JM Jr., Ruckert RR. Rhinovirus. In: Richman DD, Whitley RJ, Hayden FG, eds. Clinical Virology virology, study of viruses and their role in disease. Many viruses, such as animal RNA viruses and viruses that infect bacteria, or bacteriophages, have become useful laboratory tools in genetic studies and in work on the cellular metabolic control of gene expression . New York: Churchill Livingstone, 1997:1025-47. (4.) Couch RB. The common cold: Control? J Infect Dis 1984;150:167-73. (5.) Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25:20-4. (6.) Godfrey JC, Conant Sloane B, Smith DS, et al. Zinc gluconate and the common cold: A controlled clinical study. J Int Med Res 1992;20:234-46. (7.) Mossad SB, Macknin ML, Medendorp SV, Mason P. Zinc gluconate lozenges for treating the common cold. A randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. , double-blind, placebo-controlled study. Ann Intern Med 1996;125:81-8. (8.) Jackson JL, Lesho E, Peterson C, Zinc and the common cold: A meta-analysis revisited. J Nutr 2000; 130(5S Suppl): 1512S-5S. (9.) Macknin ML, Piedmonte M, Calendine C, et al. Zinc gluconate lozenges for treating the common cold in children: A randomized controlled trial A randomized controlled trial (RCT) is a scientific procedure most commonly used in testing medicines or medical procedures. RCTs are considered the most reliable form of scientific evidence because it eliminates all forms of spurious causality. . JAMA JAMA abbr. Journal of the American Medical Association 1998;279:1962-7. (10.) Korant BD, Kauer JC, Butterworth BE. Zinc ions inhibit replication of rhinoviruses. Nature 1974;248:588-90. (11.) Korant BD, Butterworth BE. Inhibition by zinc of rhinovirus protein cleavage: Interaction of zinc with capsid capsid /cap·sid/ (kap´sid) the shell of protein that protects the nucleic acid of a virus; it is composed of structural units, or capsomers. cap·sid n. polypeptides. J Virol 1976;18:298-306. (12.) Kelly RW, Abel MH. Copper and zinc inhibit the metabolism of prostaglandin by the human uterus. Biol Reprod 1983;28:883-9. (13.) Novick SG, Godfrey JC, Godfrey NJ, Wilder HR. How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action. Med Hypotheses 1996;46:295-302. |
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