Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Zinc gluconate lozenges for treating the common cold in children: a randomized controlled trial. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. 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. Two randomized controlled trials of zinc gluconate lozenge therapy of experimentally induced rhinovirus colds. Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infections in Australian adults. Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges. Zinc gluconate and the common cold: a controlled clinical study. Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds.
Adults and children in the United States get two to six colds per year. Evidence that zinc is effective therapy for colds is inconsistent.
                To test the efficacy of zinc acetate lozenges in reducing the duration of symptoms of the common cold.
                Randomized, double-blind, placebo-controlled trial.
                Detroit Medical Center, Detroit, Michigan.
                50 ambulatory volunteers recruited within 24 hours of developing symptoms of the common cold.
                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.
                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.
                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 x 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]).
                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. The common cold is one of the most frequently occurring illnesses and is responsible for substantial morbidity and economic loss. Biochemical evidence suggests that zinc may be an effective treatment, and zinc gluconate glycine (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults.
                To determine the efficacy of ZGG treatment of colds in children and adolescents.
                A randomized, double-masked, placebo-controlled study.
                Two suburban school districts in Cleveland, Ohio.
                A total of 249 students in grades 1 through 12 were enrolled within the first 24 hours of experiencing at least 2 of 9 symptoms of the common cold.
                Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day (in grades 7-12).
                Time to resolution of cold symptoms based on subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing.
                Time to resolution of all cold symptoms did not differ significantly between students receiving zinc (n = 124) and those receiving placebo (n = 125) (median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no significant differences in the time to resolution of any of the 9 symptoms studied. Compared with controls, more students in the zinc group reported adverse effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05).
                In this community-based, randomized controlled trial, ZGG lozenges were not effective in treating cold symptoms in children and adolescents. Further studies with virologic testing are needed to clarify what role, if any, zinc may play in treating cold symptoms. The common cold is one of the most frequent human illnesses and is responsible for substantial morbidity and economic loss. No consistently effective therapy for the common cold has been well documented, but evidence suggests that several possible mechanisms may make zinc an effective treatment.
                To test the efficacy of zinc gluconate lozenges in reducing the duration of symptoms caused by the common cold.
                Randomized, double-blind, placebo-controlled study.
                Outpatient department of a large tertiary care center.
                100 employees of the Cleveland Clinic who developed symptoms of the common cold within 24 hours before enrollment.
                Patients in the zinc group (n = 50) received lozenges (one lozenge every 2 hours while awake) containing 13.3 mg of zinc from zinc gluconate as long as they had cold symptoms. Patients in the placebo group (n = 50) received similarly administered lozenges that contained 5% calcium lactate pentahydrate instead of zinc gluconate.
                Subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever (assessed by oral temperature).
                The time to complete resolution of symptoms was significantly shorter in the zinc group than in the placebo group (median, 4.4 days compared with 7.6 days; P < 0.001). The zinc group had significantly fewer days with coughing (median, 2.0 days compared with 4.5 days; P = 0.04), headache (2.0 days and 3.0 days; P = 0.02), hoarseness (2.0 days and 3.0 days; P = 0.02), nasal congestion (4.0 days and 6.0 days; P = 0.002), nasal drainage (4.0 days and 7.0 days; P < 0.001), and sore throat (1.0 day and 3.0 days; P < 0.001). The groups did not differ significantly in the resolution of fever, muscle ache, scratchy throat, or sneezing. More patients in the zinc group than in the placebo group had side effects (90% compared with 62%; P < 0.001), nausea (20% compared with 4%; P = 0.02), and bad-taste reactions (80% compared with 30%; P < 0.001),
                Zinc gluconate in the form and dosage studied significantly reduced the duration of symptoms of the common cold. The mechanism of action of this substance in treating the common cold remains unknown. Individual patients must decide whether the possible beneficial effects of zinc gluconate on cold symptoms outweigh the possible adverse effects. Zinc lozenges have been used for treatment of the common cold; however, the results remain controversial.
                Fifty ambulatory volunteers were recruited within 24 h of developing symptoms of the common cold for a randomized, double-blind, placebo-controlled trial of zinc. Participants took 1 lozenge containing 13.3 mg of zinc (as zinc acetate) or placebo every 2-3 h while awake. The subjective scores for common cold symptoms were recorded daily. Plasma zinc, soluble interleukin (IL)-1 receptor antagonist (sIL-1ra), soluble tumor necrosis factor receptor 1, soluble vascular endothelial cell adhesion molecule, and soluble intercellular adhesion molecule (sICAM)-1 were assayed on days 1 and 5.
                Compared with the placebo group, the zinc group had a shorter mean overall duration of cold (4.0 vs. 7.1 days; P < .0001) and shorter durations of cough (2.1 vs. 5.0 days; P < .0001) and nasal discharge (3.0 vs. 4.5 days, P = .02) Blinding of subjects was adequate, and adverse effects were comparable in the 2 groups. Symptom severity scores were decreased significantly in the zinc group. Mean changes in plasma levels of zinc, sIL-1ra, and ICAM-1 differed significantly between groups.
                Administration of zinc lozenges was associated with reduced duration and severity of cold symptoms. We related the improvement in cold symptoms to the antioxidant and anti-inflammatory properties of zinc. The therapeutic efficacy of zinc gluconate lozenge therapy in experimentally induced rhinovirus infection was assessed in two randomized controlled trials in susceptible adult volunteers. In trial 1, lozenges containing either zinc gluconate (23 mg of elemental zinc) or placebo were given 36 h after nasal inoculation of rhinovirus type 39 and administered eight times per day for 5 days. All of the volunteers had early cold symptoms at the time that treatment was begun. In trial 2, the same lozenge regimen was used, beginning 2 h after nasal inoculation with rhinovirus type 13, and continued for 7 days. Zinc therapy did not reduce the severity or duration of cold symptoms or the frequency or duration of viral shedding in either trial. Viral titers were measured in trial 2 and were shown to be unaffected by zinc therapy. Nasal mucus weights and the numbers of paper tissues used were slightly higher in zinc recipients. A statistically significant increase in levels of zinc in serum was documented in zinc recipients after 5 days of therapy. These data suggest that zinc gluconate lozenge therapy is not therapeutically useful in the treatment of rhinovirus colds. Effervescent lozenges containing 10 mg of zinc acetate were evaluated as a treatment of upper respiratory tract infections in a double-blind randomized trial by using a placebo which was indistinguishable to most observers in taste and appearance from the active material. Of the 70 treatment courses used by 55 individuals in 34 families, 63 (33 zinc and 30 placebo) were considered evaluable, in that the volunteer used the medication at least four times daily for at least 3 days, the average utilization being 5.4 days at an average dose of six lozenges daily. Six users of zinc reported nausea (versus no placebo users), and eight reported an unpleasant taste or aftertaste (versus one placebo user). No benefit was observed among the users of zinc acetate. The mean duration of symptoms in users of the zinc was 12.1 days, compared with 7.7 days in those who used the placebo. Nor was any beneficial effect of zinc evident among the four zinc-treated versus the two placebo-treated individuals from whom rhinovirus was grown. Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS) A report in 1984 on the success of zinc gluconate against common cold symptoms could not be confirmed in three subsequent studies, which are now known to have used formulations that inactivated zinc. A non-chelating formulation including glycine, which releases 93% of contained zinc into saliva, was tested in a randomized, placebo-controlled, double-blind trial in 73 young adults. Efficacy was recorded in symptom diaries using a symptom severity rating. Patients' symptoms first appeared 1.34 days prior to entry to the study in both groups. Disappearance of symptoms occurred after an additional 4.9 days for zinc-treated patients versus 6.1 days for placebo-treated patients. A difference was noted in the efficacy of treatment if it was started 1 day after symptom onset: cold duration was an additional 4.3 days in zinc-treated patients compared with 9.2 days for placebo-treated patients. Cough, nasal drainage and congestion were the symptoms most affected, and only mild side-effects were noted. Two clinical trials were conducted, one involving 273 subjects with experimental rhinovirus colds and the other involving 281 subjects with natural colds. Symptomatic volunteers were randomized to receive oral lozenges containing zinc gluconate (13.3 mg), zinc acetate (5 or 11.5 mg), or placebo. The median duration of illness in zinc gluconate recipients was 2.5 days, contrasted with 3.5 days in the placebo recipients (P=.035), in the experimental colds study. Zinc gluconate had no effect on symptom severity and zinc acetate had no effect on either duration or severity. Neither formulation had an effect on the duration or severity of natural cold symptoms. Evaluation of blinding, taste, and adverse events revealed no significant differences among the 4 treatment arms. Zinc compounds appear to have little utility for common-cold treatment.
Zinc administered within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people but some caution is needed due to the heterogeneity of the data. As the zinc lozenges formulation has been widely studied and there is a significant reduction in the duration of cold at a dose of ≥ 75 mg/day, for those considering using zinc it would be best to use it at this dose throughout the cold. Regarding prophylactic zinc supplementation, currently no firm recommendation can be made because of insufficient data. When using zinc lozenges (not as syrup or tablets) the likely benefit has to be balanced against side effects, notably a bad taste and nausea.