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Is zinc effective for treatment and prevention of the common cold?
The common cold is one of the most widespread illnesses, with adults averaging 2-4 episodes per year. Morbidity associated with the common cold is not trivial. The median duration of illness is 7.4 days, with 25% of cases lasting approximately 2 weeks. Although the exact mechanism of zinc treatment for the common cold is unknown, ionized zinc is thought to assist T cells which kill virus-infected cells. Ionized zinc may act by inhibiting the formation of viral capsid proteins and/or by stabilizing and protecting cell membranes. The majority of viral replication occurs within 1 day of symptom onset, and this is the time interval for which intervention might be most beneficial, although administration within 3 days may still have benefit.
A recent Cochrane review evaluated 13 therapeutic trials (966 patients) and 2 preventive trials (394 patients). Common cold duration was reduced if zinc was taken within the first 24 hours of cold symptom onset (standardized mean difference [SMD], -0.97; 95% confidence interval [CI], -1.56 to -.038, P = .001). Illness severity was also reduced (SMD, -0.39; 95% CI, -0.77 to -0.02, P = .04).
Another recent systematic review of 13 clinical trials evaluating zinc lozenges found similar benefit. The author hypothesized that substantial variation in study outcomes was the result of differences in the 7-fold variation in the total daily zinc dosage. Five of the studies reviewed used < 75 mg/day of zinc and none found a beneficial effect, whereas 7 of 8 comparisons using > 75 mg/day of zinc found statistical benefit. The author estimated that lozenges containing 75 mg/day or more of zinc could reduce the duration of colds by 32% (95% CI, 27%-37%) and possibly more with zinc acetate formulations.
Eby reviewed 15 randomized controlled trials of zinc lozenges and found efficacy to strongly correlate with ionized zinc content at physiologic concentration in a dose-response manner. Best results were achieved with lozenges having only 1 ligand (acetate or gluconate) and consequent high ionic zinc content. A lozenge with the same dose of zinc as another may have a different level of free zinc if it contains substances that bind zinc ions tightly, such as citrate, tartrate, or glycine. Products that do not release ionic zinc may, in fact, make colds worse. Zinc ions may also be partially inactivated due to complex formation by components of saliva.
Contact time is also important. Lozenges are thought to be most efficacious when dissolved slowly in the mouth over 20-30 minutes, releasing > 18 mg of zinc and administered every 2 hours. Intranasal administration of zinc is not recommended due to potential loss of the sense of smell (anosmia) which can be permanent. A recent FDA news release advised consumers to stop using intranasal zinc products due to several reports of anosmia.
The Cochrane review also found a favorable prophylactic effect of zinc administration upon the incidence of colds. The incidence rate ratio of developing a cold was less in the zinc group (0.64; 95% CI, 0.47-0.88, P = .006). Zinc supplementation in children resulted in fewer absentee days from school (SMD, -0.37; 95% CI, -0.7 to -0.04, P = .03).
Use of zinc lozenges can result in adverse effects such as nausea (possibly reduced by eating a small amount of food prior to administration), bad taste in the mouth, diarrhea, and dry mouth. The 2011 Cochrane review found zinc lozenges to be more likely to produce adverse effects (especially altered taste and nausea) than syrup formulations but possibly fewer systemic toxicities. Other adverse effects are possible. T-cell activity may be impaired by administration of 300 mg of zinc per day for 1 month or more. Large doses of zinc can compete with copper and manganese absorption, resulting in blood abnormalities. In addition, zinc lozenges (and presumably tablets and syrup) may cause drug-drug interactions through chelation of antimicrobials such as tetracyclines and fluoroquinolones.
The Cochrane review concluded that zinc lozenges or syrup administered within 24 hours of symptom onset reduces the duration and severity of the common cold in healthy people. Also, zinc supplementation for at least 5 months reduces cold incidence, school absenteeism, and prescription of antibiotics in children. However, due to differences in study populations, dosages, formulations, and duration of treatment, it is difficult to make firm recommendations about the duration, formulation, and duration of therapy.Use of zinc is advised with caution. Furthermore, due to lack of data, supplementation is not recommended for patients with underlying chronic illness, immunodeficiency, asthma, and other comorbidities for which common cold symptoms might be especially troublesome.
Researchers agree that more investigation is needed to define the optimal dose, duration, and formulation of zinc needed to produce clinical benefit without undue adverse effects. In the meantime, zinc acetate lozenges having 18 mg or more of ionized zinc used every 2 hours while awake has been suggested as an effective treatment for the common cold.
When given within 24 hours of onset of symptoms, zinc reduces the duration and severity of the common cold in healthy people, according to the results of a Cochrane systematic review reported online February 16 in the Cochrane Database of Systematic Reviews.
"This review strengthens the evidence for zinc as a treatment for the common cold," said lead author Dr. Meenu Singh, from the Post Graduate Institute of Medical Education and Research in Chandigarh, India, in a news release. "However, at the moment, it is still difficult to make a general recommendation, because we do not know very much about the optimum dose, formulation or length of treatment."
To evaluate the effect of zinc on common cold symptoms, the reviewers searched CENTRAL (2010, Issue 2), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May week 3, 2010), and EMBASE (1974 to June 2010). Inclusion criteria were randomized, double-blind, placebo-controlled trials in which zinc was used for 5 or more consecutive days to treat the common cold, or for 5 or months or longer for prevention. Data were independently extracted and trial quality examined by 2 reviewers.
The search identified 13 therapeutic trials enrolling a total of 966 participants, and 2 preventive trials enrolling a total of 394 participants, that met selection criteria. Zinc intake was associated with a significant decrease in duration of common cold symptoms (standardized mean difference [SMD], −0.97; 95% confidence interval [CI], −1.56 to −0.38; P = .001), as well as in severity (SMD, −0.39; 95% CI, −0.77 to −0.02; P = .04).
The proportion of participants symptomatic after 7 days of treatment was lower in the zinc group vs the control group (odds ratio [OR], 0.45; 95% CI, 0.2 - 1.00; P = .05). The zinc group also fared better than the control group in incidence rate ratio (IRR) for development of a cold (IRR, 0.64; 95% CI, 0.47 - 0.88; P = .006), school absence (P = .0003), and prescription of antibiotics (P < .00001).
However, overall adverse events were higher in the zinc group (OR, 1.59; 95% CI, 0.97 - 2.58; P = .06), as were bad taste (OR, 2.64; 95% CI, 1.91 - 3.64; P < .00001) and nausea (OR, 2.15; 95% CI, 1.44 - 3.23; P = .002).
"Our review only looked at zinc supplementation in healthy people," Dr. Singh said. "But it would be interesting to find out whether zinc supplementation could help asthmatics, whose asthma symptoms tend to get worse when they catch a cold."
Limitations of this review also include those inherent in the individual studies, such as placebo-blinding adequately described in only 6 trials, and allocation concealment unclear in 5 studies.
"[U]nlike trials relying on experimentally-induced rhinoviral colds, findings from large community-based trials will address issues relating to the diversity of and generalisability to the common cold," the review authors conclude. "In addition, given its toxicological profile, the potential for zinc to induce adverse effects at the doses participants are required to take also needs to be determined."
The study authors have disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online February 16, 2011. Abstract
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