The study reported by Macknin et al1 in this issue of THE JOURNAL on zinc gluconate lozenges for treating children with the common cold represents yet another wave of single-agent assaults on this common malady. The evidence this study provides is welcome, even though no beneficial effects of zinc lozenges on treatment of the common cold among school-aged children are demonstrated. The authors are laudably forthcoming regarding the potential biases in their well-executed study. They also set an appropriately high methodologic standard for future studies and allude to design improvements in future trials that will advance this field.
It is notable that children in the study still experienced adverse effects at what the authors consider to be relatively low doses of zinc lozenges (a total of 50-60 mg/d). These adverse effects probably enabled the students to discern what treatment they were receiving. Zinc lozenge–related adverse effects, although not severe, combined with the prescribed frequency of dosing (ie, 5-6 times per day) mitigate against adherence to treatment in everyday life. Thus, the effectiveness of zinc lozenges can be expected to be quite less than that demonstrated in efficacy trials.
This study is preceded by at least 10 randomized controlled trials of zinc lozenges for adult patients with colds (5 trials had positive results and 5 had negative results) and no less than 3 reviews of some of the same trials.2 - 4 Several theories exist as to why zinc should palliate the common cold. One theory maintains that the zinc ion blocks human rhinovirus adhesion to the nasal epithelium, as observed in vitro. Although rhinoviruses account for a substantial proportion of upper respiratory tract infections, several other viruses contribute to the epidemiology of upper respiratory tract infection. It is unclear whether zinc inhibits viral docking to epithelial cells for viruses other than rhinovirus. Other theories for the zinc effect invoke immune enhancement, cytoprotection, and anti-inflammatory effects that may curtail upper respiratory tract infections.
The lack of a specific theoretical framework for a zinc effect is troublesome and reminiscent of prior attempts to cure the common cold with other immunologically active micronutrients, such as vitamin C and vitamin A. Like these vitamins, zinc has immune-enhancing properties at the deficiency end of the nutritional spectrum; however, too much zinc can be toxic to the immune system for the replete host. Although zinc inhibition of viral docking is intriguing, the retrospective application of the theoretical framework for how zinc works for the common cold is bothersome and has created confusion in this literature. Thus, the search for the "magic bullet" that will relieve the multitude of symptoms associated with the common cold continues.
Zinc appears to have an important role in child health in developing countries. Zinc supplementation in the range of 10 to 20 mg/d has been shown to be effective in reducing diarrheal disease, improving growth and immune response, and enhancing neuropsychological functions of malnourished preschool children in a number of developing countries.5 - 9 Presumably, these children are responsive because they were zinc deficient, although assessing zinc status is difficult. Thus, zinc supplementation may have an important role in similarly disadvantaged, lower socioeconomic settings with low dietary zinc intake or a high incidence of diarrheal disease.
However, demonstrating the effects of zinc lozenges on the common cold in largely nutritionally replete children may be quite difficult, although mild zinc deficiency has been demonstrated in various parts of the United States.10 The effect sizes are likely to be small and require a commensurably large sample size. More objective and sensitive measures of treatment response also are required. The long-term effect of taking many grams of zinc a few times a year during childhood also must be considered. The specter of regular zinc treatment of the common cold has been described as a "kind of uncontrolled nutritional experiment"10 with potential effects on growth, immune function, neurology, and other micronutrient statuses of children, who developmentally have more at stake than adults.
Evidence to support recommendations for zinc lozenges for common cold treatment for children is lacking at this time. More research is needed before zinc can be recommended for this purpose. But it remains an intriguing therapy to pursue, especially if (1) other viruses are inhibited by zinc, (2) palatable forms of bioavailable zinc ions can be developed, (3) the frequency of dosing can be reduced, (4) adverse effects can be reduced, and (5) there are no long-term implications of zinc supplementation during childhood. Future trials among children and adolescents should use formulations with adequate zinc ion availability; address issues of treatment adherence, palatability, and dose frequency of the lozenge; perform virologic testing; and control for comorbidity among children in the study design. The study by Macknin et al1 by no means closes the door on zinc gluconate lozenges. Rather, it opens the field to more studies among children in different geographic locales, with more varied socioeconomic and dietary risk factors, and during cold seasons plagued by other viruses.
Practitioners will be faced with the parent who asks, "If not an antibiotic, if not a cough and cold medicine, if not zinc, then what can I give my child for this cold?" It is difficult to answer this question in an evidence-based manner. Although many alternative therapies for the common cold have been described,11 none has the weight of evidence behind it to warrant recommendation at this time. Fortunately, the common cold is usually a benign, self-limited infection that affords clinicians the luxury of waiting for more data before being pressed to make therapeutic recommendations.
The regularity with which medical findings seem to reverse themselves in the public eye is producing a great deal of skepticism. Physicians, patients, and the public are frequently bombarded by new developments but often lose the thread of the plodding science needed to critically appraise and evaluate the final outcome of those new developments. It would be important for clinicians to present information on zinc to parents in an even-handed manner because many parents are already asking about zinc, probably are trying it themselves, and are eager to provide relief to their children. It becomes incumbent on the practitioner to sort out the chaos of the medical information the public encounters, restore a critical appraisal of new developments, and present a balanced picture of the risks and benefits of potential cures—while waiting for the final analysis—all in the 10 minutes or less allotted to the acute care visit.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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