Zinc Supplementation Reduces Common Cold Duration among Healthy Adults: A Systematic Review of Randomized Controlled Trials with Micronutrients Supplementation
Authors: Min Xian Wang
Junxiong Pang
Shwe Sin Win
Journal: American Journal of Tropical Medicine and Hygiene (2020)
Discipline: CLINICAL MEDICINE
Keywords: common cold; vitamin C; micronutrients; zinc; vitamin D
Affiliations: Centre for Infectious Disease Epidemiology and Research, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

Abstract:  The common cold had resulted in significant economic and social burden worldwide. The effect of vitamin C on preventing common cold in healthy adults has been investigated extensively, but not that of other micronutrients. Thus, we aim to assess the effects of providing micronutrients singly through oral means, on cold incidence, and/or management (in terms of cold duration and symptom severity) in healthy adults from systematically searched randomized controlled trials. From four electronic databases, 660 identified studies were screened and data were extracted from 20 studies (zinc, 10; vitamin D, 8; and vitamins A and E, 2). The quality of selected studies was assessed using the Cochrane risk of bias tool and certainty in the outcomes was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. The review found that micronutrients supplementation, except vitamin C, may not prevent cold incidence or reduce symptom severity among healthy adults. However, zinc supplementation was observed to potentially reduce cold duration by 2.25 days (when zinc is provided singly, 95% CI: -3.39, -1.12). This suggests that zinc supplementation may reduce the overall burden due to common cold among healthy adults. 

Retracted: No

PubPeer comments:
 **Several errors in the analysis of micronutrients for colds** Wang et al. [1] write in their abstract that u201c*zinc supplementation was observed to potentially reduce cold duration by 2.25 days (when zinc is provided singly, 95% CI: -3.39, -1.12). This suggests that zinc supplementation may reduce the overall burden due to common cold among healthy adults*u201d. The estimate of 2.25 days is based on 6 controlled trials, all of which used zinc lozenges (Fig 3 [1]). There is strong evidence that zinc lozenges have a treatment effect on colds [2-7]; however, none of the previous meta-analyses on zinc lozenges was cited by Wang. There is no evidence that traditional zinc supplementation has effects on cold duration. Instead, two trials in which nasal zinc application was beneficial [8,9] gives additional support to the concept that it is the local administration of zinc in the oral-pharyngeal-nasal region that explains the benefit in the 6 zinc lozenge trials in Wangu2019s Fig. 3 [1]. Wang et al. wrote that in the zinc trials there was u201c*serious inconsistency observed (I2 = 83%, P 0.00001)*u201d. However, there is no inconsistency if the relative scale is used [6,7]. The inconsistency reported by Wang is explained by inappropriate scale and including trials that had low doses of zinc. Wang further writes: u201c*Effects on pneumonia prevention: Vitamins A and E: Only one study reported the effects of micronutrient supplementation on pneumonia prevention (ref. 28)*u201d. However, ref. 28 did not study vitamin A. It studied beta-carotene [10]. Wang further writes of their ref. 28: u201c*none of the changes in pneumonia risk were statistically significant (vitamin A, RR: 0.98, 95% CI: 0.84, 1.13; vitamin E, RR: 1.03, 95% CI: 0.89, 1.19).*u201d The beta-carotene finding is for 26,148 participants aged 50 to 64 years, whereas the vitamin E findings is for all the 29,133 participants (ie also 65-69 years were included in the vitamin E estimate). Thus, Wang extracted the above findings from different lines of Table 3 [10], though presents them as if they were comparable. Furthermore, in the Discussion section Wang et al. describe that in the same trial (ref. 28[10]) there was strong evidence of heterogeneity in the effects of beta-carotene [i.e. not vitamin A] and vitamin E (Wang references 53-55)[11-13]. Therefore the estimates for the entire participant population shown in their Results section are irrelevant. When there is strong evidence of heterogeneity, a single overall estimate is misleading. In the Discussion section, Wang et al. also write: u201c*Comparatively, vitamin E supplementation can prevent pneumonia incidence by an additional 3% in nonsmoking subjects (ref 55).*u201d However, it is not evident where the 3% comes from ref. 55 [13]. Table 2 in ref. 55 reported that u201c*Effect of vitamin E on the occurrence of pneumonia in nonsmoking males by leisure-time exercise: Total: RR = 0.28 (95% CI 0.11-0.69)*u201d[13]. 1. https: www.ncbi.nlm.nih.gov pmc articles PMC7356429 2. https: www.ncbi.nlm.nih.gov pmc articles PMC3136969 3. https: www.ncbi.nlm.nih.gov pmc articles PMC4359576 4. https: www.ncbi.nlm.nih.gov pmc articles PMC5061795 5. https: www.ncbi.nlm.nih.gov pmc articles PMC5410113 6. https: www.ncbi.nlm.nih.gov pmc articles PMC5418896 7. https: www.ncbi.nlm.nih.gov pmc articles PMC5427521 8. https: doi.org 10.1177 014556130007901008 9. https: doi.org 10.1093 qjmed hcg004 10. https: doi.org 10.1378 chest.125.2.557 11. https: doi.org 10.3177 jnsv.64.374 12. https: www.ncbi.nlm.nih.gov pmc articles PMC3046185 13. https: www.ncbi.nlm.nih.gov pmc articles PMC5055121 ,