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TCIM Research

Jennifer Hunter (2021-2022 WINNER)

Published on 10/2/2023

Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials

Jennifer Hunter1, Susan Arentz2, Joshua Goldenberg3, Guoyan Yang4, Jennifer Beardsley4, Stephen P Myers2,5, Dominik Mertz6, Stephen Leeder7

1 NICM Health Research Institute, Western Sydney University, Penrith, New South Wales, Australia
2 NICM Health Research Institute, Western Sydney University, Penrith, New South Wales, Australia.
3 Helfgott Research Institute, National University of Natural Medicine, Portland, Oregon, USA.
4 Seattle, Washington, USA.
5 National Centre for Naturopathic Medicine, Southern Cross University, Lismore, New South Wales, Australia.
6 Division of Infectious Diseases, Department of Medicine, Health Sciences, McMaster University, Hamilton, Ontario, Canada.
7 The Menzies Centre for Health Policy, The University of Sydney, Sydney, New South Wales, Australia.


Objective: To evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults.

Seventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Twenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD -1.20 points, 95% CI -0.66 to -1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD -0.15, 95% CI -0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality).

In adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted.