In a recent publication in BMJ, researchers explored the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults.
The review included 28 clinical trials involving 5,446 adults and was published in 17 English and Chinese research databases. None of the trials specifically examined the use of zinc for the prevention or treatment of COVID-19. The researchers indicated that the most common zinc formulations used were lozenges, followed by nasal sprays and gels containing either zinc acetate or gluconate salts. Doses varied substantially depending on the formulation and whether zinc was used for prevention or treatment.
The pooled analysis of the results of 25 trials revealed that compared with placebo, zinc lozenges or nasal spray prevented five RTIs in 100 individuals a month. Three of the studies suggested that zinc was effective in curbing the risk of severe symptoms, including fever and influenza-like illness.
The researchers found that, 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 decreases 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 (standardized MD -0.15, 95% CI -0.43 to 0.13, low certainty/quality).
Nonserious adverse events (AEs) (e.g., nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, number needed to harm [NNHarm] = 7, moderate certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low certainty/quality), and no serious AEs were reported in the 25 randomized, controlled trials that monitored them (low certainty/quality).
The authors wrote, "The marginal benefits, strain specificity, drug resistance and potential risks of other over-the-counter and prescription medications makes zinc a viable 'natural' alternative for the self-management of non-specific [respiratory tract infections]."
The authors concluded that in adult populations unlikely to be zinc-deficient, there was some evidence suggesting zinc might prevent RTI symptoms and shorten duration. They also noted that nonserious AEs may limit tolerability for some and that the comparative efficacy/effectiveness of different zinc formulations and doses were uncertain. The GRADE certainty/quality of the evidence was limited by a high risk of bias, small sample sizes, and/or heterogeneity.
The authors also noted, "We were unable to answer questions about the comparative efficacy, effectiveness and acceptability of different zinc formulations and doses, and their mechanisms of action. Prior to recommending zinc, patient preferences, financial and opportunity costs, and availability of different zinc interventions should be considered. Clarification of the efficacy and mechanism of zinc in viral respiratory infections, including SARS-CoV-2 infections, warrants further research."
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