A zinc supplement might help stave off the symptoms of respiratory tract infections (RTI), such as coughing, congestion, and sore throat, and cut illness duration, suggests a pooled analysis of the available evidence, in BMJ Open. None of the trials specifically looked at the use of zinc for the prevention or treatment of COVID-19.
But the quality of the evidence on which these findings are based is variable, and itʼs not clear what an optimal formulation or dose of this nutrient might be, caution the researchers.
Respiratory tract infections include colds, flu, sinusitis, pneumonia, and COVID-19. Most infections clear up by themselves, but not all. And they often prove costly in terms of their impact on health services and time taken in sick leave.
Zinc has a key role in immunity, inflammation, tissue injury, blood pressure, and in tissue responses to lack of oxygen. As a result, it has generated considerable interest during the current pandemic for the possible prevention and treatment of COVID-19 infection.
In response to calls for rapid evidence appraisals to inform self-care and clinical practice, the researchers evaluated zinc for the prevention and treatment of SARS-CoV-2, the virus responsible for COVID-19, and other viral respiratory tract infections.
When that review was published, the results of several relevant clinical trials werenʼt yet available, so this current review brings the available evidence up to date.
The review includes 28 clinical trials involving 5446 adults, published in 17 English and Chinese research databases up to August 2020. None of the trials specifically looked at the use of zinc for the prevention or treatment of COVID-19.
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.
Pooled analysis of the results of 25 trials showed that compared with dummy treatment (placebo), zinc lozenges or nasal spray prevented five respiratory tract infections in 100 people a month. These effects were strongest for curbing the risk of developing more severe symptoms, such as fever and influenza-like illnesses. But this is based on only three studies. On average, symptoms cleared up two days earlier with the use of either a zinc spray or liquid formulation taken sublingual than when a placebo was used.
During the first week of illness, participants who used sublingual or nasal spray zinc were nearly twice as likely to recover as those who used placebo: 19 more adults out of 100 were likely to still have symptoms a week later if they didnʼt use zinc supplements.
While zinc wasnʼt associated with an easing in average daily symptom severity, it was associated with a clinically significant reduction in symptom severity on day 3.
Side effects, including nausea and mouth/nose irritation, were around 40% more likely among those using zinc, but no serious side effects were reported in the 25 trials that monitored them.
However, compared with placebo, sublingual zinc didnʼt reduce the risk of developing an infection or cold symptoms after inoculation with human rhinovirus, nor were there any differences in illness duration between those who used zinc supplements and those who didnʼt.
Nor was the comparative effectiveness of different zinc formulations and doses clear. And the quality, size, and design of the included studies varied considerably.
“The marginal benefits, strain specificity, drug resistance and potential risks of other over-the-counter and prescription medications make zinc a viable ‘naturalʼ alternative for the self-management of non-specific [respiratory tract infections], the researchers write.
“[Zinc] also provides clinicians with a management option for patients who are desperate for faster recovery times and might be seeking an unnecessary antibiotic prescription,” they add.
“However, clinicians and consumers need to be aware that considerable uncertainty remains regarding the clinical efficacy of different zinc formulations, doses and administration routes, and the extent to which efficacy might be influenced by the ever-changing epidemiology of the viruses that cause [respiratory tract infections],” they caution.
And how exactly zinc might exert its therapeutic effects on respiratory infections, including COVID-19, warrants further research, they conclude.
Study details
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 Hunter, Susan Arentz, Joshua Goldenberg, Guoyan Yang, Stephen Myers, Dominik Mertz, Stephen Leeder.
Published in British Medical Journal on 2 November
Abstract
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.
Method
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.
Results
Twenty-eight RCTs with 5446 participants were identified. None was 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).
Conclusions
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 was 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.
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