A new rapid systematic review and meta-analysis of randomised controlled trials shows zinc can prevent symptoms and shorten the duration of a community-acquired acute viral respiratory tract infections, such as the common cold and flu-like illnesses. When participants were purposely infected with human rhinovirus strains, the risk reduction was insignificant. Rhinovirus is one of the most common causes of upper respiratory tract infections. Other common respiratory viruses include coronavirus, adenovirus, parainfluenza virus, and influenza virus.
The review findings published today in BMJ Open) included 28 randomised controlled trials (RCTs), with 5,446 adult participants of all age groups. However, none of the RCTs were specific to SARS-CoV-2 due to results of those trials pending at the time.
The international team of researchers from Western Sydney University, the University of Sydney, Southern Cross University, McMaster University and the National University of Natural Medicine found that:
- *When zinc was used for prevention, there was a 28% lower risk of contracting symptoms consistent with the common cold and a 68% lower risk of contracting a flu-like illness. However, the protective effects of zinc were insignificant (4% lower risk) when participants were purposely infected with human rhinovirus.
- *When used for treatment, zinc was found to shorten the duration of symptoms by around 2 days and reduce day 3 symptomatic severity around the peak of illness, but the reduction in overall symptom severity were insignificant"
- *While there was an increased risk of non-serious adverse events that may limit tolerability for some (such as nausea or mouth and nasal irritation), the risk of serious adverse events (such as copper deficiency from oral zinc and loss of smell from zinc nasal sprays and gels) was low.
Integrative medicine doctor and lead author of the review, Associate Professor Jennifer Hunter from Western Sydney University's NICM Health Research Institute, said the findings build on previous systematic reviews and add important new evidence for the role of zinc as potentially more than a dietary supplement for zinc deficient populations.
"It is commonly thought that zinc's role in preventing and treating infections is only for people who are zinc deficient; our findings really challenge this notion," says Associate Professor Hunter.
"The two large trials from China found very low dose zinc nasal spray reduced the risk of clinical illness. The two smaller trials in the US that evaluated the preventive effects of oral zinc excluded people who were zinc deficient. All the other trials that evaluated zinc for treating the common cold were in populations where zinc deficiency is very unlikely."
However, Associate Professor Hunter says not all the review findings favoured zinc.
"Our systematic review was the first to include studies where participants were purposely infected with human rhinovirus, a common cause of upper respiratory tract infections. We found in these studies there was no significant protective effect from zinc lozenge use, either before or after being inoculated," Associate Professor Hunter says.
"These human rhinovirus trials were very small, making the findings unreliable. However, it still raises the questions about whether the insignificant antiviral effects that were observed from zinc in the laboratory also apply in the real world, at least against rhinoviruses."
The researchers also highlighted in their findings the challenges around the variability of zinc formulations and doses, and their mechanisms of action.
"Clinicians and consumers need to be aware that considerable uncertainty remains regarding the clinical efficacy of different zinc formulations, doses and administration routes," says Associate Professor Hunter.
"At the moment there just isn't enough research to say whether a zinc nasal spray, versus a nasal gel, versus a lozenge, versus oral zinc is any better or worse than the others. Most of the trials used zinc gluconate or zinc acetate formulations, but that doesn't mean that other zinc compounds are less effective."
Despite these uncertainties, Associate Professor Hunter says zinc products are widely available, affordable, and generally safe, including the short-term use of high dose zinc lozenges and capsules that was used in many of the trials.
"Two things people want to know when they get a cold is how long is it going to last, and how sick am I going to get? We found that zinc probably reduces the duration of illness and there were quite a few signals that told us that zinc has the potential to reduce severity, particularly at that peak time of illness between days 2 and 4. This provides clinicians and patients with a viable alternative to the inappropriate use of antibiotics, that continues to be a major problem globally," she says.
The review findings also align with calls for more immuno-nutrition research, particularly in populations with a higher SARS-CoV-2 risk, with the researchers commenting from the review findings and preliminary SARS-CoV-2 research, it is plausible that zinc may be effective when used on its own.
"Now well into the pandemic, and quickly learning that a lot of therapies that have worked for other viral infections don't necessarily work for COVID-19, we cannot assume the results apply to COVID-19," says Associate Professor Hunter.
