Judy Stone, MD
November 08, 2021
A new study published in BMJ Open adds to the evidence that zinc is effective against viral respiratory infections, such as colds.
Jennifer Hunter, PhD, BMed, of Western Sydney University's NICM Health Research Institute, New South Wales, Australia, and colleagues conducted a meta-analysis of 28 randomized controlled trials (RCTs). They searched 17 English and Chinese databases to identify the trials and then used the Cochrane rapid review technique for the analysis.
The trials included 5446 adults who had received zinc in a variety of formulations and routes — oral, sublingual, and nasal spray. The researchers separately analyzed whether zinc prevented or treated respiratory tract infections (RTIs).
Oral or intranasal zinc prevented five RTIs per 100 person-months (95% CI, 1 – 8; numbers needed to treat, 20). There was a 32% lower relative risk (RR) of developing mild to moderate symptoms consistent with a viral RTI.
Use of zinc was also associated with an 87% lower risk of developing moderately severe symptoms (incidence rate ratio, 0.13; 95% CI, 0.04 – 0.38) and a 28% lower risk of developing milder symptoms. The largest reductions in RR were for moderately severe symptoms consistent with an influenza-like illness.
Symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI, 0.61 – 3.50; very low-certainty quality of evidence). There were clinically significant reductions in day 3 symptom severity scores (mean difference, -1.20 points; 95% CI, -0.66 to -1.74; low-certainty quality of evidence) but not in overall symptom severity. Participants who used sublingual or topical nasal zinc early in the course of illness were 1.8 times more likely to recover before those who used a placebo.
However, the investigators found no benefit of zinc when patients were inoculated with rhinovirus; there was no reduction in the risk of developing a cold. Asked about this disparity, Hunter said, "It might well be that when inoculating people to make sure they get infected, you give them a really high dose of the virus. [This] doesn't really mimic what happens in the real world."
On the downside of supplemental zinc, there were more side effects among those who used zinc, including nausea or gastrointestinal discomfort, mouth irritation, or soreness from sublingual lozenges (RR, 1.41; 95% CI, 1.17 – 1.69; number needed to harm, 7; moderate-certainty quality of evidence). The risk for a serious adverse event, such as loss of smell or copper deficiency, was low. Although not found in these studies, postmarketing studies have found that there is a risk for severe and in some cases permanent loss of smell associated with the use of nasal gels or sprays containing zinc. Three such products were recalled from the market.
The trial could not provide answers about the comparative efficacy of different types of zinc formulations, nor could the investigators recommend specific doses. The trial was not designed to assess zinc for the prevention or treatment of COVID-19.
Asked for independent comment, pediatrician Aamer Imdad, MBBS, assistant professor at the State University of New York Upstate Medical University, Syracuse, New York, told Medscape Medical News, "It's a very comprehensive review for zinc-related studies in adults" but was challenging because of the "significant clinical heterogeneity in the population."
Imdad explained that zinc has "absolutely" been shown to be effective for children with diarrhea. The World Health Organization has recommended it since 2004. "The way it works in diarrhea is that it helps with the regeneration of the epithelium.... It also improves the immunity itself, especially the cell-mediated immunity." He raised the question of whether it might work similarly in the respiratory tract. Imdad has a long-standing interest in the use of zinc for pediatric infections. In regards to this study, he concluded, "I think we still need to know the nuts and bolts of this intervention before we can recommend it more specifically."
Hunter said, "We don't have any high-quality studies that have evaluated zinc orally as treatment once you're actually infected and have symptoms of the cold or influenza, or COVID."
Asked about zinc's possible role, Hunter said, "So I do think it gives us a viable alternative. More people are going, 'What can I do?' And you know as well as I do people come to you, and [they say], 'Well, just give me something. Even if it's a day or a little bit of symptom relief, anything to make me feel better that isn't going to hurt me and doesn't have any major risks.' So I think in the short term, clinicians and consumers can consider trying it."
Hunter was not keen on giving zinc to family members after they develop an RTI: "Consider it. But I don't think we have enough evidence to say definitely yes." But she does see a potential role for "people who are at risk of suboptimal zinc absorption, like people who are taking a variety of pharmaceuticals [notably proton pump inhibitors] that block or reduce the absorption of zinc, people with a whole lot of the chronic diseases that we know are associated with an increased risk of worse outcomes from respiratory viral infections, and older adults. Yes, I think [for] those high-risk groups, you could consider using zinc, either in a moderate dose longer term or in a higher dose for very short bursts of, like, 1 to 2 weeks."
Hunter concluded, "Up until now, we all commonly thought that zinc's role was only for people who were zinc deficient, and now we've got some signals pointing towards its potential role as an anti-infective and anti-inflammatory agent in people who don't have zinc deficiency."
But both Hunter and Imdad emphasized that zinc is not a game changer. There is a hint that it produces a small benefit in prevention and may slightly shorten the duration of RTIs. More research is needed.
Hunter has received payment for providing expert advice about traditional, complementary, and integrative medicine, including nutraceuticals, to industry, government bodies, and nongovernmental organizations and has spoken at workshops, seminars, and conferences for which registration, travel, and/or accommodation has been paid for by the organizers. Imdad has disclosed no relevant financial relationships.