REF-1597 · Nault et al., 2024 · Cochrane Database of Systematic Reviews 2024, issue · Paper · PubMed · Free full text

Across 34 placebo-controlled trials in 8526 children and adults (no athletes described), zinc taken to prevent colds may make little or no difference to the risk of catching one (RR 0.93, 95% CI 0.85 to 1.01; low certainty), zinc started once a cold has begun may shorten it by about two days (−2.37 days, −4.21 to −0.53; low certainty, trials highly inconsistent), and treatment probably brings more non-serious side effects (RR 1.34; moderate certainty). From the abstract

Main caveat: Written from the abstract; trial-level details of forms, doses and timing were not read.
fairly strong evidenceMeasured on a mixed groupRead from the abstract only

Nault and colleagues pooled placebo-controlled randomised trials of zinc, in any form, given to children or adults either to prevent colds and upper respiratory infections or to treat them.

They searched MEDLINE, Embase, CENTRAL, LILACS and CINAHL up to 22 May 2023, and Web of Science and two trial registries up to 14 June 2023, and judged risk of bias with the Cochrane tool and certainty with GRADE. Thirty-four trials with 8526 participants qualified: 15 on prevention and 19 on treatment, 22 in adults and 12 in children, 18 of them in the USA.

Half used lozenges, zinc gluconate most often. Most trials had an unclear or high risk of bias in one domain or more. Taken for prevention, zinc may make little or no difference to the chance of a cold or the number of colds, and probably little or no difference to how long a cold lasts once it comes.

Started when a cold is under way, zinc may shorten it, though the trials disagree widely, and it probably brings more non-serious side effects. The authors stress the wide variation in products, co-treatments and outcomes and the incomplete reporting.

Participants

34 trials, 8526 participants; 22 trials in adults, 12 in children.
Settings: USA 18; India, Indonesia, Iran and Turkey two each; eight more countries one each (Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, UK).
Prevention trials (15): common cold (8) or upper respiratory infection (7); treatment trials (19): almost all (17) common cold.

Protocol

Search: MEDLINE, Embase, CENTRAL, LILACS and CINAHL up to 22 May 2023; Web of Science Core Collection and two trial registries to 14 June 2023; reference checking, citation searching and contact with authors.
Eligibility: randomised trials, any form of zinc against placebo, prevention or treatment of the common cold or upper respiratory infection; zinc combined with other minerals, vitamins or herbs excluded.
Primary outcomes: proportion developing colds (prevention only), cold duration in days, adverse events attributable to zinc, and complications of the cold.
Forms: 17 of 34 trials used lozenges (3 prevention, 14 treatment) of acetate, gluconate or orotate, gluconate most often (9 of 17); the other 17 used capsules (1), dissolved powders (3), tablets (5), syrups (4) or nasal zinc (4).
Funding and interests: one author reports US National Institutes of Health funding for Cochrane Complementary Medicine, paid to the institution; one is a statistical editor for the Cochrane respiratory infections group with no role in this review; the others declare none.

Key Results

OutcomeEffect (95% CI)Trials (people)Certainty
Prevention: developing a coldRR 0.93 (0.85 to 1.01); I² 20%9 (1449)low
Prevention: number of colds over 5-18 monthsMD −0.90 (−1.93 to 0.12); I² 96%2 (1284)low
Prevention: duration of colds that occurred (days)MD −0.63 (−1.29 to 0.04); I² 77%3 (740)moderate
Prevention: global symptom severitySMD 0.04 (−0.35 to 0.43); I² 0%2 (101)low
Prevention: adverse eventsRR 1.11 (0.84 to 1.47); I² 0%7 (1517)very low
Prevention: serious adverse eventsRR 1.67 (0.78 to 3.57); I² 0%3 (1563)low
Treatment: duration of the cold (days)MD −2.37 (−4.21 to −0.53); I² 97%8 (972)low
Treatment: cold still present at the end of follow-upRR 0.52 (0.21 to 1.27); I² 65%5 (357)very low
Treatment: global symptom severitySMD −0.03 (−0.56 to 0.50); I² 78%2 (261)very low
Treatment: change in global symptom severityRR 1.02 (0.85 to 1.23)1 (114)low
Treatment: non-serious adverse eventsRR 1.34 (1.15 to 1.55); I² 44%16 (2084)moderate
Thirty-one trials (2422 participants) reported non-serious adverse events; no treatment trial reported serious adverse events, and no trial gave clear information on complications of the cold.

Practical Application

Zinc taken to prevent colds may make little or no difference, while zinc taken once a cold has started may shorten it by about two days, probably with more minor side effects: across 34 trials in children and adults (no athletes described), prevention made little or no difference (RR 0.93, 95% CI 0.85 to 1.01) and treatment −2.37 days (−4.21 to −0.53), both low certainty.
The treatment estimate swings widely between trials (I² 97%), so how much a given product, form or dose helps is not known; picolinate is not among the forms the abstract names.
Zinc changes none of the illness rules: a fever means stop, and training resumes gradually after it has resolved (REF-609); most respiratory illness costs a day of training or less (SYNTH-36); illness in athletes goes with heavy load, competition, travel and short sleep (PHYS-35).
A published critique lists shortcomings of the review (Hemilä and Chalker 2024, Frontiers in Medicine, DOI 10.3389/fmed.2024.1470004); it was not read here, so its arguments are not stated.
Not from this paper; the base's own practice: trial any supplement in training first and choose third-party-tested products (SYNTH-67).

Limitations

Written from the abstract; trial-level details of forms, doses and timing were not read.
Children and adults; no athletes.
The treatment effect is very inconsistent between trials (I² 97%) and low certainty.
Most trials with an unclear or high risk of bias in one domain or more; incomplete reporting.
A published critique lists shortcomings of the review (not read).
Searches ran to mid-2023.
How this entry was checked and changed
Why this level

risk of bias read in the abstract: most trials had an unclear or high risk of bias in one domain or more, and the efficacy outcomes are low or very low certainty (moderate only for cold duration in the prevention trials and for side effects in the treatment trials), which caps a review at A- (rule 1)