ZincAcetate / gluconate lozenges · 4 claims

The 2024 Cochrane review covered 34 trials and 8,526 participants. On duration it concluded there is probably little or no difference: mean difference −0.63 days (95% CI −1.29 to 0.04), I²=77%, 3 studies, 740 participants, moderate certainty. Confidence across the review was mostly low to very low, and most studies were at unclear or high risk of bias in at least one domain.

A published critique disputes the pooling. Hemilä and Chalker argue the analysis mixed lozenges with capsules, powders, tablets, syrups and intranasal routes — despite the proposed mechanism being local action in the mouth and throat — and mixed a paediatric trial in with adult ones despite significant heterogeneity between them (P=0.0001).

Re-analysing the same Cochrane-included trials, restricted to lozenges in adults and using ratio of means, they report colds shortened by 37% (95% CI 27–46%, P=10⁻⁹). Earlier work found 33% across seven trials at above 75 mg/day.

Both analyses are defensible. Which one you believe turns on whether you think route of administration should have been separated before pooling.

• MetaNault D, et al. Zinc for prevention and treatment of the common cold Cochrane Database Syst Rev 2024 · doi 10.1002/14651858.CD014914.pub2 · 34 trials, 8,526 participants
• MetaHemilä H, Chalker E. Shortcomings in the Cochrane review on zinc for the common cold (2024) Front Med 2024;11:1470004 · PMID 39478818 · re-analysis RoM 0.63

Cochrane found little or no reduction in the risk of developing a cold: RR 0.93 (95% CI 0.85 to 1.01), I²=20%, 9 studies, 1,449 participants, low certainty. The interval crosses 1. Over five to eighteen months of follow-up, the mean number of colds also showed no clear difference.

A separate 2021 rapid review of 28 trials and 5,446 participants reported zinc preventing roughly 5 upper respiratory infections per 100 person-months, with a number needed to treat of 20 — a modest effect at best.

The distinction matters commercially. Zinc is sold as immune support, implying prevention. The stronger case is for shortening a cold you have already caught.

• MetaNault D, et al. Prevention outcomes RR 0.93, 9 studies, 1,449 participants, low certainty
• MetaHunter J, Arentz S, Goldenberg J, et al., as summarised in Merck Manual zinc entry BMJ Open 2021;11(11):e047474 · 28 trials, 5,446 participants

Between 2000 and 2009 the FDA received more than 130 reports of anosmia — permanent loss of the sense of smell — associated with intranasal zinc products. A 2009 advisory told consumers to stop using them and the formulations were voluntarily withdrawn. FDA analysis supported olfactory tissue damage as the mechanism.

Cochrane notes that trials of intranasal zinc did not themselves report anosmia cases and that information on specific side effects is uncertain. Four of the 34 included studies used intranasal administration.

The practical rule is simple and unaffected by the duration dispute: lozenges, never nasal sprays.

• RegFDA anosmia reports and 2009 advisory on intranasal zinc products, as collated Over 130 reports 2000–2009; voluntary market withdrawal
• MetaCochrane plain language summary: intranasal zinc and reported side effects No anosmia cases reported within included trials; side effect information uncertain

Over a dozen placebo-controlled trials produced varying results, and the composition of the lozenge and the zinc dose effectively explain the variation. In seven trials using acetate or gluconate lozenges above 75 mg/day elemental zinc, cold duration shortened by 33% (95% CI 21–45%, P=10⁻⁷).

A 2017 meta-analysis separating the salts found high-dose zinc acetate at above 75 mg/day achieved around 40% and gluconate around 28%. In three zinc acetate trials the recovery rate rose with a rate ratio of 3.1 (95% CI 2.1–4.7).

The origin story is worth knowing: the effect was noticed when a three-year-old with leukaemia let a zinc tablet dissolve in her mouth rather than swallowing it. Dissolution, not ingestion, is the whole proposition.

• MetaHemilä H, Chalker E, summarising dose and salt-form effects across the lozenge trial literature Front Med 2024;11:1470004
• MetaHemilä H. Zinc lozenges and the common cold: meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage JRSM Open 2017;8(5):2054270417694291