AdverseEffectsofExcessiveZincIntakeinInfants andChildrenAged0–3Years:ASystematicReview andMeta-Analysis

Abstract

Zincsupplementationreducesmorbidity,butevidencesuggeststhatexcessiveintakescanhavenegativehealthconsequences.Currentguidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187)aimedtodeterminethelevelsofzincintakeatwhichadverseeffectsareobservedinyoungchildren.Studiesreportingpotential adverseeffectsofzincintakeinchildrenaged0–3ywereidentified(frominceptiontoAugust2020)inMEDLINE,Embase,andtheCochraneLibrary, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrinreceptor,hemoglobin,hematocrit,andtheoddsofanemiain≥1ofthesubgroupsinvestigated.Lactulose:mannitolratiowasimproved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. Thesynthesizeddatacanbeusedtoundertakeadose–responseanalysistoupdatecurrentguidelinesofULsofzincintakeforyoungchildren.