Abstract：
Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, 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 transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved 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. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.
摘要：
补充锌可降低发病率，但是有证据表明，过量摄入会对健康产生负面影响。从成人数据推断幼儿锌摄入量上限（ULs）的当前指南。本系统综述(PROSPERO；注册号。CRD42020215187）旨在确定在幼儿中观察到不利影响的锌摄入量水平。在MEDLINE中确定了报告0-3岁儿童锌摄入潜在不利影响的研究（从开始到2020年8月），Embase,还有Cochrane图书馆,对研究设计没有限制。对锌摄入的临床和物理影响进行了叙述，并对生化结局进行荟萃分析.随机效应模型用于生成森林地块，以按年龄类别检查证据，剂量,剂量持续时间，锌的化学式，和锌与安慰剂相比。乔安娜·布里格斯研究所关键评估清单，偏差2的Cochrane风险，以及建议评估的分级，发展,和评估（GRADE）指南用于评估偏倚风险并评估证据的确定性。58项研究评估了3至70mg/d锌剂量的可能不良反应。来自39项研究的数据有助于荟萃分析。补锌对血清铁蛋白有不良影响，血浆/血清铜浓度，血清转铁蛋白受体，血红蛋白,血细胞比容,和≥1个亚组的贫血几率。补充锌可提高乳果糖：甘露醇比例，对C反应蛋白没有显著影响，红细胞超氧化物歧化酶，锌原卟啉，血胆固醇,缺铁性贫血。证据的确定性,根据等级评估，非常低到中等。尽管在一些亚组中观察到补锌可能的不良反应，目前尚不清楚这些发现是否具有临床意义.合成数据可用于进行剂量反应分析，以更新当前的幼儿锌摄入量ULs指南。
