Methods of Assessment of Zinc Status in Humans: An Updated Review and Meta-analysis

Context The assessment of zinc status is difficult but essential for the identification of zinc deficiency and evaluation of interventions to improve zinc status. Objective The purpose of this systematic review (SR) and meta-analysis was to update the previously published SR of biomarkers of zinc status, conducted by the European Micronutrient Recommendations Aligned (EURRECA) network in 2009, to answer the question: Which putative measures (biomarkers) of zinc status appropriately reflect a change in zinc intake of at least 2 weeks? Data Sources A structured search strategy was used to identify articles published between January 2007 and September 2022 from MEDLINE (Ovid), Embase (Ovid), Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles were identified using previously defined eligibility criteria. Data Extraction Data were extracted and combined with data from the previous SR. Data Analysis A random-effects model was used to calculate pooled mean differences using STATA (StataCorp). The risk of bias and the certainty of evidence for all outcomes were assessed. Additional data on 7 of the 32 previously reported biomarkers were identified, along with data on an additional 40 putative biomarkers from studies published since 2007. Pooled data analysis confirmed that, in healthy participants, both plasma/serum zinc concentration and urinary zinc excretion responded to changes in zinc intake (plasma/serum: mean effect [95% CI], controlled studies: 2.17 mu mol/L [1.73, 2.61]; P < .005, I-2 = 97.8; before-and-after studies: 2.87 <mu>mol/L [2.45, 3.30]; P < .005, I-2 = 98.1%; urine zinc: 0.39 mmol/mol creatinine [0.17, 0.62]; P < .005, I-2 = 81.2; 3.09 mu mol/day [0.16, 6.02]; P = .039, I-2 = 94.3). Conclusion The updated analyses support the conclusion that plasma/serum and urinary zinc respond to changes in zinc intake in studies of healthy participants. Several additional putative biomarkers were identified, but more studies are needed to assess the sensitivity and reliability. Systematic Review Registration PROSPERO no. CRD42020219843.