**2. Methods**

#### *2.1. Search Strategy, Selection Criteria, and Data Extraction*

A computerized literature search of MEDLINE and the Cochrane database did not identify any previous systematic reviews on the prevalence of zinc deficiency in IBD. The present systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, adhering to the PRISMA 27-item checklist [11]. An *a priori* protocol for the search strategy and inclusion criteria was established and recorded, with no particular changes to the information provided at registration on PROS-PERO, a prospective international registry of systematic reviews (CRD42023330824). We

performed separate searches in the US National Library of Medicine (PubMed), Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, Scopus, Ovid, and Google Scholar to retrieve original articles investigating serum zinc levels and the prevalence of zinc deficiency in IBD populations. The primary objective was to assess a pooled prevalence of a plasma zinc concentration deficit in IBD settings. We also considered the gray literature using the massive preprint archive https://arxiv.org/in (accessed on 1 August 2020) in the study selection phase, and the database http://www.opengrey.eu/to (accessed on 1 August 2020) to access notable conference abstracts and other non-peerreviewed material. No exclusion criteria were applied to language, the defined deficiency status cut-off, nor population age, general health status, country, recruitment settings (hospital, community, or home care), and study setting (trials, cohort, or cross-sectional). We used only original articles investigating IBD populations and providing disease-specific prevalence data separately for Crohn's and ulcerative colitis, as an inclusion criterion.

The research strategy used in PubMed and MEDLINE and adapted to the other four electronic sources included the keywords "zinc", "inflammatory bowel disease", "Crohn's disease", and "ulcerative colitis" combined through the use of Boolean indicators such as "AND" and "OR". The search strategy used the Boolean indicator "NOT" to rule out letters, revisions, and meta-analyses. The literature search had no time restriction, and papers were retrieved until 1 May 2022. No language restrictions were made. Two researchers (RZ, AS) conducted the searches, reviewed titles and abstracts of articles retrieved separately and in duplicate, checked full texts, and selected the papers for inclusion in the study. Technical reports, letters to the editor, and systematic and narrative review articles were excluded. Inter-rater reliability (IRR) was used to estimate inter-coder agreement and the κ statistic to measure accuracy and precision. In accordance with PRISMA concepts and the quality assessment steps, a coefficient k of at least 0.9 was obtained in all data extraction steps [12].
