Preclinical perspectives on common iron fortificants and their bioavailability in rat models: a systematic review and meta-analysis.

BACKGROUND: Numerous preclinical studies on improving iron bioavailability to address iron deficiency anemia have been published; however, no preclinical systematic reviews with pairwise meta-analyses have been conducted. Therefore, it is essential to systematically review, summarize, and evaluate the evidence regarding the effects of iron fortificants in animal studies. METHODS: The initial articles were identified in four scientific databases (PubMed, Web of Science Core Collection, Scopus, and EBSCO) on 10 January 2026. The final included articles were collected after the initial articles were scanned and sorted. The data were extracted for pairwise meta-analysis. Hemoglobin (Hb) was the primary outcome. RESULTS: A total of 23 studies were included in this systematic review. Data from 13 rat experiments, including 56 comparisons, were analyzed using pairwise meta-analysis. The results of the meta-analysis showed that the overall effects of sodium iron ethylenediaminetetraacetate (NaFeEDTA) and ferrous fumarate on Hb were equivalent to those of ferrous sulfate (FeSO4). Ferric pyrophosphate (FePP) and ferric orthophosphate (FePO4) were inferior to FeSO4. CONCLUSION: The meta-analysis results suggest that both NaFeEDTA and ferrous fumarate are effective in improving Hb concentration. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/recorddashboard, CRD420261280933.