Is Iron Combined With Lactoferrin More Effective Than Iron Alone in Improving Iron Metabolism in Children With or Without Anemia? A Systematic Review and Meta-analysis of Controlled Clinical Trials

CONTEXT: Lactoferrin (LF), a major iron-binding protein, has been proposed as a delivery system through which iron can be absorbed from human milk to enhance iron status. However, the effects of combining LF with iron on iron status in children remain to be comprehensively evaluated. OBJECTIVE: To investigate whether iron combined with bovine LF is more effective than iron alone in improving iron status in children with or without anemia, thereby clarifying the potential adjuvant role of LF in anemia therapy. DATA SOURCES: A systematic search of PubMed, Web of Science, Embase, and the Cochrane Library was conducted for clinical trials published up to December 2024. DATA EXTRACTION: Population characteristics and mean difference (MD) in iron metabolism indicators were extracted and analyzed. A random-effects model was used to estimate pooled effects. RESULTS: A total of 160 studies were identified, of which 10 were included in qualitative synthesis and 8 in meta-analysis. Overall, LF supplementation showed an additional effect on serum ferritin compared with iron alone (MD, 3.52 µg/L; 95% CI, 0.66-6.38; P = .02). However, no significant effects were observed on hemoglobin, serum iron, or serum transferrin receptor levels (all P > .05). CONCLUSION: The combination of LF and iron did not improve hemoglobin status in children with or without anemia compared with iron alone, but it modestly increased serum ferritin. These findings suggest that LF may play a specific adjuvant role in regulating iron storage rather than enhancing hemoglobin levels. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021259371.