Comparative Effects between Oral Lactoferrin and Ferrous Sulfate Supplementation on Iron-Deficiency Anemia: A Comprehensive Review and Meta-Analysis of Clinical Trials

Systematic review and meta-analysis of 11 clinical trials in participants with iron deficiency or iron-deficiency anemia. Most studies enrolled women, especially pregnant women at high risk for IDA, with some nonpregnant women and some healthy participants.

Oral lactoferrin was evaluated as the active supplement across 11 clinical trials, with pooled active-arm N = 680. It was compared with ferrous sulfate for correction of iron deficiency or iron-deficiency anemia; the extracted record does not report the lactoferrin dose, formulation, or treatment duration.

Overall, lactoferrin performed better than ferrous sulfate for improving iron status and erythropoiesis, although ferrous sulfate showed higher fractional iron absorption. Compared with ferrous sulfate, lactoferrin improved serum iron by WMD 41.44 ug/dL (95% CI: 26.29, 56.59; I2 = 98%), ferritin by WMD 13.6 ng/mL (95% CI: 4.53, 22.66; I2 = 99%), and hemoglobin by WMD 11.80 g/L (95% CI: 8.19, 15.41; I2 = 96%). Lactoferrin also reduced IL-6 by WMD −45.59 pg/mL (95% CI: −50.82, −40.36; I2 = 85%), while fractional iron absorption was lower by WMD −2.08% (95% CI: −3.85, 0.31; I2 = 0%). The authors concluded that lactoferrin may be a superior option for improving iron status and hemoglobin, but additional research is needed to confirm the anti-inflammatory effect and iron-absorption findings.

The evidence base was small and highly heterogeneous, with very high I2 values for several key outcomes. Most trials involved pregnant women, limiting generalizability, and dose/formulation details were not consistently reported in the extracted record. The authors also noted the need for more research to clarify anti-inflammatory effects and iron-absorption dynamics.