Mikulic · The Journal of nutrition 2020 · randomized crossover trial · n=25

Iron Absorption is Greater from Apo-Lactoferrin and is Similar Between Holo-Lactoferrin and Ferrous Sulfate: Stable Iron Isotope Studies in Kenyan Infants.

Cited 42 times in the scientific literature.

Level 2 - randomized trial

Individual randomized crossover trial

PubMed 32886113 · doi:10.1093/jn/nxaa226 · record verified 2026-08-29

What was done

In a crossover trial, researchers measured fractional iron absorption (FIA) using stable iron isotopes in 25 Kenyan infants (mean age 4.2 ± 0.9 months; mean hemoglobin 109 ± 11 g/L). Each infant received three maize-based test meals: 1) 1.5 mg iron as 54Fe-labeled ferrous sulfate (FeSO4); 2) 1.42 mg iron as 58Fe-labeled FeSO4 given with 1.41 g bovine apo-lactoferrin (apo-Lf; 0.56% iron saturation); and 3) 1.41 g bovine holo-lactoferrin (holo-Lf; 47.26% iron saturation) carrying 1.5 mg iron as 57Fe. FIA was determined by erythrocyte incorporation of the isotopic labels.

What was found

FIA was significantly higher from the apo-Lf + FeSO4 meal (geometric mean: 9.8%; -SD and +SD: 5.4% and 17.5%) than from FeSO4 alone (geometric mean: 6.3%; -SD and +SD: 3.2% and 12.6%; P = 0.002) or holo-Lf (geometric mean: 5.0%; -SD and +SD: 2.8% and 8.9%; P < 0.0001). There was no significant difference in FIA between holo-Lf and FeSO4 alone (P = 0.24). Adding apo-Lf to FeSO4 increased fractional iron absorption by 56%.

Why it matters

This study shows that bovine apo-lactoferrin enhances iron absorption from ferrous sulfate in young infants, while holo-lactoferrin provides comparable iron bioavailability to ferrous sulfate alone. This suggests lactoferrin may serve as an effective vehicle or enhancer for infant iron supplementation in settings where poorly absorbed iron risks adverse gut microbiome effects.

Limits

The trial had a small sample size (n = 25) in a single geographic cohort of Kenyan infants. It evaluated single-meal isotope absorption rather than sustained long-term feeding, and clinical outcomes such as microbiome alterations, diarrhea incidence, and iron status improvement were not measured.

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