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Cited by 41Iron Metabolism and DisordersInfant Nutrition and HealthChild Nutrition and Water Access

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

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Mikulic, Nadja, Uyoga, Mary A, Mwasi, Edith, Stoffel, Nicole U, Zeder, Christophe, Karanja, Simon, Zimmermann, Michael B·2020·The Journal of Nutrition
DOI 10.1093/jn/nxaa226
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Abstract

Background Whether lactoferrin (Lf) binds iron to facilitate its absorption or to sequester iron from potential enteropathogens remains uncertain. Bovine Lf is added to many infant formulas, but previous studies in infants reported that Lf had no effect on or inhibited iron absorption. The effects of the apo (iron-free) or the holo (iron-loaded) forms of Lf on iron absorption are unclear.Objectives Our objective was to compare iron absorption from a maize-based porridge containing: 1) labeled ferrous sulfate (FeSO4) alone; 2) labeled FeSO4 given with bovine apo-Lf; and 3) intrinsically labeled bovine holo-Lf.Methods In a crossover study, we measured iron absorption in Kenyan infants (n = 25; mean ± SD age 4.2 ± 0.9 months; mean ± SD hemoglobin 109 ± 11 g/L) from maize-based test meals containing: 1) 1.5 mg of iron as 54Fe-labeled FeSO4; 2) 1.42 mg of iron as 58Fe-labeled FeSO4, given with 1.41 g apo-Lf (containing 0.08 mg iron); and 3) 1.41 g holo-Lf carrying 1.5 mg iron as 57Fe. The iron saturation levels of apo- and holo-Lf were 0.56% and 47.26%, respectively primary outcome was fractional iron absorption (FIA), assessed by erythrocyte incorporation of isotopic labels.Results The FIA from the meal containing apo-Lf + FeSO4 (geometric mean, 9.8%; -SD and +SD, 5.4% and 17.5%) was higher than from the meals containing FeSO4 (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 when comparing the meals containing holo-Lf versus FeSO4 alone (P = 0.24).Conclusions The amount of iron absorbed from holo-Lf was comparable to that of FeSO4, and the addition of apo-Lf to a test meal containing FeSO4 significantly increased (+56%) iron absorption. These findings suggest that Lf facilitates iron absorption in young infants. Because Lf binds iron with high affinity, it could be a safe way to provide iron to infants in low-income countries, where iron fortificants can adversely affect the gut microbiome and cause diarrhea. This study was registered at clinicaltrials.gov as NCT03617575.

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  • Transferrin and lactoferrin have been implicated in nutritional immunity by iron sequestration from invading pathogens, with evidence that lactoferrin can increase iron absorption by 56%.

    “Transferrin and lactoferrin have been implicated in nutritional immunity by iron sequestration from invading pathogens, with evidence that lactoferrin can increase iron absorption by 56% [46-48].”

    From Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota (2021) · cites this paper as [47]

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Research works printed but not linked: 3

  1. [2]2. Baker HM, Baker EN. A structural perspective on lactoferrin function. Biochem Cell Biol 2012;90(3):320-8.
  2. [11]11. Lonnerdal B. Iron in human milk and cow's milk-effects of binding ligands on bioavailability. In Lonnerdal B, editor. Iron metabolism in infants. Boca Raton (FL): CRC Press; 1990;87-107.
  3. [41]41. Baker HMand Baker EN. A structural perspective on lactoferrin function. Biochem Cell Biol 2015;90:320-8.

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Authors
Mikulic, N., Uyoga, M. A., Mwasi, E., Stoffel, N. U., Zeder, C., Karanja, S., & Zimmermann, M. B.
Affiliations
  • ETH Zurich (CH)
  • Jomo Kenyatta University of Agriculture and Technology (KE)
Corresponding author
Mikulic, Nadja
ORCID
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2020-12
Volume
150
Issue
12
Pages
3200-3207
ISSN
0022-3166 (ISSN-L)
DOI
10.1093/jn/nxaa226
OpenAlex
W3083499910
Cited by
41
References
42
Citations by year
2026: 4 · 2025: 7 · 2024: 9 · 2023: 4 · 2022: 10 · 2021: 5 · 2020: 2
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition (publishedVersion)
  • PubMed (publishedVersion)
  • Repository for Publications and Research Data (ETH Zurich) (publishedVersion, other-oa)
  • ETH Zürich Research Collection
Funders
Eidgenössische Technische Hochschule Zürich
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
  • Health Sciences › Nursing › Nutrition and Dietetics › Child Nutrition and Water Access
Keywords
lactoferrin, iron absorption, apo-lactoferrin, ferrous sulfate, iron stable isotopes, erythrocyte iron incorporation, infant formula, iron deficiency, iron saturation, hemoglobin, anemia
MeSH terms
Biological Transport, Female, Ferrous Compounds, Humans, Infant, Iron, Iron Isotopes, Kenya, Lactoferrin, Male, Milk, Human, Cross-Over Studies, Infant Formula

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