Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula: A Randomized Controlled Trial

Maria Björmsjö, Olle Hernell, Bo Lönnerdal, Staffan K Berglund, Maria Björmsjö, Olle Hernell, Bo Lönnerdal, Staffan K Berglund

Abstract

Objectives: Compared to formula-fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti-infective and anti-inflammatory protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants.

Methods: In a double-blind controlled trial, term formula-fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low-iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low-iron formula with no added lactoferrin (Lf-; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula [CF]; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age.

Results: No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF-β)1, TGF-β2, tumor necrosis factor alfa (TNF-α) or interleukin2 (IL-2) at 4, 6, or 12 months, except of higher TGF-β2 at 6 months in the CF group in comparison to the low iron groups combined (P = 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months.

Conclusions: Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well-nourished and healthy population.

Trial registration: ClinicalTrials.gov NCT02103205.

Conflict of interest statement

The authors report no other conflicts of interest.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Figures

FIGURE 1
FIGURE 1
Trial profile. Three infants discontinued intervention due to gastrointestinal symptoms (n = 2, CF, LF+) and extensive eczema (n = 1, LF−). They remained in the study. Six infants were lost to follow-up due to early withdrawal (n = 2, Lf−, BF), gastrointestinal side effects (n = 3, CF) and extensive data collection (n = 1, BF). Additional four infants were lost to follow up at 12 months of age (reasons not given). BF = breastfed; CF = control formula; Lf− = no added lactoferrin; Lf+ = added lactoferrin.

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Source: PubMed

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