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

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.