Immunological effects of alpha-lactalbumin-enriched low-protein infant formula: A randomized controlled trial.

Objectives: Breast-fed (BF) have lower risk of infections during infancy compared to those formula-fed (FF). A higher content of alpha-lactalbumin (α-lac) in breast milk, which may promote a more favorable gut microbiota, could be one reason. In this study, we evaluated whether increased concentration of α-lac in low-protein infant formula affects the immune response and the incidence of infections during infancy.

Methods: In a double-blinded randomized controlled trial, healthy-term infants (n = 245) received low-protein infant formulas with α-lac-enriched whey (α-lac-EW; 1.75 g protein/100 kcal, 27% α-lac) or casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal, 14% α-lac), or standard formula (SF; 2.2 g protein/100 kcal, 10% α-lac) from 2 to 6 months. BF constituted a reference group. Cytokines and high-sensitivity C-reactive protein (hsCRP) were measured during intervention and infection-related morbidity, and treatment was evaluated until 12 months.

Results: Serum interleukin-6 (IL-6) was lower in BF than in all FF groups during intervention (p < 0.001). No other differences in cytokines (tumor necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGF-β1], TGF-β2, IL-1, IL-10, IL-12, interferon gamma [INF-γ]) or hsCRP were found among the study groups. Infection-related morbidity did not differ among study groups, except slight differences in the use of antibiotics during (α-lac-EW vs. CGMP-RW [p = 0.008]) and after intervention (α-lac-EW vs. BF [p = 0.016]).

Conclusions: Increased α-lac concentration in low-protein infant formula to levels similar to breast milk did not affect the cytokine profile and had minor effect on infection-related morbidity. The higher IL-6 concentrations in FF than in BF needs further investigation.