The provision of essential and non-essential amino acids for breast-fed infants is the major function of milk proteins. In addition, breast-fed infants might benefit from bioactivities of milk proteins, which are exhibited in the intestine during the digestive phase and by absorption of intact proteins or derived peptides. For lactoferrin, osteopontin and milk fat globule membrane proteins/lipids, which have not until recently been included in substantial amounts in infant formulas, in vitro experiments and animal models provide a convincing base of evidence for bioactivities, which contribute to the protection of the infant from pathogens, improve nutrient absorption, support the development of the immune system and provide components for optimal neurodevelopment. Technologies have become available to obtain these compounds from cow´s milk and the bovine compounds also exhibit bioactivities in humans. Randomized clinical trials with experimental infant formulas incorporating lactoferrin, osteopontin, or milk fat globule membranes have already provided some evidence for clinical benefits. This review aims to compare findings from laboratory and animal experiments with outcomes of clinical studies. There is good justification from basic science and there are promising results from clinical studies for beneficial effects of lactoferrin, osteopontin and the milk fat globule membrane complex of proteins and lipids. Further studies should ideally be adequately powered to investigate effects on clinically relevant endpoints in healthy term infants.

Animal studies show that the lactation period contributes to metabolic programming of the offspring and that oral leptin and insulin show bioactivity. Stage of lactation, duration of gestation, maternal body composition, and maternal diet seem to influence the concentrations of small molecules in human milk. Variability of small molecule concentrations seems higher in preterm milk than in term milk. Insulin in human milk shows concentrations similar to plasma. Leptin concentration is lower in milk than in plasma and reflects maternal body mass index. Early in lactation, leptin could contribute to mediating the association between maternal and infant body composition.