ALFoNS - Growth and Metabolism in Infants Fed Protein-reduced, Alpha-lactalbumin Enriched Formula Compared to Breastfed Infants

Background: Breast milk is the best source of nutrition for the rapidly growing infant since it contains all the necessary nutrients in the right proportions. If the mother cannot breast-feed, chooses not to breast-feed or has to stop early, an adapted formula is from a nutritional perspective the only alternative during the first four to six months of age and also the best alternative throughout the rest of the first year of life together with suitable complementary foods. Formula composition has through the years developed to resemble as close as possible the composition of breast milk resulting in physiological effects in the infant to more resemble that of the breast-fed infant. However, there are still considerable differences between the dietary intake of the breast-fed infant and its metabolism compared to infants who are fed formula. Furthermore, research suggests that breast-fed infants have a lower risk of overweight and obesity in childhood and adolescence, lower risk of acute otitis media (AOM), upper airway- and gastrointestinal infections, and possibly a lower risk of high blood pressure and diabetes type 2 as adults which probably depend on different protein composition and concentration in formula and breastmilk. The optimal protein level of formula is still under debate. The investigators know that the protein concentration of formula is unnecessarily high, but until now it has been difficult to reduce it further due to the potential risk of shortage of some of the essential amino acids, i.e. those amino acids that have to be delivered from the diet.

The concentration of alpha-lactalbumin, the predominating whey protein in breast milk, is still low in formula. The composition of the protein in breast milk and formula thus differs considerably and consequently also the amino acid pattern in serum between infants who are breast-, or formula-fed. Alpha-lactalbumin has many potential positive effects which may explain some of the differences between breast-fed and formula-fed infants and when added to formula makes it more similar to the composition of breast milk. Alpha-lactalbumin contains a higher concentration of cysteine, a precursor of taurine, which is important for neurodevelopment. However, it is foremost the concentration of tryptophan that is higher in alpha-lactalbumin, an amino acid which otherwise is a limiting factor when lowering the protein level in formula. Tryptophan is a precursor of serotonin, a neurotransmitter important for stress management, cognition under stress and sleep latency.

Recently, new whey protein sources which contain higher concentrations of alpha-lactalbumin have become available. Studies show that protein is still too high in formula resulting in higher concentrations of urea nitrogen and most amino acids in infants who are fed formula compared to those who are breast-fed, which indicates that formula-fed infants still have excessive protein intake. Thus, there should be no problem in further reducing the protein level of formula during the first 6 months of life by increasing the proportion of alpha-lactalbumin. In this way the investigators might achieve a growth pattern and a metabolism more similar to that of the breast-fed infant. Acid whey protein is already in use today by some producers to obtain whey to casein ratio more similar to that of breast milk and to increase the concentration of tryptophan, which is an alternative, in increasing the proportion of alpha-lactalbumin. In this study the investigators intend to study both possibilities.

Alpha-lactalbumin has been suggested to influence the gut bacterial flora with a positive antimicrobial effect and improved immune function of the infant. Hypothetically, an increased intake of alpha-lactalbumin may result in fewer infections in formula-fed infants and thus decrease the differences in infection prevalence between formula- and breast-fed infants. Alpha-lactalbumin also seems to influence the uptake of minerals, such as iron, which could be important for iron status of the infant. Thus, iron status may improve in formula-fed infants when alpha-lactalbumin is added to formula, which has previously been shown by us and others.

With metabolomics, chemical processes involving metabolites, small molecule substrates, intermediates and products of metabolism are studied. Specifically, metabolomics is identifies a unique chemical fingerprints that specific cellular processes leave behind". Differences in metabolomics between the different groups will be studied Objectives: The purpose of the present study is to evaluate the effect of feeding infants a protein-reduced infant formula with high or low levels of alpha-lactalbumin on growth, metabolic markers and gut microbiota composition.