Low-protein formula with alpha-lactalbumin in early infancy: Effects on protein metabolism, immune response and growth

Low-protein formula with alpha-lactalbumin in early infancy -Effects on protein metabolism, immune response and growth Background: Formula-fed (FF) infants have higher protein intake during infancy than breastfed (BF) infants, which may lead to higher weight gain and increased risk of overweight.Enrichment with alpha-lactalbumin-enriched whey (-lac-EW) or casein glycomacropeptide-reduced whey (CGMP-RW) to infant formula may enable further reduction of formula protein by improving the amino acid profile.BF infants have lower risk of infections, where the higher -lac content in breast milk may promote a more favorable gut microbiota.The aims of this thesis were to evaluate if feeding low-protein (LP) infant formula with -lac-EW or CGMP-RW would affect nutrient intake, protein metabolism, immune response and growth to be more similar to BF infants compared to feeding standard infant formula (SF), during and after intervention.Method: In a double-blinded prospective controlled trial, 245 healthy term infants were randomized to one of two LP formulas: -lac-EW (1.75 g protein/100 kcal, 27% -lac) or CGMP-RW (1.76 g protein/100 kcal, 14% -lac), or SF (2.2 g protein/100 kcal, 10% -lac) from 2 to 6 months, with a follow-up visit at 12 months.BF infants served as the reference.Growth, dietary intake and health outcomes were assessed, and serum analysed for insulin, C-peptide, IGF-1 and cytokines, and in a subgroup of 200 infants, urea and amino acids in serum and metabolomics in serum, urine and faeces.Results: Growth was mostly higher in FF compared to BF infants during intervention.Both LP groups had similar blood urea nitrogen (BUN) to BF infants.Serum branched chain amino acids (BCAAs) were lower in LP groups than in SF group, but still higher than in BF infants during intervention.Weight gain 6-12 months and BMI at 12 months were higher in SF than BF, but similar in LP groups and BF.Serum insulin at 12 months was higher in SF than BF group, but comparable in LP groups and BF infants.BF infants displayed a more efficient oxidation in serum and of disposal of BCAAs in urine than all FF groups.Faecal metabolome remained different in BF and FF groups throughout the intervention.Cytokines were similar in all study groups, except for interleukin-6 that was higher in all FF than in BF.Morbidity did not differ among the study groups during the intervention. Conclusions:Feeding LP formula with -lac-EW or CGMP-RW during early infancy was safe and resulted in normal growth and protein metabolism more similar to BF infants.The similar weight gain, BMI and serum insulin postintervention in LP groups and BF infants, indicate that a reduced protein intake early in infancy, through lower serum BCAAs may have induced imprinting effects on insulin secretion and growth post-intervention.A reduced protein intake during early infancy could thus decrease the risk of childhood overweight.Despite improved formula protein quantity and quality, BF infants were found to oxidate and eliminate excessive amino acids and side-products more efficiently than FF infants, indicating that protein adjustment alone in infant formula do not fully replicate the metabolic effects of breast milk.The lack of effect of increased -lac concentration in formula on inflammatory response and morbidity, as well as the different faecal metabolome in BF than in all FF groups throughout the intervention, indicate that other factors than protein influence the gut microbiota and thus probably the immune response.