Protein intake is higher in formula-fed than in breast-fed infants during infancy, which may lead to an increased risk of being overweight. Applying alpha-lactalbumin (α-lac)-enriched whey or casein glycomacropeptide (CGMP)-reduced whey to infant formula may enable further reduction of formula protein by improving the amino acid profile. Growth, nutrient intake, and protein metabolites were evaluated in a randomized, prospective, double-blinded intervention trial where term infants received standard formula (SF:2.2 g protein/100 kcal; n = 83) or low-protein formulas with α-lac-enriched whey (α-lac-EW;1.75 g protein/100 kcal; n = 82) or CGMP-reduced whey (CGMP-RW;1.76 g protein/100 kcal; n = 80) from 2 to 6 months. Breast-fed infants (BF; n = 83) served as reference. Except between 4 and 6 months, when weight gain did not differ between α-lac-EW and BF (p = 0.16), weight gain was higher in all formula groups compared to BF. Blood urea nitrogen did not differ between low-protein formula groups and BF during intervention, but was lower than in SF. Essential amino acids were similar or higher in α-lac-EW and CGMP-RW compared to BF. Conclusion: Low-protein formulas enriched with α-lac-enriched or CGMP-reduced whey supports adequate growth, with more similar weight gain in α-lac-enriched formula group and BF, and with metabolic profiles closer to that of BF infants.

High protein intake during infancy results in accelerated early weight gain and potentially later obesity. The aim of this follow-up study at 12 months was to evaluate if modified low-protein formulas fed during early infancy have long-term effects on growth and metabolism. In a double-blinded RCT, the ALFoNS study, 245 healthy-term infants received low-protein formulas with either alpha-lactalbumin-enriched whey (α-lac-EW; 1.75 g protein/100 kcal), casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal), or standard infant formula (SF; 2.2 g protein/100 kcal) between 2 and 6 months of age. Breastfed (BF) infants served as a reference. At 12 months, anthropometrics and dietary intake were assessed, and serum was analyzed for insulin, C-peptide, and insulin-like growth factor 1 (IGF-1). Weight gain between 6 and 12 months and BMI at 12 months were higher in the SF than in the BF infants (p = 0.019; p < 0.001, respectively), but were not significantly different between the low-protein formula groups and the BF group. S-insulin and C-peptide were higher in the SF than in the BF group (p < 0.001; p = 0.003, respectively), but more alike in the low-protein formula groups and the BF group. Serum IGF-1 at 12 months was similar in all study groups. Conclusion: Feeding modified low-protein formula during early infancy seems to reduce insulin resistance, resulting in more similar growth, serum insulin, and C-peptide concentrations to BF infants at 6-months post intervention. Feeding modified low-protein formula during early infancy results in more similar growth, serum insulin, and C-peptide concentrations to BF infants 6-months post intervention, probably due to reduced insulin resistance in the low-protein groups.

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.