Low-Protein Formulas with Alpha-Lactalbumin-Enriched or Glycomacropeptide-Reduced Whey: Effects on Growth, Nutrient Intake and Protein Metabolism during Early Infancy: A Randomized, Double-Blinded Controlled Trial

Abstract

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.

Keywords: CGMP; alpha-lactalbumin; amino acids; energetic efficiency; infant formula; infant growth; low protein; obesity; protein metabolism; protein quality.

Figure 1

Study flowchart. Randomization, allocation and follow-up in intention-to-treat and per protocol (PP) populations. SF, standard formula; α-lac-EW, experimental formula with α-lactalbumin-enriched whey; CGMP-RW, experimental formula with reduced CGMP whey; BF, breast-fed. Reasons for lost to follow-up: * Gastrointestinal adverse events, such as vomiting, stomach ache, flatulence or constipation. ** Congenital genetic disease affecting growth.

Figure 2

Unadjusted mean (95% CI) of z-score weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), HC-for-age (HCAZ) and BMI-for-age (BMIZ) in study groups compared by one-way ANOVA, post hoc Bonferroni. ^a all FF groups significantly different vs. BF. ^b SF significantly different vs. BF. ^c CGMP-RW significantly different vs. BF. SF, standard formula; α-lac-EW, experimental formula with α-lactalbumin-enriched whey; CGMP-RW, experimental formula with reduced CGMP whey; BF, breast-fed.

Figure 3

Mean (±SD) plasma concentration of essential and nonessential amino acids in the randomized subgroup (n = 50 in each group) at four and six months of age. Groups compared by one-way ANOVA, post hoc Bonferroni. p value < 0.05 are considered statistically significant and marked by superscript letters. ^a Significantly different vs. BF. ^b SF vs. α-lac-EW. ^c SF vs. CGMP-RW. ^d α-lac-EW vs. CGMP-RW. SF, standard formula; α-lac-EW, experimental formula with α-lactalbumin enriched-whey; CGMP-RW, experimental formula with reduced CGMP whey; BF, breast-fed.

Figure 4

Mean (± SD) total BCCA (isoleucine, leucine, valine) plasma concentration in the randomized subgroup (n = 50 in each group) at four and six months of age. Groups compared by one-way ANOVA, post hoc Bonferroni. p value < 0.05 are considered statistically significant and marked by superscript letters. ^a Significantly different vs. BF. ^b SF vs. α-lac-EW. ^c SF vs. CGMP-RW. SF, standard formula; α-lac-EW, experimental formula with α-lactalbumin enriched whey; CGMP-RW, experimental formula with reduced CGMP whey; BF, breast-fed.