Postprandial metabolic response of breast-fed infants and infants fed lactose-free vs regular infant formula: A randomized controlled trial

Abstract

Lactose intolerance is a major concern driving the growth of lactose-free foods including lactose-free infant formula. It is unknown what the metabolic consequence is of consumption of a formula where lactose has been replaced with corn syrup solids (CSS). Here, a randomized double-blinded intervention study was conducted where exclusively formula-fed infants were fed formula containing either lactose or CSS-based infant formula and compared with an equal number of exclusively breast-fed infants. Plasma metabolites and insulin were measured at baseline, 15, 30, 60, 90 and 120 min after feeding. Differences in plasma metabolite profiles for formula-fed infants included a rapid increase in circulating amino acids, creatinine and urea compared with breast-fed infants. At 120 min post-feeding, insulin was significantly elevated in formula-fed compared with breast-fed infants. Infants fed lactose-based formula had the highest levels of glucose at 120 min, and leucine, isoleucine, valine and proline at 90 and 120 min, whereas infants fed CSS-based formula had the lowest levels of non-esterified fatty acids at all time points, and glucose at 120 min. Overall, these differences highlight that changes in infant formula composition impact infant metabolism, and show that metabolomics is a powerful tool to help with development of improved infant formulas.

Figure 1

Principal components analysis (PCA) reveals differences between breastfed and formula-fed infants at baseline and after feeding. (A) PCA of baseline plasma samples from breastfed infants (green) and formula-fed infants (red). All formula fed infants were grouped together since all were consuming regular infant formula prior to the start of the experiment. Infants were acclimated to the taste of the formula for 1–3 feedings prior to the experiment. (B) PCA of plasma post-prandial metabolites from infants that were breastfed (green), infants that were fed lactose-based infant formula (red), and infants that were fed corn-syrup solids (CSS)-based infant formula (blue).

Figure 2

Post-prandial concentration of plasma metabolites and serum insulin. In green are concentrations in the plasma or serum of breastfed infants; red are infants fed lactose-based formula; and in blue are infants fed CSS-based formula.

Figure 3

Correlation of serum metabolite concentrations. (A) Correlation of serum insulin concentrations (in μIU/mL) with plasma glucose, isoleucine, leucine or valine (in μmoles/L). (B) Correlation of serum NEFA (in μmoles/L) with plasma acetoacetate or 3-hydroxybutyrate (in μmoles/L). The correlation coefficient and p-value are indicated for each.

Figure 4

Study design. (A) Flow diagram of participant recruitment. (B) Study design.