Context: The protective effect of breast-feeding against later obesity may be explained by the lower protein content compared with formula milk. However, the metabolic mechanisms remain unknown.
Objective: We studied the metabolic response to a higher or lower protein supply in infancy.
Design and setting: The Childhood Obesity Project study is a double-blind, randomized, multicenter intervention trial. Infants were randomized to receive a higher (HP) or lower protein (LP) content infant formula or were breast-fed.
Patients and interventions: Plasma samples of 691 infants who received formula milk with different protein content (HP, 2.05 g per 100 mL; LP, 1.25 g per 100 mL) or were breast-fed were collected.
Main outcome measures: Changes in plasma amino acid and acylcarnitine concentrations of 6-month-old infants according to different dietary protein supply were determined by liquid chromatography coupled to tandem mass spectrometry.
Results: Twenty-nine metabolites differed significantly between the formula groups. Branched-chain amino acids (BCAAs) were the most discriminant metabolites. Their degradation products, the short-chain acylcarnitines C3, C4, and C5, were also significantly elevated in the HP group. A breakpoint analysis confirmed that with increasing BCAAs, the ratio between acylcarnitines and BCAAs decreases. Long-chain acylcarnitines were decreased in HP infants.
Conclusions: BCAAs seem to play a pivotal role in the effect of a high-protein diet on β-oxidation and fat storage. We provide new evidence for a possible saturation of the BCAA degradation pathway that may represent the mechanism by which high-protein intake affects the metabolic regulation. Moreover, it appears to inhibit the initial step of the β-oxidation, thus leading to high early weight gain and body fat deposition.
Trial registration: ClinicalTrials.gov NCT00338689.