title: Milk protein intake, the metabolic-endocrine response, and growth in infancy: data from a randomized clinical trial.
abstract: BACKGROUND
  Protein intake in early infancy has been suggested to be an important risk factor for later obesity, but information on potential mechanisms is very limited.
  
  
  OBJECTIVE
  This study examined the influence of protein intake in infancy on serum amino acids, insulin, and the insulin-like growth factor I (IGF-I) axis and its possible relation to growth in the first 2 y of life.
  
  
  METHODS
  In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow-milk-based infant and follow-on formulas with lower protein (LP; 1.77 and 2.2 g protein/100 kcal) or higher protein (HP; 2.9 and 4.4 g protein/100 kcal) contents for the first year. Biochemical variables were measured at age 6 mo in 339 infants receiving LP formula and 333 infants receiving HP formula and in 237 breastfed infants.
  
  
  RESULTS
  Essential amino acids, especially branched-chain amino acids, IGF-I, and urinary C-peptide:creatinine ratio, were significantly (P < 0.001) higher in the HP group than in the LP group, whereas IGF-binding protein (IGF-BP) 2 was lower and IGF-BP3 did not differ significantly. The median IGF-I total serum concentration was 48.4 ng/mL (25th, 75th percentile: 27.2, 81.8 ng/mL) in the HP group and 34.7 ng/mL (17.7, 57.5 ng/mL) in the LP group; the urine C-peptide:creatinine ratios were 140.6 ng/mg (80.0, 203.8 ng/mg) and 107.3 ng/mg (65.2, 194.7 ng/mg), respectively. Most essential amino acids, IGF-I, C-peptide, and urea increased significantly in both the LP and HP groups compared with the breastfed group. Total IGF-I was significantly associated with growth until 6 mo but not thereafter.
  
  
  CONCLUSIONS
  HP intake stimulates the IGF-I axis and insulin release in infancy. IGF-I enhances growth during the first 6 mo of life. This trial was registered at clinicaltrials.gov as NCT00338689.
authors.affiliation: Children's Memorial Health Institute, Warsaw, Poland. p.socha@czd.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Socha
authors.forename: Veit
authors.initials: V
authors.lastname: Grote
authors.forename: Dariusz
authors.initials: D
authors.lastname: Gruszfeld
authors.forename: Roman
authors.initials: R
authors.lastname: Janas
authors.forename: Hans
authors.initials: H
authors.lastname: Demmelmair
authors.forename: Ricardo
authors.initials: R
authors.lastname: Closa-Monasterolo
authors.forename: Joaquín Escribano
authors.initials: JE
authors.lastname: Subías
authors.forename: Silvia
authors.initials: S
authors.lastname: Scaglioni
authors.forename: Elvira
authors.initials: E
authors.lastname: Verduci
authors.forename: Elena
authors.initials: E
authors.lastname: Dain
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Langhendries
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Perrin
authors.forename: Berthold
authors.initials: B
authors.lastname: Koletzko
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose / Q000032:analysis; D001942:Breast Feeding; D002096:C-Peptide / Q000097:blood / Q000652:urine; D002657:Child Development; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism*; D002149:Energy Intake; D005260:Female; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008892:Milk; D008894:Milk Proteins / Q000008:administration & dosage* / Q000032:analysis; D009765:Obesity / Q000453:epidemiology / Q000517:prevention & control; D016601:RNA-Binding Proteins / Q000097:blood; D012307:Risk Factors; D044465:White People
chemical_list: D000597:Amino Acids, Branched-Chain; D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; C498779:IGF2BP2 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D008894:Milk Proteins; D016601:RNA-Binding Proteins; D007334:Insulin-Like Growth Factor I; D003404:Creatinine