A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial

• Published in: The American journal of clinical nutrition Vol. 111; no. 5; pp. 962 - 974
• Main Authors: Kouwenhoven, Stefanie MP, Antl, Nadja, Finken, Martijn JJ, Twisk, Jos WR, van der Beek, Eline M, Abrahamse-Berkeveld, Marieke, van de Heijning, Bert JM, Schierbeek, Henk, Holdt, Lesca M, van Goudoever, Johannes B, Koletzko, Berthold V
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2020; Oxford University Press; American Society for Clinical Nutrition, Inc
• Subjects: Age; Amino acids; Amino Acids - analysis; Amino Acids - metabolism; Anthropometry; Babies; Baby foods; Body composition; Body fat; Body weight gain; Breastfeeding & lactation; Child Development; Control methods; Dietary Proteins - analysis; Dietary Proteins - metabolism; Double-Blind Method; Double-blind studies; Equivalence; Fat-free body mass; Female; growth; Growth rate; Humans; Infant; Infant Formula - analysis; Infant Health; infant nutrition; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infants; Male; Parameters; protein intake; protein quality; protein quantity; Proteins; Randomization; Safety; Urea; PP; AST; infants; FMI; protein intake; AE; IAAO; amino acids; FM; ITT; ALT; protein quality; FFM; MUAC; infant nutrition; protein quantity; mLP; body composition; CTRL; safety; growth; FFMI
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/nqz308

A high protein intake in early life is associated with a risk of obesity later in life. The essential amino acid requirements of formula-fed infants have been reassessed recently, enabling a reduction in total protein content and thus in protein intake. We aimed to assess the safety of an infant formula with a modified amino acid profile and a modified low-protein (mLP) content in healthy term-born infants. Outcomes were compared with a specifically designed control (CTRL) infant formula. In this double-blind, randomized controlled equivalence trial, infants received either mLP (1.7 g protein/100 kcal; n = 90) or CTRL formula (2.1 g protein/100 kcal; n = 88) from enrollment (age ≤ 45 d) to 6 mo of age. A breastfed group served as a reference (n = 67). Anthropometry and body composition were determined at baseline, 17 wk (including safety blood parameters), and 6 mo of age. The primary outcome was daily weight gain from enrollment up until the age of 17 wk (at an equivalence margin of ±3.0 g/d). Weight gain from baseline (mean ± SD age: 31 ± 9 d) up to the age of 17 wk was equivalent between the mLP and CTRL formula groups (27.9 and 28.8 g/d, respectively; difference: −0.86 g/d; 90% CI: −2.36, 0.63 g/d). No differences in other growth parameters, body composition, or in adverse events were observed. Urea was significantly lower in the mLP formula group than in the CTRL formula group (−0.74 mmol/L; 95% CI: −0.97, −0.51 mmol/L; P < 0.001). Growth rates, fat mass, fat-free mass, and several essential amino acids were significantly higher in both formula groups than in the breastfed reference group. Feeding an infant formula with a modified amino acid profile and a lower protein content from an average age of 1 mo until the age of 6 mo is safe and supports an adequate growth, similar to that of infants consuming CTRL formula. This trial was registered at www.trialregister.nl as Trial NL4677.