A systematic review to reassess the formula for early life growth
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Published Version
Date
2026-06-11
Authors
Nilaweera, Kanishka N.
van Sinderen, Douwe
Cotter, Paul D.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Published Version
Abstract
Mammals have species-specific adaptations to sustain growth during the suckling stage of life. These include species-specific milk composition and associated whey protein (WP)-to-casein (CN) ratio. Consuming milk (proteins) from other species may therefore cause different growth outcomes during early life. This systematic review examined the effect of intake of feeds with a high bovine WP-to-CN ratio on growth outcomes in infants, piglets, and rodent pups, focusing on milk and/or protein intake, body weight, and gut morphology and its cellular activity. The relevant studies were identified from PUBMedR using the keywords, “whey,” “infant formula,” and “growth” for infant studies and “whey” and “suckling stage” for animal studies. Of the original research articles reviewed (280 in total), 16 infant (with 3207 participants) and 13 animal studies met the imposed inclusion criteria and were independently reviewed by the authors. Data show that consumption of infant formula with bovine whey-to-casein ratio equal to or exceeding that of human milk (60:40), and with proteins supplying ≥8% of total energy, is associated with a discordance between energy intake and weight gain, consistent with net nutrient loss. Data from porcine and rodent models further indicate that the nutrient loss occurs because of reduced nutrient absorption through the gut, and that the effect appears to be driven primarily by bovine WP. We present further evidence supporting a role for gut microbiota in mediating the reduced nutrient absorption and that hydrolysis of bovine WP mitigates, at least some of, this effect and increases growth compared with formulas with intact proteins. We envisage that these findings, based on proteins sourced from cow’s milk, will inform improvements in infant formula that increases nutrient absorption and support healthier growth using a protein content much lower than the current regulatory threshold of 1.8 g/100 kcal.
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Keywords
Breastfeeding , Energy balance , Glucagon-like peptide , Lactation , Suckling , α-lactalbumin , [APCMicrobiome] , [Microbiology]
Citation
Nilaweera, K N, van Sinderen, D & Cotter, P D 2026, 'A systematic review to reassess the formula for early life growth', Advances in Nutrition, vol. 17, no. 7, 100660, pp. 1-16. https://doi.org/10.1016/j.advnut.2026.100660