Early Programming by Protein Intake: The Effect of Protein on Adiposity Development and the Growth and Functionality of Vital Organs

Abstract

This article reviews the role of protein intake on metabolic programming early in life. The observations that breastfeeding in infancy reduces the risk of being overweight and obese later in life and the differences in the protein content between formula milk and human milk have generated the early protein hypothesis. The present review focuses on a mechanistic approach to programmed adiposity and the growth and development of other organs by protein intake in infancy, which may be mediated by branched-chain amino acids, insulin, and insulin-like growth factor 1 via the mammalian target of rapamycin. Observational studies and clinical trials have shown that lowering the protein content in infant and follow-on formulas may reduce the risk of becoming obese later in life. The recent body of evidence is currently being translated into new policies. Therefore, the evolution of European regulatory laws and recommendations by expert panels on the protein content of infant and follow-on formulas are also reviewed. Research gaps, such as the critical window for programming adiposity by protein intake, testing formulas with modified amino acids, and the long-term consequences of differences in protein intake on organ functionality among well-nourished infants, have been identified.

Intake of Energy and Protein is Associated with Overweight Risk at Age 5.5 Years: Results from the Prospective TEDDY Study

“…Our findings, therefore, seem to indicate that a greater protein intake may be relevant for both initiating and maintaining overweight in children. However, we found no evidence for potential programming effects by protein intake in very early life as suggested by other studies (11,31,32). Instead, a greater energy intake during the first year of life was found to be a strong predictor of overweight at the age of 5.5 years in our data.…”

Associations between Maternal Body Composition and Appetite Hormones and Macronutrients in Human Milk

“…Concentrations of appetite hormones and macronutrients present in HM influence regulation of appetite, energy expenditure pathways and growth trajectory in the developing infant [8,54,55]. Maternal adiposity may play a critical role in regulation of concentrations of HM leptin, adiponectin, protein and lactose, and thus of the ingested dose of these components by the infant.…”

Diversity and Nutrient Composition of the Diets of Breastfed Infants

“…8,11,12,20 Studies have shown an association between high protein intake (>14% of the total energy consumption) and the development of obesity later in life due to stimulation of insulin-like growth factor, which results in rapid growth and increased fat accumulation. [4][5][6]27 However, Tang and Krebs found that in breastfed infants, a higher protein intake from meats was associated with greater linear growth and weight gain without excessive adiposity, suggesting that high protein intake may differ between breastfed and formula-fed infants as well as the source of protein. 28 In this study, approxi- -19 mately 23% of the infants consumed levels of protein greater than 14% of the total energy.…”

“…[1][2][3] Interventions to reduce the risk of obesity in later life and undernutrition include the timely introduction of high quality complementary foods containing micronutrients but not excessive protein, based on the principles of responsive feeding. [1][2][3][4][5][6] Studies published from industrialized countries found dietary supplements and enriched or fortified foods to be significant contributors to micronutrient intake. [7][8][9][10][11][12][13][14][15] The Feeding Infants and Toddlers Study (FITS) conducted in 2002 and replicated in 2008 assessed the usual nutrient intake and food consumption patterns of United States (US) children in a large national sample.…”