Supplementation with a Whey Protein Concentrate Enriched in Bovine Milk Exosomes Improves Longitudinal Growth and Supports Bone Health During Catch-Up Growth in Rats

Background: Undernutrition impairs linear growth while restoration of nutritional provisions leads to accelerated growth patterns. However, the composition of the nutrition provided is key to facilitating effective catch-up growth without compromising bone quantity, quality, and long-term health. Methods: We evaluated the role of a whey protein concentrate enriched in bovine milk exosomes (BMEs) in modulating the proliferative properties of human chondrocytes in vitro and studied how these effects might impact bone quantity and quality measured as longitudinal tibia growth, bone mineral content (BMC) and density (BMD), and trabecular micro-CT parameters in stunted rats during catch-up growth. Results: BMEs promoted proliferation in C28/I2 human chondrocytes mediated by mTOR-Akt signaling. In a stunting rat model, two-week supplementation with BMEs during refeeding was associated with improved tibia BMD, trabecular microstructure (trabecular number (Tb. N.) and space (Tb. Sp.)), and a more active growth plate (higher volume, surface, and thickness) compared to non-supplemented stunted rats. Positive effects on physis translated to significantly longer tibias without compromising bone quality when extending the refeeding period for another two weeks. Conclusions: Overall, BME supplementation positively contributed to longitudinal bone growth and improved bone quantity and quality during catch-up growth. These findings might be relevant for improving diets aimed at addressing the nutritional needs of children undergoing undernutrition during early life.