β-Lactoglobulin: A novel bioactive whey protein with incretin-modulating and muscle anabolic properties

β-Lactoglobulin (BLG), the predominant whey protein in bovine milk, has emerged as a promising bioactive compound, rich in leucine, with metabolic and muscle anabolic properties. This narrative review synthesizes current evidence on BLG's bioactive properties specifically pertaining to its role in glucose regulation, muscle anabolic signaling and protein synthesis across preclinical and clinical studies. BLG's distinctive β-barrel structure contributes to enhanced bioavailability and sustained amino acid availability. Its acid-resistant structure enables rapid gastric transit and intestinal hydrolysis during ingestion, forming bioactive peptides. Preclinical studies in mouse and cell models demonstrate glucose-lowering effects of BLG comparable to metformin mediated by DPP-4 and α-glucosidase inhibition, AMPK activation and stimulation of hepatic glucose uptake. Human studies reveal insulinotropic and incretin modulating effects of BLG, while also inducing canonical muscle insulin and anabolic signaling pathways (Akt, mTOR, and 4EBP1) and stimulating protein synthesis – even under catabolic inflammatory conditions. Given its apparent effects on muscle anabolic signaling and protein synthesis, BLG likely promotes muscle mass accretion with potential application in a range of muscle-centric and metabolic conditions. This should encourage research on its long-term efficacy and optimal dosing for muscle mass preservation, glucose tolerance, and metabolic health. • β-Lactoglobulin (BLG) is a leucine-rich whey protein with bioactive properties. • BLG shows glucose-lowering effects comparable to metformin via AMPK activation in rodents. • Bioactive peptides of BLG inhibit DPP-4 and α-glucosidase in vitro. • In humans, BLG stimulates the release of incretin hormones GLP-1 and GIP. • BLG activates the mTOR-pathway and stimulates muscle protein synthesis even under inflammatory conditions.