Postprandial metabolic responses to a glycomacropeptide-based protein substitute in different meal contexts - Implications for phenylketonuria (PKU).

BACKGROUND: Casein glycomacropeptide supplemented with amino acids (CGMP-AA) is used in the treatment of phenylketonuria (PKU). However, its acute metabolic effects when consumed with other foods remain poorly understood. This study investigated the impact CGMP-AA consumed alone or with two low-protein meals providing carbohydrates with either fibre or fat. METHODS: In this randomised crossover trial, fifteen healthy adults (27.0 ± 7.9 y; 7 females) consumed: A) CGMP-AA alone; B) CGMP-AA with low-protein bread and unpeeled apple; or C) CGMP-AA with low-protein bread and olive oil. Blood samples were collected over 120 min to assess glucose, insulin, C-peptide, amino acids, and appetite-related hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY)). RESULTS: Co-ingestion with low-protein foods had limited effects on total essential and large neutral amino acid concentrations over 120 min, but increased Tyr incremental area under the curve (iAUC(0-120min)) and peak concentration (Cmax) compared with CGMP-AA alone. Meal B elicited the highest glucose, insulin, and C-peptide iAUC(0-120min) and Cmax, followed by meal C, whereas meal A induced minimal glycaemic and insulinaemic excursions. Meal C produced the greatest GIP response, whereas GLP-1 and PYY did not differ between test meals. CONCLUSIONS: In healthy adults, CGMP-AA elicited distinct acute postprandial responses depending on whether it was consumed alone or with low-protein foods. CGMP-AA consumed with food is not metabolically equivalent to CGMP-AA consumed alone, and carbohydrate-with-fibre and carbohydrate-with-fat meal contexts affect distinct aspects of the postprandial response. These findings should be confirmed in individuals with PKU before being translated into dietary recommendations.