Protein Substitute Absorption: A Randomised Controlled Trial Comparing CGMP vs. Amino Acids vs. Micellar Casein in...

Background: The rate at which amino acids (AAs) are absorbed from casein glycomacropeptide (CGMP) when given as a protein substitute in phenylketonuria (PKU) is unknown. This three-way randomised, controlled, crossover study aimed to compare the AA absorption profile of phenylalanine (Phe)-free L-amino acids (L-AAs), low-Phe CGMP (CGMP) and casein in healthy adult subjects. Methods: Area under the curve (AUC) was measured over 240 minutes after ingesting one dose of each protein source on three separate occasions, under the same test conditions. A total of 0.4 g/kg protein equivalent of each test product (L-AA, CGMP and casein) was given. Fasted blood samples were collected from healthy volunteers at 30, 60, 90, 120, 150, 180 and 240 minutes post-test. Insulin, blood urea nitrogen, glucose and total (TAAs), essential (EAAs), large neutral (LNAAs) and branch chain (BCAAs) amino acids were measured at each time point. Results: A total of 20 subjects (11 females), median age 43 y (range 23-49), with a median BMI 24.2 (20-30.5) were recruited. AUC was compared across groups. Statistically significant differences were noted for: AUC for TAAs and BCAAs between CGMP and L-AAs vs. casein [TAAs p = 0.008 and p = 0.03; BCAAs p = <0.001 and p = 0.002]. There were no AUC differences between L-AAs and CGMP. AUC was largest for L-AAs, then CGMP and finally casein. For LNAAs, EAAs, insulin, glucose and urea, there were no statistically significant differences. There was a consistent delivery of AAs for casein demonstrated by a sustained curve, but the absorption curves for L-AAs and CGMP were transient, rising rapidly and falling, with the exception of tyrosine with CGMP which showed a gradual increase over 240 minutes in contrast to L-AAs and casein. Conclusions: Amino acids from CGMP and L-AAs were absorbed more rapidly than casein, inferring CGMP did not mimic casein, a slow-release protein source. The tyrosine concentration curve for CGMP suggests a beneficial effect on the Phe: tyrosine ratio. Kinetic labelled studies will help bring greater understanding on the utilisation of AAs particularly important for protein synthesis.