{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:19:36Z","timestamp":1770268776258,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Birmingham Children Hospital Charity Grant and Nutricia Research Grant Nutricia Ltd., Trowbridge, UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u201349), with a median BMI 24.2 (20\u201330.5) 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 = &lt;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.<\/jats:p>","DOI":"10.3390\/nu17162671","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:56:06Z","timestamp":1755590166000},"page":"2671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protein Substitute Absorption: A Randomised Controlled Trial Comparing CGMP vs. Amino Acids vs. Micellar Casein in Healthy Volunteers"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-8699","authenticated-orcid":false,"given":"Anne","family":"Daly","sequence":"first","affiliation":[{"name":"Birmingham Children\u2019s Hospital, NHS Trust, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"given":"Alex","family":"Pinto","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, NHS Trust, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-3621","authenticated-orcid":false,"given":"Sharon","family":"Evans","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, NHS Trust, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"given":"Tarekegn","family":"Geberhiwot","sequence":"additional","affiliation":[{"name":"Queen Elizabeth Hospital, NHS Trust, Birmingham B15 2GW, UK"}]},{"given":"Richard","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Health Data Science, University of Liverpool, Liverpool L69 3GJ, UK"}]},{"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School (NMS), Faculdade de Ciencias Medicas (FCM), Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School (NMS), Faculdade de Ciencias Medicas (FCM), Universidade Nova de Lisboa, Campo Martires da Patria, 1169-056 Lisbon, Portugal"},{"name":"Reference Centre of Inherited Metabolic Disease, Centro Hospitalar Universitario de Lisboa Central, 1069-166 Lisbon, Portugal"},{"name":"Comprehensive Health Research Centre (CHRC), NOVA Medical School, Faculdade de Ciencias Medicas NMS\/FCM, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6305-6333","authenticated-orcid":false,"given":"Jonathan","family":"Tang","sequence":"additional","affiliation":[{"name":"Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, NHS Trust, Steelhouse Lane, Birmingham B4 6NH, UK"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ajhg.2020.06.006","article-title":"The Genetic Landscape and Epidemiology of Phenylketonuria","volume":"107","author":"Hillert","year":"2020","journal-title":"Am. 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