{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:33:25Z","timestamp":1778103205067,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vitaflo International Ltd","award":["0000"],"award-info":[{"award-number":["0000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>In Phenylketonuria (PKU), the peptide structure of the protein substitute (PS), casein glycomacropeptide (CGMP), is supplemented with amino acids (CGMP-AA). CGMP may slow the rate of amino acid (AA) absorption compared with traditional phenylalanine-free amino acids (Phe-free AA), which may improve nitrogen utilization, decrease urea production, and alter insulin response. Aim: In children with PKU, to compare pre and postprandial AA concentrations when taking one of three PS\u2019s: Phe-free AA, CGMP-AA 1 or 2. Methods: 43 children (24 boys, 19 girls), median age 9 years (range 5\u201316 years) were studied; 11 took CGMP-AA1, 18 CGMP-AA2, and 14 Phe-free AA. Early morning fasting pre and 2 h postprandial blood samples were collected for quantitative AA on one occasion. A breakfast with allocated 20 g protein equivalent from PS was given post fasting blood sample. Results: There was a significant increase in postprandial AA for all individual AAs with all three PS. Postprandial AA histidine (p &lt; 0.001), leucine (p &lt; 0.001), and tyrosine (p &lt; 0.001) were higher in CGMP-AA2 than CGMP-AA1, and leucine (p &lt; 0.001), threonine (p &lt; 0.001), and tyrosine (p = 0.003) higher in GCMP-AA2 than Phe-free AA. This was reflective of the AA composition of the three different PS\u2019s. Conclusions: In PKU, the AA composition of CGMP-AA influences 2 h postprandial AA composition, suggesting that a PS derived from CGMP-AA may be absorbed similarly to Phe-free AA, but this requires further investigation.<\/jats:p>","DOI":"10.3390\/nu12082443","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T08:28:35Z","timestamp":1597393715000},"page":"2443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Preliminary Investigation to Review If a Glycomacropeptide Compared to L-Amino Acid Protein Substitute Alters the Pre- and Postprandial Amino Acid Profile in Children with Phenylketonuria"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-8699","authenticated-orcid":false,"given":"Anne","family":"Daly","sequence":"first","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, 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":"Dietetic Department, Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"given":"Alex","family":"Pinto","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"given":"Richard","family":"Jackson","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Centre, University of Liverpool, Brownlow Hill, Liverpool L69 3GL, UK"}]},{"given":"Catherine","family":"Ashmore","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Centre for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"ref_1","unstructured":"World Health Organisation, Food and Agriculture Organization of the United Nations, and United Nations University (2007). Protein and Amino Acid Requirements in Human Nutition. Report of a Joint WHO\/FAO\/UNU Expert Consultation, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1023\/B:BOLI.0000031099.79046.65","article-title":"Protein substitutes for PKU: What\u2019s new?","volume":"27","author":"Macdonald","year":"2004","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1136\/bmj.1.4905.57","article-title":"Treatment of phenylketonuria with a diet low in phenylalanine","volume":"1","author":"Woolf","year":"1995","journal-title":"Br. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"van Vliet, D., Bruinenberg, V.M., Mazzola, P.N., van Faassen, M.H., de Blaauw, P., Kema, I.P., Fokkema, M.R.H., van Anholt, R.D., van der Zee, E.A., and van Spronsen, F.J. (2015). Large Neutral Amino Acid Supplementation Exerts Its Effect through Three Synergistic Mechanisms: Proof of Principle in Phenylketonuria Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143833"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1017\/S0954422418000173","article-title":"Optimising amino acid absorption: Essential to improve nitrogen balance and metabolic control in phenylketonuria","volume":"32","author":"MacDonald","year":"2019","journal-title":"Nutr. Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s13594-012-0095-0","article-title":"Chemical and functional properties of glycomacropeptide (GMP) and its role in the detection of cheese whey adulteration in milk: A review","volume":"93","author":"Neelima","year":"2013","journal-title":"Dairy Sci. Technol."},{"key":"ref_7","first-page":"289","article-title":"Toward Sustainable Amino Acid Production","volume":"159","author":"Usuda","year":"2017","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"ref_8","first-page":"58","article-title":"Nutritional Management of Phenylketonuria","volume":"68","author":"Macleod","year":"2010","journal-title":"Ann. Nestle Eng."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s10545-008-0952-4","article-title":"Nutritional management of PKU with glycomacropeptide from cheese whey","volume":"32","author":"Ney","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/glycob\/cwt162","article-title":"Structural and functional characteristics of bovine milk protein glycosylation","volume":"24","author":"Kane","year":"2014","journal-title":"Glycobiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14930","DOI":"10.1073\/pnas.94.26.14930","article-title":"Slow and fast dietary proteins differently modulate postprandial protein accretion","volume":"94","author":"Boirie","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E340","DOI":"10.1152\/ajpendo.2001.280.2.E340","article-title":"The digestion rate of protein is an independent regulating factor of postprandial protein retention","volume":"280","author":"Dangin","year":"2001","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/jn\/132.1.125","article-title":"Peripheral and splanchnic metabolism of dietary nitrogen are differently affected by the protein source in humans as assessed by compartmental modeling","volume":"132","author":"Fouillet","year":"2002","journal-title":"J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1093\/jn\/nxaa024","article-title":"Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans","volume":"150","author":"Gorissen","year":"2020","journal-title":"J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12970-020-0340-5","article-title":"Anabolic response to essential amino acid plus whey protein composition is greater than whey protein alone in young healthy adults","volume":"17","author":"Park","year":"2020","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1093\/jn\/135.5.1080","article-title":"Casein and soy protein meals differentially affect whole-body and splanchnic protein metabolism in healthy humans","volume":"135","author":"Luiking","year":"2005","journal-title":"J. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"126514","DOI":"10.1016\/j.foodchem.2020.126514","article-title":"Impact of caseins and whey proteins ratio and lipid content on in vitro digestion and ex vivo absorption","volume":"319","author":"Saha","year":"2020","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1097\/MCO.0b013e328341368c","article-title":"Plasma amino acid imbalance: Dangerous in chronic diseases?","volume":"14","author":"Roth","year":"2011","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1023\/A:1025186217369","article-title":"Administration of protein substitute and quality of control in phenylketonuria: A randomized study","volume":"26","author":"Macdonald","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_20","first-page":"S115","article-title":"Utilisation of amino acid mixtures in adolescents with phenylketonuria","volume":"155","author":"Herrmann","year":"1996","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1159\/000107678","article-title":"Effects of Various Dietary Amino Acid Preparations for Phenylketonuric Patients on the Metabolic Profiles along with Postprandial Insulin and Ghrelin Responses","volume":"51","author":"Weigel","year":"2007","journal-title":"Ann. Nutr. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1136\/adc.74.5.412","article-title":"Factors affecting the variation in plasma phenylalanine in patients with phenylketonuria on diet","volume":"74","author":"Macdonald","year":"1996","journal-title":"Arch. Dis. Child."},{"key":"ref_23","first-page":"E885","article-title":"Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria","volume":"302","author":"Solverson","year":"2012","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.3945\/ajcn.2008.27280","article-title":"Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids","volume":"89","author":"MacLeod","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1177\/0148607180004006548","article-title":"Use of a Peptide Rather Than Free Amino Acid Nitrogen Source in Chemically Defined \u201cElemental\u201d Diets","volume":"4","author":"Silk","year":"1980","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-017-0685-2","article-title":"The complete European guidelines on phenylketonuria: Diagnosis and treatment","volume":"12","author":"Macdonald","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/jhn.12438","article-title":"Glycomacropeptide in children with phenylketonuria: Does its phenylalanine content affect blood phenylalanine control?","volume":"30","author":"Daly","year":"2017","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ymgme.2017.04.003","article-title":"Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria","volume":"121","author":"Ney","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/ejcn.2017.38","article-title":"Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source","volume":"71","author":"Pinto","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ymgme.2010.04.003","article-title":"Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria","volume":"100","author":"MacLeod","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6352919","DOI":"10.1155\/2018\/6352919","article-title":"Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels","volume":"2018","author":"Ahring","year":"2018","journal-title":"J. Nutr. Metab."},{"key":"ref_32","first-page":"143","article-title":"Plasma Amino Acid Response to Ingestion of L-Amino Acids and Whole Protein","volume":"16","author":"Gropper","year":"1993","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1172\/JCI106724","article-title":"Intestinal transport of dipeptides in man: Relative importance of hydrolysis and intact absorption","volume":"50","author":"Adibi","year":"1971","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/S0016-5085(19)33741-2","article-title":"Impaired Jejunal Absorption Rates of Essential Amino Acids Induced by Either Dietary Caloric or Protein Deprivation in Man","volume":"59","author":"Adibi","year":"1970","journal-title":"Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1017\/S000711457500030X","article-title":"Changes in plasma amino acid concentrations in man after ingestion of an amino acid mixture simulating casein, and a tryptic hydrolysate of casein","volume":"34","author":"Marrs","year":"1975","journal-title":"Br. J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/jcp.20339","article-title":"Molecular mechanisms of glutamine action","volume":"204","author":"Curi","year":"2005","journal-title":"J. Cell. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1093\/ajcn\/85.4.996","article-title":"Metabolic effects of amino acid mixtures and whey protein in healthy subjects: Studies using glucose-equivalent drinks","volume":"85","author":"Nilsson","year":"2007","journal-title":"Am. J. Clin. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/8\/2443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:00:40Z","timestamp":1760176840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/8\/2443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,14]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["nu12082443"],"URL":"https:\/\/doi.org\/10.3390\/nu12082443","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,14]]}}}