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The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial

Introduction: In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. Aim: To study the impact of CGMP-AA on blood Phe variability usi...

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Autores principales: Daly, Anne, Evans, Sharon, Chahal, Satnam, Santra, Saikat, Pinto, Alex, Gingell, Cerys, Rocha, Júlio César, van Spronsen, Francjan, Jackson, Richard, MacDonald, Anita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471794/
https://www.ncbi.nlm.nih.gov/pubmed/30823411
http://dx.doi.org/10.3390/nu11030520
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author Daly, Anne
Evans, Sharon
Chahal, Satnam
Santra, Saikat
Pinto, Alex
Gingell, Cerys
Rocha, Júlio César
van Spronsen, Francjan
Jackson, Richard
MacDonald, Anita
author_facet Daly, Anne
Evans, Sharon
Chahal, Satnam
Santra, Saikat
Pinto, Alex
Gingell, Cerys
Rocha, Júlio César
van Spronsen, Francjan
Jackson, Richard
MacDonald, Anita
author_sort Daly, Anne
collection PubMed
description Introduction: In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. Aim: To study the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU. Methods: This was a 6-week randomised controlled cross-over study comparing CGMP-AA vs. Phe-free l-amino acids (l-AA) assessing blood Phe and tyrosine (Tyr) variability over 24 h in 19 children (7 boys) with PKU, with a median age of 10 years (6–16). Subjects were randomised to 3 dietary regimens: (1) R1, CGMP-AA and usual dietary Phe (CGMP + Phe); (2) R2, CGMP-AA − Phe content of CGMP-AA from usual diet (CGMP − Phe); and (3) R3, l-AA and usual dietary Phe. Each regimen was administered for 14 days. Over the last 48 h on days 13 and 14, blood spots were collected every 4 h at 08 h, 12 h, 16 h, 20 h, 24 h, and 04 h. Isocaloric intake and the same meal plan and protein substitute dosage at standardised times were maintained when blood spots were collected. Results: Eighteen children completed the study. Median Phe concentrations over 24 h for each group were (range) R1, 290 (30–580), R2, 220 (10–670), R3, 165 (10–640) μmol/L. R1 vs. R2 and R1 vs. R3 p < 0.0001; R2 vs. R3 p = 0.0009. There was a significant difference in median Phe at each time point between R1 vs. R2, p = 0.0027 and R1 vs. R3, p < 0.0001, but not between any time points for R2 vs. R3. Tyr was significantly higher in both R1 and R2 [70 (20–240 μmol/L] compared to R3 [60 (10–200) μmol/L]. In children < 12 years, blood Phe remained in the target range (120–360 μmol/L), over 24 h, for 75% of the time in R1, 72% in R2 and 64% in R3; for children aged ≥ 12 years, blood Phe was in target range (120–600 μmol/L) in R1 and R2 for 100% of the time, but 64% in R3. Conclusions: The residual Phe in CGMP-AA increased blood Phe concentration in children. CGMP-AA appears to give less blood Phe variability compared to l-AA, but this effect may be masked by the increased blood Phe concentrations associated with its Phe contribution. Reducing dietary Phe intake to compensate for CGMP-AA Phe content may help.
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spelling pubmed-64717942019-04-25 The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial Daly, Anne Evans, Sharon Chahal, Satnam Santra, Saikat Pinto, Alex Gingell, Cerys Rocha, Júlio César van Spronsen, Francjan Jackson, Richard MacDonald, Anita Nutrients Article Introduction: In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. Aim: To study the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU. Methods: This was a 6-week randomised controlled cross-over study comparing CGMP-AA vs. Phe-free l-amino acids (l-AA) assessing blood Phe and tyrosine (Tyr) variability over 24 h in 19 children (7 boys) with PKU, with a median age of 10 years (6–16). Subjects were randomised to 3 dietary regimens: (1) R1, CGMP-AA and usual dietary Phe (CGMP + Phe); (2) R2, CGMP-AA − Phe content of CGMP-AA from usual diet (CGMP − Phe); and (3) R3, l-AA and usual dietary Phe. Each regimen was administered for 14 days. Over the last 48 h on days 13 and 14, blood spots were collected every 4 h at 08 h, 12 h, 16 h, 20 h, 24 h, and 04 h. Isocaloric intake and the same meal plan and protein substitute dosage at standardised times were maintained when blood spots were collected. Results: Eighteen children completed the study. Median Phe concentrations over 24 h for each group were (range) R1, 290 (30–580), R2, 220 (10–670), R3, 165 (10–640) μmol/L. R1 vs. R2 and R1 vs. R3 p < 0.0001; R2 vs. R3 p = 0.0009. There was a significant difference in median Phe at each time point between R1 vs. R2, p = 0.0027 and R1 vs. R3, p < 0.0001, but not between any time points for R2 vs. R3. Tyr was significantly higher in both R1 and R2 [70 (20–240 μmol/L] compared to R3 [60 (10–200) μmol/L]. In children < 12 years, blood Phe remained in the target range (120–360 μmol/L), over 24 h, for 75% of the time in R1, 72% in R2 and 64% in R3; for children aged ≥ 12 years, blood Phe was in target range (120–600 μmol/L) in R1 and R2 for 100% of the time, but 64% in R3. Conclusions: The residual Phe in CGMP-AA increased blood Phe concentration in children. CGMP-AA appears to give less blood Phe variability compared to l-AA, but this effect may be masked by the increased blood Phe concentrations associated with its Phe contribution. Reducing dietary Phe intake to compensate for CGMP-AA Phe content may help. MDPI 2019-02-28 /pmc/articles/PMC6471794/ /pubmed/30823411 http://dx.doi.org/10.3390/nu11030520 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Daly, Anne
Evans, Sharon
Chahal, Satnam
Santra, Saikat
Pinto, Alex
Gingell, Cerys
Rocha, Júlio César
van Spronsen, Francjan
Jackson, Richard
MacDonald, Anita
The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial
title The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial
title_full The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial
title_fullStr The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial
title_full_unstemmed The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial
title_short The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial
title_sort effect of glycomacropeptide versus amino acids on phenylalanine and tyrosine variability over 24 hours in children with pku: a randomized controlled trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471794/
https://www.ncbi.nlm.nih.gov/pubmed/30823411
http://dx.doi.org/10.3390/nu11030520
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