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The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice

Many phenylketonuria (PKU) patients cannot adhere to the severe dietary restrictions as advised by the European PKU guidelines, which can be accompanied by aggravated neuropsychological impairments that, at least in part, have been attributed to brain monoaminergic neurotransmitter deficiencies. Sup...

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Autores principales: van Vliet, Danique, van der Goot, Els, van Ginkel, Wiggert G., van Faassen, Martijn H. J. R., de Blaauw, Pim, Kema, Ido P., Martinez, Aurora, Heiner-Fokkema, M. Rebecca, van der Zee, Eddy A., van Spronsen, Francjan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770592/
https://www.ncbi.nlm.nih.gov/pubmed/31546852
http://dx.doi.org/10.3390/nu11092252
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author van Vliet, Danique
van der Goot, Els
van Ginkel, Wiggert G.
van Faassen, Martijn H. J. R.
de Blaauw, Pim
Kema, Ido P.
Martinez, Aurora
Heiner-Fokkema, M. Rebecca
van der Zee, Eddy A.
van Spronsen, Francjan J.
author_facet van Vliet, Danique
van der Goot, Els
van Ginkel, Wiggert G.
van Faassen, Martijn H. J. R.
de Blaauw, Pim
Kema, Ido P.
Martinez, Aurora
Heiner-Fokkema, M. Rebecca
van der Zee, Eddy A.
van Spronsen, Francjan J.
author_sort van Vliet, Danique
collection PubMed
description Many phenylketonuria (PKU) patients cannot adhere to the severe dietary restrictions as advised by the European PKU guidelines, which can be accompanied by aggravated neuropsychological impairments that, at least in part, have been attributed to brain monoaminergic neurotransmitter deficiencies. Supplementation of large neutral amino acids (LNAA) to an unrestricted diet has previously been shown to effectively improve brain monoamines in PKU mice of various ages. To determine the additive value of LNAA supplementation to a liberalized phenylalanine-restricted diet, brain and plasma monoamine and amino acid concentrations in 10 to 16-month-old adult C57Bl/6 PKU mice on a less severe phenylalanine-restricted diet with LNAA supplementation were compared to those on a non-supplemented severe or less severe phenylalanine-restricted diet. LNAA supplementation to a less severe phenylalanine-restricted diet was found to improve both brain monoamine and phenylalanine concentrations. Compared to a severe phenylalanine-restricted diet, it was equally effective to restore brain norepinephrine and serotonin even though being less effective to reduce brain phenylalanine concentrations. These results in adult PKU mice support the idea that LNAA supplementation may enhance the effect of a less severe phenylalanine-restricted diet and suggest that cerebral outcome of PKU patients treated with a less severe phenylalanine-restricted diet may be helped by additional LNAA treatment.
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spelling pubmed-67705922019-10-30 The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice van Vliet, Danique van der Goot, Els van Ginkel, Wiggert G. van Faassen, Martijn H. J. R. de Blaauw, Pim Kema, Ido P. Martinez, Aurora Heiner-Fokkema, M. Rebecca van der Zee, Eddy A. van Spronsen, Francjan J. Nutrients Article Many phenylketonuria (PKU) patients cannot adhere to the severe dietary restrictions as advised by the European PKU guidelines, which can be accompanied by aggravated neuropsychological impairments that, at least in part, have been attributed to brain monoaminergic neurotransmitter deficiencies. Supplementation of large neutral amino acids (LNAA) to an unrestricted diet has previously been shown to effectively improve brain monoamines in PKU mice of various ages. To determine the additive value of LNAA supplementation to a liberalized phenylalanine-restricted diet, brain and plasma monoamine and amino acid concentrations in 10 to 16-month-old adult C57Bl/6 PKU mice on a less severe phenylalanine-restricted diet with LNAA supplementation were compared to those on a non-supplemented severe or less severe phenylalanine-restricted diet. LNAA supplementation to a less severe phenylalanine-restricted diet was found to improve both brain monoamine and phenylalanine concentrations. Compared to a severe phenylalanine-restricted diet, it was equally effective to restore brain norepinephrine and serotonin even though being less effective to reduce brain phenylalanine concentrations. These results in adult PKU mice support the idea that LNAA supplementation may enhance the effect of a less severe phenylalanine-restricted diet and suggest that cerebral outcome of PKU patients treated with a less severe phenylalanine-restricted diet may be helped by additional LNAA treatment. MDPI 2019-09-19 /pmc/articles/PMC6770592/ /pubmed/31546852 http://dx.doi.org/10.3390/nu11092252 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
van Vliet, Danique
van der Goot, Els
van Ginkel, Wiggert G.
van Faassen, Martijn H. J. R.
de Blaauw, Pim
Kema, Ido P.
Martinez, Aurora
Heiner-Fokkema, M. Rebecca
van der Zee, Eddy A.
van Spronsen, Francjan J.
The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice
title The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice
title_full The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice
title_fullStr The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice
title_full_unstemmed The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice
title_short The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice
title_sort benefit of large neutral amino acid supplementation to a liberalized phenylalanine-restricted diet in adult phenylketonuria patients: evidence from adult pah-enu2 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770592/
https://www.ncbi.nlm.nih.gov/pubmed/31546852
http://dx.doi.org/10.3390/nu11092252
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