TY - JOUR
T1 - The effects of large neutral amino acid supplements in PKU
T2 - An MRS and neuropsychological study
AU - Schindeler, Suzanne
AU - Ghosh-Jerath, Suparna
AU - Thompson, Susan
AU - Rocca, Antonella
AU - Joy, Pamela
AU - Kemp, Allan
AU - Rae, Caroline
AU - Green, Kathryn
AU - Wilcken, Bridget
AU - Christodoulou, John
PY - 2007/5
Y1 - 2007/5
N2 - Objective: To determine the effects of large neutral amino acid (LNAA) supplements on brain and plasma phenylalanine (Phe) levels and other metabolites in early treated subjects with classical phenylketonuria (PKU), and to investigate the relationship between these metabolites and neuropsychological performance. Methods: This was a prospective, double blind, cross over study consisting of four two-week phases with a 4 week washout period. Sixteen subjects (7 males), with classical PKU were recruited into the study and completed all 4 phases. Each phase consisted of either the LNAA supplement or placebo, and either the patient's usual medical product or not. Subjects were instructed to follow their usual Phe restricted diet, maintain energy intake and complete a 3-day food record during each phase. At the end of each phase, brain Phe and other metabolites were measured by proton magnetic resonance spectroscopy (MRS), and plasma amino acids quantified. A detailed neuropsychological assessment was performed on the same day as the MRS and plasma collection. Results: There was no correlation between plasma and brain Phe, but few of the plasma Phe readings were over 1200 μmol/L. Plasma Phe decreased with LNAA supplementation when patients were not taking their medical formula. LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and cognitive flexibility. Measures of attention were better on medical product, with or without LNAA supplements. Conclusions: LNAA supplementation was associated with a trend to a lowering of plasma Phe levels. LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and flexibility. For individuals already complying with diet and PKU medical product, additional supplementation with LNAA is of limited value. LNAA supplementation may be of benefit to those unable to comply with PKU medical product by reducing plasma Phe, perhaps by competing with Phe at the level of transport across the gut.
AB - Objective: To determine the effects of large neutral amino acid (LNAA) supplements on brain and plasma phenylalanine (Phe) levels and other metabolites in early treated subjects with classical phenylketonuria (PKU), and to investigate the relationship between these metabolites and neuropsychological performance. Methods: This was a prospective, double blind, cross over study consisting of four two-week phases with a 4 week washout period. Sixteen subjects (7 males), with classical PKU were recruited into the study and completed all 4 phases. Each phase consisted of either the LNAA supplement or placebo, and either the patient's usual medical product or not. Subjects were instructed to follow their usual Phe restricted diet, maintain energy intake and complete a 3-day food record during each phase. At the end of each phase, brain Phe and other metabolites were measured by proton magnetic resonance spectroscopy (MRS), and plasma amino acids quantified. A detailed neuropsychological assessment was performed on the same day as the MRS and plasma collection. Results: There was no correlation between plasma and brain Phe, but few of the plasma Phe readings were over 1200 μmol/L. Plasma Phe decreased with LNAA supplementation when patients were not taking their medical formula. LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and cognitive flexibility. Measures of attention were better on medical product, with or without LNAA supplements. Conclusions: LNAA supplementation was associated with a trend to a lowering of plasma Phe levels. LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and flexibility. For individuals already complying with diet and PKU medical product, additional supplementation with LNAA is of limited value. LNAA supplementation may be of benefit to those unable to comply with PKU medical product by reducing plasma Phe, perhaps by competing with Phe at the level of transport across the gut.
UR - http://www.scopus.com/inward/record.url?scp=34047251011&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2007.02.002
DO - 10.1016/j.ymgme.2007.02.002
M3 - Article
C2 - 17368065
AN - SCOPUS:34047251011
SN - 1096-7192
VL - 91
SP - 48
EP - 54
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1
ER -