The effects of large neutral amino acid supplements in PKU: an MRS and neuropsychological study.
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 micromol/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.
Schindeler
Suzanne
S
Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, Australia.
Ghosh-Jerath
Suparna
S
Thompson
Susan
S
Rocca
Antonella
A
Joy
Pamela
P
Kemp
Allan
A
Rae
Caroline
C
Green
Kathryn
K
Wilcken
Bridget
B
Christodoulou
John
J
D000328:Adult; D021542:Amino Acids, Neutral / Q000008:administration & dosage / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D014443:Tyrosine / Q000097:blood
D021542:Amino Acids, Neutral; D014443:Tyrosine; D010649:Phenylalanine