Schindeler Suzanne, Ghosh-Jerath Suparna, Thompson Susan, Rocca Antonella, Joy Pamela, Kemp Allan, Rae Caroline, Green Kathryn, Wilcken Bridget, Christodoulou John
Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, Australia.
Mol Genet Metab. 2007 May;91(1):48-54. doi: 10.1016/j.ymgme.2007.02.002. Epub 2007 Mar 23.
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.
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.
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.
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.
确定大中性氨基酸（LNAA）补充剂对经典型苯丙酮尿症（PKU）早期治疗患者脑和血浆苯丙氨酸（Phe）水平及其他代谢物的影响，并研究这些代谢物与神经心理表现之间的关系。
这是一项前瞻性、双盲、交叉研究，包括四个为期两周的阶段，中间有4周的洗脱期。16名经典型PKU患者（7名男性）被纳入研究并完成了所有4个阶段。每个阶段包括LNAA补充剂或安慰剂，以及是否服用患者常用的医疗产品。受试者被要求遵循其通常的低苯丙氨酸饮食，维持能量摄入，并在每个阶段完成一份3天的食物记录。在每个阶段结束时，通过质子磁共振波谱（MRS）测量脑苯丙氨酸和其他代谢物，并对血浆氨基酸进行定量分析。在进行MRS和采集血浆的同一天进行详细的神经心理评估。
血浆和脑苯丙氨酸之间无相关性，但少数血浆苯丙氨酸读数超过1200微摩尔/升。当患者未服用其医疗配方时，补充LNAA可使血浆苯丙氨酸降低。补充LNAA对执行功能有特定影响，尤其是在语言生成和认知灵活性方面。无论是否补充LNAA，服用医疗产品时注意力测试结果更好。
补充LNAA有使血浆苯丙氨酸水平降低的趋势。补充LNAA对执行功能有特定影响，尤其是在语言生成和灵活性方面。对于已经遵守饮食和PKU医疗产品的个体，额外补充LNAA的价值有限。补充LNAA可能对那些无法遵守PKU医疗产品的人有益，也许是通过在肠道转运水平上与苯丙氨酸竞争来降低血浆苯丙氨酸。
