Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, 9700 RB Groningen, The Netherlands.
Nutrients. 2019 Sep 19;11(9):2252. doi: 10.3390/nu11092252.
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.
许多苯丙酮尿症（PKU）患者无法遵守欧洲 PKU 指南建议的严格饮食限制，这可能伴随着神经心理损伤的加重，这些损伤至少部分归因于脑单胺能神经递质的缺乏。在限制饮食之外补充大量非必需氨基酸（LNAA）已被证明可有效改善各种年龄 PKU 小鼠的脑单胺。为了确定 LNAA 补充对宽松的苯丙氨酸限制饮食的附加价值，在 10 至 16 个月大的 C57Bl/6 PKU 小鼠上，比较了补充 LNAA 的低严重度苯丙氨酸限制饮食与非补充的严重或低严重度苯丙氨酸限制饮食对脑单胺和氨基酸浓度的影响。结果发现，补充 LNAA 可改善低严重度苯丙氨酸限制饮食的脑单胺和苯丙氨酸浓度。与严格的苯丙氨酸限制饮食相比，它同样有效地恢复脑去甲肾上腺素和 5-羟色胺，尽管降低脑苯丙氨酸浓度的效果较差。这些成年 PKU 小鼠的结果支持 LNAA 补充可能增强低严重度苯丙氨酸限制饮食效果的观点，并表明接受低严重度苯丙氨酸限制饮食治疗的 PKU 患者的大脑预后可能受益于额外的 LNAA 治疗。
