EFFECTS OF ASPARTAME INTAKE ON PHENYLKETONURIA CARRIERS

在美国，大约有1/50的人是这种缺陷的携带者 在纯合子中导致疾病的苯丙氨酸羟基酶 苯丙酮尿症(PKU)。PKU患者患有发育性疾病 与中枢神经系统有关的异常。北大女大学生 怀孕需要严格控制苯丙氨酸的饮食，因为 血液中苯丙氨酸或其代谢产物的水平会导致不同的 胎儿畸形的程度。阿斯巴甜的介绍 (L-天冬氨基-L-苯丙氨酸-α甲酯)供 普通人群，如果长期使用会影响健康 苯丙氨酸羟化酶的活性或如果额外的负荷 阿斯巴甜中的苯丙氨酸被转移到其他代谢物，如 苯乙胺和其他苯丙氨酸的芳香酸。人口 最容易受到阿斯巴甜影响的是携带者 对于北大来说，尤其是女性。显然，大多数这样的女性不会知道 他们的运营商状态。对这样的女性来说，危险将是增加 孕期血液苯丙氨酸及其代谢物水平 可能会导致发育迟缓或智力低下的人。 事实上，阿斯巴甜的影响也可能发生在更年轻的人身上， 特别是北大的运营商。在这些情况下， 苯丙氨酸代谢物可能导致行为问题和学习 残疾人士。 建议研究长期摄入阿斯巴甜对血药浓度的影响。 苯乙胺、苯丙氨酸和酪氨酸的芳香酸以及 摄入量对苯丙氨酸体内活性的影响 正常人、PKU专职携带者和患者的羟基酶 伴有良性高苯丙氨酸血症。良性高苯丙氨酸血症不 要求饮食限制苯丙氨酸和 这一缺陷估计为1/70。参与这项研究的个人 将给予阿斯巴甜12周，剂量相当于或更高 而不是预计的日使用量。体内苯丙氨酸羟基酶的测定 活度将基于测量在血浆中的转化率 D5-苯丙氨酸为D4-酪氨酸。血液和尿苯丙氨酸，酪氨酸， 苯乙胺，苯丙氨酸和酪氨酸的有机酸，如 将测量苯丙酮酸、苯乳酸和苯乙酸。 由于总氨基酸分析将在每个样本上进行，其他 感兴趣的氨基酸，如天冬氨酸、谷氨酸、色氨酸和 支链氨基酸将在整个试验期内进行研究。

Approximately 1/50 individuals in the US are carriers for the defect phenylalanine hydroxylase which, in the homozygous, results in the disease phenylketonuria (PKU). Patients with PKU suffer from developmental abnormalities related to the central nervous system. Females with PKU who become pregnant require strict dietary control of phenylalanine since high levels of blood phenylalanine, or its metabolites, result in various degrees of fetal abnormalities. The introduction of aspartame (L-aspartyl-L-phenylalanine-alphamethyl ester) for consumption by the general population, may increase health hazards if long term use affects the activity of phenylalanine hydroxylase or if the additional load of phenylalanine from aspartame is diverted to other metabolites such as phenylethylamine and other aromatic acids of phenylalanine. The population that will be most vulnerable to the effects of aspartame would be carriers for PKU, notably females. Obviously, most such females will not know of their carrier state. The danger for such females would be an increase in blood levels of phenylalanine and its metabolites during pregnancy, which may lead to developmentally delayed or mentally retarded individuals. Indeed, the effects of aspartame may also occur in younger individuals, specifically carriers for PKU. In these cases an increase in the levels of phenylalanine metabolites may lead to behavior problems and learning disabilities. It is proposed to study the effects of long term aspartame intake on levels of phenylethylamine, the aromatic acids of phenylalanine and tyrosine and the effect of such intake on the in vivo activity of phenylalanine hydroxylase in normal individuals, obligate carriers for PKU and patients with benign hyperphenylalaninemia. Benign hyperphenylalaninemia does not require dietary restriction of phenylalanine and the carrier frequency for this defect is estimated to be 1/70. Individuals enrolled in the study will be given, for 12 weeks, aspartame in doses corresponding to, or higher than the projected daily use. Assays of in vivo phenylalanine hydroxylase activity will be based on measurement in the plasma of the conversion of d5-phenylalanine to d4-tyrosine. Blood and urine phenylalanine, tyrosine, phenylethylamine, the organic acids of phenylalanine and tyrosine, such as phenylpyruvic, phenyllactic, and phenylacetic acids will be measured. Since the total amino acid analysis will be performed on each sample, other amino acids that are of interest such as aspartic, glutamic, tryptophan and the branched chain amino acids will be studied throughout the trial period.