EFFECTS OF ASPARTAME INTAKE ON PHENYLKETONURIA CARRIERS

在美国，大约1/50的人是缺陷的携带者。 苯丙氨酸羟化酶，在纯合子中， 苯丙酮尿症（PKU）。 PKU患者患有发育性 与中枢神经系统有关的异常。 患有苯丙酮尿症的女性 怀孕需要严格控制苯丙氨酸的饮食，因为高 血液中苯丙氨酸或其代谢物的水平，导致各种 胎儿畸形的程度。 关于我们 （L-乙酰基-L-苯丙氨酸-N-甲基酯） 一般人群，如果长期使用， 苯丙氨酸羟化酶的活性，或者如果苯丙氨酸羟化酶的额外负荷 苯丙氨酸从甜菜碱转移到其他代谢物， 苯乙胺和苯丙氨酸的其它芳族酸。 人口 最容易受到病毒影响的是携带者 尤其是女性。 显然，大多数这样的女性不会知道 的运营商状态。 对这些雌性来说， 苯丙氨酸及其代谢物的血液水平在怀孕期间， 可能导致发育迟缓或智力迟钝的个体。 事实上，阿替西泮的影响也可能发生在年轻人身上， 尤其是PKU的携带者 在这些情况下， 苯丙氨酸代谢物可能导致行为和学习问题 残疾。 建议研究长期摄入甜菜碱对 苯乙胺，苯丙氨酸和酪氨酸的芳香酸， 这种摄入对苯丙氨酸的体内活性的影响 正常人、PKU专性携带者和患者中羟化酶 患有良性高苯丙氨酸血症 良性高苯丙氨酸血症不 需要限制苯丙氨酸的饮食和携带频率， 该缺陷估计为1/70。 参加研究的个人 在12周内，将给予相当于或高于 比预计的日常使用。 体内苯丙氨酸羟化酶的测定 活性将基于在等离子体中测量的 D5-苯丙氨酸转化为D4-酪氨酸。 血和尿中的苯丙氨酸酪氨酸 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。 由于将对每份样品进行总氨基酸分析，因此， 感兴趣的氨基酸，如天冬氨酸、谷氨酸、色氨酸和 将在整个试验期间研究支链氨基酸。

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.