Neuropsychological and biochemical investigations in heterozygotes for phenylketonuria during ingestion of high dose aspartame (a sweetener containing phenylalanine)

Abstract

Aspartame, a high intensity sweetener, is used extensively worldwide in over 5,000 products. Upon ingestion, aspartame is completely metabolized to two amino acids and methanol (approximately 50% phenylalanine, 40% aspartic acid, and 10% methanol). The effects of aspartame on cognitive function, electroencephalograms (EEGs) and biochemical parameters were evaluated in 48 adult (21 men, 27 women) heterozygotes for phenylketonuria (PKUH), PKUH subjects whose carrier status had been proven by DNA analysis ingested aspartame (either 15 or 45 mg/kg/day) and placebo for 12 weeks on each treatment using a randomized, double-blind, placebo-controlled, crossover study. A computerized battery of neuropsychological tests was administered at baseline weeks -2 and -1, and during treatment at weeks 6, 12, 18, and 24. Samples for plasma amino acids and urinary organic acids were also collected during these visits. EEGs were evaluated by conventional and spectral analysis at baseline week -1 and treatment weeks 12 and 24. The results of the neuropsychological tests demonstrated that aspartame had no effect on cognitive function. Plasma phenylalanine significantly increased, within the normal range for PKUH, at 1 and 3 h following the morning dose of aspartame in the group receiving the 45 mg/kg per day dose only. There were no significant differences in the conventional or spectral EEG analyses, urinary organic acid concentrations, and adverse experiences when aspartame was compared with placebo. This study reaffirms the safety of aspartame in PKUH and refutes the speculation that aspartame affects cognitive performance, EEGs, and urinary organic acids.

Evaluation of an aspartame loading test for the detection of heterozygotes for classical phenylketonuria

“…The number of foods containing this sweetener increased from only 4 in 1984 to approximately D.F. : discriminant function 5000 products in the 1990's (Trefz et al 1994). The tolerated daily amount is up to 34 mg/kg, equivalent to the ingestion of approximately 19mg/kg Phe, 15.2 mg/kg Asp and 3.7 mg/kg methanol.…”

Cognitive slowing in multiple sclerosis is strongly associated with brain volume reduction

“…The ANT tasks [6], each provide a speed score, a speed fluctuation score and an accuracy of performance (% errors) score. On the basis of normative data obtained in various studies [5,18,19], from healthy subjects and stratified by age (mean age 30, 40, 50, 60 years old), the scores were transformed into Z-scores for each response variable. In the pursuit and tracking tasks, the mean distance and distance fluctuation variables were subjected to a similar Z-score transformation.…”

The complete European guidelines on phenylketonuria: diagnosis and treatment

“…Aspartame (E951) (1-aspartyl-1-Phe methylester) is an intense sweetener derived from a dipeptide composed of Phe (50%), aspartic acid (40%) and methanol (10%) [ 286 , 287 ]. It is a source of Phe.…”

“…The approximate amounts of aspartame in foods are: a 360 ml can of diet coke is 130 mg, 1 portion aspartame flavoured jelly is 40 mg, 1 teaspoon of artificial sweetener 15–20 mg and 1 piece of sugar-free chewing gum 5 mg. In the 1980’s/1990’s, many small intervention (controlled and uncontrolled) studies examined the impact of aspartame in patients with PKU, with most studies demonstrating a small, but consistent, increase in blood Phe concentrations with aspartame [ 287 – 295 ]. Fortunately, there are many other artificial sweeteners available that do not contain Phe.…”