Aspartame is a commonly used artificial sweetener that is a methyl ester of an L-aspartate and L-phenylalanine dipeptide (L-aspartyl-L-phenylalanine methyl ester). Aspartame ingestion has been shown to result in some gastrointestinal discomfort including nausea, diarrhoea and abdominal pain. However, of more concern is the neurological reactions that can manifest in some sensitive individuals. Generally, these brain effects of aspartame include mood changes, insomnia and seizures. The neurotoxicity associated with aspartame intake is thought to derive from the increase in phenylalanine plasma concentrations, which results from the metabolism of the phenylalanine via one of two pathways. Aspartame can be metabolised in the intestine to aspartate, phenylalanine and methanol by hydrolytic enzyme, which allows absorption of the amino acids and methanol across the lumen of the gut. Alternatively aspartame is demethylated in the lumen of the gut and the resultant dipeptide hydrolysed in the enterocytes prior to absorption.
Interestingly, high plasma and brain levels of phenylalanine are know to cause neurological problems in the disease phenylketonurea (PKU). Phenylketonurea is an inherited disorder that results in a build up of phenylalanine in the plasma due to a congenital deficiency of the enzyme phenylalanine hydroxylase. This enzyme normally converts phenylalanine to tyrosine, but a deficiency causes excess phenylalanine to spill over into the plasma and cause toxicity. The neurological problems associated with phenylketonurea include seizures and tremours, and eventually leads to brain retardation if not treated with a low phenylalanine diet. However, the plasma levels of phenylalanine that occur following aspartame ingestion are much lower that would occur in a sufferer of phenylketonurea. For example, toxicity is usually seen with phenylalanine at around 100µmol/dL plasma, but ingesting 34mg of aspartame results in plasma levels of just 6 to 11µmol/dL, well within the normal range.
In fact, 22L of aspartame sweetened beverage would only raise plasma levels of phenylalanine to around 49µmol/dL, still over 50% lower than the threshold toxicity. A linear relationship may exist between plasma phenylalanine and brain toxicity, such that lower doses have more subtle effects, perhaps being manifest initially only in sensitive individuals. This would fit well with the reports of side effects that are consistent in their nature, although not serious in most cases. In addition, aspartame may decrease brain levels of serotonin, through competition between tryptophan and phenylalanine for transport across the blood brain barrier. Because tryptophan is a precursor of serotonin, decreasing brain levels of this amino acid has a inhibitory effect on the metabolic pathway. Interestingly, the symptoms of low serotonin levels include insomnia and mood changes, and therefore low serotonin may contribute to the neurotoxicity seen with aspartame ingestion.
RdB
