Aspartame, Serotonin and Rats

The macronutrient composition of the diet is known to have a direct influence on the amino acid content of the blood. In turn the plasma amino acid levels are known to be able to alter brain chemistry by shifting the balance of neurotransmitter production between the 5-hydroxyindoles and the catecholamines. The large neutral amino acids comprise a sub group of the dietary amino acids derived from protein foods, and include valine, leucine, isoleucine (the branched chain amino acids), as well as phenylalanine, tyrosine and tryptophan. Once in the blood following a meal, these amino acids compete with each other for transport into the brain on the L-type amino acid transporter. In the brain the amino acids are transported into neurones where they are converted into a variety of different neurotransmitters which play important roles in brain function.

Generally, consumption of high carbohydrate foods result in an insulin response which causes the transport of the branched chain amino acids and other LNAA (excluding tryptophan) into muscle cells. This raises the ratio of tryptophan to other LNAA in the blood which facilitates increased transport of tryptophan into the brain. In the brain, tryptophan is transported into neurones where it is converted first to 5 hydroxytryptophan and then to serotonin (5-hydroxyindoles) (here). In contrast, a high protein meal causes the tryptophan to LNAA ratio in the blood to decrease because protein foods are poor sources of tryptophan (1 to 2 %) but are rich in leucine, valine, isoleucine, phenylalanine and tyrosine. This increases the transport of phenylalanine into the brain, where it is converted to DOPA, adrenaline and noradrenaline (catecholamines) (here).

Aspartame (3-amino-N-(α-carboxyphenylethyl) succinamic acid, N-methyl ester), is a methyl ester of the dipeptide aspartyl-phenylalanine and is used commercially as an artificial sweetener (NutraSweet, AminoSweet, Equal or Spoonful) because it is about 180 times sweeter than sugar. Aspartame is digested to phenylalanine, aspartate and methanol, which are then absorbed into the blood. Aspartame consumption therefore provides the blood with phenylalanine, but none of the other LNAA. Thus phenylalanine can be transported into the brain, where it is converted to catecholamines. Alternatively, it can be converted to tyrosine in the liver, which then enters the brain and converted to catecholamines. Either way, consumption of sufficient amounts of phenylalanine is able to raise brain levels of the catecholamine neurotransmitters. Because aspartame and carbohydrates have contrasting effects on neurotransmitter production, it is important to understand the metabolic effects of them in combination.

Research published in the American Journal of Clinical Nutrition in 19841, fed rats a meals consisting of aspartame, glucose or a combination of the two. Aspartame administration alone raised levels of phenylalanine and tyrosine in both the plasma and brain. In contrast consumption of glucose caused an increase in plasma and brain levels of tryptophan as would be expected following the effects of insulin on the muscle uptake of the LNAA. When aspartame was administered with glucose however, it blocked the increase in plasma and brain levels of tryptophan seen with administration of glucose alone, and amplified the increase in phenylalanine concentrations seen with aspartame alone. Thus aspartame appears able to block the physiological increase that carbohydrates normally produce in brain tryptophan but amplify the increase in brain levels of phenylalanine seen with aspartame ingestion.

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1Yokogoshi, H., Roberts, C. H., Caballero, B. and Wurtman, R. J. 1984. Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxyindoles. American Journal of Clinical Nutrition. 40: 1-7

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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