Administration of the artificial sweetener aspartame (L-aspartyl-phenylalanylmethylester) in fairly large doses (200 mg/kg) to rats elevates brain levels of phenylalanine and, especially, tyrosine. These effects are enhanced if animals eat a carbohydrate concurrently (because the resulting secretion of insulin lowers plasma levels of other large neutral amino acids that compete with phenylalanine and tyrosine for brain uptake). We propose a program of research to examine some of the physiological and behavioral consequences of these brain changes, and to assess the likelihood that similar changes occur in human subjects. We believe that this research is important both because of the widespread and growing use of the sweetener and because it may yield useful information about certain basic-science questions (e.g., the equivalence of amino acid doses for humans and rats; the extents to which techniques commonly used to measure blood-pressure changes in rats have their own affects on the whether aspartame can modify the synthesis and release of catecholamines from physiologically-active neurons; 2) comparing the dose-response relationship for plasma amino acid levels and ratios in rats and humans given aspartame alone, or with particular dietary carbohydrates. (For example, if - as seems likely - brain phenylalanine levels can be predicted from the ratio of plasma phenylalanine to the sum of other LNAA, then it should be possible to determine which aspartame dose, given to a human, is likely to elevate brain phenylalanine to the same extent as a certain ose given to rats.); 3) extending our preliminary observations showing that aspartame (200 mg/kg) can lower blood pressure in hypertensive rats (presumably by raising brain tyrosine); and, 4) determining whether aspartame doses that probably alter brain tryptophan and serotonin levels affect subsequent food intake and nutrient choice.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Neurological Sciences Subcommittee 1 (NLS)
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Massachusetts Institute of Technology
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