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Effect of Aspartame Loading upon Plasma and Erythrocyte Amino Acid Levels in Phenylketonuric Heterozygotes and Normal Adult Subjects^1,2,

Departments of Pediatrics and Biochemistry and the Child Development Clinic, The University of Iowa College of Medicine, Iowa City, Iowa 52242

Aspartame is a dipeptide (L-aspartyl-L-phenylalanyl-methylester) with a sweetening power 180 to 200 times that of sucrose. Questions about aspartame safety have arisen because of concern about potential toxic effects of its constituent amino acids, aspartate and phenylalanine, particularly in subjects heterozygous for phenylketonuria. Plasma and red cell amino acid levels were measured in eight female subjects known to be heterozygous for phenylketonuria and 12 subjects assumed to be normal (six male, six female), after aspartame administration (34 mg/kg) in orange juice. No changes in either plasma or erythrocyte aspartate levels were noted at any time after aspartame loading in either group, indicating rapid metabolism of the aspartate administered. In the normal subjects, plasma phenylalanine levels (mean ± SD) increased from fasting levels (5.66 ± 1.21 µmoles/100 ml) to values in the normal postprandial range (11.11 ± 2.49 µmoles/100 ml) and essentially returned to baseline by 8 hours. In the hererozygous subjects, mean peak plasma phenylalanine levels were higher (16.03 ± 2.25 µmoles/100 ml) and the plasma concentrationtime curve broader. However, maximum plasma phenylalanine levels were only slightly above values noted postprandially in the human infant and adult. Erythrocyte phenylalanine levels showed similar, but smaller changes. The data indicate slightly slower, but adequate metabolism and clearance of the phenylalanine portion of aspartame by the phenylketonuric heterozygote.

KEY WORDS: • aspartame • phenylalanine • phenylketonuria

¹ Supported in part by a grant-in-aid from G. D. Searle, Chicago, Illinois.

² These data were presented in preliminary form at the American Society of Clinical Nutrition meeting, July, 1976, East Lansing, Michigan. J. Nutr. 106, xxxiii.

Manuscript received 20 September 1978.