MODERATE CHANGES IN PLASMA PHENYLALANINE CONCENTRATIONS AFFECT BRAIN ELECTRICAL DISCHARGE

Abstract

We previously demonstrated that large changes in blood phenylalanine (phe) concentrations (500 - 2000 pM) decreased plasma L-DOPA, slowed brain electrical discharge and prolonged performance (Fed. Res. 20:112, 1986). In this study we ask whether moderately elevated plasma phe affects brain function. Six heterozygotes for phenylketonuria (PKU) and 2 normal controls were studied in a crossover, blinded protocol of 4, 2-week intervals. Volunteers ingested a constant diet of 40-50 mg/kg/day phe supplemented either with 100 mg/kg/day phe or placebo. On the last three days of each period the mean power frequency of three electroencephalograms (MPF) were measured. Plasma phe rose in both heterozygotes and controls on ingesting supplemental phe from a mean placebo phe concentration of 99 ± 20 to 140 ± 166 μM. The range of changes was from −200 to +400 μM. There was an inverse relationship between changes in plasma phe above 50 μM and changes in the MPF. By regression analysis 100 μM change in plasma phe produced an inverse change of 0.12 CPS in MPF. We conclude that plasma phe concentrations are raised by phe ingestion in both PKU heterozygotes and homozygous normal, and that alterations in brain electrical discharge are induced by intermediate changes in blood phe concentrations supporting a linear rather than threshold relationship to altered brain function.