Effect of high-dose tyrosine supplementation on brain function in adults with phenylketonuria

J Pediatr. 1995 Dec;127(6):936-43. doi: 10.1016/s0022-3476(95)70031-5.


Objectives: To characterize abnormalities of brain function in patients with phenylketonuria (PKU) who had relaxed or stopped the dietary regimen and to test whether oral high-dose tyrosine (Tyr) supplementation has a beneficial effect.

Design: Comparison with a control group; double-blind, placebo-controlled study comprising six test times; crossover treatment groups; oral high-dose Tyr therapy (100 mg/kg body weight per day) or placebo administration for 4 weeks.

Subjects: Twenty-four early-treated patients with PKU aged 20.8 (16 to 25) years; 24 control subjects.

Methods: Plasma concentrations of phenylalanine and Tyr were monitored. Neuropsychologic tasks, visual evoked potentials, and spectral analysis of electroencephalographic activity were used to evaluate brain function.

Results: When patients with PKU were compared with control subjects, deficits in certain aspects of brain function were confirmed (i.e., a decreased ability to sustain attention, prolonged latencies of visual evoked potential peaks N1 and P2, and a reduced amount of fast-wave activity on the electroencephalogram). Baseline plasma phenylalanine and Tyr concentrations were in the typical range of adult patients with PKU. The plasma Tyr concentration increased approximately 200% during Tyr supplementation, but no beneficial effects were observed.

Conclusions: High-dose Tyr supplementation cannot be recommended as an "alternative" treatment for patients with PKU after relaxation or termination of strict dietary adherence.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / drug effects*
  • Brain / physiopathology*
  • Cognition Disorders / diagnosis
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electroencephalography
  • Evoked Potentials, Visual
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Phenylalanine / blood
  • Phenylketonurias / drug therapy*
  • Phenylketonurias / physiopathology*
  • Placebos
  • Psychological Tests
  • Reaction Time
  • Tyrosine / administration & dosage*
  • Tyrosine / pharmacology*
  • Tyrosine / therapeutic use*


  • Placebos
  • Tyrosine
  • Phenylalanine