Dietary Threonine Reduces Plasma Phenylalanine Levels in Patients With Hyperphenylalaninemia

Abstract

ABSTRACTBackgroundIn order to achieve normal intellectual development, the plasma phe‐nylalanine (PHE) levels of patients with hyperphenylalaninemia should not exceed toxic levels. This goal is usually accomplished by employing special diets in which the patient's protein intake is in the form of PHE‐free mixtures of amino acids. There is evidence from our own observations in animals and a preliminary observation in patients with hyperphenylalaninemia that supplemental dietary threonine (THR) might decrease plasma PHE concentrations.MethodsIn this placebo‐controlled crossover study, the effect of supplemental oral THR on the plasma amino acid concentrations of 12 patients with hyperphenylalaninemia was investigated. Before starting the first treatment period of this cross‐over study, the patients were randomly assigned to one of two groups supplemented either with approximately 50 mg THR/kg per day or with a similar amount of maltodextrin as placebo. After a feeding period of 8 weeks and a wash‐out period of 8 weeks, the supplements were crossed over and the study continued for an additional 8 weeks. Blood was obtained at the start and the end of each supplementation period.ResultsDietary THR supplementation of approximately 50 mg/kg per day resulted in a significant decrease of plasma PHE levels (P = 0.0234). There was a close positive correlation between plasma and urinary PHE concentrations (P < 0.001) indicating that the lower plasma PHE levels in the THR supplemented patients were not caused by higher urinary excretion of PHE.ConclusionsThe data of the present study show that oral THR supplementation has a clear plasma‐PHE‐reducing effect but they do not allow any conclusion about the mechanisms responsible for the observed effect. Although it seems attractive on the basis of the present data to use THR supplementation in patients with hyperphenylalaninemia, the mechanism of the observed effect should be clarified before introduction of such a treatment in these patients.