Optimising amino acid absorption: essential to improve nitrogen balance and metabolic control in phenylketonuria

• Type of Material: Article
• Authors: Anita MacDonald, Birmingham Children’s Hospital; Rani H Singh, Emory University; Julio Cesar Rocha, Centro Hospitalar do Porto; Francjan J. van Spronsen, University of Groningen
• Language: English
• Date: 2019-06-01
• Publisher: Cambridge University Press (CUP): PDF allowed
• Publication Version: Final Published Version
• Copyright Statement: © The Authors 2018.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1017/S0954422418000173
• Title of Journal or Parent Work: Nutrition Research Reviews
• ISSN: 0954-4224
• Volume: 32
• Issue: 1
• Start Page: 70
• End Page: 78
• Grant/Funding Information: The authors thank APR Applied Pharma Research S.A. (Balerna Switzerland) for financially supporting the project.
• Keywords: NUTRITION MANAGEMENT; Nitrogen balance; Life Sciences & Biomedicine; Phenylketonuria; Amino acids; Protein synthesis; CIRCADIAN PERIODICITY; SYSTEM-L; COGNITIVE OUTCOMES; TYROSINE SUPPLEMENTATION; INCRETIN HORMONE; Science & Technology; Amino acid mixtures; BODY-COMPOSITION; Absorption; Phenylalanine; PROTEIN-SYNTHESIS; BARRIER PHENYLALANINE TRANSPORT; Nutrition & Dietetics; PLASMA PHENYLALANINE
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery; Health Sciences, Nutrition

Abstract

It has been nearly 70 years since the discovery that strict adherence to a diet low in phenylalanine prevents severe neurological sequelae in patients with phenylalanine hydroxylase deficiency (phenylketonuria; PKU). Today, dietary treatment with restricted phenylalanine intake supplemented with non-phenylalanine amino acids to support growth and maintain a healthy body composition remains the mainstay of therapy. However, a better understanding is needed of the factors that influence N balance in the context of amino acid supplementation. The aim of the present paper is to summarise considerations for improving N balance in patients with PKU, with a focus on gaining greater understanding of amino acid absorption, disposition and utilisation. In addition, the impact of phenylalanine-free amino acids on 24 h blood phenylalanine/tyrosine circadian rhythm is evaluated. We compare the effects of administering intact protein v. free amino acid on protein metabolism and discuss the possibility of improving outcomes by administering amino acid mixtures so that their absorption profile mimics that of intact protein. Protein substitutes with the ability to delay absorption of phenylalanine and tyrosine, mimicking physiological absorption kinetics, are expected to improve the rate of assimilation into protein and minimise fluctuations in quantitative plasma amino acid levels. They may also help maintain normal glycaemia and satiety sensation. This is likely to play an important role in improving the management of patients with PKU.