Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial

• Published in: The American journal of clinical nutrition Vol. 104; no. 2; pp. 334 - 345
• Main Authors: Ney, Denise M, Stroup, Bridget M, Clayton, Murray K, Murali, Sangita G, Rice, Gregory M, Rohr, Frances, Levy, Harvey L
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Nutrition, Inc 01.08.2016; American Society for Nutrition
• Subjects: Adolescent; Adult; adverse effects; amino acid composition; Amino acids; analysis of covariance; Analysis of Variance; blood; Caseins - chemistry; Caseins - therapeutic use; Clinical trials; cognitive disorders; Cross-Over Studies; Dietary Proteins - chemistry; Dietary Proteins - therapeutic use; Energy and Protein Metabolism; Feeding Behavior; Female; food intake; food records; Foods, Specialized; Gastrointestinal Diseases - etiology; Gastrointestinal Diseases - prevention & control; gastrointestinal system; Humans; Hunger; inventories; Male; medical foods; Metabolism; Middle Aged; Nutrition; Patient Satisfaction; Peptide Fragments - chemistry; Peptide Fragments - therapeutic use; Peptides; phenylalanine; Phenylalanine - administration & dosage; Phenylalanine - blood; phenylketonuria; Phenylketonurias - blood; Phenylketonurias - diet therapy; proteins; Young Adult; medical food; inborn errors of amino acid metabolism; phenylalanine; threonine; tyrosine; executive function; sapropterin dihydrochloride
• DOI: 10.3945/ajcn.116.135293
• ISSN: 0002-9165; 1938-3207

To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria. This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15-49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained. The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA-MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean ± SE increase in plasma Phe (62 ± 40 μmol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 ± 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (-85 ± 40 μmol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 ± 34 μmol/L, GMP-MFs = 497 ± 34 μmol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different. GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP-MFs than with AA-MFs may enhance dietary adherence for individuals with phenylketonuria. This trial was registered at www.clinicaltrials.gov as NCT01428258.