title: Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Nutritional Sciences, ney@nutrisci.wisc.edu.
authors.forename: Denise M
authors.identifier: http://orcid.org/0000-0002-2260-5313
authors.initials: DM
authors.lastname: Ney
authors.affiliation: Departments of Nutritional Sciences.
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Stroup
authors.affiliation: Statistics, and Plant Pathology, University of Wisconsin-Madison, Madison, WI;
authors.forename: Murray K
authors.initials: MK
authors.lastname: Clayton
authors.affiliation: Departments of Nutritional Sciences.
authors.forename: Sangita G
authors.initials: SG
authors.lastname: Murali
authors.affiliation: Waisman Center and Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI; and.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Rice
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Frances
authors.initials: F
authors.lastname: Rohr
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Harvey L
authors.initials: HL
authors.lastname: Levy
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002364:Caseins / Q000737:chemistry / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004044:Dietary Proteins / Q000737:chemistry / Q000627:therapeutic use*; D005247:Feeding Behavior; D005260:Female; D019648:Foods, Specialized; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006815:Hunger; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000178:diet therapy*; D055815:Young Adult
chemical_list: D002364:Caseins; D004044:Dietary Proteins; D010446:Peptide Fragments; C065989:caseinomacropeptide; D010649:Phenylalanine
keywords: executive function; inborn errors of amino acid metabolism; medical food; phenylalanine; sapropterin dihydrochloride; threonine; tyrosine