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.Design: 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.

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

“…In addition, hypersecretion of creatinine by proximal tubules with potential renal dysfunction [32–34] was noted in 5 of 8 participants, in spite of normal plasma electrolytes, blood urea nitrogen, and estimated glomerular filtration rate [17]. The average urinary total protein excretion was not significantly different for GMP-MF and AA-MF.…”

Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria

“…We conducted metabolomics analysis of a subset of plasma (n=18) and 24-hr urine (n=9) samples obtained from PKU subjects who completed our randomized, controlled, crossover trial where 30 early-treated PKU subjects consumed, for 3-wk each, their usual low-Phe diet combined with AA-MF or GMP-MF (6). The University of Wisconsin-Madison Health Sciences Institutional Review Board approved the study protocol.…”

“…There was a 3-wk washout period between treatments during which subjects consumed their usual AA-MF (6). The 18 plasma samples were chosen to include the 9 subjects who consented to provide 24-hr urine samples for both AA-MF and GMP-MF treatments and to represent the median plasma Phe response from the total sample of 30 subjects (6).…”

“…In our recent randomized, controlled, crossover trial, we observed a disparity between intake and plasma concentrations of Tyr and Trp (6). Despite significantly higher intakes of Tyr and Trp in subjects consuming a low-Phe diet in combination with AA-MF compared with GMP-MF, fasting plasma concentrations of Tyr and Trp were not significantly different.…”

“…The absence of aromatic amino acids in GMP (Phe, Tyr and Trp) enables the formulation of a variety of palatable GMP-MF for the management of PKU and tyrosinemia. Because GMP is not a complete protein, it requires supplementation with the following indispensable amino acids for PKU: Arg, His, Leu, Trp and Tyr (6, 7). Individuals who are diagnosed in infancy and maintain control of blood Phe levels within 120–360 μM/L show IQs within the normal range, although neurocognitive symptoms, such as decreased executive function, and neuropsychological symptoms, such as anxiety and depression, persist (8, 9).…”