Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids

Abstract

Background: Phenylketonuria (PKU) requires a lifelong low-phenylalanine diet that provides the majority of protein from a phenylalanine-free amino acid (AA) formula. Glycomacropeptide (GMP), an intact protein formed during cheese production, contains minimal phenylalanine.

Objective: The objective was to investigate the effects of substituting GMP food products for the AA formula on acceptability, safety, plasma AA concentrations, and measures of protein utilization in subjects with PKU.

Design: Eleven subjects participated in an inpatient metabolic study with two 4-d treatments: a current AA diet (AA diet) followed by a diet that replaced the AA formula with GMP (GMP diet) supplemented with limiting AAs. Plasma concentrations of AAs, blood chemistries, and insulin were measured and compared in AA (day 4) and GMP diets (day 8).

Results: The GMP diet was preferred to the AA diet in 10 of 11 subjects with PKU, and there were no adverse reactions to GMP. There was no significant difference in phenylalanine concentration in postprandial plasma with the GMP diet compared with the AA diet. When comparing fasting with postprandial plasma, plasma phenalyalanine concentration increased significantly with the AA but not with the GMP diet. Blood urea nitrogen was significantly lower, which suggests decreased ureagenesis, and plasma insulin was higher with the GMP diet than with the AA diet.

Conclusions: GMP, when supplemented with limiting AAs, is a safe and highly acceptable alternative to synthetic AAs as the primary protein source in the nutritional management of PKU. As an intact protein source, GMP improves protein retention and phenylalanine utilization compared with AAs.

Figures

FIGURE 1

The concentration of total amino acids (AAs) and blood urea nitrogen in postprandial plasma with ingestion of the glycomacropeptide (GMP) or the AA diet. Plasma was obtained 2.5 h after eating breakfast; n = 11 with the exception of blood urea nitrogen on study days 5 and 6 for which n = 6. Total plasma AAs indicate the sum of all AAs measured in plasma. Values are means ± SEMs. Total plasma AAs increased and blood urea nitrogen decreased with ingestion of the GMP diet when compared with day 4 of the AA diet. There was a significant effect of time in the repeated-measures ANOVA. *Significantly different from the AA diet on day 4, P < 0.05 (paired t test, pairing on subject).

FIGURE 2

Concentrations of phenylalanine in plasma of individual subjects with phenylketonuria (n = 11) after consuming the amino acid (AA) diet or the glycomacropeptide (GMP) diet for 4 d. Blood was obtained 2.5 h after eating breakfast, and plasma was isolated for analysis of the complete AA profile. Subjects showed a range of plasma phenylalanine concentrations after consuming the AA diet or the GMP diet for 4 d. There was no significant difference in the concentration of phenylalanine in plasma when the last day of the AA diet (day 4) was compared with the last day of the GMP diet (day 8); P = 0.173 by paired t test, pairing on subject. Group mean ± SEM was 619 ± 82 μmol/L (AA diet) and 676 ± 92 μmol/L (GMP diet). The mean change in the concentration of phenylalanine in plasma was 57 ± 52 μmol/L. phe, phenylalanine.

FIGURE 3

The concentration of phenylalanine in postprandial (PP; 2.5 h after eating breakfast) compared with fasting (fast, overnight fast) plasma in subjects with phenylketonuria fed glycomacropeptide (GMP) compared with the amino acid (AA) diet for 4 d. Group means and the response of individual subjects are shown; n = 6 (day 4 compared with day 8). There was no significant change in plasma phenylalanine concentration comparing fasting with PP concentrations when consuming the GMP diet (P = 0.349); however, the AA diet showed a significant increase in plasma phenylalanine (P = 0.048) by paired t test, pairing on subject. phe, phenylalanine.

FIGURE 4

Concentrations of threonine and isoleucine in postprandial plasma after consuming the glycomacropeptide (GMP) diet for 4 d (days 5–8). Values are mean ± SEM; n = 11, of plasma obtained 2.5 h after breakfast. For study days 3 and 4, all subjects consumed an amino acid (AA) diet; on days 5–8, all AA formula was replaced with GMP food products. There was a significant effect of time in the repeated-measures ANOVA. *Significantly different from the last day of the AA diet (day 4), P < 0.05 (paired t test, pairing on subject). **Significantly different from the last day of the AA diet (day 4), P < 0.0001. There was no further significant increase in plasma concentration of isoleucine and threonine after days 5 and 7, respectively. ile, isoleucine; thr, threonine.