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.

Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids [Erratum: 2010 Apr., v. 91, no. 4, p. 1072]

Phenylketonuria (PKU) is a well-described inborn error of amino acid metabolism that has been treated for >60 years. Enzyme deficiency causes accumulation of phenylalanine (Phe) and if left untreated will lead to profound and irreversible intellectual disability in most children. Traditionally, it has been managed with a low-Phe diet supplemented with a Phe-free protein substitute although newer treatment options mainly in combination with diet are available for some subgroups of patients with PKU, for example, sapropterin, large neutral amino acids, and glycomacropeptide. The diet consists of three parts: 1) severe restriction of dietary Phe; 2) replacement of non-Phe l-amino acids with a protein substitute commonly supplemented with essential fatty acids and other micronutrients; and 3) low-protein foods from fruits, some vegetables, sugars, fats and oil, and special low-protein foods (SLPF). The prescription of diet is challenging for health professionals. The high-carbohydrate diet supplied by a limited range of foods may program food preferences and contribute to obesity in later life. Abnormal tasting and satiety-promoting protein substitutes are administered to coincide with peak appetite times to ensure their consumption, but this practice may impede appetite for other important foods. Intermittent dosing of micronutrients when combined with l-amino acid supplements may lead to their poor bioavailability. Much work is required on the ideal nutritional profiling for special SLPF and Phe-free l-amino acid supplements. Although non-diet treatments are being studied, it is important to continue to fully understand all the consequences of diet therapy as it is likely to remain the foundation of therapy for many years.

https://www.dovepress.com/getfile.php?fileID=33857

Dietary intervention in the management of phenylketonuria: current perspectives.

In phenylketonuria (PKU), synthetic protein derived from L-amino acids (AAs) is essential in a low-phenylalanine (Phe) diet. Glycomacropeptide (GMP), an intact protein, is very low in Phe in its native form. It has been modified and adapted for PKU to provide an alternative protein source through supplementation with rate-limiting amino acids (GMP-AAs), although it still contains residual Phe. This review aims to systematically evaluate published intervention studies on the use of GMP-AAs in PKU by considering its impact on blood Phe control (primary aim) and changes in tyrosine control, nutritional biomarkers, and patient acceptability or palatability (secondary aims). Four electronic databases were searched for articles published from 2007 to June 2018. Of the 274 studies identified, only eight were included. Bias risk was assessed and a quality appraisal of the body of evidence was completed. A meta-analysis was performed with two studies with adequate comparable methodology which showed no differences between GMP-AAs and AAs for any of the interventions analysed. This work underlines the scarcity and nature of studies with GMP-AAs interventions. All were short-term with small sample sizes. There is a need for better-designed studies to provide the best evidence-based recommendations.

https://www.mdpi.com/2072-6643/10/11/1794/pdf

The Use of Glycomacropeptide in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis

Background
In phenylketonuria (PKU), there are no data available for children with respect to evaluating casein glycomacropeptide (CGMP) as an alternative to phenylalanine-free protein substitutes [Phe-free L-amino acid (AA)]. CGMP contains a residual amount of phenylalanine, which may alter blood phenylalanine control.

Methods
In a prospective 6-month pilot study, we investigated the effect on blood phenylalanine control of CGMP-amino acid (CGMP-AA) protein substitute in 22 PKU subjects (13 boys, nine girls), median age (range) 11 years (6–16 years). Twelve received CGMP-AA and nine received Phe-free L-AA, (1 CGMP-AA withdrawal). Subjects partially or wholly replaced Phe-free L-AA with CGMP-AA. If plasma phenylalanine exceeded the target range, the CGMP-AA dose was reduced and replaced with Phe-free L-amino acids. The control group remained on Phe-free L-AAs. Phenylalanine, tyrosine and Phe : Tyr ratio concentrations were compared with the results for the previous year.

Results
In the CGMP-AA group, there was a significant increase in blood phenylalanine concentrations (pre-study, 275 μmol L−1; CGMP-AA, 317 μmol L−1; P = 0.02), a decrease in tyrosine concentrations (pre-study, 50 μmol L−1; CGMP-AA, 40 μmol L−1; P = 0.03) and an increase in Phe : Tyr ratios (pre-study, Phe : Tyr 1 : 5.5; CGMP-AA, Phe : Tyr 1 : 8; P = 0.02).

Conclusions
In the control group, there was a nonsignificant fall in phenylalanine concentrations (pre-study, 325 μmol L−1; study, 280 μmol L−1; P = 0.9) and no significant changes for tyrosine or Phe : Tyr ratios (P = 0.9). Children taking the CGMP-AA found it more acceptable to L-AA. Blood phenylalanine control declined with CGMP-AA but, by titrating the dose of CGMP-AA, blood phenylalanine control remained within target range. The additional intake of phenylalanine may have contributed to the change in blood phenylalanine concentration. CGMP-AA use requires careful monitoring in children.

Glycomacropeptide in children with phenylketonuria: does its phenylalanine content affect blood phenylalanine control?

Whey proteins processing and emergent derivatives: An insight perspective from constituents, bioactivities, functionalities to therapeutic applications

Dietary therapy is the most common therapy applied in treatment of Phenylketonuria (PKU) with restriction of intake of most natural proteins that are rich in Phenylalanine (Phe). Recently, it has been claimed that caseinoglycomacropeptide (GMP), derived of whey, may be used to replace the amino acid formulae (AAF). The Aim of Work. To study the feasibility of use of GMP for partial replacement of artificial formula in treatment of children with PKU. Methods. Ten patients with PKU were included in the study. They received the recommended daily allowances of protein in the form of AAF or a combination of AAF and GMP. The percent of intake of GMP in phases 1 and 2 was 50% and zero%, respectively. Results. The median and interquartiles of phenyl alanine Phe levels phase were not significantly different in phases I and II, 376 (167–551) μmol/L versus 490 (289–597) μmol/L, respectively. Phenylalanine/tyrosine ratio, amino acids, and other laboratory data showed no significant difference between the two phases. Conclusion. GMP may be used to replace 50% of the protein intake to improve the nutritive value and palatability of diet and to provide a more satisfactory diet. No toxicity or side effects were reported in patients on that regimen.

/pdf/the-use-of-glycomacropeptide-in-dietary-management-of-gtfgywm12r.pdf

Nayera Abdulazim

Papers

The Use of Glycomacropeptide in Dietary Management of Phenylketonuria.