Nutritional management of PKU with glycomacropeptide from cheese whey

Abstract

Individuals with phenylketonuria (PKU) must follow a lifelong low-phenylalanine (Phe) diet to prevent neurological impairment. Compliance with the low-Phe diet is often poor owing to restriction in natural foods and the requirement for consumption of a Phe-free amino acid formula or medical food. Glycomacropeptide (GMP), a natural protein produced during cheese-making, is uniquely suited to a low-Phe diet because when isolated from cheese whey it contains minimal Phe (2.5-5 mg Phe/g protein). This paper reviews progress in evaluating the safety, acceptability and efficacy of GMP in the nutritional management of PKU. A variety of foods and beverages can be made with GMP to improve the taste, variety and convenience of the PKU diet. Sensory studies in individuals with PKU demonstrate that GMP foods are acceptable alternatives to amino acid medical foods. Studies in the PKU mouse model demonstrate that GMP supplemented with limiting indispensable amino acids provides a nutritionally adequate source of protein and improves the metabolic phenotype by reducing concentrations of Phe in plasma and brain. A case report in an adult with classical PKU who followed the GMP diet for 10 weeks at home indicates safety, acceptability of GMP food products, a 13-14% reduction in blood Phe levels (p<0.05) and improved distribution of dietary protein throughout the day compared with the amino acid diet. In summary, food products made with GMP that is supplemented with limiting indispensable amino acids provide a palatable alternative source of protein that may improve dietary compliance and metabolic control of PKU.

Conflict of interest statement

Competing interests: None declared

Figures

Fig. 1

The concentration of Phe in five sections of brain—cerebellum, brain stem, hypothalamus, parietal cortex, and anterior piriform cortex—of PKU mice fed the glycomacropeptide (GMP) or amino acid (AA) diet for 47 days. Values are means±SEM; n = 8. *Different from the AA diet, p ≤ 0.001. This figure was previously published by Ney et al (2008) and is reproduced with permission of the copyright owner, American Society for Nutrition

Fig. 2

Mean Phe concentrations obtained after an overnight fast before breakfast from a single PKU subject fed an amino acid (AA) or glycomacropeptide (GMP) diet for 15 weeks at home. Data are shown for 6 weeks of the 15-week study period when only foods with known Phe content were provided to the subject: weeks 3 and 15 (AA diet) and weeks 4, 7, 11 and 13 (GMP diet). Phe concentrations in blood and plasma were corrected for Phe intake and expressed as μmol Phe/L per 100 mg Phe intake. Phe concentration was determined using one of two methods, blood spot collection analysed with tandem mass spectroscopy (MS/MS) and measurement of plasma Phe with an AA analyser. Values are means±SE; AA diet (n = 4 plasma Phe and n = 4 blood Phe), GMP diet (n = 4 plasma Phe and n = 8 blood Phe). *Different from the AA diet, p < 0.05