Abstract
For many years, the main nitrogen source for patients with phenylketonuria (PKU) was phenylalanine-free amino acid supplements. Recently, casein glycomacropeptide (GMP) supplements have been prescribed due to its functional and sensorial properties. Nevertheless, many doubts still persist about the metabolic effects of GMP compared to free amino acids (fAA) and intact proteins such as casein (CAS). We endeavour to compare, in rats, the metabolic effects of different nitrogen sources. Twenty-four male Wistar rats were fed equal energy density diets plus CAS (control, n = 8), fAA (n = 8) or GMP (n = 8) for 8 weeks. Food, liquid intake and body weight were measured weekly. Blood biochemical parameters and markers of glycidic metabolism were assessed. Glucagon-like peptide-1 (GLP-1) was analysed by ELISA and immunohistochemistry. Food intake was higher in rats fed CAS compared to fAA or GMP throughout the treatment period. Fluid intake was similar between rats fed fAA and GMP. Body weight was systematically lower in rats fed fAA and GMP compared to those fed CAS, and still, from week 4 onwards, there were differences between fAA and GMP. None of the treatments appeared to induce consistent changes in glycaemia, while insulin levels were significantly higher in GMP. Likewise, the production of GLP-1 was higher in rats fed GMP when compared to fAA. Decreased urea, total protein and triglycerides were seen both in fAA and GMP related to CAS. GMP also reduced albumin and triglycerides in comparison to CAS and fAA, respectively. The chronic consumption of the diets triggers different metabolic responses which may provide clues to further study potential underlying mechanisms.
Highlights
Phenylketonuria (PKU, OMIM # 261600) stems from the body’s inability to metabolize the essential amino acid phenylalanine (Phe) to tyrosine (Tyr) due to deficient activity of phenylalanine hydroxylase (PAH) with resultant cognitive impairment [1]
Except for weeks 3 and 6, food intake was significantly lower in rats fed experimental diets when compared to the CAS diet, and the organoleptic features of those diets mainly consisting of free amino acids (fAA) and GMP plus amino acids might have been responsible for the differences found
One important message of this study is the lower food intake of rats fed fAA and GMP, and this finding could be associated with a different palatability which is an issue in PKU patients
Summary
Phenylketonuria (PKU, OMIM # 261600) stems from the body’s inability to metabolize the essential amino acid phenylalanine (Phe) to tyrosine (Tyr) due to deficient activity of phenylalanine hydroxylase (PAH) with resultant cognitive impairment [1]. This can be avoided with a Phe-restricted diet in combination with protein substitutes and special 4.0/). GMP is a whey-based bioactive peptide derived from the hydrolysis of milk κ-casein that presents beneficial properties on human health but whose formulations are not completely devoid of Phe [7]. According to the available data from clinical studies, GMP presents a better taste and improves satiety and nitrogen retention. In preclinical studies with PKU mice, there is evidence that GMP reduces Phe in the brain, improves bone health and acts as prebiotic [8]
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