Unveiling the Metabolic Effects of Glycomacropeptide

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.

Glycomacropeptide: A comprehensive understanding of its major biological characteristics and purification methodologies

“…Administering GMP in combination with glucose to prediabetic patients resulted in a notable reduction in postprandial glycemia, suggesting a modulatory effect on glucose metabolism. This finding hints at GMP's potential in managing blood sugar levels, which could have implications for metabolic disorders such as diabetes (Pena et al, 2021;Sauvé et al, 2021). Furthermore, investigations using animal models have unveiled GMP's possible role in combating obesity.…”

Glycomacropeptide-Based Protein Substitutes for Children with Phenylketonuria in Italy: A Nutritional Comparison

“…A putative explanation is that amino acids, especially leucine, which is contained in large amounts in Phe-free amino acid supplements, act as important triggers of insulin secretion [21]. In a study on a murine model, Pena et al [22] analysed the chronic effects of casein (CAS), free amino acids (L-AAs), and GMP on glycaemic metabolism by assessing its biochemical markers in blood. No significant differences in glycaemia were observed among the three treatments, while insulin levels were significantly higher in rats fed with GMP than those fed with L-AAs, in contrast to what was expected.…”

In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU)

“…A recent meta-analysis showed that growth impairment is still a reality in some patients with PKU under a Phe-restricted diet, while the same was not found in those patients not requiring dietary restriction [8]. The different absorption kinetics of AAs from different sources may impact nitrogen balance and involve several distinct metabolic pathways [10]. Slowly digested proteins provide the efficient postprandial utilization of dietary nitrogen [11], whereas free AAs are absorbed too rapidly to support anabolic requirements [12].…”