Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria

Abstract

Phenylketonuria (PKU) requires a lifelong low-phenylalanine (phe) diet where protein needs are met by consumption of a phe-free amino acid (AA) formula; complaints of persistent hunger are common. Foods made with glycomacropeptide (GMP), an intact protein that contains minimal phe and may promote satiety, provide an alternative to AA formula. The objective was to assess the ability of a GMP breakfast to promote satiety and affect plasma concentrations of AAs, insulin, and the appetite stimulating hormone ghrelin in those with PKU, when compared to an AA-based breakfast. Eleven PKU subjects (8 adults and 3 boys ages 11-14) served as their own controls in an inpatient metabolic study with two 4-day treatments: an AA-based diet followed by a diet replacing all AA formula with GMP foods. Plasma concentrations of AAs, insulin and ghrelin were obtained before and/or 180 minutes after breakfast. Satiety was assessed using a visual analog scale before, immediately after and 180 minutes after breakfast. Postprandial ghrelin concentration was significantly lower (p=0.03) with GMP compared to an AA-based breakfast, with no difference in fasting ghrelin. Lower postprandial ghrelin concentrations were associated with greater feelings of fullness 180 minutes after breakfast suggesting greater satiety with GMP compared to AAs. Postprandial concentrations of insulin and total plasma AAs were higher after a GMP breakfast compared to an AA-based breakfast consistent with slower absorption of AAs from GMP. These results show sustained ghrelin suppression, and suggest greater satiety with ingestion of a meal containing GMP compared with AAs.* Correspondence: Denise M. Ney, Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, WI, 53706, USA. ney@nutrisci.wisc.edu 1-608-262-4386 (phone); 1-608-262-5860 (FAX). Disclosure statementAll funding for this research was provided by NIH, the PKU community and the University of Wisconsin-Madison. A provisional patent application was filed 6/12/09, serial # 61/186690, title Glycomacropeptide (GMP) medical foods for nutritional management of phenylketonuria (PKU), and a license was executed by Cambrooke Foods, LLC on 3/8/10. A percentage of all royalty payments will be awarded to the inventors based on the license.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptMol Genet Metab. Author manuscript; available in PMC 2011 August 1. INTRODUCTIONPhenylketonuria (PKU) is an inborn error of amino acid (AA) metabolism caused by mutations in phenylalanine (phe) hydroxylase (EC 1.14.16.1...

Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

“…We have developed a new paradigm for the PKU diet utilizing low-phe foods made from the intact whey protein GMP, supplemented with limiting AAs to provide a palatable alternative to AA formula. This study extends our research in humans with PKU (30,38,54), as well as PKU mice (39) by assessing the impact of GMP, AA, and casein diets fed from weaning through adulthood on growth, body composition, energy balance, and systemic inflammation in PKU and WT mice. When fed the high-phe casein diet or the low-phe AA diet, PKU mice exhibited metabolic stress, or altered homeostasis induced by the absence of PAH activity, as reflected in increased energy expenditure and intake of food and water, Fig.…”

“…Our studies in the murine model of PAH deficiency, the Pah enu2 mouse (PKU mouse) (32,39), which mimics the phenotype of human PKU, including elevated phe concentrations and cognitive defects, indicate that a GMP diet reduces phe concentrations in plasma and brain compared with an AA diet (39). Our studies in humans with PKU (30,38,54) indicate that GMP improves protein retention, phe concentrations, and satiety and palatability of the low-phe diet. However, questions remain about the ability of GMP to support long-term growth, physiological function, and energy balance in those with PKU, especially given the rising incidence of overweight in children and adults with PKU treated with conventional AA diets (3,33).…”

“…Studies that have isolated the specific impact of GMP demonstrate that GMP promotes satiety and modulates food intake in both control subjects (8,26,56) and those with PKU (30); this response has been linked with the ability of GMP to stimulate cholecystokinin release (9) and inhibit ghrelin release after eating (30) and the high content of branched chain AA in GMP. Evidence in the present study demonstrates that GMP, compared with an AA diet, significantly lowers RER during the dark cycle in both WT and PKU mice, consistent with increased fat oxidation and supported by a significantly lower percentage of body fat in PKU mice fed GMP.…”

“…In vitro studies indicate that GMP binds cholera and E. coli enterotoxins and inhibits bacterial and viral adhesions (36), inhibits adhesion of cariogenic bacteria with usage in toothpaste (2), and modulates immune response (27,47). In vivo studies indicate that oral administration of GMP shows substantial anti-inflammatory effects in rat models of colitis and ileitis (29,46), increases zinc absorption in rhesus monkeys (22), and may promote satiety in humans (9,26,30,56). The mechanisms underlying these observations of GMP action are largely unknown, although thought to be linked with the unique chemical structure of GMP.…”

Tratamiento nutricional de la fenilcetonuria

“…2 ). Estos datos son coherentes con el punto de vista de que la sustitución de la fórmula de AA por alimentos nutricionalmente completos elaborados con GMP cambiará la dieta pobre en phe en sentido de un soporte de la saciedad [66,67] y una síntesis de proteínas [31] más fisiológi-cos y óptimos.…”