A New Phe-Free Protein Substitute Engineered to Allow a Physiological Absorption of Free Amino Acids for Phenylketonuria

Abstract

An innovative technology (Physiomimic Technology) has been applied to amino acids (AAs) formulated for patients with phenylketonuria, with the objective of masking AA taste and odor and prolonging AA release in the gut, allowing a physiological absorption. This technology entails that the AAs are processed with functional additives that are able to modify their release and their organoleptic features. Two prototypes, obtained using sodium alginate þ ethylcellulose (engP-1) or sodium alginate þ ethylcellulose þ glyceryl dibehenate (engP-2), have been tested for AA prolonged release versus the same AAs (n-engP) without the application of the Physiomimic Technology. In vitro tests indicated that the technology is able to prolong the release of the engineered AAs versus the free compounds. A crossover in vivo kinetic study in pigs showed reduced peak concentrations (C max ) and, as expected, similar areas under the concentration/time curve (up to 5 hours) for the engineered products versus the free AAs. Significantly lower C max values (P < .01) were attained for essential AAs, large neutral AAs, and branched-chain AAs, indicating that the technology is able to reduce the typical absorption peak of free AAs. Taste and odor masking has been obtained as a consequence of the AA coating. The Physiomimic Technology, applied to free AAs, provided AA mixes with improved organoleptic features and with modified AA kinetics sustaining a more physiological AA absorption.

An Observational Study Evaluating the Introduction of a Prolonged-Release Protein Substitute to the Dietary Management of Children with Phenylketonuria

“…In this study, we assessed the introduction of a novel protein substitute with a coating that supports a more physiological release of amino acids than existing substitutes and also masks their bitter taste, aftertaste and smell [16]. The study design followed the guidelines of the UK ACBS with the objective of evaluating the acceptability of the new protein substitute with a limited number of subjects and within a short evaluation time.…”

“…This may explain the favourable gastrointestinal tolerability in this study. Both excipients (ethyl cellulose and alginate) are widely used in pharmaceutical technology and recognised as safe for use in medical foods [16]. It would be important to observe whether benefits to gastrointestinal tolerance could be observed longer-term, particularly if the study product provided a higher proportion of protein-substitute intake.…”

“…Furthermore, children may take up to an hour to take their full dose of protein substitute, with some failing to take the prescribed quantity [15]. Although reasons for poor adherence to protein substitutes are multiple, the bitter taste and aftertaste of synthetic amino acids are frequently reported as important factors [9,16]. Manufacturers have tried to improve the taste by lowering the quantities of unpalatable sulphurous and dicarboxylic amino acids and adding flavourings and sweeteners, but the results have been suboptimal [17], with minimal impact on aftertaste [18].…”

“…There is a need for more palatable and physiological protein substitutes that are both effective at reducing 24 h variability in phenylalanine levels and are accepted by patients. Here, we report outcomes from an observational study assessing the introduction of a prolonged-release protein substitute to the diets of children with PKU [16,23].…”

Amino Acid Plasma Profiles from a Prolonged-Release Protein Substitute for Phenylketonuria: A Randomized, Single-Dose, Four-Way Crossover Trial in Healthy Volunteers

“…PT TM modifies the release and absorption of AAs, while masking their taste and odour, with positive effects on the typically unpleasant aftertaste of traditional AA formulations. This study was based on preliminary evidence obtained from a porcine model, where application of PT TM to free AA mixtures reduced C max by 18% while maintaining a similar overall increase in plasma AAs [ 18 ].…”