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

Mika Scheinin,Anita Macdonald,Anna Barassi,Giorgio Reiner,Jouni Junnila,Essi Sarkkinen,Zsófia Lovró

doi:10.3390/nu12061653

Abstract

Several disorders of amino acid (AA) metabolism are treated with a protein-restricted diet supplemented with specific AA mixtures. Delivery kinetics impacts AA absorption and plasma concentration profiles. We assessed plasma profiles after ingestion of an AA mixture engineered to prolong AA absorption with Physiomimic TechnologyTM (Test) in a randomized, single-dose, four-way crossover trial in healthy volunteers (Trial Registration: ISRCTN11016729). In a two-step hypothesis, the primary endpoints were (i) significant reduction in peak plasma concentrations (Cmax) of essential amino acids (EAAs) while (ii) maintaining EAA bioavailability (AUC0-300 min) compared to a free AA mixture (Reference). Secondary endpoints included effects on plasma profiles of other AA groups and effects on several metabolic markers. Thirty subjects completed the study. Both co-primary endpoints were met: Cmax for EAAs was 27% lower with the Test product compared to the Reference product (ratio, 0.726, p < 0.0001); overall plasma EAA levels from the two AA mixtures was within the pre-specified bioequivalence range (AUC0-300min ratio, 0.890 (95% CI: 0.865, 0.915)). These findings were supported by the results of secondary endpoints. Prolongation of AA absorption was associated with modulation of several metabolic markers. It will be important to understand whether this can improve the long-term management of disorders of AA metabolism.

Highlights

The estimated global incidence of all inherited disorders of amino acid (AA) metabolism is15/100,000 live births
Four subjects discontinued without receiving any dose of any product, and one subject was excluded from the per-protocol analysis because of a major protocol violation
The Cmax for essential amino acids (EAAs) was 27% lower with the Test product compared to the Reference product whereas the overall increase in plasma EAAs (AUC0-300 ) from the two AA mixtures was within the pre-specified bioequivalence range (ratio, 0.890)

Summary

Introduction

The estimated global incidence of all inherited disorders of amino acid (AA) metabolism is15/100,000 live births. The estimated global incidence of all inherited disorders of amino acid (AA) metabolism is. Phenylketonuria (PKU) represents the most common and significant disease entity, with an estimated global incidence of 7/100,000 [1], birth incidence varies by ethnicity and consanguinity, and estimates are influenced by the level of ascertainment [2]. Many inherited disorders of AA metabolism require prompt initiation of treatment at birth and lifelong. Nutrients 2020, 12, 1653 adherence to a protein-restricted diet supplemented with defined AA mixtures that lack specific. The diet must be engineered to provide adequate vitamins, minerals and other nutrients normally obtained from natural protein-containing foods. These are usually provided through appropriate supplementation of the AA mixture. More than 70 disorders of AA metabolism are managed with AA mixtures [9]

Methods

Results

Conclusion