{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:32:58Z","timestamp":1787502778363,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 &lt; 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.<\/jats:p>","DOI":"10.3390\/nu12061653","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T04:12:09Z","timestamp":1591157529000},"page":"1653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Amino Acid Plasma Profiles from a Prolonged-Release Protein Substitute for Phenylketonuria: A Randomized, Single-Dose, Four-Way Crossover Trial in Healthy Volunteers"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-9126","authenticated-orcid":false,"given":"Mika","family":"Scheinin","sequence":"first","affiliation":[{"name":"CRST Oy, It\u00e4inen Pitk\u00e4katu 4B, FI-20520 Turku, Finland"},{"name":"Institute of Biomedicine, University of Turku and TYKSLAB, Turku University Hospital, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Barassi","sequence":"additional","affiliation":[{"name":"APR Applied Pharma Research sa via Corti 5, CH-6828 Balerna, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2703-0798","authenticated-orcid":false,"given":"Jouni","family":"Junnila","sequence":"additional","affiliation":[{"name":"Oy 4Pharma Ltd., Arkadiankatu 7, FI-00100 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia","family":"Lovr\u00f3","sequence":"additional","affiliation":[{"name":"CRST Oy, It\u00e4inen Pitk\u00e4katu 4B, FI-20520 Turku, Finland"},{"name":"Institute of Biomedicine, University of Turku and TYKSLAB, Turku University Hospital, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Reiner","sequence":"additional","affiliation":[{"name":"APR Applied Pharma Research sa via Corti 5, CH-6828 Balerna, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essi","family":"Sarkkinen","sequence":"additional","affiliation":[{"name":"Food and Nutrition, Oy Medfiles Ltd. (CRO), P. O. Box 1450, FI-70701 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Women\u2019s and Children\u2019s Hospital NHS Foundation Trust, Birmingham B4 6NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"021102","DOI":"10.7189\/jogh.08.021102","article-title":"Global birth prevalence and mortality from inborn errors of metabolism: A systematic analysis of the evidence","volume":"8","author":"Waters","year":"2018","journal-title":"J. Glob. 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