Association of phenylalanine and tyrosine metabolism with mortality and response to nutritional support among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT.

Autor:	Buchmueller LC; Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes, and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.; Medical Faculty, University of Basel, Basel, Switzerland., Wunderle C; Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes, and Metabolism, Kantonsspital Aarau, Aarau, Switzerland., Laager R; Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes, and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.; Medical Faculty, University of Basel, Basel, Switzerland.; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland., Bernasconi L; Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland., Neyer PJ; Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland., Tribolet P; Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes, and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.; Department of Health Professions, Bern University of Applied Sciences, Bern, Switzerland.; Faculty of Life Sciences, University of Vienna, Vienna, Austria., Stanga Z; Division of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Mueller B; Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes, and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.; Faculty of Biomedical Sciences, Università della Svizzera italiana (USI), Lugano, Switzerland., Schuetz P; Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes, and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.; Medical Faculty, University of Basel, Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in nutrition [Front Nutr] 2024 Nov 12; Vol. 11, pp. 1451081. Date of Electronic Publication: 2024 Nov 12 (Print Publication: 2024).
DOI:	10.3389/fnut.2024.1451081
Abstrakt:	Background: Elevated phenylalanine serum level is a surrogate marker of whole-body proteolysis and has been associated with increased mortality in critically ill patients. Tyrosine is a metabolite of phenylalanine and serves as a precursor of thyroid hormones and catecholamines with important functions in the oxidative stress response among others. Herein, we examined the prognostic significance of phenylalanine, tyrosine, as well as its metabolites nitrotyrosine, L-3,4-dihydroxyphenylalanine (DOPA), and dopamine regarding clinical outcomes and response to nutritional therapy in patients at nutritional risk. Methods: This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial investigating individualized nutritional support compared to standard care in patients at risk of malnutrition. The primary outcome was 30-day all-cause mortality. Results: We analyzed data of 238 patients and found a significant association between low plasma levels of phenylalanine [adjusted HR 2.27 (95% CI 1.29 to 3.00)] and tyrosine [adjusted HR 1.91 (95% CI 1.11 to 3.28)] with increased 30-day mortality. This association persisted over a longer period, extending to 5 years. Additionally, trends indicated elevated mortality rates among patients with low nitrotyrosine and high DOPA and dopamine levels. Patients with high tyrosine levels showed a more pronounced response to nutritional support compared to patients with low tyrosine levels (HR 0.45 versus 1.46, p for interaction = 0.02). Conclusion: In medical inpatients at nutritional risk, low phenylalanine and tyrosine levels were associated with increased short-and long-term mortality and patients with high tyrosine levels showed a more pronounced response to nutritional support. Further research is warranted to gain a deeper understanding of phenylalanine and tyrosine pathways, their association with clinical outcomes in patients at nutritional risk, as well as their response to nutritional therapy. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT02517476. Competing Interests: PS reports financial support was provided by Swiss National Science Foundation. PS reports a relationship with Nestle Health Science that includes: funding grants and speaking and lecture fees. PS reports a relationship with Abbott that includes: funding grants and speaking and lecture fees. PS reports a relationship with Fresenius that includes: speaking and lecture fees. ZS reports a relationship with Nestle Health Science that includes: consulting or advisory. ZS reports a relationship with Abbott Nutrition that includes: consulting or advisory. ZS reports a relationship with Fresenius Kabi that includes: consulting or advisory. ZS reports a relationship with B. Braun that includes: consulting or advisory. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Buchmueller, Wunderle, Laager, Bernasconi, Neyer, Tribolet, Stanga, Mueller and Schuetz.)
Databáze:	MEDLINE
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