Comprehensive metabolic amino acid flux analysis in critically ill patients
Open accessAbstract
Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision on the type of protein or AA nutrition to deliver in ICU patients, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patients and matched control subjects using a novel pulse isotope method to obtain in-depth metabolic analysis. In 51 critically ill ICU patients (SOFA~6.6) and 49 healthy controls, we measured REE and body composition/phase-angle using BIA. In the postabsorptive state, we collected arterial (ized) blood for CRP and AA. Then, we administered an 8 mL solution containing 18 stable AA tracers as a pulse and calculated WBP. Enrichments: LC-MS/MS and statistics: t-test, ANCOVA. Compared to healthy, critically ill ICU patients had lower phase-angle (p < 0.00001), and higher CRP (p < 0.0001). Most AA concentrations were lower in ICU patients (p < 0.0001), except tau-methylhistidine and phenylalanine. WBP of most AA were significantly (p < 0.0001) higher with increases in glutamate (160%), glutamine (46%), and essential AA. Remarkably, net protein breakdown was lower. There were only weak relationships between AA concentrations and WBP. Critically ill ICU patients (SOFA 8-16) had lower values for phase angle (p = 0.0005) and small reductions of most plasma AA concentrations, but higher tau-methylhistidine (p = 0.0223) and hydroxyproline (p = 0.0028). Remarkably, the WBP of glutamate and glutamine were lower (p < 0.05), as was their clearance, but WBP of tau-methylhistidine (p = 0.0215) and hydroxyproline (p = 0.0028) were higher. Our study in critically ill ICU patients shows that comprehensive metabolic phenotyping was able to reveal severe disturbances in specific AA pathways, in a disease severity dependent way. This information may guide improving nutritional compositions to improve the health of the critically ill patient. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).
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Recent stable isotope studies demonstrate that amino acid conversion is improved with time, allowing an increase in whole body protein production only after the early period of the acute phase, even increasing further in the post-acute phase.
“Recent stable isotope studies [63,64] demonstrate that amino acid conversion is improved with time, allowing an increase in whole body protein production only after the early period of the acute phase, even increasing further in the post-acute phase.”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [64]
The Discussion (page unavailable) reports increased whole-body protein synthesis in ICU patients, measured using stable isotope tracers. The Methods (page unavailable) say patients were studied 4 or 14 days after admission, but the paper does not show that amino acid conversion improves over time or that protein synthesis rises only after the early acute phase and further in the post-acute phase. (LLM, conf=0.86)
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ESPEN guideline on clinical nutrition in the intensive care unit.
Singer, P., Blaser, A. R., Berger, M. M., Alhazzani, W., Calder, P. C., Casaer, M. P., Hiesmayr, M., Mayer, K., Montejo, J. C., Pichard, C., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.08.037 · Cited by 2,904 · see citing works
Self-citationGlutamine: Metabolism and Immune Function, Supplementation and Clinical Translation
Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., & Newsholme, P. (2018) · Nutrients · doi:10.3390/nu10111564 · Cited by 1,261 · see citing works
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Luiking, Y. C., Poeze, M., & Deutz, N. E. (2015) · Clinical Science · doi:10.1042/cs20140343 · Cited by 78 · see citing works
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ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit
Singer, P., Blaser, A. R., Berger, M. M., Calder, P. C., Casaer, M., Hiesmayr, M., Mayer, K., Montejo-Gonzalez, J. C., Pichard, C., Preiser, J.-C., et al. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.07.011 · Cited by 793 · see citing works
Self-citation
- Authors
- Deutz, N. E. P., Singer, P., Wierzchowska-McNew, R. A., Viana, M. V., Ben-David, I. A., Pantet, O., Thaden, J. J., Ten Have, G. A. M., Engelen, M. P. K. J., & Berger, M. M.
- Affiliations
- Texas A&M University (US)
- Tel Aviv University (IL)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Deutz, Nicolaas E.P.
- ORCID
- Venue
- Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 40
- Issue
- 5
- Pages
- 2876-2897
- ISSN
- 0261-5614 (ISSN-L)
- PMC
- PMC8172442
- OpenAlex
- W3139047201
- Cited by
- 47
- References
- 4
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 10 · 2023: 7 · 2022: 5 · 2021: 3
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- Texas A and M University
- National Institutes of Health (R01HL132887)
- Department of Foreign Affairs and Trade, Australian Government
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- amino acid metabolism, critically ill patients, phase angle, body composition, hydroxyproline, glutamate, glutamine, essential amino acids, protein nutrition, disease severity, C-reactive protein, amino acid clearance
- MeSH terms
- Aged, Amino Acids, Basal Metabolism, Body Composition, Female, Humans, Male, Middle Aged, Critical Illness, Electric Impedance
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