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Cited by 11Clinical Nutrition and GastroenterologyMetabolomics and Mass Spectrometry StudiesNutrition and Health in Aging

Association of metabolomic markers and response to nutritional support: A secondary analysis of the EFFORT trial using an untargeted metabolomics approach

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Struja, Tristan, Wolski, Witold, Schapbach, Ralph, Mueller, Beat, Laczko, Endre, Schuetz, Philipp·2021·Clinical Nutrition
DOI 10.1016/j.clnu.2021.07.029
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Abstract

BACKGROUND & AIMS: The EFFORT trial reported a substantial risk reduction for adverse events and mortality in medical in-patients receiving a nutritional support intervention. With the use of an untargeted metabolomics approach, we investigated the prognostic and therapeutic potential of metabolomic markers to understand, whether there are distinct metabolic patterns associated with malnutrition risk as assessed by the Nutritional Risk screening (NRS 2002) score, the risk of 30-day mortality and the response to nutritional support, respectively. METHODS: Out of the 2088 samples we randomly selected 120 blood samples drawn on day 1 after hospital admission and before treatment initiation. Samples were stratified by NRS 2002, treatment allocation (intervention vs. control), and mortality at 30 days, but not on the type of medical illness. We performed untargeted analysis by liquid chromatography mass spectrometry (LC-MS/MS). RESULTS: We measured 1389 metabolites in 120 patients of which 81 (67.5%) survived until day 30. After filtering, 371 metabolites remained, and 200 were matched to one or more Human Metabolome Data Base (HMDB) entries. Between group analysis showed a slight distinction between the treatment groups for patients with a NRS 3, but not for those with NRS 4 and ≥ 5. C-statistic between those who died and survived at day 30 ranged from 0.49 (95% confidence interval 0.35-0.68) for a combination of 5 metabolites/predictors to 0.66 (95% confidence interval 0.53-0.79) for a combination of 100 metabolites. Pathway analysis found significant enrichment in the pathways for nitrogen, vitamin B3 (nicotinate and nicotinamide), leukotriene, and arachidonic acid metabolisms in nutritional support responders compared to non-responders. CONCLUSION: In our heterogenous population of medical inpatients with different illnesses and comorbidities, metabolomic markers showed little prognostic and therapeutic potential for better phenotyping malnutrition and response to nutritional therapy. Future studies should focus on more selected patient populations to understand whether a metabolomic approach can advance the nutritional care of patients.

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  • In a secondary analysis of the EFFORT trial, an untargeted proteomics approach found that metabolites had only little prognostic and therapeutic potential for phenotyping the risk of malnutrition and response to nutritional therapy, due to high heterogeneity and small sample size.

    “They concluded, due to high heterogeneity and small sample size, that so far the metabolites had only little prognostic and therapeutic potential for phenotyping the risk of malnutrition and response to nutritional therapy [194] (Level of evidence 1þþ).”

    From ESPEN guideline on nutritional support for polymorbid medical inpatients (2023) · cites this paper as [194]

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Authors
Struja, T., Wolski, W., Schapbach, R., Mueller, B., Laczko, E., & Schuetz, P.
Affiliations
  • Kantonsspital Aarau (CH)
  • University of Zurich (CH)
Corresponding author
  • Struja, Tristan
  • Wolski, Witold
  • Schapbach, Ralph
ORCID
Venue
Clinical Nutrition
Publisher
Elsevier BV
Published
2021-09
Volume
40
Issue
9
Pages
5062-5070
ISSN
0261-5614 (ISSN-L)
DOI
10.1016/j.clnu.2021.07.029
OpenAlex
W3191922064
Cited by
11
References
5
Citations by year
2025: 1 · 2024: 3 · 2023: 4 · 2022: 3
FWCI
1.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Nutrition (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection (cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
Swiss National Science Foundation
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
metabolomic markers, nutritional support, malnutrition, NRS-2002, 30-day mortality, prognostic factors, treatment response, untargeted metabolomics, medical inpatients, nicotinate and nicotinamide metabolism, arachidonic acid metabolism, leukotriene metabolism, nitrogen metabolism
MeSH terms
Aged, Aged, 80 and over, Chromatography, Liquid, Female, Hospitalization, Humans, Inpatients, Male, Middle Aged, Predictive Value of Tests, Prognosis, Prospective Studies, Biomarkers, Nutrition Assessment, Randomized Controlled Trials as Topic, Treatment Outcome, Nutritional Support, Risk Assessment, Malnutrition, Tandem Mass Spectrometry, Metabolic Networks and Pathways, Metabolomics, Metabolome

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