Dataset Information

Association of tryptophan pathway metabolites with mortality and effectiveness of nutritional support among patients at nutritional risk: secondary analysis of a randomized clinical trial.

ABSTRACT: Tryptophan is an essential amino acid and is the precursor of many important metabolites and neurotransmitters. In malnutrition, the availability of tryptophan is reduced, potentially putting patients at increased risks. Herein, we investigated the prognostic implications of the tryptophan metabolism in 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 comparing individualized nutritional support to usual care in patients at risk for malnutrition. Among 238 patients with available measurements, low plasma levels of metabolites were independently associated with 30-day mortality with adjusted hazard ratios (HR) of 1.77 [95% CI 1.05-2.99, p 0.034] for tryptophan, 3.49 [95% CI 1.81-6.74, p < 0.001] for kynurenine and 2.51 [95% CI 1.37-4.63, p 0.003] for serotonin. Nutritional support had more beneficial effects on mortality in patients with high tryptophan compared to patients with low tryptophan levels (adjusted HR 0.61 [95% CI 0.29-1.29] vs. HR 1.72 [95% CI 0.79-3.70], p for interaction 0.047). These results suggest that sufficient circulating levels of tryptophan might be a metabolic prerequisite for the beneficial effect of nutritional interventions in this highly vulnerable patient population.

SUBMITTER: Ritz J

PROVIDER: S-EPMC10902466 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of tryptophan pathway metabolites with mortality and effectiveness of nutritional support among patients at nutritional risk: secondary analysis of a randomized clinical trial.

Ritz Jacqueline J Wunderle Carla C Stumpf Franziska F Laager Rahel R Tribolet Pascal P Neyer Peter P Bernasconi Luca L Stanga Zeno Z Mueller Beat B Schuetz Philipp P

Frontiers in nutrition 20240215

Tryptophan is an essential amino acid and is the precursor of many important metabolites and neurotransmitters. In malnutrition, the availability of tryptophan is reduced, potentially putting patients at increased risks. Herein, we investigated the prognostic implications of the tryptophan metabolism in 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 com ...[more]

PMID: 38425485

Similar Datasets

Project description:BackgroundElevated 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.MethodsThis 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.ResultsWe 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).ConclusionIn 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 registrationwww.clinicaltrials.gov, identifier NCT02517476.

Project description:Importance:Inflammation is a key driver of malnutrition during illness and is often accompanied by metabolic effects, including insulin resistance and reduction of appetite. However, it still remains unclear if inflammation influences the response to nutritional support among patients with disease-related malnutrition. Objective:To examine whether patients' baseline inflammatory status is associated with the effect of nutritional support on 30-day mortality. Design, Setting, and Participants: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 clinical trial conducted in 8 Swiss hospitals from April 2014 to February 2018. A total of 1950 participants who had C-reactive protein measurements at the time of admission were included in this secondary analysis. Data analysis was conducted between June and July 2019. Interventions:Hospitalized patients at risk for malnutrition were randomly assigned to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). Main Outcomes and Measures:The primary end point was 30-day mortality. Based on C-reactive protein levels at admission, patients were stratified into groups with low, moderate, or high inflammation (<10 mg/L, 10-100 mg/L, and >100 mg/L, respectively). Results:A total of 1950 patients (median [interquartile range] age, 75 [65-83] years; 1025 [52.6%] men) were included; 533 (27.3%) had low levels of inflammation, 894 (45.9%) had moderate levels of inflammation, and 523 (26.8%) had high levels of inflammation. Compared with the control group, patients receiving nutritional support showed a significant reduction in 30-day mortality, regardless of C-reactive protein level (adjusted odds ratio, 0.61; 95% CI, 0.43-0.86; P = .005). In the subgroup of patients with high inflammation, there was no beneficial effect of nutritional support (adjusted odds ratio, 1.32; 95% CI, 0.70-2.50; P = .39), providing evidence that inflammation has a significant modifying association (P for interaction = .005). Conclusions and Relevance:Based on this secondary analysis of a multicenter randomized trial, a patient's admission inflammatory status was associated with their response to nutritional support. If validated in future clinical trials, nutritional support may need to be individualized based on a patient's initial presentation and markers of inflammation. These results may also help to explain some of the heterogeneity in treatment effects of nutrition seen in previous critical care trials. Trial Registration:ClinicalTrials.gov Identifier: NCT02517476.

Project description:BackgroundIn polymorbid patients with bronchopulmonary infection, malnutrition is an independent risk factor for mortality. There is a lack of interventional data investigating whether providing nutritional support during the hospital stay in patients at risk for malnutrition presenting with lower respiratory tract infection lowers mortality.MethodsFor this secondary analysis of a randomized clinical trial (EFFORT), we analyzed data of a subgroup of patients with confirmed lower respiratory tract infection from an initial cohort of 2028 patients. Patients at nutritional risk (Nutritional Risk Screening [NRS] score ≥3 points) were randomized to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). The primary endpoint of this analysis was all-cause 30-day mortality.ResultsWe included 378 of 2028 EFFORT patients (mean age 74.4 years, 24% with COPD) into this analysis. Compared to usual care hospital nutrition, individualized nutritional support to reach caloric and protein goals showed a similar beneficial effect of on the risk of mortality in the subgroup of respiratory tract infection patients as compared to the main EFFORT trial (odds ratio 0.47 [95%CI 0.17 to 1.27, p = 0.136] vs 0.65 [95%CI 0.47 to 0.91, p = 0.011]) with no evidence of a subgroup effect (p for interaction 0.859). Effects were also similar among different subgroups based on etiology and type of respiratory tract infection and for other secondary endpoints.ConclusionThis subgroup analysis from a large nutrition support trial suggests that patients at nutritional risk as assessed by NRS 2002 presenting with bronchopulmonary infection to the hospital likely have a mortality benefit from individualized inhospital nutritional support. The small sample size and limited statistical power calls for larger nutritional studies focusing on this highly vulnerable patient population.Clinical trial registrationRegistered under ClinicalTrials.gov Identifier no. NCT02517476.

Project description:Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75; 65% female; 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels (r = .324 and r = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried's criteria (OR 0.93 [0.88, 0.98], P = .009) and Rockwood index (r = -.241, P = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], P = .049). QUIN and QUIN/KYN showed an association with increased IL-6 (r = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], P = .029 and OR 6.43 [2.23, 18.51], P = .001 respectively) and lower physical function (r = -.205 and r = -.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. Defining the underlying mechanisms may permit the development and validation of new biomarkers and therapeutics for frailty and musculoskeletal conditions targeting specific metabolites of the TRP catabolic pathway.

Dataset Information

Association of tryptophan pathway metabolites with mortality and effectiveness of nutritional support among patients at nutritional risk: secondary analysis of a randomized clinical trial.

Publications

Association of tryptophan pathway metabolites with mortality and effectiveness of nutritional support among patients at nutritional risk: secondary analysis of a randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets