AUTHOR=Ritz Jacqueline , Wunderle Carla , Stumpf Franziska , Laager Rahel , Tribolet Pascal , Neyer Peter , Bernasconi Luca , Stanga Zeno , Mueller Beat , Schuetz Philipp TITLE=Association of tryptophan pathway metabolites with mortality and effectiveness of nutritional support among patients at nutritional risk: secondary analysis of a randomized clinical trial JOURNAL=Frontiers in Nutrition VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1335242 DOI=10.3389/fnut.2024.1335242 ISSN=2296-861X 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.