Trimethylamine N-oxide (TMAO) as a prognostic marker among patients at nutritional risk. A secondary analysis of the randomized clinical trial EFFORT - Stern, A.; Wunderle, C.; Tribolet, P.; Neyer, P. J.; Bernasconi, L.; Stanga, Z.; Mueller, B.; Schuetz, P. (Eur J Clin Nutr, 2026)
BACKGROUND: Trimethylamine N-oxide (TMAO), a metabolite produced by the gut microbiota, is highly influenced by dietary factors and is linked to negative health outcomes including all-cause mortality and cardiovascular events. We evaluated the prognostic value of TMAO among hospitalized patients at nutritional risk participating in the Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) regarding clinical outcomes and response to nutritional support. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov as NCT02517476 (registered 7 August 2015) METHODS: This secondary analysis is based on the randomized-controlled EFFORT trial, which compared individualized nutritional therapy with usual care in medical inpatients at nutritional risk. We studied the association of admission TMAO concentrations with all-cause mortality after 180 days (primary endpoint) and major adverse cardiovascular events (MACE) using quartile-based regression analysis. RESULTS: Among 218 patients with available TMAO measurements, those in higher quartiles showed an increased all-cause mortality compared to the lowest quartile after 180 days (adjusted HR 1.92 95% CI 1.03-3.56, p = 0.04) and 5 years (adjusted HR 2.01 95% CI 1.23-3.31, p = 0.006). A similar trend was observed for MACE. We found no significant associations between dietary factors or nutritional history and admission TMAO levels, nor was TMAO predictive regarding the response to nutritional therapy. CONCLUSION: The risk of mortality over six months nearly doubled in patients at risk of malnutrition with elevated baseline TMAO levels. Additional research is needed to determine if dietary interventions can successfully modulate TMAO levels and, in turn, improve clinical outcomes.
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