Abstract
Background: Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source.
Objective: We hypothesized circulating TMAO derived from fish intake might cause less harm compared to red meat source by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF and outcomes.
Design: Patients were recruited from the European QUALity study on treatment in advanced CKD (EQUAL) among individuals 65 years whose eGFR had dropped for the first time to ≤20mL/min/1.73m2 during last 6 months. The association between TMAO, CMPF and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cut-offs of TMAO and CMPF, suggesting high/low red meat and fish intake.
Results: During a median of 39 months’ follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable-hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR 0.79, 95%CI 0.71, 0.89) and KRT (HR 0.80, 95%CI 0.71, 0.90), independent of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR 0.49, 95% CI 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models.
Conclusions: High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF are due to fish consumption, and/or CMPF is a protective factor remains to be verified.
Objective: We hypothesized circulating TMAO derived from fish intake might cause less harm compared to red meat source by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF and outcomes.
Design: Patients were recruited from the European QUALity study on treatment in advanced CKD (EQUAL) among individuals 65 years whose eGFR had dropped for the first time to ≤20mL/min/1.73m2 during last 6 months. The association between TMAO, CMPF and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cut-offs of TMAO and CMPF, suggesting high/low red meat and fish intake.
Results: During a median of 39 months’ follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable-hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR 0.79, 95%CI 0.71, 0.89) and KRT (HR 0.80, 95%CI 0.71, 0.90), independent of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR 0.49, 95% CI 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models.
Conclusions: High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF are due to fish consumption, and/or CMPF is a protective factor remains to be verified.
| Original language | English |
|---|---|
| Article number | nqac278 |
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | American Journal of Clinical Nutrition |
| Volume | 116 |
| Issue number | 6 |
| Early online date | 27 Sept 2022 |
| DOIs | |
| Publication status | Published - 1 Dec 2022 |