Trimethylamine-N-Oxide and Related Metabolites: Assessing Cardiovascular Risk in the Dallas Heart Study

Yeela Talmor-Barkan*, Jiao Yu, Nancy Sarah Yacovzada, Nili Schamroth Pravda, Colby Ayers, James A. de Lemos, W. H.Wilson Tang, Stanley L. Hazen, Alon Eisen, Guy Witberg, Ran Kornowski, Ian J. Neeland

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective: To evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population. Methods: We performed a case-control study of 361 participants of the Dallas Heart Study, including 88 participants with an incident atherosclerotic cardiovascular disease (ASCVD) event and 273 controls matched for age, sex, and body mass index without an ASCVD event during 12 years of follow-up (January 1, 2000, through December 31, 2015). Plasma levels of TMAO, choline, carnitine, betaine, and butyrobetaine were measured by mass spectrometry. The differential odds for incident ASCVD by metabolite levels between cases and controls were compared by a conditional logistic regression model adjusted for cardiovascular risk factors. Results: Participants with incident ASCVD had higher levels of TMAO and related metabolites compared with those without ASCVD (P<.05 for all). Those with plasma TMAO concentrations in quartile 4 had a more than 2-fold higher odds of ASCVD compared with those in quartile 1 (odds ratio, 2.77 [95% CI, 1.05 to 7.7; P=.04] for hard ASCVD and 2.41 [95% CI, 1.049 to 5.709; P=.04]). Similar trends were seen with the related metabolites choline, betaine, carnitine, and butyrobetaine. Conclusion: Our results suggest that TMAO and related metabolites are independently associated with ASCVD events. Although further studies are needed, measurement of TMAO and related metabolites may have a role in ASCVD risk stratification for primary prevention.

Original languageEnglish
JournalMayo Clinic Proceedings
StateAccepted/In press - 2024


FundersFunder number
National Center for Advancing Translational Sciences
National Institutes of Health
Office of Dietary SupplementsR01 HL103866, P01 HL147823
Office of Dietary Supplements


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