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Elevated plasma TMAO levels are associated with increased risk of atherosclerotic cardiovascular diseaseHigher TMAO Levels Linked to Increased Heart Disease Risk

Frontiers in Medicine Published September 25, 2026 DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Note that elevated TMAO levels correlate with higher ASCVD risk, but evidence is currently too weak for routine screening.

This meta-analysis of case-control studies evaluates the association between plasma trimethylamine N-oxide (TMAO) levels and atherosclerotic cardiovascular disease (ASCVD) risk across primary and secondary prevention cohorts. The analysis indicates that elevated TMAO levels (highest vs. lowest quantile) are associated with increased risk (OR = 1.39; 95% CI: 1.21-1.61). A continuous analysis of TMAO levels also showed a significant pooled SMD of 0.43 (95% CI: 0.14-0.71).

In the primary prevention cohort, elevated TMAO was associated with increased risk (OR = 1.51; 95% CI: 1.28-1.78). In the secondary prevention cohort, an association was observed (OR = 1.10; 95% CI: 0.83-1.46; P for interaction = 0.057). The authors note significant limitations, including low GRADE certainty for categorical analysis and very low GRADE certainty for continuous analysis due to extreme heterogeneity (I2 = 93.4%).

While TMAO may serve as a potential risk indicator for primary prevention, the evidence is currently insufficient to support routine clinical screening. The results represent associations rather than causal links, and the high heterogeneity in continuous analysis limits the ability to draw linear dose-response conclusions.

Researchers looked at the link between plasma trimethylamine N-oxide (TMAO) and atherosclerotic cardiovascular disease (ASCVD). This study looked at patients in both primary and secondary prevention groups to see how TMAO levels related to heart health.

The analysis found that people with the highest levels of TMAO had a significantly higher risk of heart disease compared to those with the lowest levels. This link was particularly strong in the primary prevention group. However, the researchers noted that the evidence for these findings is not very strong. The data showed a lot of variation, and the overall certainty of the results is low.

Because the evidence is currently limited and inconsistent, doctors do not yet recommend using TMAO as a routine test for patients. While the link between TMAO and heart risk is interesting, it is not enough to change how doctors treat patients today. It remains a potential marker for future research.

What this means for you:

Higher TMAO levels are linked to heart disease risk, but evidence is currently too weak for routine medical testing.

Common questions

What is TMAO and how does it affect heart health?

TMAO is a compound found in the blood. This study found a significant association between higher TMAO levels and an increased risk of atherosclerotic cardiovascular disease. In the primary prevention group, the risk was notably higher for those with high levels. However, the study only shows a link, not a direct cause.

Is TMAO used to screen patients for heart disease now?

No, doctors do not currently use TMAO for routine clinical screening. While the study shows a link between high TMAO and heart disease, the evidence is not strong enough to change current medical practices. It is currently considered a potential risk indicator for future study.

How certain are the results regarding TMAO and heart risk?

The certainty of the results is low. The study showed high variation in the data, and the researchers noted that the evidence is not yet firm enough to make definitive conclusions. Because of this uncertainty, the findings are not yet used to change how patients are treated.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedSep 2026

View Original Abstract ↓

IntroductionTrimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been implicated in atherosclerosis. However, the association between plasma TMAO levels and atherosclerotic cardiovascular disease (ASCVD) risk remains inconsistent across studies.MethodsWe searched PubMed, Embase, Cochrane, and Web of Science for case-control (including nested) studies reporting odds ratios (ORs) with 95% confidence intervals (CIs) for TMAO and ASCVD. Estimates were pooled under fixed- or random-effects assumptions according to the observed heterogeneity, supplemented by subgroup, sensitivity, and publication bias assessments.ResultsNine studies were included in this meta-analysis. Elevated TMAO levels (highest vs. lowest quantile) were significantly associated with ASCVD risk (OR = 1.39; 95% CI: 1.21–1.61; I2 = 28.8%). The continuous analysis showed a significant pooled standardized mean difference (SMD) of 0.43 (95% CI: 0.14–0.71), but with extreme heterogeneity (I2 = 93.4%). The association was stronger in the primary prevention (OR = 1.51; 95% CI: 1.28–1.78) than in the secondary prevention cohorts (OR = 1.10; 95% CI: 0.83–1.46; P for interaction = 0.057). GRADE (Grading of Recommendations Assessment, Development, and Evaluation) certainty was low for the categorical analysis and very low for the continuous analysis.DiscussionThis meta-analysis showed that high versus low plasma TMAO levels were significantly associated with increased ASCVD risk (OR = 1.39; 95% CI: 1.21–1.61), particularly in primary prevention populations (OR = 1.51; 95% CI: 1.28–1.78), and supported TMAO as a potential risk indicator for primary prevention. However, continuous analysis yielded highly unstable estimates with extreme heterogeneity (I2 = 93.4%), precluding linear dose-response conclusions, and the certainty of evidence remained low to very low. Current evidence does not yet endorse routine clinical screening but lends credence to gut microbiota-targeted preventive strategies, such as dietary modifications aimed at reducing the intake of TMAO precursors from red and processed meat. Future standardized prospective studies are necessary to establish the clinical utility of TMAO.Systematic Review RegistrationPROSPERO CRD420261357905.