Cleveland Clinic Report Links TMAO to Aortic Aneurysm Risk

October 15, 2026

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Energy & Metabolism

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On September 22, 2026, Cleveland Clinic’s Consult QD published a report linking higher blood levels of trimethylamine N-oxide (TMAO) with abdominal aortic aneurysm and later adverse events. The study was co-led by Cleveland Clinic and Tufts University.

Researchers Followed an Older Community Cohort

The researchers used the Cardiovascular Health Study, a prospective community-based cohort of 4,442 adults aged 65 or older. A prospective study follows participants over time to examine how measured factors relate to later outcomes.

The mean age was 72. Women accounted for 63% of participants, and 81% were White. These details describe the population behind the findings rather than a sample made up mainly of middle-aged men.

According to the Cleveland Clinic report, baseline abdominal ultrasound was available for 3,961 participants. Median follow-up was 12.2 years, totaling 54,402 person-years. That last figure combines the time participants contributed to follow-up.

The study focused on abdominal aortic aneurysm, or AAA. Researchers defined AAA using an infrarenal aortic diameter of at least 3.0 cm or an infrarenal-to-suprarenal aortic width ratio of at least 1.2. These measurements established the study’s definition of an aneurysm.

The analysis addressed separate questions. One concerned whether higher TMAO was associated with an aneurysm already visible on the initial ultrasound. Another concerned whether higher TMAO was associated with later surgery, rupture or aneurysm-related death.

TMAO Connects Gut Microbes With Metabolism

The report describes TMAO as a gut-microbe-derived metabolite. Gut microbes convert dietary choline and carnitine into trimethylamine. The liver then converts trimethylamine into TMAO.

Cleveland Clinic identifies red meat as a source rich in choline and carnitine. This pathway explains why diet and gut microbes appear in the discussion. The study’s clinical focus remained the relationship between measured TMAO and aneurysm outcomes.

Higher TMAO Was Associated With Aneurysms and Later Events

The report found associations with both initial ultrasound findings and adverse events during follow-up. Those outcomes deserve separate attention because aneurysm presence is not the same question as later progression.

Initial Ultrasound Findings Showed an Association

Among participants who had baseline ultrasound:

335 participants had an AAA, representing 8.5% of those screened.
Each doubling of baseline TMAO was associated with an approximately 0.3-cm greater infrarenal aortic diameter.
The highest TMAO quintile had 73% higher adjusted odds of ultrasound-detected AAA than the lowest quintile. The reported odds ratio was 1.73.

Quintiles group participants according to their measured TMAO levels. This comparison concerned aneurysms detected at the initial examination. It did not measure how much an individual aneurysm grew during follow-up.

The diameter finding also describes a difference associated with TMAO levels across participants. It should not be read as a claim that doubling someone’s TMAO would make that person’s aorta grow by the reported amount.

Follow-Up Captured Repair, Rupture and Death

During follow-up, 79 participants experienced at least one adverse AAA event. Cleveland Clinic reported the following event counts:

53 underwent operative repair.
25 had an aneurysm rupture.
15 died from aneurysm-related causes.

These categories can overlap. Adding them together does not produce a count of separate people because a participant could contribute to more than one category.

In adjusted analyses, participants in the highest TMAO tertile had 2.46 times the risk of adverse aortic events compared with those in the lowest tertile. The further-adjusted estimate was 2.09. Each doubling of TMAO was associated with a 28% higher hazard of an adverse AAA event.

These are comparisons between groups within this cohort. They are not absolute probabilities that tell a reader how likely an event is for him personally. Keeping that distinction clear prevents a substantial relative association from becoming an unsupported personal risk estimate.

The researchers also reported that adding TMAO improved discrimination in standard clinical risk models. In plain language, that means the models became better at distinguishing participants by outcome.

The Evidence Leaves Cause and Clinical Use Unsettled

The findings are relevant to aortic research. Several questions still stand between this association and a change in care.

An Association Does Not Establish a Prevention Target

This was an observational cohort study, not a treatment trial. It does not establish that TMAO causes AAA or that lowering TMAO prevents aneurysm growth, rupture or death.

Co-senior author Stanley Hazen interpreted the findings as supporting TMAO as a risk factor for AAA and its adverse outcomes. He also suggested that a blood test might help predict aneurysm risk among apparently healthy older people.

Hazen called for human intervention trials to determine whether lowering TMAO through diet or targeted microbial treatments could improve aneurysm outcomes. That is a proposed research direction rather than a demonstrated human benefit. Earlier preclinical work described in the report connected TMAO with vascular inflammation and cellular injury, but it does not fill that clinical gap.

Existing Aneurysms Complicate the Interpretation

A separate European Heart Journal commentary questioned the timing of TMAO measurements and the role of baseline aneurysm size or status in the event analyses. Its central concern was whether the analysis fully separated risk associated with existing aneurysm burden from risk of later progression.

That distinction matters. A marker could reflect disease already present. It could help predict progression among people who have an aneurysm, or it could identify risk of developing new disease. Those are different roles that need to be clarified before clinical use.

The commentary therefore provides a counterpoint to reading the result as proof that TMAO predicts progression beyond established aneurysm anatomy. A link with later events alone does not settle which of these questions the marker answers.

Kidney Function and Population Details Matter

Cleveland Clinic identifies renal function as a key determinant of TMAO clearance. The association persisted after adjustment for renal function and other factors. That adjustment does not resolve the separate questions about measurement timing and baseline aneurysm burden.

The cohort’s older age also limits direct application to younger men. Its findings should not be treated as evidence about every man over 45. The report described a stronger association in men, with the same direction of association in women, but supplied no male-specific effect size.

Better Model Performance Needs Clinical Confirmation

The report did not state the size of the improvement in risk-model discrimination. That leaves the practical value of adding TMAO unquantified in the available account.

Cleveland Clinic vascular surgeon Francis Caputo was not involved in the study. He said aneurysm biology may matter alongside diameter and growth when clinicians assess risk. He also cautioned that prospective confirmation would be needed before these findings could change risk assessment or treatment.

Clinical Assessment Remains the Basis for Decisions

For men concerned about aortic disease, the supported next step is a discussion with a clinician about personal risk and appropriate screening or follow-up. This research does not establish a new screening recommendation or replace imaging-based assessment.

The diet-related pathway is not a reason to self-test, change medication or adopt a restrictive diet to lower TMAO. Personal decisions belong with qualified care rather than a single emerging marker.

For readers tracking longer-term health, this finding belongs within a broader evidence picture. Research on physical capability and cardiovascular health and stress-related metabolic concerns addresses separate questions rather than turning one blood result into a complete health assessment.

What this changes: TMAO gains support as an emerging research marker for AAA, but this report does not change current screening or treatment practices.

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TMAO raises a difficult question: when does an interesting blood marker become useful for everyday health decisions? Everfitguys helps men 45 and older sort supported healthy aging claims from promising research through plain-English reporting focused on staying physically capable and mentally sharp, without turning early findings into medical advice.

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