What does a high level of Trimethylamine N-oxide (TMAO) indicate?

From the Guidelines

A high level of trimethylamine N-oxide (TMAO) in the blood is a strong indicator of increased risk of cardiovascular disease, including heart attack, stroke, and heart failure, as evidenced by recent studies 1.

Key Findings

• TMAO is produced when gut bacteria metabolize certain nutrients found in animal products, particularly red meat, eggs, and dairy, and then converted to TMAO by the liver 1.
• Elevated TMAO levels have been associated with atherosclerosis (hardening of the arteries), inflammation, and blood clot formation, which can lead to cardiovascular problems 1.
• A high TMAO level can also contribute to a leaky gut, defined by increased intestinal permeability, causing systemic inflammation and a variety of health problems 1.

Recommendations

• To reduce high TMAO levels, dietary modifications are recommended, including limiting consumption of red meat and other animal products while increasing plant-based foods, particularly those rich in fiber 1.
• Prebiotics and probiotics may help by promoting beneficial gut bacteria, and regular exercise can also improve gut microbiome health and potentially reduce TMAO levels 1.
• No specific medications directly target TMAO reduction, though some research suggests that certain medications like aspirin or statins might indirectly affect levels 1.

Clinical Implications

• If you have high TMAO levels, consult with a healthcare provider who can evaluate your overall cardiovascular risk profile and recommend appropriate lifestyle changes or medical interventions 1.
• It is essential to address TMAO levels to mitigate the risk of cardiovascular disease, as recent studies have consistently shown a strong link between high TMAO levels and adverse cardiovascular outcomes 1.

From the Research

High Levels of Trimethylamine N-Oxide (TMAO)

• A high level of TMAO has been associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events in community-based older adults 2.
• Elevated serum TMAO levels have been shown to increase the risk of cardiovascular disease, including sudden death, myocardial infarction, or stroke, in patients undergoing elective coronary angiography 3.
• TMAO levels are also associated with the number of infarcted coronary arteries, which is a measure of the severity of atherosclerosis, and this association is independent of dyslipidemia 3.

Relationship with Kidney Function

• Higher TMAO levels are observed in advanced-stage chronic kidney disease (CKD) 3, 4.
• The relationship between TMAO and ASCVD appears to be mediated or confounded by estimated glomerular filtration rate (eGFR), and high levels of TMAO are associated with higher incidence of ASCVD in the presence of impaired renal function 2.
• TMAO may contribute to cardiovascular disease through dysregulation of lipid metabolism, enhanced macrophage foam cell formation, and platelet dysfunction in patients with CKD 4.

Mortality and Adverse Cardiovascular Events

• High TMAO levels are positively associated with all-cause mortality and adverse cardiovascular events in elderly subjects 5.
• The association between TMAO and adverse cardiovascular events remains significant in patients with CKD and heart failure, but not in patients with diabetes 5.
• Observational and experimental studies suggest a strong positive correlation between increased plasma TMAO concentrations and adverse cardiovascular events, such as myocardial infarction, stroke, and death 6.