In recent years, discoveries about the gut microbiome have changed how we understand cardiovascular diseases (CVDs). It is no longer enough to think only about cholesterol and saturated fat; we now know that the microorganisms that inhabit our gut also actively participate in heart health (or disease).

Among the compounds that mediate this relationship, trimethylamine oxide (TMAO) stands out as a key player. Produced when the gut microbiota metabolizes choline, L-carnitine, and betaine—nutrients abundant in red meat, eggs, and dairy products—TMAO has been identified as an important marker and potential cause of atherosclerosis, hypertension, and heart failure.

How is TMAO produced?

• The process begins in the gut: Nutrients such as choline, betaine, and L-carnitine, abundant in red meat, eggs, and dairy products, are metabolized by gut bacteria that produce trimethylamine (TMA).

• This gas is then transported to the liver, where the enzyme FMO3 (flavin monooxygenase 3) oxidizes it, transforming it into TMAO, which circulates in the blood and is partially eliminated by the kidneys.

• Excess TMAO interferes with cholesterol metabolism, promotes inflammation, and the formation of atherosclerotic plaques.

Studies show that elevated plasma TMAO levels are strongly associated with cardiovascular risk and mortality, even after controlling for classic factors such as age, smoking, and cholesterol.

Experimental and clinical evidence

One of the milestones in this line of research was the study "Does the metabolism of L-carnitine, a nutrient found in red meat, by the gut microbiota promote atherosclerosis?" published in 2013 by the journal Nature Medicine, which demonstrated that:

🔸Omnivores produce significantly more TMAO after consuming L-carnitine (from red meat) than vegans and vegetarians.

🔸When the same group of volunteers received antibiotics to suppress the microbiota, TMAO production dropped to almost zero, and then rose again after intestinal recolonization.

🔸In mice, diets rich in carnitine increased the formation of fatty plaques in the arteries, but this effect disappeared without an active gut microbiota.  

These findings reinforced the idea that the cardiovascular risk linked to red meat is not only due to the fats, but also to the interaction between its nutrients and the gut microbiota.

TMAO: The Silent Villain of the Heart

TMAO has also been identified as an early marker of serious cardiac events, potentially predicting the risk of heart attack more accurately than cholesterol alone.

Diet and microbiota: the antidote lies in plants.

On the other hand, plant-based diets appear to act as a natural countermeasure to the TMAO cycle. A scientific review highlights that people who follow plant-based dietary patterns exhibit:

✔ Lower abundance of TMA-producing bacteria, and greater presence of beneficial species such as Prevotella and Faecalibacterium prausnitzii.

✔ Increased production of short-chain fatty acids, such as butyrate and propionate, which strengthen the intestinal barrier and reduce systemic inflammation.

✔ Lower plasma levels of TMAO, which translates to a lower risk of atherosclerosis and cardiovascular mortality.

Furthermore, clinical studies show that long-term veganism and vegetarianism reduce the risk of coronary heart disease by up to 29% compared to omnivorous diets, an effect partly mediated by a reduction in TMAO.

How to modulate TMAO through feeding.

✅ Increase your consumption of:

• Vegetable fibers (oats, beans, fruits and vegetables);

• Fermented foods (vegetable kefir, sauerkraut, kombucha);

• Sources of polyphenols (green tea, grapes, pure cocoa, olive oil);

• Water and regular physical activity (both reduce intestinal dysbiosis).

🚫 Reduce your consumption of:

• Red and processed meats;

• Eggs;

• Whole dairy products and supplements containing L-carnitine.

The science of TMAO represents a turning point in cardiovascular nutrition. It reveals that what we eat acts not only through its caloric or fat content, but also through how it nourishes (or unbalances) our gut microbiota.

While animal products rich in choline and carnitine increase the production of this toxic metabolite, plant-based diets, rich in fiber, polyphenols, and anti-inflammatory compounds, modulate the gut in a protective way, reducing TMAO and cardiovascular inflammation.

In short: your heart is only as healthy as your gut. And your gut is only as balanced as what you put on your plate.

References:

Zhen J. et al. The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Frontiers in Endocrinology (2023).
https://doi.org/10.3389/fendo.2023.1085041

Koeth RA et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosisNature Medicine (2013).
https://doi.org/10.1038/nm.3145

Kumar A., ​​Chidambaram V., Mehta J.L. Vegetarianism, microbiota, and cardiovascular health: looking back, and forward. European Journal of Preventive Cardiology (2022).
https://doi.org/10.1093/eurjpc/zwac128