TMAO: What the Gut-Heart Marker Tells You

TL;DR: TMAO, short for trimethylamine-N-oxide, is a compound your gut bacteria and liver make from nutrients in red meat, eggs, and fish, and your kidneys clear it. Higher blood levels are linked to more heart disease across many studies, so it turns up on advanced cardiac panels and gets blamed on red meat. But the link is probably not a simple cause and effect. Fish raises TMAO more than any other food yet protects the heart, genetic studies do not support TMAO as a cause, and much of the association may come from kidney function, which raises both TMAO and heart risk. No major guideline includes TMAO, and no trial shows that lowering it prevents a heart attack. It belongs well below proven, treatable markers like ApoB, Lp(a), and blood pressure.

If you have seen TMAO on an advanced heart panel, or read that red meat and eggs raise a gut compound that hurts your heart, this page sorts the science from the scare. TMAO is a fascinating piece of biology and a genuine research marker, but it has been oversold in both directions, and knowing where it fits will save you worry and money.

What is TMAO?

TMAO, short for trimethylamine-N-oxide, is a small compound your body makes from certain nutrients in food. The pathway has three steps. First, gut bacteria break down choline and L-carnitine, nutrients found in red meat, eggs, dairy, and some fish, into a gas called trimethylamine, or TMA. Second, the liver uses an enzyme called FMO3 to turn TMA into TMAO. Third, the kidneys clear TMAO from the blood. That last step turns out to matter a great deal, as you will see below.

Two things follow from the pathway. Your gut bacteria shape how much TMAO you make, so two people eating the same steak can end up at different levels. And your genes matter too: people born with a weak FMO3 enzyme cannot convert TMA to TMAO well, which causes a rare condition called fish odor syndrome and shows that FMO3 is the step that sets the pace.

Why is TMAO linked to heart disease?

Interest in TMAO began with a series of studies from a Cleveland Clinic lab. A 2011 paper in Nature first tied TMAO to cardiovascular disease and showed that feeding it to mice sped up plaque buildup in arteries.¹ Two years later, a study of 4,007 patients having heart imaging found that those in the top quarter of TMAO levels had about 2.5 times the risk of heart attack, stroke, or death over the next three years, even after accounting for the usual risk factors.² A companion study traced one source to L-carnitine in red meat and found that vegans and vegetarians, whose gut bacteria have adapted to less meat, made very little TMAO after a carnitine dose.³

Larger reviews backed up the association. A 2017 analysis pooling many studies found that higher TMAO carried roughly 1.6 times the risk of major heart events.⁴ Another 2017 review of 26,167 people reported that higher TMAO was tied to nearly double the risk of death, rising about 8% for each 10-unit increase in the level.⁵ A 2024 review of 30 studies and nearly 49,000 people found the link held but was smaller than the early reports suggested, closer to 1.4 times the risk of heart events, the kind of softening you often see as a young field gathers more data.¹¹

Does TMAO cause heart disease, or only track it?

Here is where the story gets more interesting, and where the headlines usually stop. Three lines of evidence suggest TMAO is more of a passenger than a driver.

The first is what nutrition researchers call the fish paradox. Fish, and deep-sea fish above all, is loaded with ready-made TMAO that your body absorbs directly, without needing gut bacteria. In a controlled feeding study, fish raised blood TMAO 46 to 62 times more than beef or eggs, within about 15 minutes of eating.⁶ Yet fish is one of the most heart-protective foods we have. A marker whose single largest dietary source moves the opposite way from heart risk cannot be a simple cause of that risk.

The second is genetics. When researchers use inherited gene variants to test cause and effect, a method called Mendelian randomization, lifelong genetically higher TMAO does not track with coronary disease, heart attack, or stroke.⁷ That kind of study is not the final word, since TMAO is driven more by diet and gut bacteria than by genes, but it gives no support to the idea that TMAO drives disease.

The third, and probably the biggest, is the kidney. TMAO is cleared by the kidneys, so anything that lowers kidney function raises TMAO, and reduced kidney function is a powerful heart risk on its own. When studies account for kidney function, the TMAO signal shrinks and often fades. A 2023 study found that kidney function, more than diet or gut bacteria, is the main thing setting a person's TMAO level, so a high TMAO often reflects reduced kidney function; the same study found the relationship runs both ways, with TMAO in turn able to worsen kidney scarring.⁸ In some analyses, reduced kidney function explained more than half of the apparent link between TMAO and heart events. So a high TMAO may be telling you about early kidney strain as much as anything else.

Should you test your TMAO?

For most people, there is little reason to test it. TMAO is not part of the major cardiovascular guidelines. The 2019 American College of Cardiology and American Heart Association prevention guideline lists the markers worth adding to a risk estimate, things like Lp(a), ApoB, high-sensitivity CRP, and coronary calcium scoring, and TMAO is not among them.¹² European guidelines leave it out as well. It is sold as a stand-alone lab test through a few reference labs and bundled into some functional-medicine panels, but it is not a test any guideline body endorses for judging risk.

The deeper problem is that a TMAO result does not change what you would do. There is no treatment aimed at TMAO, and no trial has shown that lowering it prevents a single heart attack or stroke. Every step that lowers TMAO, eating less red meat, eating more plants, protecting your kidneys, is something a good prevention plan already includes for reasons that are settled. Paying to measure the number rarely adds a decision.

How do you lower TMAO, and does it help?

If you want to lower TMAO anyway, diet is the main lever. Plant-forward eating and a Mediterranean pattern with less red meat both bring it down, and a trial swapping meat for plant-based alternatives lowered TMAO on average.⁹ That same trial found the effect was uneven and depended on the order in which people ate the two diets, a reminder of how noisy and person-specific TMAO can be.

You may read about DMB, a compound in some cold-pressed olive oils and vinegars that blocks the gut step of TMAO production. It lowered TMAO and artery plaque in mice, which is promising science, but it has never been tested as a treatment in people.¹⁰ The plain summary is that we can move the number in humans but have no proof that moving it changes health.

Where TMAO fits at Fishtown Medicine in Philadelphia

We treat TMAO as a research marker rather than a target. If a patient arrives with a high TMAO from an outside panel, we do not chase it. We put it in its place, well below the markers that are proven to cause heart disease and that we can treat, which is where your attention belongs. ApoB (a count of the harmful cholesterol particles), Lp(a) (a mostly inherited particle you check once), blood pressure, blood sugar and insulin resistance, and a coronary calcium score do far more to sharpen and lower your risk.

A surprising TMAO is not useless, though. Because kidney function drives it, an unexplained high value is a fair reason to check your kidneys with a cystatin C or a simple panel. And because diet drives it, it can open a conversation about red meat and overall eating quality. We use it that way, as a soft prompt rather than a number to hunt down, whether you are in Fishtown or Cherry Hill.

Guidance from the Clinic

"Every few months someone brings me a high TMAO from an online heart panel, worried they have done themselves harm with red meat. What I want them to know is that TMAO is a marker we are still learning to read, and the science has some strange holes: fish raises it more than steak does, yet fish is good for the heart, and much of the risk it seems to carry may come from the kidneys rather than the gut. I would rather we spend that worry on the things we know cause heart disease and can fix, your ApoB, your blood pressure, your Lp(a). If your TMAO is high for no clear reason, I check your kidneys and look at your diet, and that is about as far as the number takes us today."

Related at Fishtown Medicine

• The Advanced Tests Your Doctor Isn't Ordering - which markers earn a place on a panel
• ApoB and Heart Health - the cholesterol particle count that TMAO cannot replace
• Cardiac Biomarkers: Troponin and NT-proBNP - reading other cardiac markers in context
• High CRP: What an Elevated Inflammation Marker Means - a marker that did earn guideline standing
• Artificial Sweeteners and Erythritol - another blood-level-versus-diet story from the same research group
• High Fibrinogen: What It Means for Your Heart - another marker that predicts risk without being a treatment target

Scientific References

1. Wang Z, Klipfell E, Bennett BJ, et al. "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease." Nature. 2011;472(7341):57-63.
2. Tang WHW, Wang Z, Levison BS, et al. "Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk." New England Journal of Medicine. 2013;368(17):1575-1584.
3. Koeth RA, Wang Z, Levison BS, et al. "Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis." Nature Medicine. 2013;19(5):576-585.
4. Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L. "Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death: a systematic review and meta-analysis of prospective studies." Journal of the American Heart Association. 2017;6(7):e004947.
5. Schiattarella GG, Sannino A, Toscano E, et al. "Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis." European Heart Journal. 2017;38(39):2948-2956.
6. Cho CE, Taesuwan S, Malysheva OV, et al. "Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: a randomized controlled trial." Molecular Nutrition & Food Research. 2017;61(1):1600324.
7. Jia J, Dou P, Gao M, et al. "Assessment of causal direction between gut microbiota-dependent metabolites and cardiometabolic health: a bidirectional Mendelian randomization analysis." Diabetes. 2019;68(9):1747-1755.
8. Andrikopoulos P, Aron-Wisnewsky J, Chakaroun R, et al. "Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide." Nature Communications. 2023;14:5843.
9. Crimarco A, Springfield S, Petlura C, et al. "A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood - Meat Eating Alternative Trial (SWAP-MEAT)." American Journal of Clinical Nutrition. 2020;112(5):1188-1199.
10. Wang Z, Roberts AB, Buffa JA, et al. "Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis." Cell. 2015;163(7):1585-1595.
11. Khan QA, Asad M, Ali AH, et al. "Gut microbiota metabolites and risk of major adverse cardiovascular events and death: a systematic review and meta-analysis." Medicine (Baltimore). 2024;103(22):e37825.
12. Arnett DK, Blumenthal RS, Albert MA, et al. "2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease." Circulation. 2019;140(11):e596-e646.