Someone recently challenged me about eating eggs.
His concern was reasonable.
Egg yolks contain choline. Certain bacteria in the intestine can use choline to produce trimethylamine, or TMA. The liver then converts TMA into trimethylamine N-oxide, better known as TMAO.
Higher blood TMAO has been associated with atherosclerosis, cardiovascular events, kidney disease, diabetes, and mortality in observational research. So the conclusion appears simple:
Eggs contain choline.
Choline can become TMAO.
TMAO is associated with cardiovascular disease.
Therefore, eggs must damage the arteries.
The pathway is real.
The conclusion is not that simple.
What I want you to understand is this: a biological pathway tells us what can happen. It does not automatically tell us what happened inside your body, how large the effect was, or whether that effect caused disease.
This is where most people miss the point.
We should not dismiss TMAO. We should also not build an entire cardiovascular strategy around one isolated metabolite.
The pattern matters.
Egg yolks are one of the richest dietary sources of choline.
Choline is not a toxin. It is an essential nutrient involved in cell-membrane structure, acetylcholine production, liver function, lipid transport, methylation, and nervous-system health.
When you eat choline-containing food, several things can happen.
Some of the choline is absorbed and used by the body directly.
Some reaches bacteria in the intestine.
Certain bacterial communities can convert choline into TMA. That TMA travels to the liver, where an enzyme system converts it into TMAO.
The pathway looks like this:
Choline → gut bacteria → TMA → liver → TMAO
But the amount of TMAO produced is not determined by choline intake alone.
Two people can eat the same number of eggs and produce very different TMAO responses.
That difference may be influenced by:
The composition and activity of the gut microbiome
Kidney filtration and clearance
Existing metabolic disease
The food form in which choline is consumed
The person’s usual dietary pattern
Genetics affecting liver conversion
Age and health status
The timing of the blood test
Baseline TMAO before the meal
A randomized trial comparing eggs with supplemental choline found that four eggs per day did not significantly raise fasting TMAO or platelet reactivity in participants with normal kidney function, while a choline supplement did raise fasting TMAO. This matters because the same nutrient may behave differently when delivered inside a whole food versus an isolated supplement.
Another intervention found that eating up to three eggs daily increased plasma choline while fasting TMAO remained unchanged.
A separate crossover trial found that two eggs per day increased choline and carotenoid concentrations without increasing plasma TMAO compared with an oatmeal breakfast.
Most importantly, a recent systematic review and meta-analysis of randomized controlled trials examined egg consumption and circulating choline, betaine, and TMAO. The combined evidence did not support a clear overall increase in circulating TMAO from egg consumption, although individual studies and individual responses were not identical.
That does not prove eggs are harmless for everyone.
It tells us that egg consumption does not reliably produce the same TMAO response in every person.
Food is the input.
Biology is the interpreter.
The gut microbiome is not one permanent collection of bacteria.
It changes with diet, medications, antibiotics, age, disease, travel, environment, sleep, bowel function, and many other exposures.
Some microbial communities appear more capable of producing TMA from dietary precursors than others.
In a randomized feeding study, researchers found substantial differences in TMAO responses to animal foods. Fish produced a much larger circulating and urinary TMAO response than eggs or beef, and individual responses were influenced by gut-microbiome composition.
This creates an important question.
If TMAO itself automatically caused arterial damage in direct proportion to the amount detected after a meal, how should we interpret fish?
Fish can contain TMAO directly and may raise circulating TMAO much more than eggs. Yet fish consumption is frequently associated with cardiovascular benefits in broader dietary research.
That does not disprove the TMAO hypothesis.
It shows why the source, timing, metabolic context, and complete biological pattern matter.
A temporary rise after eating a food may not have the same meaning as persistently elevated fasting TMAO in someone with kidney impairment, diabetes, inflammation, high ApoB, and established plaque.
Those are very different biological situations.
Higher TMAO has repeatedly been associated with cardiovascular risk.
This deserves attention.
Mechanistic work suggests TMAO may influence platelet responsiveness, thrombosis pathways, vascular inflammation, cholesterol handling, and other processes relevant to cardiovascular disease. For example, experimental and observational research has connected higher TMAO with platelet hyperreactivity and thrombotic risk.
However, association does not settle the direction of causality.
Does TMAO contribute to disease?
Does disease raise TMAO?
Do both occur?
The answer may depend on the person.
A bidirectional Mendelian randomization analysis found evidence suggesting that type 2 diabetes and impaired kidney function can increase TMAO concentrations. The study did not find strong evidence that genetically predicted TMAO itself caused several major cardiometabolic diseases.
A later review concluded that the causal question remains unsettled. Some genetic analyses have not supported a direct causal relationship with cardiometabolic disease, while other analyses suggest possible effects on blood pressure and pathways connected with kidney function.
What does that mean practically?
It means an elevated TMAO result could represent several possibilities:
Greater production of TMA by the microbiome
Greater conversion of TMA into TMAO by the liver
Reduced clearance of TMAO by the kidneys
A metabolic environment associated with both higher TMAO and cardiovascular risk
A recent dietary exposure
A combination of these factors
The question is not only, “Is TMAO elevated?”
The better question is:
“Why is it elevated, and what else is happening in the same person?”
Imagine two people both receive a TMAO result of 12 µmol/L.
The first person has:
Normal creatinine
Strong cystatin C-based kidney filtration
No albumin in the urine
Good fasting and post-meal glucose regulation
Low ApoB
Low blood pressure
Low inflammatory markers
No detectable plaque on available imaging
A temporary rise after a high-TMAO meal
The second person has:
Declining kidney function
Elevated urine albumin
Diabetes or insulin resistance
High ApoB
Elevated blood pressure
High oxidized LDL
Existing coronary calcium or carotid plaque
Persistently elevated fasting TMAO
The laboratory number may be similar.
The cardiovascular pattern is not.
The second person has multiple interacting signals that already support a higher-risk arterial environment.
In that situation, TMAO may provide additional information.
In the first person, removing a nutrient-dense food solely because of one result may not address the real drivers of risk.
This is why I do not treat TMAO as a verdict.
I treat it as a clue.
At this point, the main idea should be clear. The problem is not only whether TMAO is high. The problem is understanding the signal underneath it.
In the paid section, I’m going to walk through the laboratory pattern, testing sequence, practical egg experiment, safety considerations, and how I would apply this without guessing.
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