TMAO – What Does the Research Say?

If you’re thinking there’s a typo here, I did not mean LMAO! In fact, TMAO is a compound that’s received a of attention over the past few years and surprise surprise without much solid evidence has created a sense of fear in consumers yet again. Let’s set the facts straight and give you the research so you can decide for yourself.

What does TMAO stand for?

First off, TMAO is the acronym for the compound trimethylamine-N-oxide. Since that is obviously such a mouthful, TMAO has been used widely across scientific literature for short.

Why does TMAO have such a bad rap?

TMAO is a compound that has been shown in some studies to increase risk of cardiovascular disease, leading people to become terrified to consume foods that naturally contain or produce TMAO during their metabolism.

For instance, many read this study that showed a higher rate of atherosclerosis development when choline was added to the diet of a specific species of mice who were already at risk for heart disease and become skeptical of TMAO.

However, what most people don’t realize is that there was a major flaw in this study in that this species of mice lacked an important protein found in humans that actually helps reverse cholesterol transport in the body.

This same animal model was repeated with the human gene added into the mice and guess what, TMAO was raised but atherosclerosis did not ensue! 

Where is TMAO found?

Absolutely! So, TMAO can actually take on a few different forms so let’s look a little closer at each of them below.

TMAO in Fish

One of the most common forms of TMAO is its action as an osmolyte (or substance) that is naturally present in fish. In this capacity it offers a protective layer that helps keep the enzymes within the fish safe from the salt water.

Thus, fish naturally have a high TMAO concentration.

If you follow the AHA and FDA recommendations to eat fish twice a week, you will certainly have a high level of TMAO circulating until your kidneys naturally do their thing to rid your body of this (aka your own detox system)!

TMAO in this capacity is considered a biomarker (or indicator) that you’re eating fish, not that you are going to get heart disease, gestational diabetes or anything else in healthy individuals. 

TMAO Produced in the Gut

TMAO can also be produced from microbes in the gut that help metabolize choline. (Curious what choline is? Then I highly recommend you revisit the post here first! For a quick refresher, choline is found in foods like eggs, beef, pork, chicken, lima beans, liver as well as dietary supplements.)

It’s well known every single individual has a very diverse gut microbiota, with both good and bad guys taking up residence in there.

The amount of TMAO produced here varies tremendously on the micrbiome in addition to each individual’s health states.

Does having a circulating TMAO mean one is at higher risk for those cardio-metabolic diseases?

Not exactly.

It can actually mean a few different things, like perhaps that individual has a higher prevalence of those “bad” gut microbes that produce more of the TMAO.

Solution: Improve the balance of your good gut bacteria with dietary changes like more fermented foods, not cutting out fish, eggs or a choline supplement. 

It can also mean someone has improper kidney functioning. For instance, if someone has poor functioning kidneys (remember that natural detox system), then they’re likely going to have higher TMAO circulating in their body. 

Solution: Address kidney functioning and the underline dietary and medical therapies to improve their GFR rate, if possible.

And, last but certainly not least, insulin resistance can also play a role!

Solution: Evaluate insulin resistance and see if other dietary concerns need to be addressed.

Do dietary sources of choline impact cardiovascular risk?

Again, choline is an essential nutrient critical for fetal brain development with emerging evidence of impact on cognitive function.

It’s also found in foods that have been given some heat lately if you’ve read the latest from the Cleveland Clinic and perhaps caused some confusion as to if they should be consumed or not.

While I highly encourage you to absorb all the information you can for yourself on this subject matter, there are a few interesting things about the latest study discussed by the Cleveland Clinic that was addressed in this editorial by researchers from Cornell.

Here’s the link to check out the editorial yourself, but a great point was made by authors Kevin Klatt and Marie Caudill I’m going to cite below:

…history reminds us to be cautious about the preemptive translation of this evidence into public health and clinical recommendations.

The field of nutrition has seen multiple instances where promising associations, coupled to preclinical evidence and trials with surrogate outcomes, have not yielded clear evidence of benefits in large randomized controlled trials, and in some cases, have led to unintended harm.

This current trial was relatively small, with no control group or random treatment allocation, and utilized a single, ex vivo surrogate outcome without established thresholds to assess thrombotic risk.

Pressing the trimethylamine N-oxide narrative

As we noted above, choline serves as a precursor to TMAO.

Simply put, if you eat choline containing foods or foods that contain TMAO (like fish, beef, pork, eggs), you will naturally have higher levels of circulating TMAO in your blood.

Interestingly enough there is plenty of evidence to support the notion that dietary choline does not impact cardiovascular risk.

A recent systematic review did not find a link between dietary choline and cardiovascular risk. Plus, current research indicates that eggs are a bioavailable source of choline that does not significantly impact levels of TMAO in healthy adults.

And, in case that wasn’t enough, in another study that compared choline food sources and TMAO, the highest increase in TMAO was observed with fish consumption, which is important given the known connection between fish intake and reduced cardiovascular risk.

Fish raises TMAO more than 50 times that of choline. Yet, fish has long been recognized as protecting against the risk of heart disease and continues to be recognized as an important part of a healthy diet!

Now, what about choline supplements and the impact it has on health?

To date, no controversial effects have been shown on human participants in the randomized control trials that have ensued using choline supplementation as a means to evaluate maternal and infant health markers.

More research is certainly needed though to look long term at the health of women, men and children to ensure the current recommendations continue to hold true.

What is my stance?

I highly encourage you to proceed with caution before taking out entire foods that are so rich in nutrition because of media hype around an acronym like TMAO. 

TMAO in my opinion is not to be feared. It’s more so an educational point to understand that our body functions as a whole, not in parts!

In order for our health to be complete, we need to ensure the entire body is working synergistically together to metabolize and process the foods and supplements we consume.

Science is a beautiful thing but it’s also always evolving, as will the TMAO discussion. We have to stay on our toes to ensure we help communicate the latest facts, not fads, when it comes to your health!

Can you give me a brief 411 so I can remember all of this?

TMAO is indicative of a biomarker for having consumed foods like fish, egg yolks, or meats. The amount circulating in your body is dependent upon the make-up of your gut!

Before eliminating nutrients that are already under consumed, consider taking a look at your microbiome and focusing on healthy ways to feed your gut (like this post on probiotic rich foods here!)

I’d love to hear from you on this topic! Please feel free to comment below, send me an email or shoot me a message over on Instagram!