Trimethylamine N-Oxide (TMAO) is a metabolite produced by certain gut bacteria during the digestion of nutrients such as choline, phosphatidylcholine and L-carnitine found in red meat, fish and eggs. TMAO has been strongly correlated with cardiovascular disease (CVD) via platelet hyperactivity, increased foam cell responses and decreased reverse cholesterol transport (2,3).

It has been proposed that this may be part of the reason why some of these foods, specifically red meat, are correlated with heart disease. However, there is no guarantee that your specific gut bacteria will produce TMAO when you eat choline- and L-carnitine-rich foods. TMAO, therefore, illustrates the nuances that should be appreciated in nutritional sciences and functional medicine. For instance, the Mediterranean diet is largely regarded as one of the best diets for longevity and prevention of disease. Yet, this diet, consisting of a lot of choline-rich fish, may greatly increase TMAO levels in people with a certain gut microbiome composition. Many people report remission of chronic diseases and other miraculous health results with the carnivore diet, yet this may be creating a cardiotoxic soup of TMAO in the gastrointestinal tract of some populations. With cardiovascular disease being the silent killer that it is, I argue that TMAO should be assessed in anybody who plans to eat foods linked to its increase.

While I dream of a future where we can all fully assess our microbiomes and how they may relate to a variety of specific diseases, these types of tests are still very much in their infancy and do not offer much more than telling us whether our bacteria are good or bad. Therefore, the best way to assess whether you have TMAO-producing bacteria (those with the TMA lyase) is to simply test TMAO via a blood test when eating a typical diet of these foods. If you aren’t someone who eats red meat, fish, or eggs, then TMAO doesn’t have to be a concern for you. However, these foods can offer many health-promoting nutrients as long as your gut microbiome agrees with them—again, the nuance of nutrition.

Like anything in the nutrition world, TMAO is not without controversy. It’s important to note that TMAO is correlated with CVD risk and not necessarily causative. Some theorize that TMAO levels are a marker of other underlying processes or conditions that contribute to cardiovascular risk, rather than a direct cause of CVD. It has also been shown to have some protective functions, such as supporting the immune system and offering protective effects on cells from hydrostatic and osmotic pressure (4).

My current verdict on TMAO is that there is much more evidence to show that it is harmful than beneficial, especially at higher levels. I also appreciate that it is a relatively inexpensive marker (about $20) that can tell us a lot more about our gut microbiome. The good news about the microbiome is that it is highly adaptable, so this might be the motivator some people need to address their gut health so that they can enjoy that delicious grass-fed steak.

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References

1. Ahmadmehrabi S, Tang WHW. Gut microbiome and its role in cardiovascular diseases.Curr Opin Cardiol. 2017;32(6):761-766. doi:10.1097/HCO.0000000000000445
2. Duttaroy AK. Role of Gut Microbiota and Their Metabolites on Atherosclerosis, Hypertension and Human Blood Platelet Function: A Review.Nutrients. 2021;13(1):144. Published 2021 Jan 3. doi:10.3390/nu13010144
3. Zhang Y, Wang Y, Ke B, Du J. TMAO: how gut microbiota contributes to heart failure.Transl Res. 2021;228:109-125. doi:10.1016/j.trsl.2020.08.007
4. Nowiński A, Ufnal M. Trimethylamine N-oxide: A harmful, protective or diagnostic marker in lifestyle diseases?.Nutrition. 2018;46:7-12. doi:10.1016/j.nut.2017.08.001