Systematic reviews & meta-analysis of prospective studies have found elevated serum TMAO concentrations to be linked to:

1. A 62% increased risk of all-cause mortality
2. A 23% higher risk of cardiovascular events

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Overview of TMAO

Elevated levels of TMAO (Trimethylamine N-oxide) have been associated with an increased risk of heart disease, Type 2 diabetes, cerebral vascular issues & fatty liver.

In the body, it is produced in the liver from trimethylamine, which is generated by gut bacteria that metabolize certain nutrients like choline & carnitine. While certain foods contain nutrients that can be converted into TMAO, some foods contain TMAO inherently.

Understanding which foods contain TMAO can therefore be important if you care about your longevity.

Why Does TMAO Matter in Cardiovascular Health?

• TMAO is thought to contribute to atherosclerosis by altering cholesterol metabolism & promoting inflammation in arterial walls.
• It may also affect platelet function, increasing the risk of clot formation.
• Studies suggest that TMAO could be a marker for gut microbiota composition, which in turn affects various metabolic pathways.

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Why Do Some Foods Inherently Contain TMAO?

TMAO (Trimethylamine N-oxide) is a molecule that plays a role in the osmoregulation of marine animals. It helps to stabilize proteins and other biological molecules, allowing these animals to survive in high-salinity environments. The molecule also counteracts the effects of urea, which some marine animals produce to balance internal and external osmotic pressures.

The concentration of TMAO varies among different types of marine animals due to their unique metabolic pathways & osmoregulatory requirements. The molecule itself is less prevalent in freshwater fish & understood to be absent in terrestrial animals & plants.

Here are Some Foods Containing INHERENT TMAO:

(Listed from High to Low)

Saltwater Fish

• Examples: Mackerel, herring, cod, sardines, sword fish, halibut.
• TMAO Levels: These fish have some of the highest TMAO concentrations, often several-fold higher than their freshwater counterparts. The elevated levels are important for maintaining their cellular function in the hypertonic conditions of saltwater habitats.
• Nutritional Profile: Some are rich in beneficial omega-3 fatty acids. However, the high TMAO content is worth considering.

Shellfish

• Examples: Oysters, clams, mussels, and scallops.
• TMAO Levels: Can be lower than in saltwater fish, but still noteworthy. The reduced levels may be attributed to their distinct metabolic pathways and the fact that they are often filter feeders, which may limit their exposure to high-salinity conditions.
• Nutritional Profile: These are good sources of protein and essential minerals (zinc & iron).

Squid and Octopus

• Examples: Various species of quid & various species of octopus.
• TMAO Levels: These cephalopods have moderate TMAO levels, which are intermediate between those of shellfish and crustaceans. This can be due to their unique metabolic & osmoregulatory systems.
• Nutritional Profile: They are high in protein and low in fat, but the TMAO content can remain a consideration for those concerned about cardiovascular health.

Crustaceans

• Examples: Crab, lobster, shrimp, and crayfish.
• TMAO Levels: These have the lowest TMAO levels among marine animals but still contain the molecule. Their exoskeletons & different osmoregulatory mechanisms may contribute to the lower TMAO concentrations.
• Nutritional Profile: Crustaceans are high in protein and low in fat, making them a good dietary choice, although the TMAO levels should be considered.

Freshwater Fish

• Examples: Trout, catfish, tilapia, and carp.
• TMAO Levels: These fish have much lower TMAO levels, as their freshwater habitats do not necessitate high levels of osmoregulatory molecules.
• Nutritional Profile: Generally, these fish are lower in omega-3 fatty acids compared to saltwater fish and have reduced TMAO levels.

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Note:

1. The list focuses on foods that inherently contain TMAO.

2. It does not include foods that can be converted into TMAO in the body.

3. The TMAO content can also vary based on factors like species and diet of the fish.

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Stay tuned for upcoming episodes in the 'Nutritional Excellence' series where we will continue to dig into TMAO:

• Various compounds that metabolise into TMAO in the body
• What foods contain these compounds
• Possible dietary interventions/replacements can be made

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​In a previous episode of the ongoing Nutritional Excellence series, I discussed in detail how TMAO is linked to disease & dysfunction. ​

​If you have missed it, you can read about it here:​

​TMAO​ ...The Hidden Danger in Your Plate that Increases Heart Attack Risk by 23%... ​ Read article

Disclaimer

This information is not medical advice. This content and other content on this website is for informational and educational purposes only and is not intended to be a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.

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References

• Yu, D.; Shu, X.; Rivera, E.S.; Zhang, X.; Cai, Q.; Calcutt, M.W.; Xiang, Y.; Li, H.; Gao, Y.; Wang, T.J.; et al. Urinary Levels of Trimethylamine-N-Oxide and Incident Coronary Heart Disease: A Prospective Investigation Among Urban Chinese Adults. J. Am. Hear. Assoc. 2019, 8, e010606.
• Hagen, I.V.; Helland, A.; Bratlie, M.; Midttun, Ø.; McCann, A.; Sveier, H.; Rosenlund, G.; Mellgren, G.; Ueland, P.M.; Gudbrandsen, O.A. TMAO, creatine and 1-methylhistidine in serum and urine are potential biomarkers of cod and salmon intake: A randomised clinical trial in adults with overweight or obesity. Eur. J. Nutr. 2019, 59, 2249–2259.
• Yin, X.; Gibbons, H.; Rundle, M.; Frost, G.; McNulty, B.A.; Nugent, A.P.; Walton, J.; Flynn, A.; Brennan, L. The Relationship between Fish Intake and Urinary Trimethylamine-N-Oxide. Mol. Nutr. Food Res. 2020, 64, e1900799.
• Farhangi, M.A. Gut microbiota-dependent trimethylamine N-oxide and all-cause mortality: Findings from an updated systematic review and meta-analysis. Nutrients 2020, 78, 110856.
• Haghikia, A.; Li, X.S.; Liman, T.G.; Bledau, N.; Schmidt, D.; Zimmermann, F.; Kränkel, N.; Widera, C.; Sonnenschein, K.; Haghikia, A.; et al. Gut Microbiota–Dependent Trimethylamine N -Oxide Predicts Risk of Cardiovascular Events in Patients With Stroke and Is Related to Proinflammatory Monocytes. Arter. Thromb. Vasc. Biol. 2018, 38, 2225–2235.
• Tang, W.W.; Wang, Z.; Kennedy, D.J.; Wu, Y.; Buffa, J.A.; Agatisa-Boyle, B.; Li, X.S.; Levison, B.S.; Hazen, S.L. Gut Microbiota-Dependent TrimethylamineN-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease. Circ. Res. 2015, 116, 448–455.
• Gruppen, E.G.; Garcia, E.; Connelly, M.A.; Jeyarajah, E.J.; Otvos, J.D.; Bakker, S.J.L.; Dullaart, R.P.F. TMAO is Associated with Mortality: Impact of Modestly Impaired Renal Function. Sci. Rep. 2017, 7, 1–9.
• Farhangi, M.A.; Vajdi, M. Novel findings of the association between gut microbiota–derived metabolite trimethylamine N-oxide and inflammation: Results from a systematic review and dose-response meta-analysis. Crit. Rev. Food Sci. Nutr. 2020, 60, 2801–2823.

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