The unexpected role of a gut molecule in physical exertion and metabolic health
Long associated with the risks of cardiovascular and metabolic diseases, a molecule produced by gut bacteria, trimethylamine N-oxide, is now revealing a more complex profile. Recent research in exercise physiology shows that its role goes beyond that of a simple danger marker. Indeed, this substance, derived from the transformation of nutrients such as choline or carnitine by the microbiota, does more than just circulate in the blood before being eliminated by the kidneys. It interacts with several biological processes, influencing protein stability, mitochondrial energy metabolism, and even redox balance, a key mechanism for managing oxidative stress in the body.
The concentrations of this molecule in the blood depend primarily on diet, gut microbiota activity, the activity of a liver enzyme, and kidney function. Contrary to popular belief, human studies do not show a systematic link between its levels and physical condition, usual activity, or training level. Interventions based solely on physical exercise rarely significantly alter its concentrations, whereas dietary changes or supplementation with precursors like carnitine have a much more pronounced impact.
Yet, experiments suggest that this molecule could play a protective role in certain contexts. In animals subjected to intense physical stress, its administration improves endurance and reduces oxidative stress in muscles. It also promotes the preservation of mitochondrial function, which is essential for maintaining energy during prolonged exertion. These beneficial effects have also been observed in models of heart failure, where it mitigates damage and improves survival.
An intriguing paradox arises with fish consumption, which is rich in this molecule. Despite elevated blood levels after a meal, populations such as the Japanese, who consume large amounts of fish, exhibit lower mortality rates than other ethnic groups, challenging the idea of universal toxicity. Similarly, in athletes, high levels before a marathon appear to be linked to an increased cardiac response to exertion, without necessarily worsening risks.
Human studies confirm that exercise alone has little effect on the levels of this molecule. However, hypocaloric diets combined with intense training can reduce its concentrations, while carnitine supplementation increases them, regardless of physical activity. These observations highlight the dominant influence of diet on its production.
In athletes, transient variations of this molecule have been noted after prolonged exertion or high training loads. A study on professional snowboarders showed an increase in its urinary levels with intensified training, suggesting a link with physiological stress. However, its usefulness as a marker of adaptation to exertion or recovery remains to be demonstrated.
The underlying mechanisms may involve its role in managing oxidative stress. This molecule and its precursor, trimethylamine, interact with reactive oxygen species, thereby influencing the body’s antioxidant defenses. One hypothesis suggests that the ratio between the two could reflect the overall redox state, although this has not yet been confirmed in humans during exercise.
In summary, this molecule can no longer be considered a mere risk indicator. It appears to act more as an integrative signal, reflecting the interactions between diet, microbiota, metabolic stress, and physiological state. Its study opens up perspectives for a better understanding of how the body adapts to exertion and stress, although its use as a biomarker in sports or medicine remains to be clarified.
Information and Sources
Scientific Reference
DOI: https://doi.org/10.1007/s00421-026-06297-4
Title: Trimethylamine N-oxide in exercise physiology: a gut microbiota-derived signal linking metabolic stress, redox balance and cardiometabolic health
Journal: European Journal of Applied Physiology
Publisher: Springer Science and Business Media LLC
Authors: Robert A. Olek; Zsolt Radak