152. More myth debunking: TMAO, Neu5gc, Methionine/Glycine balance

TMAO Pathways

Dr. Paul Saladino explains that TMAO is produced when carnitine and choline, found in foods like meat and eggs, are metabolized by gut microbiota and further processed by the liver enzyme FMO3 1. He emphasizes that while mainstream literature often links TMAO to heart disease and stroke, these associations are not causative but merely correlations 1. Saladino also highlights that FMO3 activity is insulin-dependent, suggesting that insulin resistance could increase TMAO levels, which may explain its association with diabetes 2.

TMAO is not directly causal, but is a marker of hepatic insulin resistance.

--- Paul Saladino

This insight challenges the prevailing narrative that TMAO is inherently harmful to human health.

   

Nutrient Debate

Saladino questions the logic behind demonizing choline and carnitine, essential nutrients found in animal products, due to their role in TMAO production 3. He argues that these compounds are vital for brain function and overall health, making it illogical to consider them harmful 3. Additionally, he presents evidence that carnitine can improve mitochondrial function and alleviate depressive symptoms, further questioning the negative perception of TMAO 4.

Why would a compound that is in the most essential, the foods that have been at the center of human existence, be bad for us?

--- Paul Saladino

This perspective encourages a reevaluation of the current understanding of TMAO and its impact on health.

   

Fish Paradox

Saladino points out the paradox that fish, which contains high levels of preformed TMAO, is not associated with cardiovascular disease, unlike meat 5. He uses this to argue that TMAO may not be harmful and could have important biological roles 5. Furthermore, he criticizes studies that claim a mechanistic link between TMAO and cardiovascular disease, noting that these are often based on associations rather than causative evidence 6.

Maybe TMAO doesn't cause cardiovascular disease. Maybe TMAO has an important role in human biology.

--- Paul Saladino

This highlights the need for a more nuanced understanding of TMAO's role in human health.