This morning, a casual cruise through Reddit took me on a journey through into some interesting nutritional threads on TMAO. Red meat and eggs are rich sources of L-carnitine and choline which are fermented by gut microbes to form this seemingly atherogenic compound, Trimethylamine N-oxide -- when you feed TMAO to a mouse, it directly contributes toward the development of mouse heart disease. (That's pretty sad, right?)
Different forms of carnitine, choline, and TMG all seem to have this same metabolic fate, although the literature is sparse on how the production of TMAO from Acetyl-L-Carnitine might compare against Alpha-GPC. I have a hunch that CDP-Choline might fare better than some other forms, simply because it contains less choline and behaves a bit more like a prodrug for choline/uridine via cytidine, but I have no real data to substantiate this claim. It's less clear yet how a micronutrient like betaine travels into this conversion pathway. While vegans can cultivate a different microbiota and substantially decrease TMAO production through the avoidance of the major meat-derived sources of these compounds, this benefit seems to drop off with continued supplementation.
Choline is an essential nutrient and carnitine is a conditionally essential nutrient, so these aren't compounds that you would want to avoid -- far from it. Perhaps, choline and carnitine are actually among the most beneficial compounds in foods like red meat and eggs.
Seafood, makes this whole situation even less clear. It's rich in pre-formed TMA & TMAO, yet the heart disease risk doesn't seem to be there at all. In fact, seafood is largely described as being cardioprotective in the medical literature. So this now becomes an odd multifactorial equation to solve for x.
The power of polyphenols
Interestingly, the phytochemicals in olive oil and balsamic vinegar seemed to help prevent TMAO formation by limiting an intermediate step in conversion to TMA.
There's a saying from a famous heart surgeon, Dr. Gundry that *"the only purpose of food is to put olive oil in your mouth."* While there's an argument to be made that the oil is processed and low in micronutrients, it's also extremely high in macronutrients (ie. calories) which are essential for survival -- a macronutrient is still a nutrient. Moreover, its macronutrient content improves the uptake and the safety of other micronutrients, so examining olive oil at the meal-scale or diet-scale, rather than isolated ingredient-scale, looks rather beneficial to my eyes.
Procedures, Objectives, Strategies, and Tactics (POST)
I listened to a great podcast this afternoon with Dr. Peter Attia and Jocko Willink @ https://peterattiamd.com/jockowillink1/ What stuck with me was the discourse on strategy vs tactics. You can think of tactics as the "how", and strategies as the "why" behind the "how". Under this light, if the objective, or the "what", is to become a youthful old person, and the tactics involve studying diet and exercise to learn and apply these sorts of new, beneficial scientific findings, it begs the question -- what exactly is the overarching strategy?
A book from the great chess champion, Garry Kasparov comes to mind to think more deeply about this question. It's a book that's less about chess, and more about making decisions. He says that when most people make a mistake or face some fork in the road, they later look back on this action of the near past and think -- "Why did I make this choice instead of some other, better choice?" Or, perhaps they don't even look that far back, and simply think "I wish I didn't do that, I should have done this, instead." But what Garry does, is focus on the current state of his mental model for a decision making process. He thinks about the environment, his beliefs, and the behavior that lead to the decision making tree itself which produced a given action. Then, he updates his mental model to improve future predictions. It's not about the move at all, it's about the mechanics which spark the propellant of the move. It's an illustration of strategy over tactics. The ends, not the means.
PQQ came up as another compound that might help in limiting the production of TMAO, along with resveratrol and garlic extract. I've seen CoQ10 bundled with PQQ, so it does seem like a logical upgrade path if you're going to pick up a bottle. Ultimately, polyphenols (rich in spices + colorful foods) seem to be a sort of prebiotic that modulate the conversion of food into potentially hazardous metabolites in our favor. In the PubMed literature, probiotics weren't very effective at lowering formation or improving clearance, further echoing the idea that we might need to think two steps back.
Perhaps my strategy with regard to dietary guidance would be to try to focus on sifting out the gems from the mud. The research is often quite murky, and it's easy to get distracted by biased pontification, so it's important to read critically and keep an open mind. Whatever fact you think you've learned today will likely be fiction further down the road. So, I'm taking from this story a hint that the conscious consumption of bright, colorful foods with exotic flavors may be a better tactic than concern over some specific array of micronutrients.