What is TMAO?
TMAO = Trimethylamine N-Oxide
How is TMAO Produced?
Carnitine (ammino acid) and choline (non-mineral, non-vitamin, essential nutrient) taken in via dietary route -> gut flora chops the molecule producing TMA -> TMA goes to the liver -> hepatic flavin-containing monooxygenase (FMO) -> TMAO.
What does TMAO do?
Decreases reverse cholesterol transport (reduced HDL function, APO-A1)
Increases depositing of cholesterol in arterial wall
Associated with chronic kidney disease
Highest Levels of TMAO correlate with most severe CVD in 4000 patients studied
Studies in mice fed choline, resulting in TMAO production. This led to increased atherosclerosis. The mice were then given an antibiotic to kill the gut flora that was making TMA. This resulted in the progression of atherosclerosis stopping.
Dietary Levels of Carnitine and Choline
Comparison of Carnitine Sources
Comparison of Choline Sources
Testing the Role of Gut Flora and TMAO Production
Further evidence of the importance of dietary selected bacteria in the microbiome becomes evident in a number of studies that looked at TMAO production in participants who were omnivorous and those who were plant-based (but obviously not ethical vegans). Each group was fed a steak and blood levels of TMAO were measured over 24 hours. TMAO levels shot up in omnivores, but barely moved in the plant-based group. Why? The plant-based group lacked sufficient numbers of specialist bacteria that can chop the choline and carnitine into TMA, thus breaking the chain of TMAO production.
The Choline Paradox
Choline is considered an essential nutrient, so our bodies need it from outside sources. Are we doomed to TMAO production? With choline, you must consider the source!
A study was done with the highest plant based source of choline: Brussels sprouts. Participants were instructed to eat two cups of the sprouts a day for three weeks.
“After consumption of Brussels sprouts, a significant decrease in the urinary profile of the human FMO3 marker, metabolite, TMAO, was observed.” The study concluded that the plant based source of choline actually down regulates the FMO enzyme in the liver to reduce the TMA to TMAO conversion! The power of plants ...
Industry Attempts to Reduce TMAO
Destroy the gut flora with antibiotics so TMA won’t be producedProblem: no way to distinguish between good and bad bacteria, increases risk of drug resistant bacteria
Probiotic supplements (try to crowd out the bad bacteria)Problem: It doesn’t work, adding good bacteria doesn’t get rid of the bad
Attack liver function (stop TMA -> TMAO) by inhibiting FMOProblem: That decreased liver function already exists in some people with a geneic condition called trimethylamineuria. The build up of TMA results in body odor of dead fish! BTW, people with this condition often become vegan to stop this problem.
How to Reduce TMAO Effectively
Break the production chain in as many places as possible
Eliminate dietary sources of carnitine and animal based sources of choline
Have a fiber focused diet to encourage growth of gut bacteria that will not product TMA
Consume sources of dimethyl-1-butanol (DMB) which inhibits TMAO production (balsamic vinegars, red wine, and extra virgin olive oil are the highest sources)
Balsamic Vinegar bonus: contains acetic acid has been shown to restore the nitric oxide synthase enzyme within the endothelial cells. This is what produces nitric oxide within the artery. Nitric oxide is critical to keep blood from getting sticky, having more elastic blood vessels, and protection against atherosclerosis.
Sources
Mice and TMAO
https://www.nature.com/articles/nature09922
Choline amounts in food
https://lpi.oregonstate.edu/mic/other-nutrients/choline
Carnitine amounts in food
https://ods.od.nih.gov/factsheets/Carnitine-HealthProfessional/
Brussels Sprouts and TMAO
https://www.ncbi.nlm.nih.gov/pubmed/10509757
Industry Attempts to Reduce TMAO: https://nutritionfacts.org/video/how-to-reduce-your-tmao-levels/
Balsamic Vinegar and Nitric Oxide
Caldwell Esselstyn: https://www.youtube.com/watch?v=xDJhFn-pRwM