TMAO trimethylamine-N-oxide from carnitine and choline, egg ingestion
March 12 2016

There is some thought that damage to the circulatory system or hearts is not just due to the fat in meat, nor the saturated fat and cholesterol, but perhaps by carnitine metabolized by bacteria in the intestines after people eat red meat. It is quickly converted by the liver into yet another little-studied chemical called TMAO that gets into the blood and increases the risk of heart disease. Apparently TMAO is made more often and in larger quantities in meat eaters but less so in a vegan who had not eaten meat for several months.

Bacteria living in the human digestive tract metabolize the carnitine, turning it into trimethylamine-N-oxide, a metabolite the researchers previously linked in a 2011 study to the promotion of atherosclerosis in humans. Further, the research finds that a diet high in carnitine promotes the growth of the bacteria that metabolize carnitine, compounding the problem by producing even more of the artery-clogging TMAO.

TMAO has been shown to cause heart disease in mice. Meat eaters normally have more TMAO in their blood and they make TMAO after swallowing pills with carnitine.

Nat Med. 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.

Eggs, too? The role of lecithin and choline
When the body digests lecithin, it is broken it into its constituent parts, including the chemical choline. Intestinal bacteria metabolize choline and release a substance that the liver converts to trimethylamine N-oxide. High levels of TMAO in the blood are linked to increased risk of heart attack and stroke.

The consumption of ≥2 eggs results in an increased formation of TMAO. Choline is an essential nutrient that is required for normal human liver and muscle functions and important for normal fetal development. Additional study is needed to both confirm the association between TMAO and atherosclerosis and identify factors, microbiota and genetic, that influence the generation of TMAO before policy and medical recommendations are made that suggest reduced dietary choline intake. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr 2014.

Inflammatory bowel disease identification
Dig Dis Sci. 2015. Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease. Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease. [Dig Dis Sci. 2016]AbstractBACKGROUND:The gastrointestinal (GI) microbiome is recognized for potential clinical relevance in inflammatory bowel disease (IBD). Data suggest that there is a disease-dependent loss of microbial diversity in IBD. Trimethylamine-N-oxide (TMAO) is generated by GI anaerobes through the digestion of dietary phosphatidylcholine and carnitine in a microbial-mammalian co-metabolic pathway. IBD-related changes in the gut microbiome may result in disease-specific changes in TMAO plasma concentrations. Decreased TMAO levels are seen in IBD compared to a non-IBD population. These data suggest that TMAO may have potential as a biomarker to support IBD diagnosis as well as to assess disease activity in UC.

Emails
I have a question regarding the safety of carnitine pills. I recently read an article in The New York Times titled "Another red meat hazard". This article states that a chemical called TMAO is made in our stomachs after swallowing carnitine pills. The article said TMAO  gets into the bloodstream and increases the risk of heart disease. What are your thoughts on this?
   It appears that regular meat eaters may have bacteria in their intestines that convert carnitine pills into TMAO whereas vegans don't have this and are not potentially harmed. The research is still tentative on this topic but for the present time I don't see the need to take more than 2 or 3 carnitine pills a week and many meat, chicken or fish eaters would need even less.

What do you think of the recent research that shows that carnitine deposits cholesterol along the arteries via the production of TMAO by bacteria in the gut?
   I will update this page as more research is published.