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High levels of TMAO have been associated with an increased risk of heart disease.1
The TMAO test may be used as (1) an aid in the assessment of risk for cardiovascular disease (CVD), independent of established risk factors, (2) an aid in the determination of altered gut microbiome (gut dysbiosis) in individuals who may benefit from intensive dietary intervention, and (3) a monitor therapy aimed at reducing TMAO concentrations.
This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.
TMAO is a dietary metabolite produced by a pathway involving gut microbiota. TMAO concentrations increase in the blood after ingestion of dietary choline and L-carnitine, which are abundant in meat, eggs, liver, and wheat germ and energy drinks. Choline and L-carnitine are metabolized in the gut by microbiota to form trimethylamine (TMA), which is subsequently oxidized in the liver into TMAO by flavin monooxygenases (FMOs). TMAO concentrations have been shown to be reduced in animals and humans treated with broad-spectrum oral antibiotics confirming the requirement for gut bacteria in the formation of TMA and TMAO.2-6 TMAO has been hypothesized to promote atherosclerosis by upregulating macro-phage scavenger receptor activity and downregulating bile acid synthesis which together reduce reverse cholesterol transport.2-6
1. Garcia E, Wolak-Dinsmore J, Wang Z, et al. NMR quantification of trimethylamine-N-oxide in human serum and plasma in the clinical laboratory setting. Clin. Biochem. 2017 Nov;50(16-17):947-955. PubMed 28624482
2. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. PubMed 21475195
3. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-585. PubMed 23563705
4. Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New Eng J Med. 2013 Apr 25;368(17):1575-1584. PubMed 23614584
5. Zhu W, Gregory JC, Org E, et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016 Mar 24;165(1):111-124. PubMed 26972052
6. Senthong V, Li XS, Hudec T, et al. Plasma Trimethylamine N-Oxide, a Gut Microbe-Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden. J Am Coll Cardiol. 2016 Jun 7;67(22):2620-2628. PubMed 27256833
7. Lundstrom RC, Racicot LD. Gas chromatographic determination of dimethylamine and trimethylamine in seafoods. J Assoc Off Anal Chem. 1983 Sep;66(5):1158-1163. PubMed 6630129
8. Svensson BG, Akesson B, Nilsson A, Paulsson K. Urinary excretion of methylamines in men with varying intake of fish from the Baltic Sea. J Toxicol Environ Health. 1994 Apr;41(4):411-420. PubMed 8145282
