The metabolic fate of isotopically labeled trimethylamine-N-oxide (TMAO) in humans
Abstract
Trimethylamine-N-oxide (TMAO) is associated with chronic disease risk. However, little is known about the metabolic fate of dietary TMAO. This study sought to quantitatively elucidate the metabolic fate of orally consumed TMAO in humans. As part of a crossover feeding study, healthy young men (n=40) consumed 50-mg deuterium-labeled methyl d9-TMAO (d9-TMAO), and enrichments of TMAO and its derivatives were measured in blood for 6 h, urine and stool, as well as skeletal muscle in a subset of men (n=6). Plasma d9-TMAO was detected as early as 15 min, increased until 1 h and remained elevated through the 6-h period. TMAO exhibited an estimated turnover time of 5.3 h, and ~96% of the dose was eliminated in urine by 24 h, mainly as d9-TMAO. No d9-TMAO was detected in feces. Notably, d9-TMAO and d9-trimethylamine were detected in skeletal muscle (n=6) at 6 h, and the enrichment ratio of d9-TMAO to d9-trimethylamine was influenced by a genetic variant in flavin-containing monooxygenase isoform 3 (FMO3 G472A). These results suggest that the absorption of orally consumed TMAO is near complete and does not require processing by gut microbes. TMAO exhibits fast turnover in the circulation with the majority being eliminated in urine within 24 h. A small portion of the dose, however, is taken up by extrahepatic tissue in a manner that appears to be under the influence of FMO3 G472A polymorphism. This trial was registered at clinicaltrials.gov as NCT02558673.
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Orally consumed TMAO is largely absorbed and does not require microbial or hepatic processing, has a high turnover and rapid clearance rate, and is taken up by extrahepatic tissues.
“They reported that orally consumed TMAO is largely absorbed and does not require microbial or hepatic processing, has a high turnover and rapid clearance rate and is taken up by extrahepatic tissues.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [23]
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- Authors
- Taesuwan, S., Cho, C. E., Malysheva, O. V., Bender, E., King, J. H., Yan, J., Thalacker-Mercer, A. E., & Caudill, M. A.
- Affiliations
- Cornell University (US)
- Corresponding author
- Caudill, Marie A.
- ORCID
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 45
- Pages
- 77-82
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W2606738177
- Cited by
- 62
- References
- 24
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 4 · 2023: 5 · 2022: 11 · 2021: 7 · 2020: 6 · 2019: 5 · 2018: 9 · 2017: 1
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Jianghan University
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- trimethylamine N-oxide, urinary excretion, trimethylamine, flavin-containing monooxygenase, gut microbiota
- MeSH terms
- Administration, Oral, Adult, Deuterium, Humans, Male, Methylamines, Middle Aged, Oxygenases, Polymorphism, Genetic, Muscle, Skeletal
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