Trimethylamine‐ N ‐oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial
Abstract
SCOPE: Trimethylamine-N-oxide (TMAO), a metabolite linked to the gut microbiota, is associated with excess risk of heart disease. We hypothesized that (i) TMAO response to animal source foods would vary among healthy men and (ii) this response would be modified by their gut microbiome. METHODS AND RESULTS: A crossover feeding trial in healthy young men (n = 40) was conducted with meals containing TMAO (fish), its dietary precursors, choline (eggs) and carnitine (beef), and a fruit control. Fish yielded higher circulating and urinary concentrations of TMAO (46-62 times; p < 0.0001), trimethylamine (8-14 times; p < 0.0001), and dimethylamine (4-6-times; P<0.0001) than eggs, beef, or the fruit control. Circulating TMAO concentrations were increased within 15 min of fish consumption, suggesting that dietary TMAO can be absorbed without processing by gut microbes. Analysis of 16S rRNA genes indicated that high-TMAO producers (≥20% increase in urinary TMAO in response to eggs and beef) had more Firmicutes than Bacteroidetes (p = 0.04) and less gut microbiota diversity (p = 0.03). CONCLUSION: Consumption of fish yielded substantially greater increases in circulating TMAO than eggs or beef. The higher Firmicutes to Bacteroidetes enrichment among men exhibiting a greater response to dietary TMAO precursor intake indicates that TMAO production is a function of individual differences in the gut microbiome.
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Men with greater Firmicutes-to-Bacteroidetes enrichment produced more TMA after a challenge meal.
“A recent study in men observed that people with higher Firmicutes to Bacteroidetes enrichment generated more TMA after a challenge meal (28).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [28]
100 g of cod contains 89 mg total choline, 100 g of beef contains 73 mg, and 100 g of eggs contains 266 mg total choline.
“For example, 100 g of cod contains 89 mg total choline (choline + PtdCho + phosphocholine + sphingomyelin + glycerophosphocholine) compared to 100 g of beef, which contains 73 mg total choline, or 100 g of eggs, which contain 266 mg total choline (28).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [28]
100 g of asparagus contains 0.2 mg carnitine, 100 g of egg contains less than 1 mg, 100 g of cod contains 4 mg, and 100 g of beef contains 39 mg carnitine.
“For example, 100 g of asparagus contains 0.2 mg carnitine, 100 g of egg contains <1 mg carnitine, 100 g of cod contains 4 mg carnitine while 100 g of beef contains 39 mg carnitine, (28).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [28]
100 g of cod contains 300 mg TMAO, whereas 100 g of beef or egg contains less than 1 mg TMAO.
“For example, 100 g of cod contains 300 mg TMAO compared to 100 g of beef or of egg, which contain <1 mg TMAO (28).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [28]
TMAO itself can be absorbed without undergoing processing by gut microbes.
“Circulating TMAO concentrations in response to the fish meal was increased within 15 min of food consumption, suggesting that TMAO itself can be absorbed without undergoing processing by the gut microbes [23].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [23]
In a crossover feeding trial, consumption of diet containing TMAO precursors such as eggs, beef and fish increased blood and urine levels of TMAO.
“In a crossover feeding trial, consumption of diet containing TMAO precursors such as eggs, beef and fish increased the blood and urine levels of TMAO [23].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [23]
Fish consumption drastically increases circulating trimethylamine N-oxide levels.
“a recent clinical trial has shown contradictory results indicating that fish consumption drastically increases circulating TMA N-oxide levels”
From <i>Bacteroides vulgatus</i> and <i>Bacteroides dorei</i> Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis (2018) · cites this paper as [6]
Utilizing TMAO levels concurrently with elevated NT-proBNP improved outcome prediction in ADHF patients.
“Additionally, the authors also found that utilizing TMAO levels concurrently with elevated NT-proBNP improved outcome prediction.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [185]
In ADHF patients, inclusion of TMAO into risk models provided improved risk stratification for in-hospital mortality in combination with clinical scores.
“recent clinical data in a study of ADHF patients from Suzuki et al. show that inclusion of TMAO into risk models provided improved risk stratification for in-hospital mortality in combination with clinical scores185.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [185]
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- Authors
- Cho, C. E., Taesuwan, S., Malysheva, O. V., Bender, E., Tulchinsky, N. F., Yan, J., Sutter, J. L., & Caudill, M. A.
- Affiliations
- Cornell University (US)
- Corresponding author
- Caudill, Marie A.
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2016-08-03
- Volume
- 61
- Issue
- 1
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2465423486
- Cited by
- 405
- References
- 5
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 34 · 2023: 42 · 2022: 50 · 2021: 65 · 2020: 53 · 2019: 39 · 2018: 44 · 2017: 18 · 2016: 6
- FWCI
- 18.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Egg Nutrition Center
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- trimethylamine N-oxide, gut microbiota, animal source foods, fish consumption, choline, L-carnitine, trimethylamine, dimethylamine, Firmicutes/Bacteroidetes ratio, microbial diversity, dietary precursors, cardiovascular risk
- MeSH terms
- Gastrointestinal Microbiome, Adult, Animals, Food, Humans, Male, Meat, Methylamines, Middle Aged, Biomarkers
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