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Plasma Concentrations of Trimethylamine-N-oxide Are Directly Associated with Dairy Food Consumption and Low-Grade Inflammation in a German Adult Population
Open accessAbstract
Background Trimethylamine-N-oxide (TMAO) is a metabolite of carnitine, choline, and phosphatidylcholine, which is inversely associated with survival of cardiovascular disease (CVD) patients.Objective We examined the associations of diet with plasma concentrations of TMAO, choline, and betaine and the associations of TMAO with plasma concentrations of various cytokines.Methods Plasma TMAO, choline, and betaine concentrations were measured using LC-high resolution mass spectrometry in 271 participants, ≥18 y old, of the Second Bavarian Food Consumption Survey, conducted in 2002 and 2003. Food consumption was assessed using at least two 24-h dietary recalls. Cytokines were measured in plasma with enzyme-linked immunosorbent assays. Geometric mean concentrations of TMAO, choline, and betaine by categories of meat, dairy food, egg, and fish consumption were computed, adjusted for sex, age, and BMI. Multivariable-adjusted geometric mean concentrations of cytokines [tumor necrosis factor-α (TNF-α), soluble TNF receptors (sTNF-R) p55, sTNF-R p75, interleukin-6 (IL-6), and C-reactive protein (CRP)] were computed by quartiles of TMAO concentration using general linear models.Results Meat, egg, or fish consumption was not associated with TMAO, choline, or betaine concentrations (all P-trend ≥ 0.05). With increases in milk and other dairy food consumption, the plasma TMAO concentration increased [geometric mean bottom quartile of milk consumption: 2.08 μM (95% CI: 1.69, 2.57 μM); compared with top quartile: 3.13 μM (95% CI: 2.56, 3.84 μM); P-trend = 0.008]. Participants in the top TMAO quartile had higher plasma concentrations of TNF-α, sTNF-R p55, and sTNF-R p75 than participants in the bottom quartile (percentage difference ranging between 14.4% and 17.3%; all P-trend < 0.05), but there were no differences in plasma concentrations of CRP and IL-6 (all P-trend ≥ 0.05).Conclusions Results of this study conducted among healthy adults from the general population do not indicate a strong effect of diet on plasma concentrations of TMAO, choline, or betaine, with the exception of a positive association between dairy food consumption and plasma TMAO concentrations. Also, plasma TMAO concentrations were positively associated with inflammation. Whether habitual diet is strongly linked to the plasma TMAO concentration, a potential marker of CVD risk, needs to be determined in further studies.
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“nowadays there is convincing evidence suggesting an association between TMAO and inflammation [8,9,10,11,12]”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [10]
In the citing paper
“The study performed by Rohrmann et al. [10] described a link between low grade inflammation and plasma TMAO levels. When the concentration of plasma TMAO was augmented there was an overexpression of TNF-α, IL-6 and C-reactive protein.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [10]
In the citing paper
“In a small study in healthy Bavarian subjects, dietary intake of fish, meat, or eggs was not associated with plasma TMAO concentrations, but dairy intake was positively associated with plasma TMAO concentrations (94).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [94]
In the citing paper
“In a study involving 271 participants, consumption of meat, egg, or fish was not associated with TMAO, choline, or betaine concentrations [24].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [24]
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Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
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Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,400
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Wang, Z., Tang, W. H. W., Buffa, J. A., Fu, X., Britt, E. B., Koeth, R. A., Levison, B. S., Fan, Y., Wu, Y., & Hazen, S. L. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu002 · Cited by 559
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The Gut Microbiota and Inflammation: An Overview
Bander, Z. A., Nitert, M. D., Mousa, A., & Naderpoor, N. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17207618 · Cited by 804
“[119] identified a positive association between TMAO levels and TNF-α, but not IL-6 in humans.”
BackgroundJaneiro, M., Ramírez, M., Milagro, F., Martínez, J., & Solas, M. (2018) · Nutrients · doi:10.3390/nu10101398 · Cited by 631
Trimethylamine N-oxide: the good, the bad and the unknown.
Velasquez, M., Ramezani, A., Manal, A., & Raj, D. (2016) · Toxins · doi:10.3390/toxins8110326 · Cited by 504
“In a study involving 271 participants, consumption of meat, egg, or fish was not associated with TMAO, choline, or betaine concentrations [24].”
BackgroundTrimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease
Zeisel, S. H., & Warrier, M. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064732 · Cited by 475
“In a small study in healthy Bavarian subjects, dietary intake of fish, meat, or eggs was not associated with plasma TMAO concentrations, but dairy intake was positively associated with plasma TMAO concentrations (94).”
BackgroundGut microbiota and cardiovascular disease: opportunities and challenges
Kazemian, N., Mahmoudi, M., Halperin, F. A., Wu, J. C., & Pakpour, S. (2020) · Microbiome · doi:10.1186/s40168-020-00821-0 · Cited by 404
Metadata
- Authors
- Rohrmann, S., Linseisen, J., Allenspach, M., von Eckardstein, A., & Müller, D.
- Affiliations
- University of Zurich (CH)
- Helmholtz Munich (DE)
- Corresponding author
- Rohrmann, Sabine
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 146
- Issue
- 2
- Pages
- 283-289
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2231380317
- Cited by
- 197
- References
- 47
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 18 · 2023: 19 · 2022: 22 · 2021: 25 · 2020: 33 · 2019: 17 · 2018: 15 · 2017: 13 · 2016: 5
- FWCI
- 11.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Site cant be reached (submittedVersion, cc-by)
- OPUS (Augsburg University) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Ministry of Environment
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- trimethylamine N-oxide, milk consumption, choline, betaine, low-grade inflammation, cytokines, TNF-α, soluble TNF receptors, interleukin-6, C-reactive protein, dietary intake, cardiovascular risk, plasma biomarkers, German adults, dietary surveys, dietary assessment, 24-hour dietary recall
- MeSH terms
- Adult, Animals, Betaine, C-Reactive Protein, Choline, Dairy Products, Diet, Diet Surveys, Feeding Behavior, Female, Germany, Humans, Inflammation, Male, Methylamines, Middle Aged, Milk, Tumor Necrosis Factor-alpha, Interleukin-6, Receptors, Tumor Necrosis Factor, Type I
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