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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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“choline or L-carnitine were related to higher BMI and greater visceral adiposity (6,16,17).”
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“For example, fish and red meat intakes were positively correlated with circulating TMAO in studies from Germany and Italy (10, 11), whereas another study from Germany found that consumption of dairy, but not meat, eggs, or fish, was positively associated with plasma TMAO (8).”
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Gut microbiota dependant trimethylamine N-oxide and hypertension
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“TMAO was directly associated with dairy food consumption such as milk and Low-Grade inflammation (Rohrmann et al., 2016).”
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“Evidence for a modulatory role of dairy products on TMAO concentrations in blood or urine is inconsistent [18,22,23,51] but this may be explained in part by the type of dairy product considered.”
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“In fact, higher plasma TMAO was found after the ingestion of fish than after ingestion of red meat and eggs [14,15].”
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“Dairy intake positively correlates with the plasma TMAO concentration (Rohrmann et al., 2016).”
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“Clinical studies have demonstrated that plasma and urine TMAO concentrations increase transiently after ingestion of choline or carnitine supplements [29], red meat [25], fish [30], dairy [31], and egg ingestion [32].”
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“Moreover, high TMAO levels seem to be related to inflammation, for instance by activating the NLRP3 inflammasome [32–34], or by correlating with elevated plasma tumor necrosis factor (TNF)-α levels in an otherwise healthy population [35].”
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“, who observed few relationships between diet and fasting TMAO but did observe a relationship between TMAO and inflammation [37].”
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“Grain products 118 (64, 192) 119 (61, 200) 118 (63, 195) 116 (660, 180) 120 (65, 184)”
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“However, the dietary contributions to plasma TMAO concentrations have been inconsistent in the literature (11, 22, 23, 24, 29, 30, 31, 32).”
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“Similar for eggs, that are rich in choline and whose consumption has been associated with TMAO levels [84,89,92], however, not in all studies [85,93,94].”
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“While the mechanism remains speculative, most authors agree that the inflammation associated with the presence of TMAO is linked to the increased production of pro-inflammatory cytokines such as TNFα, IL-6, and IL-1β [113] or the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and N…”
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“[47] found a positive association between TMAO and inflammation among German adults.”
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“Plasma TMAO concentrations increase with increased consumption of milk and other dairy products, and TMAO concentration has been inversely correlated with HDL-C [53].”
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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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