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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There is convincing evidence suggesting an association between TMAO and inflammation.
“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]
Low grade inflammation is linked to plasma TMAO levels; when plasma TMAO concentration is augmented, TNF-α, IL-6 and C-reactive protein are overexpressed.
“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 a small study of healthy Bavarian subjects, fish, meat, or egg intake was not associated with plasma TMAO, but dairy intake was positively associated with plasma TMAO.
“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 <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [94]
In a study involving 271 participants, consumption of meat, egg, or fish was not associated with TMAO, choline, or betaine concentrations.
“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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“Currently, evidence suggests that inflammation is a potential contributor to the connection between TMAO and cancer [87], but further evidence is required in order to validate this.”
BackgroundIntra-individual variation of plasma trimethylamine-N-oxide (TMAO), betaine and choline over 1 year
Kühn, T., Rohrmann, S., Sookthai, D., Johnson, T., Katzke, V., Kaaks, R., von Eckardstein, A., & Müller, D. (2017) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0374 · Cited by 110 · see citing works
“This notion is supported by recent results from the Second Bavarian Food Consumption Survey (BVS II) [33] that did not point to strong associations between habitual intake of animal foods and TMAO concentrations overall, even though slightly higher TMAO levels were observed in individuals with higher milk intake.”
ResultSelf-citationWinther, S. A., Oellgaard, J., Tofte, N., Tarnow, L., Wang, Z., Ahluwalia, T. S., Jorsal, A., Theilade, S., Parving, H., Hansen, T. W., et al. (2019) · Diabetes Care · doi:10.2337/dc19-0048 · Cited by 111 · see citing works
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The bright and the dark sides of L-carnitine supplementation: a systematic review
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“In a separate investigation, researchers discovered a positive correlation between TMAO levels in plasma and plasma levels of sTNFR p75, TNF-α, and sTNF-R p55 in German adults [77].”
BackgroundBergeron, N., Williams, P. T., Lamendella, R., Faghihnia, N., Grube, A., Li, X., Wang, Z., Knight, R. D., Jansson, J. K., Hazen, S. L., et al. (2016) · British Journal Of Nutrition · doi:10.1017/s0007114516004165 · Cited by 101 · see citing works
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“Nevertheless, current findings on the association between fish consumption and TMAO levels are inconsistent between studies, as one study reported a lack of an association between the two aforementioned parameters [21].”
BackgroundResultBacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases
Stec, A., Sikora, M., Maciejewska, M., Paralusz-Stec, K., Michalska, M. N., Sikorska, E., & Rudnicka, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043494 · Cited by 85 · see citing works
Gut Microbiota in Obesity and Metabolic Abnormalities: A Matter of Composition or Functionality?
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“choline or L-carnitine were related to higher BMI and greater visceral adiposity (6,16,17).”
BackgroundYu, D., Shu, X., Rivera, E. S., Zhang, X., Cai, Q., Calcutt, M. W., Xiang, Y., Li, H., Gao, Y., Wang, T. J., et al. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.010606 · Cited by 79 · see citing works
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“Moreover, it is related to the synthesis of N-Nitroso compounds, which are involved in epigenetic alterations and DNA-damage that can lead to the induction of cancer [241].”
A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO)
Barrea, L., Muscogiuri, G., Annunziata, G., Laudisio, D., de Alteriis, G., Tenore, G. C., Colao, A., & Savastano, S. (2019) · Nutrients · doi:10.3390/nu11061310 · Cited by 73 · see citing works
Trimethylamine N -oxide: heart of the microbiota–CVD nexus?
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“(2016)(86) Male 50 years, female 44 years, BMI 26·1 kg/m2 male, 25·2 kg/m2 female 104 100 Male 2·55 (95 % CI 2·17, 2·99) 167 0 Female 2·52 (95 % CI 2·22, 2·86)”
BackgroundInfluentialBiomarker of food intake for assessing the consumption of dairy and egg products
Münger, L. H., Garcia‐Aloy, M., Vázquez‐Fresno, R., Gille, D., Rosana, A. R. R., Passerini, A., Soria-Florido, M. T., Pimentel, G., Sajed, T., Wishart, D. S., et al. (2018) · Genes & Nutrition · doi:10.1186/s12263-018-0615-5 · Cited by 68 · see citing works
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“Our prospective study had a representative patient cohort with median TMAO levels similar to those reported in other studies in German populations [24,28].”
ResultElevated plasma trimethylamine-N-oxide levels are associated with diabetic retinopathy
Liu, W., Wang, C., Xia, Y., Xia, W. T., Liu, G., Ren, C., Gu, Y., Li, X., & Lu, P. (2020) · Acta Diabetologica · doi:10.1007/s00592-020-01610-9 · Cited by 64 · see citing works
Balancing the Equation: A Natural History of Trimethylamine and Trimethylamine-N-oxide
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“They are directly associated with the consumption of animal-derived foods (2, 3) containing choline, phosphatidylcholine, and l-carnitine, which are processed by gut bacteria resulting in the release of various metabolites including trimethylamine (TMA), into the blood.”
BackgroundMei, Z., Chen, G., Wang, Z., Usyk, M., Yu, B., Baeza, Y. V., Humphrey, G. C., Benítez, R. A. S., Li, J., Williams-Nguyen, J. S., et al. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab001 · Cited by 60 · see citing works
“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).”
BackgroundFarhangi, M. A., & Vajdi, M. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1770199 · Cited by 59 · see citing works
Tacconi, E., Palma, G., Biase, D. D., Luciano, A., Barbieri, M., de Nigris, F., & Bruzzese, F. (2023) · Nutrients · doi:10.3390/nu15030563 · Cited by 62 · see citing works
“Whether TMAO levels are correlated with milk and dairy products remains controversial [44].”
BackgroundDietary Fats and the Gut Microbiota: Their impacts on lipid-induced metabolic syndrome
Basak, S., Banerjee, A., Pathak, S., & Duttaroy, A. K. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.105026 · Cited by 58 · see citing works
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Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods
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“Two papers [17,29] showed a positive association between dairy food consumption and plasma TMAO concentrations.”
BackgroundSamulak, J. J., Sawicka, A. K., Hartmane, D., Grı̄nberga, S., Pugovičs, O., Łysiak−Szydłowska, W., & Olek, R. A. (2018) · Annals of Nutrition and Metabolism · doi:10.1159/000495037 · Cited by 54 · see citing works
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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).”
BackgroundChen, Y., Yang, C. H., Dai, Q., Tan, J., Dou, C., & Luo, F. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-01872-9 · Cited by 50 · see citing works
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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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Therapeutic potential of natural products against atherosclerosis: Targeting on gut microbiota
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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].”
BackgroundWu, Y., Rong, X., Pan, M., Wang, T., Yang, H., Chen, X., Xiao, Z., & Zhao, C. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.840171 · Cited by 42 · see citing works
“Dairy intake positively correlates with the plasma TMAO concentration (Rohrmann et al., 2016).”
BackgroundDe-coding the complex role of microbial metabolites in cancer
Escriva, P. P., Bernardino, C. C. T., & Letellier, E. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115358 · Cited by 45 · see citing works
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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].”
BackgroundXiong, X., Zhou, J. W., Fu, Q., Xu, X., Wei, S., Yang, S., & Chen, B. (2022) · Lipids in Health and Disease · doi:10.1186/s12944-022-01673-3 · Cited by 39 · see citing works
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Self-citationTrimethylamine-N-oxide and its biological variations in vegetarians.
Obeid, R., Awwad, H. M., Keller, M., & Geisel, J. (2017) · European Journal of Nutrition · doi:10.1007/s00394-016-1295-9 · Cited by 38 · see citing works
Characteristics of Victims of Fall-Related Accidents during Mountain Hiking
Faulhaber, M., Ruedl, G., Schneider, F., Walter, D., Sterr, R., Schobersberger, W., Schwendinger, F., & Pocecco, E. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17031115 · Cited by 36 · see citing works
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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].”
BackgroundLi, D., Chen, R., Xu, X., Hou, Y., Li, Z., Huang, C., Zhang, G., Wang, B., Li, B., & Chu, X. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156138 · Cited by 32 · see citing works
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“, who observed few relationships between diet and fasting TMAO but did observe a relationship between TMAO and inflammation [37].”
BackgroundResultFlorea, C. M., Roşu, R., Moldovan, R., Vlase, L., Toma, V. A., Decea, N., Bâldea, I., & Filip, G. A. (2024) · Food and Chemical Toxicology · doi:10.1016/j.fct.2023.114429 · Cited by 30 · see citing works
Parys, A. V., Brække, M. S., Karlsson, T. R., Vinknes, K. J., Tell, G. S., Haugsgjerd, T. R., Ueland, P. M., Øyen, J., Dierkes, J., Nygard, O. K., et al. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab367 · Cited by 30 · see citing works
“Grain products 118 (64, 192) 119 (61, 200) 118 (63, 195) 116 (660, 180) 120 (65, 184)”
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“Several measures have been introduced for the monitoring of PTB, like the examination of the previous history of PTB, a short cervix (<25 mm), vaginal pH, pro-inflammatory cytokines (IL-6) in cervicovaginal fluid (CVF), or fetal fibronectin (FFN) Metabolites 2020, 10, 349; doi:10.3390/metabo10090349 www.mdpi.com/journ…”
BackgroundInfluentialCamelo-Castillo, A. J., Rivera‐Caravaca, J. M., Orenes‐Piñero, E., Ramírez-Macías, I., Roldán, V., Lip, G. Y. H., & Marín, F. R. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10040715 · Cited by 28 · see citing works
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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).”
BackgroundThe microbial-mammalian metabolic axis
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“Our finding is consistent with recent studies in healthy individuals [44, 45].”
ResultHeinrich‐Sanchez, Y., & Vital, M. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2525403 · Cited by 26 · see citing works
“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].”
Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations
Barrea, L., Muscogiuri, G., Pugliese, G., Graziadio, C., Maisto, M., Pivari, F., Falco, A., Tenore, G. C., Colao, A., & Savastano, S. (2021) · Nutrients · doi:10.3390/nu13051671 · Cited by 25 · see citing works
Metabolite profile comparisons between ascending and descending colon tissue in healthy adults
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Microbiota, a New Playground for the Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Diseases
Rousseau, G. (2021) · Marine Drugs · doi:10.3390/md19020054 · Cited by 24 · see citing works
“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…”
BackgroundTrimethylamine N-Oxide (TMAO) and cancer risk: Insights into a possible link
Saha, B., Banerjee, A., Pathak, R., Duttaroy, A. K., & Pathak, S. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118592 · Cited by 24 · see citing works
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“[47] found a positive association between TMAO and inflammation among German adults.”
BackgroundGut microbiota: A potential therapeutic target for management of diabetic retinopathy?
Yempén, R. E. A., Venzel, R., Campos, M. C. P., de Oliveira, L. P., Lins, R. V. D., Pessoni, A. M., Fanaro, G. B., Souza, A. D. O., Calaza, K. D. C., Alves, J. L. D. B., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120060 · Cited by 22 · see citing works
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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].”
BackgroundAndreu‐Sánchez, S., Ahmad, S., Kurilshikov, A., Beekman, M., Ghanbari, M., van Faassen, M. H. J. R., van den Munckhof, I., Steur, M., Harms, A. C., Hankemeier, T., et al. (2024) · iMeta · doi:10.1002/imt2.183 · Cited by 19 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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