Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels
Open accessAbstract
Recent studies have revealed strong associations between systemic trimethylamine N-oxide (TMAO) levels, atherosclerosis and cardiovascular risk. In addition, plasma L-carnitine levels in patients with high TMAO concentrations predicted an increased risk for cardiovascular disease and incident major adverse cardiac events. The aim of the present study was to investigate the relation between TMAO and L-carnitine plasma levels and diabetes. Blood plasma samples were collected from 12 and 20 weeks old db/db mice and patients undergoing percutaneous coronary intervention. Diabetic compared to non-diabetic db/L mice presented 10-fold higher TMAO, but lower L-carnitine plasma concentrations at 12 weeks of age. After 8 weeks of observation, diabetic db/db mice had significantly increased body weight, insulin resistance and TMAO concentration in comparison to non-diabetic control. In 191 patients undergoing percutaneous coronary intervention the median (interquartile range) plasma concentration of TMAO was 1.8 (1.2-2.6) µmol/L. Analysis of the samples showed a bivariate association of TMAO level with age, total cholesterol and L-carnitine. The multivariate linear regression analysis revealed that, in addition to L-carnitine as the strongest predictor of log transformed TMAO (p<0.001), the parameters of age, diabetes status and body mass index (BMI) were independently associated with increased log transformed TMAO levels (p<0.01).Our data provide evidence that age, diabetes and BMI are associated with higher TMAO levels independently of L-carnitine. These data support the hypothesis of TMAO as a cardiovascular risk marker and warrant further investigation of TMAO for diabetes research applications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Differences in characteristics and disease status of participants across studies might affect TMAO levels and therefore partly explain inconsistency in associations.
“Differences in characteristics and disease status of participants across studies might affect TMAO levels14, 27, 28 and therefore partly explain such inconsistency.”
From Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta‐Analysis of Prospective Studies (2017) · cites this paper as [27]
In 191 patients undergoing coronary intervention, plasma TMAO was independently associated with age, diabetes, and body mass index.
“In a group of 191 patients undergoing coronary intervention, plasma TMAO concentrations were independently associated with the patients' age, diabetes, and body mass index (35).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [35]
Vascular tissue factor promotes thrombosis and vascular inflammation, particularly in patients with type 2 diabetes who have higher levels of circulating trimethylamine N-oxide.
“Vascular TF promotes thrombosis and vascular inflammation123, particularl y in patients with type 2 diabetes who have higher levels of circulating TMAO124–126.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [126]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597 · see citing works
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 · see citing works
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 3,402 · see citing works
Prediabetes: a high-risk state for diabetes development
Tabák, A. G., Herder, C., Rathmann, W., Brunner, E. J., & Kivimäki, M. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60283-9 · Cited by 2,958 · see citing works
Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes
and the WHO Multinational Study Group, Morrish, N. J., Wang, S.-L., Stevens, L. K., Fuller, J. H., & Keen, H. (2001) · Diabetologia · doi:10.1007/pl00002934 · Cited by 1,288 · see citing works
Bennett, B. J., Vallim, T. Q. D. A., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.011 · Cited by 1,070 · see citing works
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 · see citing works
Intestinal microbiota, diet and health
Power, S. E., O'Toole, P. W., Stanton, C., Ross, R. P., & Fitzgerald, G. F. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114513002560 · Cited by 476 · see citing works
Kinetics, Pharmacokinetics, and Regulation of l‐Carnitine and Acetyl‐l‐carnitine Metabolism
Rebouche, C. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1320.003 · Cited by 426 · see citing works
Molecular enzymology of carnitine transfer and transport
Ramsay, R. R., Gandour, R. D., & van der Leij, F. R. (2001) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(01)00147-9 · Cited by 387 · see citing works
Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet
Gao, X., Liu, X., Xu, J., Xue, C., Xue, Y., & Wang, Y. (2014) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2014.03.001 · Cited by 360 · see citing works
Wang, Z., Levison, B. S., Hazen, J. E., Donahue, L., Li, X.-M., & Hazen, S. L. (2014) · Analytical Biochemistry · doi:10.1016/j.ab.2014.03.016 · Cited by 320 · see citing works
TMAO: A small molecule of great expectations
Ufnal, M., Żądło‐Dobrowolska, A., & Ostaszewski, R. (2015) · Nutrition · doi:10.1016/j.nut.2015.05.006 · Cited by 319 · see citing works
Miller, C. A., Corbin, K. D., da Costa, K.-A., Zhang, S., Zhao, X., Galanko, J. A., Blevins, T., Bennett, B. J., O’Connor, A., & Zeisel, S. H. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.114.087692 · Cited by 240 · see citing works
Lever, M., George, P. M., Slow, S., Bellamy, D., Young, J. M., Ho, M., McEntyre, C. J., Elmslie, J. L., Atkinson, W., Molyneux, S. L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114969 · Cited by 223 · see citing works
Endoplasmic Reticulum Stress Plays a Key Role in the Pathogenesis of Diabetic Peripheral Neuropathy
Lupachyk, S., Watcho, P., Stavniichuk, R., Shevalye, H., & Obrosova, I. G. (2013) · Diabetes · doi:10.2337/db12-0716 · Cited by 188 · see citing works
Gut microbiota metabolism of l-carnitine and cardiovascular risk
Ussher, J. R., Lopaschuk, G. D., & Arduini, A. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.10.013 · Cited by 170 · see citing works
Lloyd, A. J., Favé, G., Beckmann, M., Lin, W., Tailliart, K., Xie, L., Mathers, J. C., & Draper, J. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.017921 · Cited by 130 · see citing works
Trimethylamine: Metabolic, Pharmacokinetic and Safety Aspects
Bain, M., Fornasini, G., & Evans, A. (2005) · Current Drug Metabolism · doi:10.2174/1389200054021807 · Cited by 98 · see citing works
Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk
Tang, W., Wang, Z., & Levison, B. S. (2013) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2013.06.007 · Cited by 88 · see citing works
Metabolic Effects of L-carnitine on Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis
Vidal‐Casariego, A., Peláez, R. B., Faedo, C. M., Calvo-Gracia, F., Valero-Zanuy, M. Á., Pérez, L. M. L., & Compés, C. C. (2013) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0033-1333688 · Cited by 85 · see citing works
Dambrova, M., Skapare‐Makarova, E., Konrade, I., Pugovics, O., Grinberga, S., Tirzite, D., Petrovska, R., Kalvins, I., & Liepins, E. (2013) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.135 · Cited by 63 · see citing works
Self-citationDisposition and Metabolite Kinetics of Oral L‐carnitine in Humans
Bain, M. A., Milne, R. W., & Evans, A. M. (2006) · The Journal of Clinical Pharmacology · doi:10.1177/0091270006292851 · Cited by 46 · see citing works
Risks and Benefits of Carnitine Supplementation in Diabetes
Dambrova, M., & Liepinsh, E. (2014) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0034-1390481 · Cited by 22 · see citing works
Self-citationEpidemiology of Cardiovascular Disease in Patients with Type 1 Diabetes: European Perspective
Matteucci, E., & Giampietro, O. (2014) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0034-1367062 · Cited by 14 · see citing works
Liepinsh, E., Skapare, E., Vavers, E., Konrāde, I., Strēle, I., Grı̄nberga, S., Pugovičs, O., & Dambrova, M. (2012) · Nutrition Research · doi:10.1016/j.nutres.2012.03.010 · Cited by 13 · see citing works
Self-citationTang, W. H. W., Allayee, H., Lusis, A. J., Roberts, R., McPherson, R., Wang, Z., Bennett, B. J., Stewart, A. F. R., Hartiala, J., & Hazen, S. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/r6hc-3s06 · Cited by 6 · see citing works
Zhao, X., Galanko, J. A., Blevins, T., Miller, C. A., Zeisel, S. H., Zhang, S., O’Connor, A., Bennett, B. J., Costa, K. A. D., & Corbin, K. D. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/jwwk-yp40 · Cited by 4 · see citing works
Alberti (1998) · doi:10.1002/(sici)1096-9136(199807)15:7
Flagged first, then by citations
Research works printed but not linked: 3
- Grinberga S, Dambrova M, Latkovskis G et al. Determination of trimeth- ylamine-N-oxide in combination with l-carnitine and γ-butyrobetaine in human plasma by UPLC/MS/MS. Biomed Chromatogr 2015; 29: 1670-1674
- Li X, Chen Y, Liu J et al. Serum metabolic variables associated with impaired glucose tolerance induced by high-fat-high-cholesterol diet in Macaca mulatta. Exp Biol Med (Maywood) 2012; 237: 1310-1321
- McEntyre CJ, Lever M, Chambers ST et al. Variation of betaine, N,N- dimethylglycine, choline, glycerophosphorylcholine, taurine and tri- methylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period. Ann Clin Biochem 2015; 52: 352-360
Cited by
Sorted by citations
Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
Nogal, A., Valdes, A. M., & Menni, C. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1897212 · Cited by 917 · see citing works
Schwingshackl, L., Hoffmann, G., Lampousi, A.-M., Knüppel, S., Iqbal, K., Schwedhelm, C., Bechthold, A., Schlesinger, S., & Boeing, H. (2017) · European Journal of Epidemiology · doi:10.1007/s10654-017-0246-y · Cited by 799 · see citing works
Yang, W., & Cong, Y. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00661-4 · Cited by 701 · see citing works
Heianza, Y., Ma, W., Manson, J. E., Rexrode, K. M., & Qi, L. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.004947 · Cited by 544 · see citing works
The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease
Vogt, N. M., Romano, K. A., Darst, B. F., Engelman, C. D., Johnson, S. C., Carlsson, C. M., Asthana, S., Blennow, K., Zetterberg, H., Bendlin, B. B., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0451-2 · Cited by 471 · see citing works
Li, X. S., Obeid, S., Klingenberg, R., Gencer, B., Mach, F., Räber, L., Windecker, S., Rodondi, N., Nanchen, D., Muller, O., et al. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehw582 · Cited by 479 · see citing works
Trimethylamine <i>N</i> -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 · see citing works
Microbial modulation of cardiovascular disease
Brown, J. M., & Hazen, S. L. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.149 · Cited by 440 · see citing works
Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction
Chen, S., Henderson, A., Petriello, M. C., Romano, K. A., Gearing, M., Miao, J., Schell, M., Sandoval-Espinola, W. J., Tao, J., Sha, B., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.021 · Cited by 427 · see citing works
Precision Nutrition and the Microbiome, Part I: Current State of the Science
Mills, S., Stanton, C., Lane, J. A., Smith, G., & Ross, R. P. (2019) · Nutrients · doi:10.3390/nu11040923 · Cited by 406 · see citing works
Trimethylamine-N-Oxide Instigates NLRP3 Inflammasome Activation and Endothelial Dysfunction
Boini, K. M., Hussain, T., Li, P.-L., & Koka, S. S. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000484623 · Cited by 302 · see citing works
Schugar, R. C., Shih, D. M., Warrier, M., Helsley, R. N., Burrows, A., Ferguson, D., Brown, A. L., Gromovsky, A. D., Heine, M., Chatterjee, A., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.077 · Cited by 291 · see citing works
Ke, Y., Li, D., Zhao, M., Liu, C., Liu, J., Zeng, A., Shi, X., Cheng, S., Pan, B., Zheng, L., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.01.007 · Cited by 285 · see citing works
Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans
Meijnikman, A. S., Gerdes, V. E. A., Nieuwdorp, M., & Herrema, H. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00192 · Cited by 280 · see citing works
Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism
Ding, L., Chang, M., Guo, Y., Zhang, L., Xue, C., Yanagita, T., Zhang, T., & Wang, Y. (2018) · Lipids in Health and Disease · doi:10.1186/s12944-018-0939-6 · Cited by 250 · see citing works
Diet, genetics, and the gut microbiome drive dynamic changes in plasma metabolites
Fujisaka, S., Avila-Pacheco, J., Soto, M., Kostic, A., Dreyfuss, J. M., Pan, H., Ussar, S., Altindis, E., Li, N., Bry, L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.060 · Cited by 231 · see citing works
“Another bacterial metabolite reported to have a negative effect on glucose metabolism (Dambrova et al., 2016) that is decreased by antibiotics in the plasma is TMAO, and this occurs with little effect on the cecal levels of the metabolite.”
BackgroundMetabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption
Romano, K. A., Martinez-del Campo, A., Kasahara, K., Chittim, C. L., Vivas, E. I., Amador-Noguez, D., Balskus, E. P., & Rey, F. E. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.07.021 · Cited by 224 · see citing works
Trimethylamine- N -Oxide: Friend, Foe, or Simply Caught in the Cross-Fire?
Cho, C. E., & Caudill, M. A. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.10.005 · Cited by 218 · see citing works
Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes
Shan, Z., Sun, T., Huang, H., Chen, S., Chen, L., Luo, C., Yang, W., Yang, X., Yao, P., Cheng, J., et al. (2017) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.157107 · Cited by 210 · see citing works
Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide
Zhu, Y., Li, Q., & Jiang, H. (2020) · Apmis · doi:10.1111/apm.13038 · Cited by 204 · see citing works
Ge, X., Zheng, L., Zhuang, R., Yu, P., Xu, Z., Liu, G., Xi, X., Zhou, X., & Fan, H. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz064 · Cited by 194 · see citing works
Lyu, M., Wang, Y., Fan, G., Wang, X., Xu, S.-Y., & Zhu, Y. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02146 · Cited by 193 · see citing works
Nogal, A., Louca, P., Zhang, X., Wells, P. M., Steves, C. J., Spector, T. D., Falchi, M., Valdes, A. M., & Menni, C. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.711359 · Cited by 187 · see citing works
Gut microbiome and its role in cardiovascular diseases
Ahmadmehrabi, S., & Tang, W. H. W. (2017) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000445 · Cited by 185 · see citing works
Zhuang, R., Ge, X., Han, L., Yu, P., Gong, X., Meng, Q., Zhang, Y., Fan, H., Zheng, L., Liu, Z., et al. (2019) · Obesity Reviews · doi:10.1111/obr.12843 · Cited by 184 · see citing works
Heianza, Y., Sun, D., Li, X., DiDonato, J. A., Bray, G. A., Sacks, F. M., & Qi, L. (2019) · Gut · doi:10.1136/gutjnl-2018-316155 · Cited by 177 · see citing works
The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid
Del Rio, D., Zimetti, F., Caffarra, P., Tassotti, M., Bernini, F., Brighenti, F., Zini, A., & Zanotti, I. (2017) · Nutrients · doi:10.3390/nu9101053 · Cited by 172 · see citing works
“Similarly, it has been associated with other chronic diseases, such as diabetes [10] and cancer [11], further strengthening the pathological implications of this microbiota metabolite.”
BackgroundFu, B. C., Hullar, M. A. J., Randolph, T. W., Franke, A. A., Monroe, K. R., Cheng, I. C., Wilkens, L. R., Shepherd, J., Madeleine, M. M., Marchand, L. L., et al. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa015 · Cited by 171 · see citing works
Trimethylamine N‐oxide: breathe new life
Subramaniam, S., & Fletcher, C. (2018) · British Journal of Pharmacology · doi:10.1111/bph.13959 · Cited by 171 · see citing works
Bekhit, A. E. A., Giteru, S. G., Holman, B. W. B., & Hopkins, D. L. (2021) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12764 · Cited by 169 · see citing works
Microbiome, trimethylamine N-oxide, and cardiometabolic disease
Tang, W. H. W., & Hazen, S. L. (2017) · Translational Research · doi:10.1016/j.trsl.2016.07.007 · Cited by 160 · see citing works
Unravelling the involvement of gut microbiota in type 2 diabetes mellitus
Arora, A., Behl, T., Sehgal, A., Singh, S., Sharma, N., Bhatia, S., Sobarzo‐Sánchez, E., & BUNGAU, S. G. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119311 · Cited by 145 · see citing works
Trimethylamine N-oxide impairs pyruvate and fatty acid oxidation in cardiac mitochondria
Makrecka‐Kuka, M., Volska, K., Antone, U., Vilšķe̅rsts, R., Grı̄nberga, S., Bandere, D., Liepinsh, E., & Dambrova, M. (2017) · Toxicology Letters · doi:10.1016/j.toxlet.2016.12.017 · Cited by 142 · see citing works
Self-citationBarrea, L., Annunziata, G., Muscogiuri, G., Laudisio, D., Somma, C. D., Maisto, M., Tenore, G. C., Colao, A., & Savastano, S. (2018) · Nutrition · doi:10.1016/j.nut.2018.11.015 · Cited by 131 · see citing works
Trimethylamine N -oxide: A harmful, protective or diagnostic marker in lifestyle diseases?
Nowiński, A., & Ufnal, M. (2017) · Nutrition · doi:10.1016/j.nut.2017.08.001 · Cited by 130 · see citing works
Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes
Huda, M. N., Kim, M., & Bennett, B. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.632335 · Cited by 129 · see citing works
Fang, Q., Zheng, B., Liu, N., Liu, J., Liu, W., Huang, X., Zeng, X., Chen, L., Li, Z., & Ouyang, D. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.682482 · Cited by 116 · see citing works
Gut Metabolite TMAO Induces Synaptic Plasticity Deficits by Promoting Endoplasmic Reticulum Stress
Govindarajulu, M., Pinky, P. D., Steinke, I., Bloemer, J., Ramesh, S., Kariharan, T., Rella, R. T., Bhattacharya, S., Dhanasekaran, M., Suppiramaniam, V., et al. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00138 · Cited by 113 · see citing works
Brown, J. M., & Hazen, S. L. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.765388 · Cited by 108 · see citing works
High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction
Singh, G. B., Zhang, Y., Boini, K. M., & Koka, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143570 · Cited by 102 · see citing works
Trimethylamine N-oxide impairs β-cell function and glucose tolerance
Kong, L., Zhao, Q., Jiang, X., Hu, J., Jiang, Q., Li, S., Peng, X., Wang, S., Chen, Y., Wan, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46829-0 · Cited by 98 · see citing works
From role of gut microbiota to microbial-based therapies in type 2-diabetes
Leylabadlo, H. E., Sanaie, S., Heravi, F. S., Ahmadian, Z., & Ghotaslou, R. (2020) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2020.104268 · Cited by 92 · see citing works
Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases
Constantino-Jonapa, L. A., Espinoza-Palacios, Y., Escalona‐Montaño, A. R., Hernández-Ruiz, P., Amezcua-Guerra, L. M., Amedei, A., & Aguirre‐García, M. M. (2023) · Biomedicines · doi:10.3390/biomedicines11020431 · Cited by 97 · see citing works
Leustean, A. M., Ciocoiu, M., Sava, A. C., Costea, C. F., Floria, M., Tărniceriu, C. C., & Tănase, D. M. (2018) · Journal of Diabetes Research · doi:10.1155/2018/5205126 · Cited by 92 · see citing works
Metabolic functions of the human gut microbiota: the role of metalloenzymes
Rajakovich, L. J., & Balskus, E. P. (2018) · Natural Product Reports · doi:10.1039/c8np00074c · Cited by 89 · see citing works
Lakshmi, G. B. V. S., Yadav, A. K., Mehlawat, N., Jalandra, R., Solanki, P. R., & Kumar, A. (2021) · Scientific Reports · doi:10.1038/s41598-020-80122-6 · Cited by 88 · see citing works
Zeng, Y., Guo, M., Xia, F., Teng, F., Tan, X., Li, X., Wang, M., Long, Y., & Xu, Y. (2021) · Advances in Nutrition · doi:10.1093/advances/nmab010 · Cited by 88 · see citing works
Trimethylamine N-Oxide and Risk of Cardiovascular Disease and Mortality
Kanitsoraphan, C., Rattanawong, P., Charoensri, S., & Senthong, V. (2018) · Current Nutrition Reports · doi:10.1007/s13668-018-0252-z · Cited by 85 · see citing works
Yu, 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
Plasma concentration of trimethylamine-N-oxide and risk of gestational diabetes mellitus
Li, P., Zhong, C., Li, S., Sun, T., Huang, H., Chen, X., Zhu, Y., Hu, X., Peng, X., Zhang, X., et al. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy116 · Cited by 78 · see citing works
Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults
Erickson, M. L., Malin, S. K., Wang, Z., Brown, J. M., Hazen, S. L., & Kirwan, J. P. (2019) · Nutrients · doi:10.3390/nu11010179 · Cited by 78 · see citing works
Ottiger, M., Nickler, M., Steuer, C., Bernasconi, L., Huber, A., Christ‐Crain, M., Henzen, C., Hoess, C., Thomann, R., Zimmerli, W., et al. (2017) · Nutrition · doi:10.1016/j.nut.2017.07.001 · Cited by 75 · see citing works
Communication Between the Microbiota and Mammalian Immunity
Ost, K. S., & Round, J. L. (2018) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090817-062307 · Cited by 74 · see citing works
Trimethylamine N -oxide: heart of the microbiota–CVD nexus?
Naghipour, S., Cox, A. J., Peart, J. N., Toit, E. F. D., & Headrick, J. P. (2020) · Nutrition Research Reviews · doi:10.1017/s0954422420000177 · Cited by 75 · see citing works
Farhangi, M. A., Vajdi, M., & Asghari-Jafarabadi, M. (2020) · Nutrition Journal · doi:10.1186/s12937-020-00592-2 · Cited by 72 · see citing works
Association of TrimethylamineN-Oxide and Related Metabolites in Plasma and Incident Type 2 Diabetes
Lemaître, R. N., Jensen, P. N., Wang, Z., Fretts, A. M., McKnight, B., Nemet, I., Biggs, M. L., Sotoodehnia, N., Otto, M. C. D. O., Psaty, B. M., et al. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.22844 · Cited by 71 · see citing works
Phillips, I. R., & Shephard, E. A. (2019) · Xenobiotica · doi:10.1080/00498254.2019.1643515 · Cited by 71 · see citing works
Ilyas, A., Wijayasinghe, Y. S., Khan, I., Samaloty, N. M. E., Adnan, M., Dar, T. A., Poddar, N. K., Singh, L. R., Sharma, H., & Khan, S. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.964624 · Cited by 71 · see citing works
Microbiota impacts on chronic inflammation and metabolic syndrome - related cognitive dysfunction
Arnoriaga‐Rodríguez, M., & Fernández‐Real, J. M. (2019) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09537-5 · Cited by 67 · see citing works
Liu, Z., Tan, X., Li, Q., Liao, G., Fang, A., Zhang, D., Chen, P., Wang, X., Luo, Y., Long, J., et al. (2018) · Nutrition & Metabolism · doi:10.1186/s12986-018-0319-2 · Cited by 64 · see citing works
Balancing the Equation: A Natural History of Trimethylamine and Trimethylamine-N-oxide
Loo, R. L., Chan, Q. M., Nicholson, J. K., & Holmes, E. C. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00851 · Cited by 60 · see citing works
Papandreou, C., Bulló, M., Zheng, Y., Ruiz‐Canela, M., Yu, E., Guasch‐Ferré, M., Toledo, E., Clish, C. B., Corella, D., Estruch, R., et al. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy058 · Cited by 63 · see citing works
Diet‐derived microbial metabolites in health and disease
Roager, H. M., & Dragsted, L. O. (2019) · Nutrition Bulletin · doi:10.1111/nbu.12396 · Cited by 60 · see citing works
Farhangi, 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
TMA/TMAO in Hypertension: Novel Horizons and Potential Therapies
Zhang, W., Wang, Y., Zhang, A., Ding, Y., Zhang, X., Jia, Q.-J., Zhu, Y., Li, Y., Lv, S., & Zhang, J. (2021) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-021-10115-x · Cited by 59 · see citing works
Gao, X., Tian, Y., Randell, E. W., Zhou, H., & Sun, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00168 · Cited by 59 · see citing works
The Interface of Vibrio cholerae and the Gut Microbiome
Cho, J. Y., Liu, R., Macbeth, J. C., & Hsiao, A. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1937015 · Cited by 58 · see citing works
Metabolites of Gut Microbiota and Possible Implication in Development of Diabetes Mellitus
Guo, Z., Pan, J., Zhu, H., & Chen, Z. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c07851 · Cited by 57 · see citing works
DiNicolantonio, J. J., McCarty, M. F., & O’Keefe, J. H. (2019) · Open Heart · doi:10.1136/openhrt-2018-000890 · Cited by 56 · see citing works
Studies of xenobiotic-induced gut microbiota dysbiosis: from correlation to mechanisms
Chi, L., Tu, P., Ru, H., & Lü, K. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1921912 · Cited by 58 · see citing works
Intertwined Relationship of Mitochondrial Metabolism, Gut Microbiome and Exercise Potential
Imdad, S., Lim, W., Kim, J., & Kang, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052679 · Cited by 57 · see citing works
Yamagata, K., Hashiguchi, K., Yamamoto, H., & Tagami, M. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000747 · Cited by 57 · see citing works
Yang, J. J., Shu, X., Herrington, D. M., Moore, S. C., Meyer, K. A., Ose, J., Menni, C., Palmer, N. D., Eliassen, A. H., Harada, S., et al. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa430 · Cited by 53 · see citing works
Alzheimer’s disease and gut microbiota: does trimethylamine N-oxide (TMAO) play a role?
Arrona Cardoza, P., Spillane, M. B., & Morales Marroquin, E. (2022) · Nutrition Reviews · doi:10.1093/nutrit/nuab022 · Cited by 53 · see citing works
The Relationship between Fish Intake and Urinary Trimethylamine‐ N ‐Oxide
Yin, X., Gibbons, H., Rundle, M., Frost, G. S., McNulty, B. A., Nugent, A. P., Walton, J., Flynn, A., & Brennan, L. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900799 · Cited by 54 · see citing works
Mu, C., Corley, M. J., Lee, R. W. Y., Wong, M., Pang, A. P. S., Arakaki, G., Miyamoto, R. H., Rho, J. M., Mickiewicz, B., Dowlatabadi, R., et al. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00581 · Cited by 54 · see citing works
Yang, J. J., Lipworth, L. P., Shu, X., Blot, W. J., Xiang, Y., Steinwandel, M. D., Li, H., Gao, Y., Zheng, W., & Yu, D. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz318 · Cited by 53 · see citing works
Kuka, J., Ozola, M., Makrecka‐Kuka, M., Liepinsh, E., Grı̄nberga, S., Sevostjanovs, E., Vilks, K., Liepinsh, E., & Dambrova, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-71470-4 · Cited by 52 · see citing works
Self-citationMechanisms linking gut microbial metabolites to insulin resistance
Jang, H. R., & Lee, H. (2021) · World Journal of Diabetes · doi:10.4239/wjd.v12.i6.730 · Cited by 52 · see citing works
Eyüpoğlu, D., Guzelce, E. C., Açıkgöz, A., Uyanık, E., Bjørndal, B., Berge, R. K., Svardal, A. M., & Yıldız, B. O. (2019) · Clinical Endocrinology · doi:10.1111/cen.14101 · Cited by 51 · see citing works
Association between Plasma Trimethylamine N-Oxide Levels and Type 2 Diabetes: A Case Control Study
Kalagi, N. A., Thota, R. N., Stojanovski, E., Alburikan, K. A., & Garg, M. L. (2022) · Nutrients · doi:10.3390/nu14102093 · Cited by 50 · see citing works
Ozola, M., Vilšķe̅rsts, R., Korzh, S., Cirule, H., Sevostjanovs, E., Dambrova, M., & Makrecka‐Kuka, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.622741 · Cited by 50 · see citing works
Self-citationDong, Z., Liang, Z., Guo, M., Hu, S., Shen, Z., & Hai, X. (2018) · Disease Markers · doi:10.1155/2018/1578320 · Cited by 49 · see citing works
Vasishta, S., Ganesh, K., Umakanth, S., & Joshi, M. B. (2022) · Metabolomics · doi:10.1007/s11306-022-01905-8 · Cited by 45 · see citing works
Neri-Rosario, D., Martínez-López, Y. E., Esquivel-Hernandez, D. A., Sánchez-Castañeda, J. P., Padrón-Manrique, C., Vázquez-Jiménez, A., Giron-Villalobos, D., & Reséndis-Antonio, O. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1170459 · Cited by 49 · see citing works
Trimethylamine/Trimethylamine-N-Oxide as a Key Between Diet and Cardiovascular Diseases
He, S., Jiang, H., Zhuo, C., & Jiang, W. (2021) · Cardiovascular Toxicology · doi:10.1007/s12012-021-09656-z · Cited by 45 · see citing works
PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels
Huang, J., Liu, L., Chen, C., & Gao, Y. (2020) · BMC Endocrine Disorders · doi:10.1186/s12902-019-0486-9 · Cited by 45 · see citing works
Rizo‐Roca, D., Henderson, J. D., & Zierath, J. R. (2025) · Journal of Internal Medicine · doi:10.1111/joim.20090 · Cited by 43 · see citing works
Living with the enemy: from protein-misfolding pathologies we know, to those we want to know
Emwas, A.-H. M., Alghrably, M., Dhahri, M., Sharfalddin, A. A., Alsiary, R., Jaremko, M., Faa, G., Campagna, M., Congiu, T., Piras, M., et al. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101391 · Cited by 43 · see citing works
Ufnal, M., & Nowiński, A. (2019) · Medical Hypotheses · doi:10.1016/j.mehy.2019.109271 · Cited by 41 · see citing works
Dong, F., Jiang, S., Tang, C., Wang, X., Ren, X., Wei, Q., Tian, J., Hu, W., Guo, J. Z., Fu, X., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.11.010 · Cited by 44 · see citing works
Enalapril decreases rat plasma concentration of TMAO, a gut bacteria-derived cardiovascular marker
Konop, M., Radkowski, M., Grochowska, M., Perlejewski, K., Samborowska, E., & Ufnal, M. (2018) · Biomarkers · doi:10.1080/1354750x.2018.1432689 · Cited by 41 · see citing works
Roy, S. S., yuzefpolskaya, M., Nandakumar, R., Colombo, P. C., & Demmer, R. T. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227482 · Cited by 40 · see citing works
Krueger, E. S., Lloyd, T. S., & Tessem, J. S. (2021) · Nutrients · doi:10.3390/nu13082873 · Cited by 40 · see citing works
Microbiota and metabolites in rheumatic diseases
Tong, Y., Marion, T. N., Schett, G. A., Luo, Y., & Liu, Y. (2020) · Autoimmunity Reviews · doi:10.1016/j.autrev.2020.102530 · Cited by 39 · see citing works
TMAO and diabetes: from the gut feeling to the heart of the problem
Jaworska, K., Kuś, M., & Ufnal, M. (2025) · Nutrition and Diabetes · doi:10.1038/s41387-025-00377-8 · Cited by 39 · see citing works
Yadav, A. K., Verma, D., Sajwan, R. K., Poddar, M., Yadav, S. K., Verma, A. K., & Solanki, P. R. (2022) · Biosensors · doi:10.3390/bios12090733 · Cited by 38 · see citing works
Wang, A., Dongcheng, C., Zhang, H., Li, Q., Yan, Z., Qiu, Y., Xu, H., & Keji, C. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.02.018 · Cited by 37 · see citing works
- Authors
- Dambrova, M., Latkovskis, G., Kuka, J., Strele, I., Konrade, I., Grinberga, S., Hartmane, D., Pugovics, O., Erglis, A., & Liepinsh, E.
- Affiliations
- Latvijas Organiskās Sintēzes Institūts (LV)
- Pauls Stradiņš Clinical University Hospital (LV)
- Riga Stradins University, Riga, Latvia
- Latvian Institute of Organic Synthesis, Riga, Latvia
- Paul Stradins Clinical University Hospital, Riga, Latvia
- Corresponding author
- Dambrova, M.
- Venue
- Experimental and Clinical Endocrinology & Diabetes
- Publisher
- Georg Thieme Verlag KG
- Published
- 2016-04-28
- Volume
- 124
- Issue
- 04
- Pages
- 251-256
- ISSN
- 0947-7349 (ISSN-L)
- 1439-3646
- OpenAlex
- W2342504128
- Cited by
- 229
- References
- 29
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 24 · 2023: 20 · 2022: 31 · 2021: 30 · 2020: 22 · 2019: 25 · 2018: 25 · 2017: 18 · 2016: 4
- FWCI
- 24.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Experimental and Clinical Endocrinology & Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- trimethylamine N-oxide, diabetes mellitus, L-carnitine, db/db mice, insulin resistance, cardiovascular risk markers, percutaneous coronary intervention, body mass index, age, atherosclerosis, plasma biomarkers
- MeSH terms
- Age Factors, Aged, Animals, Cardiovascular Diseases, Carnitine, Diabetes Mellitus, Disease Models, Animal, Female, Humans, Male, Methylamines, Middle Aged, Body Mass Index, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review
