Table Info

Table 2.

Comparison between long-term and short-term impact of increased TMAO levels

Short-term impact	Long-term impact
Enhances endurance performance in athletes	Elevates fasting plasma TMAO levels
Improvs liver fat utilization and ketogenesis	Associated with a higher risk of ASCVD, Atherosclerosis, AF, and stroke
Higher levels observed in acute MI	Potential negative on cardiovascular health. Particularly concerned in older adults with compromised renal function
Associated with reduced ST-segment dispersion in ACS	Linked to a higher prevalence of prediabetes and T2DM
Associated with reduced ST-segment dispersion in ACS	Requires careful assessment due to potential adverse effects on cardiovascular health

MI: myocardial infarction; ACS: acute coronary syndrome; TMAO: trimethylamine-N-oxide; ASCVD: atherosclerotic cardiovascular disease; AF: atrial fibrillation; T2DM: type 2 diabetes mellitus

Declarations

Author contributions

HSW: Conceptualization, Writing—original draft, Writing—review & editing, Supervision, Validation. FR: Writing—original draft, Writing—review & editing. AWI: Writing—original draft, Writing—review & editing. JAK: Writing—original draft, Writing—review & editing. AAS: Writing—original draft.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Alhasaniah AH. l-carnitine: Nutrition, pathology, and health benefits. Saudi J Biol Sci. 2023;30:103555. [DOI] [PubMed] [PMC]

Sawicka AK, Renzi G, Olek RA. The bright and the dark sides of L-carnitine supplementation: a systematic review. J Int Soc Sports Nutr. 2020;17:49. [DOI] [PubMed] [PMC]

Vecchio M, Chiaramonte R, Testa G, Pavone V. Clinical Effects of L-Carnitine Supplementation on Physical Performance in Healthy Subjects, the Key to Success in Rehabilitation: A Systematic Review and Meta-Analysis from the Rehabilitation Point of View. J Funct Morphol Kinesiol. 2021;6:93. [PubMed] [PMC]

Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576–85. [DOI] [PubMed] [PMC]

Gatarek P, Kaluzna-Czaplinska J. Trimethylamine N-oxide (TMAO) in human health. EXCLI J. 2021;20:301–19. [DOI] [PubMed] [PMC]

Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, Donapetry-García C, Pedre-Piñeiro AM. Significance of l-carnitine for human health. IUBMB Life. 2017;69:578–94. [DOI] [PubMed]

Fielding R, Riede L, Lugo JP, Bellamine A. l-Carnitine Supplementation in Recovery after Exercise. Nutrients. 2018;10:349. [DOI] [PubMed] [PMC]

Ferreira GC, McKenna MC. L-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain. Neurochem Res. 2017;42:1661–75. [DOI] [PubMed] [PMC]

Virmani MA, Cirulli M. The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation. Int J Mol Sci. 2022;23:2717. [DOI]

10.

Carnitine [Internet]. [Cited 2024 Oct 10]. Available from: https://ods.od.nih.gov/factsheets/Carnitine-HealthProfessional/

11.

Zeisel SH, Warrier M. Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease. Annu Rev Nutr. 2017;37:157–81. [DOI] [PubMed]

12.

Velasquez MT, Ramezani A, Manal A, Raj DS. Trimethylamine N-Oxide: The Good, the Bad and the Unknown. Toxins (Basel). 2016;8:326. [DOI] [PubMed] [PMC]

13.

Ufnal M, Zadlo A, Ostaszewski R. TMAO: A small molecule of great expectations. Nutrition. 2015;31:1317–23. [DOI] [PubMed]

14.

Mudimela S, Vishwanath NK, Pillai A, Morales R, Marrelli SP, Barichello T, et al. Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders. Drug Discov Today. 2022;27:103334. [DOI] [PubMed] [PMC]

15.

Evans M, Dai L, Avesani CM, Kublickiene K, Stenvinkel P. The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison. Clin Kidney J. 2023;16:1804–12. [DOI] [PubMed] [PMC]

16.

Scarpellini E, Tack J. Obesity and metabolic syndrome: an inflammatory condition. Dig Dis. 2012;30:148–53. [DOI] [PubMed]

17.

Yang Y, Yang B, Li X, Xue L, Liu B, Liang Y, et al. Higher circulating Trimethylamine N-oxide levels are associated with worse severity and prognosis in pulmonary hypertension: a cohort study. Respir Res. 2022;23:344. [DOI]

18.

Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116:448–55. [DOI] [PubMed] [PMC]

19.

Borges NA, Stenvinkel P, Bergman P, Qureshi AR, Lindholm B, Moraes C, et al. Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study. Probiotics Antimicrob Proteins. 2019;11:648–54. [DOI] [PubMed]

20.

Barrea L, Muscogiuri G, Annunziata G, Laudisio D, de Alteriis G, Tenore GC, et al. A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO). Nutrients. 2019;11:1310. [DOI] [PubMed] [PMC]

21.

Dambrova M, Latkovskis G, Kuka J, Strele I, Konrade I, Grinberga S, et al. Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels. Exp Clin Endocrinol Diabetes. 2016;124:251–6. [DOI] [PubMed]

22.

Constantino-Jonapa LA, Espinoza-Palacios Y, Escalona-Montaño AR, Hernández-Ruiz P, Amezcua-Guerra LM, Amedei A, et al. Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases. Biomedicines. 2023;11:431. [DOI]

23.

Huguenard CJC, Cseresznye A, Darcey T, Nkiliza A, Evans JE, Hazen SL, et al. Age and APOE affect L-carnitine system metabolites in the brain in the APOE-TR model. Front Aging Neurosci. 2023;14:1059017. [DOI] [PubMed] [PMC]

24.

Samulak JJ, Sawicka AK, Hartmane D, Grinberga S, Pugovics O, Lysiak-Szydlowska W, et al. L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women. Ann Nutr Metab. 2019;74:11–7. [DOI] [PubMed]

25.

Bin-Jumah MN, Gilani SJ, Hosawi S, Al-Abbasi FA, Zeyadi M, Imam SS, et al. Pathobiological Relationship of Excessive Dietary Intake of Choline/L-Carnitine: A TMAO Precursor-Associated Aggravation in Heart Failure in Sarcopenic Patients. Nutrients. 2021;13:3453. [DOI] [PubMed] [PMC]

26.

Sharma B, Yadav DK. L-Carnitine and Chronic Kidney Disease: A Comprehensive Review on Nutrition and Health Perspectives. J Pers Med. 2023;13:298. [DOI] [PubMed] [PMC]

27.

Miller MJ, Bostwick BL, Kennedy AD, Donti TR, Sun Q, Sutton VR, et al. Chronic Oral L-Carnitine Supplementation Drives Marked Plasma TMAO Elevations in Patients with Organic Acidemias Despite Dietary Meat Restrictions. JIMD Rep. 2016;30:39–44. [DOI]

28.

Koeth RA, Wang Z, Levia R, Garcia-Garcia JC, Tang WHW, Hazen S. Abstract 16758: Gut Microbiota Metabolism of L-Carnitine, a Nutrient in Red Meat, and the Atherogenic Metabolites γ–Gammabutyrobetaine and TMAO in Humans. Circulation. 2017;136:A16758. [DOI]

29.

Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8. [DOI] [PubMed] [PMC]

30.

Walters KE, Martiny JBH. Alpha-, beta-, and gamma-diversity of bacteria varies across habitats. PLoS One. 2020;15:e0233872. [DOI] [PubMed] [PMC]

31.

Finotello F, Mastrorilli E, Di Camillo B. Measuring the diversity of the human microbiota with targeted next-generation sequencing. Brief Bioinform. 2018;19:679–92. [DOI] [PubMed]

32.

Haghikia A, Li XS, Liman TG, Bledau N, Schmidt D, Zimmermann F, et al. Gut Microbiota-Dependent Trimethylamine N-Oxide Predicts Risk of Cardiovascular Events in Patients With Stroke and Is Related to Proinflammatory Monocytes. Arterioscler Thromb Vasc Biol. 2018;38:2225–35. [DOI] [PubMed] [PMC]

33.

Gencer B, Li XS, Gurmu Y, Bonaca MP, Morrow DA, Cohen M, et al. Gut Microbiota-Dependent Trimethylamine N-oxide and Cardiovascular Outcomes in Patients With Prior Myocardial Infarction: A Nested Case Control Study From the PEGASUS-TIMI 54 Trial. J Am Heart Assoc. 2020;9:e015331. [DOI] [PubMed] [PMC]

34.

Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. [DOI] [PubMed] [PMC]

35.

Sivaprakasam S, Bhutia YD, Yang S, Ganapathy V. Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis. Compr Physiol. 2017;8:299–314. [DOI] [PubMed] [PMC]

36.

Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3:858–76. [DOI] [PubMed] [PMC]

37.

Sun M, Wu W, Chen L, Yang W, Huang X, Ma C, et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun. 2018;9:3555. [DOI]

38.

Florea CM, Rosu R, Moldovan R, Vlase L, Toma V, Decea N, et al. The impact of chronic Trimethylamine N-oxide administration on liver oxidative stress, inflammation, and fibrosis. Food Chem Toxicol. 2024;184:114429. [DOI]

39.

Feller AG, Rudman D. Role of carnitine in human nutrition. J Nutr. 1988;118:541–7. [DOI] [PubMed]

40.

Li JM, Zhang Z, Kong A, Lai W, Xu W, Cao X, et al. Dietary l-carnitine regulates liver lipid metabolism via simultaneously activating fatty acid β-oxidation and suppressing endoplasmic reticulum stress in large yellow croaker fed with high-fat diets. Br J Nutr. 2023;129:29–40. [DOI] [PubMed]

41.

Hutson SM, Sweatt AJ, Lanoue KF. Branched-chain [corrected] amino acid metabolism: implications for establishing safe intakes. J Nutr. 2005;135:1557S–64S. [DOI] [PubMed]

42.

Nie C, He T, Zhang W, Zhang G, Ma X. Branched Chain Amino Acids: Beyond Nutrition Metabolism. Int J Mol Sci. 2018;19:954. [DOI] [PubMed] [PMC]

43.

Tamai Y, Chen Z, Wu Y, Okabe J, Kobayashi Y, Chiba H, et al. Branched-chain amino acids and l-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver. Biomed Pharmacother. 2021;135:111181. [DOI] [PubMed]

44.

Makrecka-Kuka M, Volska K, Antone U, Vilskersts R, Grinberga S, Bandere D, et al. Trimethylamine N-oxide impairs pyruvate and fatty acid oxidation in cardiac mitochondria. Toxicol Lett. 2017;267:32–8. [DOI] [PubMed]

45.

Vallance HD, Koochin A, Branov J, Rosen-Heath A, Bosdet T, Wang Z, et al. Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine. Mol Genet Metab Rep. 2018;15:130–3. [DOI] [PubMed] [PMC]

46.

McLeod CJ, Pagel I, Sack MN. The mitochondrial biogenesis regulatory program in cardiac adaptation to ischemia--a putative target for therapeutic intervention. Trends Cardiovasc Med. 2005;15:118–23. [DOI] [PubMed]

47.

Li M, Yang K, De Vivo I, Eliassen AH, Qureshi AA, Nan H, et al. Association between plasma L-carnitine levels and mitochondrial DNA copy number. BMC Mol Cell Biol. 2023;24:35. [DOI]

48.

Demarquoy J. Revisiting the Role of Carnitine in Heart Disease Through the Lens of the Gut Microbiota. Nutrients. 2024;16:4244. [DOI] [PubMed] [PMC]

49.

Malaguarnera M. Carnitine derivatives: clinical usefulness. Curr Opin Gastroenterol. 2012;28:166–76. [DOI] [PubMed]

50.

Lin K, Zheng W, Guo M, Zhou R, Zhang M, Liu T. The intestinal microbial metabolite acetyl l-carnitine improves gut inflammation and immune homeostasis via CADM2. Biochim Biophys Acta - Mol Basis Dis. 2024;1870:167089. [DOI]

51.

Malaguarnera M, Catania VE, Malaguarnera M. Carnitine derivatives beyond fatigue: an update. Curr Opin Gastroenterol. 2023;39:125–8. [DOI] [PubMed] [PMC]

52.

Ferrari R, Merli E, Cicchitelli G, Mele D, Fucili A, Ceconi C. Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review. Ann N Y Acad Sci. 2004;1033:79–91. [DOI] [PubMed]

53.

Smith WA, Fry AC, Tschume LC, Bloomer RJ. Effect of glycine propionyl-L-carnitine on aerobic and anaerobic exercise performance. Int J Sport Nutr Exerc Metab. 2008;18:19–36. [DOI] [PubMed]

54.

Stefan M, Sharp M, Gheith R, Lowery R, Ottinger C, Wilson J, et al. L-Carnitine Tartrate Supplementation for 5 Weeks Improves Exercise Recovery in Men and Women: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021;13:3432. [DOI] [PubMed] [PMC]

55.

Canyelles M, Borràs C, Rotllan N, Tondo M, Escolà-Gil JC, Blanco-Vaca F. Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease? Int J Mol Sci. 2023;24:1940. [DOI] [PubMed] [PMC]

56.

Blaak EE, Canfora EE. Increased circulating choline, L-carnitine and TMAO levels are related to changes in adiposity during weight loss: role of the gut microbiota? Ann Transl Med. 2018;6:S92. [PubMed] [PMC]

57.

Jacobs PL, Goldstein ER, Blackburn W, Orem I, Hughes JJ. Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males. J Int Soc Sports Nutr. 2009;6:9. [DOI] [PubMed] [PMC]

58.

Ussher JR, Lopaschuk GD, Arduini A. Gut microbiota metabolism of L-carnitine and cardiovascular risk. Atherosclerosis. 2013;231:456–61. [DOI] [PubMed]

59.

Ghonimy A, Zhang DM, Farouk MH, Wang Q. The Impact of Carnitine on Dietary Fiber and Gut Bacteria Metabolism and Their Mutual Interaction in Monogastrics. Int J Mol Sci. 2018;19:1008. [DOI] [PubMed] [PMC]

60.

Mohammadi M, Hajhossein Talasaz A, Alidoosti M. Preventive effect of l-carnitine and its derivatives on endothelial dysfunction and platelet aggregation. Clin Nutr ESPEN. 2016;15:1–10. [DOI] [PubMed]

61.

Orer GE, Guzel NA. The effects of acute L-carnitine supplementation on endurance performance of athletes. J Strength Cond Res. 2014;28:514–9. [DOI] [PubMed]

62.

Islam S, Yakout SM, Daghri NM, Alhomida AS, Khan HA. Serum levels of thrombotic markers in patients with acute myocardial infarction. Int J Clin Exp Med. 2014;7:1059–63. [PubMed] [PMC]

63.

Sinha A, Ma Y, Scherzer R, Rahalkar S, Neilan BD, Crane H, et al. Carnitine Is Associated With Atherosclerotic Risk and Myocardial Infarction in HIV-Infected Adults. J Am Heart Assoc. 2019;8:e011037. [DOI]

64.

Roncal C, Martínez-Aguilar E, Orbe J, Ravassa S, Fernandez-Montero A, Saenz-Pipaon G, et al. Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality in Peripheral Artery Disease. Sci Rep. 2019;9:15580. [DOI] [PubMed] [PMC]

65.

Li N, Zhou J, Wang Y, Chen R, Li J, Zhao X, et al. Association between trimethylamine N-oxide and prognosis of patients with acute myocardial infarction and heart failure. ESC Heart Failure. 2022;9:3846–57. [DOI]

66.

Eyipınar CD. The Effect of L-Carnitine Supplementation on Sportive Performance. Eurasia Proc Health Environ Life Sci. 2023;12:106–10. [DOI]

67.

DiNicolantonio JJ, McCarty M, OKeefe J. Association of moderately elevated trimethylamine N-oxide with cardiovascular risk: is TMAO serving as a marker for hepatic insulin resistance. Open Heart. 2019;6:e000890. [DOI] [PubMed] [PMC]

68.

Wang B, Qiu J, Lian J, Yang X, Zhou J. Gut Metabolite Trimethylamine-N-Oxide in Atherosclerosis: From Mechanism to Therapy. Front Cardiovasc Med. 2021;8:723886. [DOI] [PubMed] [PMC]

69.

Din AU, Hassan A, Zhu Y, Yin T, Gregersen H, Wang G. Amelioration of TMAO through probiotics and its potential role in atherosclerosis. Appl Microbiol Biotechnol. 2019;103:9217–28. [DOI] [PubMed]

70.

Getz GS, Reardon CA. Diet, Microbes, and Murine Atherosclerosis. Arterioscler Thromb Vasc Biol. 2018;38:2269–71. [DOI] [PubMed] [PMC]

71.

Hoseini-Tavassol Z, Hasani-Ranjbar S. Targeting TMAO and its metabolic pathway for cardiovascular diseases treatment. J Diabetes Metab Disord. 2021;20:1095–7. [DOI] [PubMed] [PMC]

72.

Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016;165:111–24. [DOI] [PubMed] [PMC]

73.

Xiong X, Zhou J, Fu Q, Xu X, Wei S, Yang S, et al. The associations between TMAO-related metabolites and blood lipids and the potential impact of rosuvastatin therapy. Lipids Health Dis. 2022;21:60. [DOI] [PubMed] [PMC]

74.

Guasti L, Galliazzo S, Molaro M, Visconti E, Pennella B, Gaudio GV, et al. TMAO as a biomarker of cardiovascular events: a systematic review and meta-analysis. Intern Emerg Med. 2021;16:201–7. [DOI] [PubMed]

75.

Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647–60. [DOI] [PubMed] [PMC]

76.

Ding L, Chang M, Guo Y, Zhang L, Xue C, Yanagita T, et al. Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism. Lipids Health Dis. 2018;17:286. [DOI] [PubMed] [PMC]

77.

He S, Jiang H, Zhuo C, Jiang W. Trimethylamine/Trimethylamine-N-Oxide as a Key Between Diet and Cardiovascular Diseases. Cardiovasc Toxicol. 2021;21:593–604. [DOI] [PubMed]

78.

Ralston SH, Penman ID, Strachan MWJ, Hobson R. Davidson’s Principles and Practice of Medicine. 23rd Edition. Sydney: Elsevier; 2018.

79.

Bao M, Li H, Li J. Circulating trimethylamine N-oxide is correlated with high coronary artery atherosclerotic burden in individuals with newly diagnosed coronary heart disease. BMC Cardiovasc Disord. 2024;24:265. [DOI] [PubMed] [PMC]

80.

Ma J, Li H. The Role of Gut Microbiota in Atherosclerosis and Hypertension. Front Pharmacol. 2018;9:1082. [DOI] [PubMed] [PMC]

81.

Zhang WQ, Wang YJ, Zhang A, Ding YJ, Zhang XN, Jia QJ, et al. TMA/TMAO in Hypertension: Novel Horizons and Potential Therapies. J Cardiovasc Trans Res. 2021;14:1117–24. [DOI]

82.

Karbach SH, Schönfelder T, Brandão I, Wilms E, Hörmann N, Jäckel S, et al. Gut Microbiota Promote Angiotensin II–Induced Arterial Hypertension and Vascular Dysfunction. J Am Heart Assoc. 2016;5:9. [DOI]

83.

Shang R, Sun Z, Li H. Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2014;14:88. [DOI] [PubMed] [PMC]

84.

Yu L, Meng G, Huang B, Zhou X, Stavrakis S, Wang M, et al. A potential relationship between gut microbes and atrial fibrillation: Trimethylamine N-oxide, a gut microbe-derived metabolite, facilitates the progression of atrial fibrillation. Int J Cardiol. 2018;255:92–8. [DOI] [PubMed]

85.

Wang Z, Tang WH, Buffa JA, Fu X, Britt EB, Koeth RA, et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J. 2014;35:904–10. [DOI] [PubMed] [PMC]

86.

Ballestri S, Lonardo A, Bonapace S, Byrne CD, Loria P, Targher G. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20:1724–45. [DOI] [PubMed] [PMC]

87.

Mbembela O, Mwasanjobe T, Manisha AM, Kilamile S, Ali HS, Ruhighira JJ, et al. Trimethylamine-N-Oxide (TMAO): Potential Benefits, and Therapeutic Targets Conceivable as a Mitigation Strategy for Cardio-Metabolic Diseases. J Metabolic Synd. 2023;12:319.

88.

Albracht-Schulte K, Islam T, Johnson P, Moustaid-Moussa N. Systematic Review of Beef Protein Effects on Gut Microbiota: Implications for Health. Adv Nutr. 2021;12:102–14. [DOI] [PubMed] [PMC]

89.

Wang Z, Bergeron N, Levison BS, Li XS, Chiu S, Jia X, et al. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur Heart J. 2019;40:583–94. [DOI] [PubMed] [PMC]

90.

Pieczynska MD, Yang Y, Petrykowski S, Horbanczuk OK, Atanasov AG, Horbanczuk JO. Gut Microbiota and Its Metabolites in Atherosclerosis Development. Molecules. 2020;25:594. [DOI] [PubMed] [PMC]

91.

Chandrasekaran P, Weiskirchen S, Weiskirchen R. Effects of Probiotics on Gut Microbiota: An Overview. Int J Mol Sci. 2024;25:6022. [DOI] [PubMed] [PMC]

92.

Tang WH, Hazen SL. Probiotic therapy to attenuate weight gain and trimethylamine-N-Oxide generation: A cautionary tale. Obesity (Silver Spring). 2015;23:2321–2. [PubMed] [PMC]

93.

Liang X, Zhang Z, Lv Y, Tong L, Liu T, Yi H, et al. Reduction of intestinal trimethylamine by probiotics ameliorated lipid metabolic disorders associated with atherosclerosis. Nutrition. 2020;79–80:110941. [DOI]

94.

Cantero MA, Guedes MRA, Fernandes R, Lollo PCB. Trimethylamine N-oxide reduction is related to probiotic strain specificity: A systematic review. Nutr Res. 2022;104:29–35. [DOI] [PubMed]

95.

Xavier-Santos D, Bedani R, Lima ED, Saad SMI. Impact of probiotics and prebiotics targeting metabolic syndrome. J Functi Foods. 2020;64:103666. [DOI]

96.

Caraceni P, Vargas V, Solà E, Alessandria C, de Wit K, Trebicka J, et al.; Liverhope Consortium. The Use of Rifaximin in Patients With Cirrhosis. Hepatology. 2021;74:1660–73. [DOI] [PubMed] [PMC]

97.

Hong CT, Chan L, Chen KY, Lee HH, Huang LK, Yang YSH, et al. Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson’s Disease: Preclinical and Clinical Studies. Cells. 2022;11:3468. [PubMed] [PMC]

98.

Patel VC, Lee S, McPhail MJW, Da Silva K, Guilly S, Zamalloa A, et al. Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial. J Hepatol. 2022;76:332–42. [DOI] [PubMed]

99.

Ponziani FR, Gerardi V, Pecere S, D’Aversa F, Lopetuso L, Zocco MA, et al. Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications. World J Gastroenterol. 2015;21:12322–33. [DOI] [PubMed] [PMC]

100.

Lathakumari RH, Vajravelu LK, Satheesan A, Ravi S, Thulukanam J. Antibiotics and the gut microbiome: Understanding the impact on human health. Med Micro. 2024;20:100106. [DOI]

101.

Wang J, Xiang Q, Gu S, Gu Y, Yao M, Huang W, et al. Short- and Long-Term Effects of Different Antibiotics on the Gut Microbiota and Cytokines Level in Mice. Infect Drug Resist. 2022;15:6785–97. [DOI] [PubMed] [PMC]

102.

Patangia DV, Anthony Ryan C, Dempsey E, Paul Ross R, Stanton C. Impact of antibiotics on the human microbiome and consequences for host health. Microbiologyopen. 2022;11:e1260. [DOI] [PubMed] [PMC]

103.

Argyridou S, Bernieh D, Henson J, Edwardson CL, Davies MJ, Khunti K, et al. Associations between physical activity and trimethylamine N-oxide in those at risk of type 2 diabetes. BMJ Open Diabetes Res Care. 2020;8:e001359. [DOI] [PubMed] [PMC]

104.

Chen J, Guo Y, Gui Y, Xu D. Physical exercise, gut, gut microbiota, and atherosclerotic cardiovascular diseases. Lipids Health Dis. 2018;17:17. [DOI] [PubMed] [PMC]

105.

Battillo DJ, Malin SK. Impact of Caloric Restriction and Exercise on Trimethylamine N-Oxide Metabolism in Women with Obesity. Nutrients. 2023;15:1455. [PubMed] [PMC]

106.

Physical Activity Guidelines for Americans, 2nd edition [Internet]. Source: U.S. Department of Health and Human Services, 2018; [cited 2024 Dec 22]. Available from: https://odphp.health.gov/healthypeople/tools-action/browse-evidence-based-resources/physical-activity-guidelines-americans-2nd-edition

107.

Grammer E, McGee J, Brown T, Clunan M, Huff A, Osborne B, et al. EFFECTS OF A LIFESTYLE INTERVENTION ON TRIMETHYLAMINE N-OXIDE (TMAO) CONCENTRATIONS IN OVERWEIGHT AND OBESE ADULTS. Int J Exercise Sci: Conf Proc. 2023;16:57.

108.

American Heart Association Recommendations for Physical Activity in Adults and Kids [Internet]. American Heart Association, Inc; 2025 [cited 2024 Dec 22]. Available from: https://www.heart.org/en/healthy-living/fitness/fitness-basics/aha-recs-for-physical-activity-in-adults

109.

Erickson ML, Malin SK, Wang Z, Brown JM, Hazen SL, Kirwan JP. Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults. Nutrients. 2019;11:179. [DOI] [PubMed] [PMC]

110.

Gigant B, Cormier A, Dorléans A, Ravelli RB, Knossow M. Microtubule-destabilizing agents: structural and mechanistic insights from the interaction of colchicine and vinblastine with tubulin. Top Curr Chem. 2009;286:259–78. [DOI] [PubMed]

111.

Zhen J, Zhou Z, He M, Han HX, Lv EH, Wen PB, et al. The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Front Endocrinol (Lausanne). 2023;14:1085041. [DOI] [PubMed] [PMC]

112.

Dannenberg L, Zikeli D, Benkhoff M, Ahlbrecht S, Kelm M, Levkau B, et al. Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy. Pharmacol Ther. 2020;213:107584. [DOI] [PubMed]

113.

Guivala SJ, Bode KA, Okun JG, Kartal E, Schwedhelm E, Pohl LV, et al. Interactions between the gut microbiome, associated metabolites and the manifestation and progression of heart failure with preserved ejection fraction in ZSF1 rats. Cardiovasc Diabetol. 2024;23:299. [DOI] [PubMed] [PMC]