Trimethylamine N-Oxide in Relation to Cardiometabolic Health-Cause or Effect?

Overview

Journal Nutrients

Date 2020 May 13

PMID 32392758

Citations 64

Authors

Christopher Papandreou

Margret More

Aouatef Bellamine

Affiliations

Soon will be listed here.

Abstract

Trimethylamine-N-oxide (TMAO) is generated in a microbial-mammalian co-metabolic pathway mainly from the digestion of meat-containing food and dietary quaternary amines such as phosphatidylcholine, choline, betaine, or L-carnitine. Fish intake provides a direct significant source of TMAO. Human observational studies previously reported a positive relationship between plasma TMAO concentrations and cardiometabolic diseases. Discrepancies and inconsistencies of recent investigations and previous studies questioned the role of TMAO in these diseases. Several animal studies reported neutral or even beneficial effects of TMAO or its precursors in cardiovascular disease model systems, supporting the clinically proven beneficial effects of its precursor, L-carnitine, or a sea-food rich diet (naturally containing TMAO) on cardiometabolic health. In this review, we summarize recent preclinical and epidemiological evidence on the effects of TMAO, in order to shed some light on the role of TMAO in cardiometabolic diseases, particularly as related to the microbiome.

Citing Articles

Association between plasma trimethylamine N-oxide and cerebral white matter hyperintensity: a cross-sectional study.

Ji X, Zhang X, Zhang J, Niu S, Xiao H, Chen H Front Aging Neurosci. 2024; 16:1498502.

PMID: 39697484 PMC: 11653083. DOI: 10.3389/fnagi.2024.1498502.

Research progress on the association between TMAO and vascular calcification in patients with chronic kidney disease.

Zhang Y, Huang L, Ou S Ren Fail. 2024; 46(2):2435485.

PMID: 39627031 PMC: 11616764. DOI: 10.1080/0886022X.2024.2435485.

Trimethylamine N-oxide: a meta-organismal axis linking the gut and fibrosis.

Jang J, Capaldi E, Smith T, Verma P, Varga J, Ho K Mol Med. 2024; 30(1):128.

PMID: 39180015 PMC: 11344357. DOI: 10.1186/s10020-024-00895-8.

Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia.

Yaqub A, Vojinovic D, Vernooij M, Slagboom P, Ghanbari M, Beekman M Alzheimers Res Ther. 2024; 16(1):113.

PMID: 38769578 PMC: 11103865. DOI: 10.1186/s13195-024-01480-1.

Trimethylamine N-Oxide Improves Exercise Performance by Reducing Oxidative Stress through Activation of the Nrf2 Signaling Pathway.

Zou H, Zhou Y, Gong L, Huang C, Liu X, Lu R Molecules. 2024; 29(4).

PMID: 38398511 PMC: 10893042. DOI: 10.3390/molecules29040759.

References

Hua X, Su Z, Deng R, Lin J, Li D, Pflugfelder S . Effects of L-carnitine, erythritol and betaine on pro-inflammatory markers in primary human corneal epithelial cells exposed to hyperosmotic stress. Curr Eye Res. 2014; 40(7):657-67. PMC: 4793974. DOI: 10.3109/02713683.2014.957776. View

Mitchell S, Smith R . Trimethylaminuria: the fish malodor syndrome. Drug Metab Dispos. 2001; 29(4 Pt 2):517-21. View

Wilson A, Teft W, Morse B, Choi Y, Woolsey S, DeGorter M . Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease. Dig Dis Sci. 2015; 60(12):3620-30. DOI: 10.1007/s10620-015-3797-3. View

Saklayen M . The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018; 20(2):12. PMC: 5866840. DOI: 10.1007/s11906-018-0812-z. View

Tang W, Wang Z, Li X, Fan Y, Li D, Wu Y . Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus. Clin Chem. 2016; 63(1):297-306. PMC: 5659115. DOI: 10.1373/clinchem.2016.263640. View

Razavi A, Potts K, Kelly T, Bazzano L . Sex, gut microbiome, and cardiovascular disease risk. Biol Sex Differ. 2019; 10(1):29. PMC: 6558780. DOI: 10.1186/s13293-019-0240-z. View

McEntyre C, Lever M, Chambers S, George P, Slow S, Elmslie J . Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period. Ann Clin Biochem. 2014; 52(Pt 3):352-60. DOI: 10.1177/0004563214545346. View

Roy S, Yuzefpolskaya M, Nandakumar R, Colombo P, Demmer R . Plasma Trimethylamine-N-oxide and impaired glucose regulation: Results from The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS). PLoS One. 2020; 15(1):e0227482. PMC: 6961885. DOI: 10.1371/journal.pone.0227482. View

Mingrone G, Greco A, Capristo E, Benedetti G, Giancaterini A, De Gaetano A . L-carnitine improves glucose disposal in type 2 diabetic patients. J Am Coll Nutr. 1999; 18(1):77-82. DOI: 10.1080/07315724.1999.10718830. View

10.

Lau K, Srivatsav V, Rizwan A, Nashed A, Liu R, Shen R . Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases. Nutrients. 2017; 9(8). PMC: 5579652. DOI: 10.3390/nu9080859. View

11.

Rath S, Rud T, Pieper D, Vital M . Potential TMA-Producing Bacteria Are Ubiquitously Found in Mammalia. Front Microbiol. 2020; 10:2966. PMC: 6964529. DOI: 10.3389/fmicb.2019.02966. View

12.

Sitkin S, Tkachenko E, Vakhitov T . METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS. Eksp Klin Gastroenterol. 2018; 12(12):6-29. View

13.

Bruck K, Stel V, Gambaro G, Hallan S, Volzke H, Arnlov J . CKD Prevalence Varies across the European General Population. J Am Soc Nephrol. 2015; 27(7):2135-47. PMC: 4926978. DOI: 10.1681/ASN.2015050542. View

14.

Bennion B, Daggett V . Counteraction of urea-induced protein denaturation by trimethylamine N-oxide: a chemical chaperone at atomic resolution. Proc Natl Acad Sci U S A. 2004; 101(17):6433-8. PMC: 404062. DOI: 10.1073/pnas.0308633101. View

15.

Jackson-Atogi R, Sinha P, Rosgen J . Distinctive solvation patterns make renal osmolytes diverse. Biophys J. 2013; 105(9):2166-74. PMC: 3824553. DOI: 10.1016/j.bpj.2013.09.019. View

16.

Fu B, Hullar M, Randolph T, Franke A, Monroe K, Cheng I . Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study. Am J Clin Nutr. 2020; 111(6):1226-1234. PMC: 7266689. DOI: 10.1093/ajcn/nqaa015. View

17.

Edwards C, Walk A, Cannavale C, Flemming I, Thompson S, Reeser G . Dietary choline is related to neural efficiency during a selective attention task among middle-aged adults with overweight and obesity. Nutr Neurosci. 2019; 24(4):269-278. DOI: 10.1080/1028415X.2019.1623456. View

18.

Yancey P . Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol. 2005; 208(Pt 15):2819-30. DOI: 10.1242/jeb.01730. View

19.

Miao J, Ling A, Manthena P, Gearing M, Graham M, Crooke R . Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nat Commun. 2015; 6:6498. PMC: 4391288. DOI: 10.1038/ncomms7498. View

20.

Liu M, Han Q, Yang J . Trimethylamine-N-oxide (TMAO) increased aquaporin-2 expression in spontaneously hypertensive rats. Clin Exp Hypertens. 2018; 41(4):312-322. DOI: 10.1080/10641963.2018.1481420. View