Evidence map›Paper›PMID 32267921›Full record

ArticleCardiovascular research2021

Plasma levels of trimethylamine-N-oxide can be increased with 'healthy' and 'unhealthy' diets and do not correlate with the extent of atherosclerosis but with plaque instability.

Yen Chin Koay, Yung-Chih Chen, Jibran A Wali, Alison W S Luk, Mengbo Li, Hemavarni Doma, Rosa Reimark, Maria T K Zaldivia, Habteab T Habtom, Ashley E Franks and 6 more

Open access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 4 pooled it
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 4 syntheses or guidelines pooled it, 110 citations in OpenAlex.

  1. Pooled it
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  4. Pooled it
  5. Trial
  6. Gut microbes · 2026
    Review
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  20. The gut microbiota in thrombosis.Nature reviews. Cardiology · 2025
    Review

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Yen Chin KoayHeart Research Institute, The University of Sydney, Sydney, NSW, Australia.
Yung-Chih ChenBaker Heart & Diabetes Institute, Melbourne, VIC, Australia.
Jibran A WaliCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Alison W S LukCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Mengbo LiCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Hemavarni DomaBaker Heart & Diabetes Institute, Melbourne, VIC, Australia.
Rosa ReimarkBaker Heart & Diabetes Institute, Melbourne, VIC, Australia.
Maria T K ZaldiviaBaker Heart & Diabetes Institute, Melbourne, VIC, Australia.
Habteab T HabtomDepartment of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia.
Ashley E FranksDepartment of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia.
Gabrielle Fusco-AllisonHeart Research Institute, The University of Sydney, Sydney, NSW, Australia.
Jean YangCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Andrew HolmesCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Stephen J SimpsonCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Karlheinz PeterBaker Heart & Diabetes Institute, Melbourne, VIC, Australia.
John F O'SullivanHeart Research Institute, The University of Sydney, Sydney, NSW, Australia.
The University of Sydney · AUBaker Heart and Diabetes Institute · AULa Trobe University · AU

Funding

Metabolomic predictors of insulin resistance and diabetesR01DK081572 · NIDDK · VANDERBILT UNIVERSITY · PI CLISH, CLARY B, GERSZTEN, ROBERT E · 2008 to 2025
$9.3M
SLEEP AND ENTRAINMENT OF SCN FUNCTIONR01HL064278 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI STROHL, KINGMAN PERKINS · 1999 to 2002
$871k
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NHLBI NIH HHS N02 HL064278NIDDK NIH HHS R01 DK081572
6 · The paper itself

Abstract

aimsThe microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has attracted major interest and controversy both as a diagnostic biomarker and therapeutic target in atherothrombosis. METHODS AND

resultsPlasma TMAO increased in mice on 'unhealthy' high-choline diets and notably also on 'healthy' high-fibre diets. Interestingly, TMAO was found to be generated by direct oxidation in the gut in addition to oxidation by hepatic flavin-monooxygenases. Unexpectedly, two well-accepted mouse models of atherosclerosis, ApoE-/- and Ldlr-/- mice, which reflect the development of stable atherosclerosis, showed no association of TMAO with the extent of atherosclerosis. This finding was validated in the Framingham Heart Study showing no correlation between plasma TMAO and coronary artery calcium score or carotid intima-media thickness (IMT), as measures of atherosclerosis in human subjects. However, in the tandem-stenosis mouse model, which reflects plaque instability as typically seen in patients, TMAO levels correlated with several characteristics of plaque instability, such as markers of inflammation, platelet activation, and intraplaque haemorrhage.

conclusionsDietary-induced changes in the microbiome, of both 'healthy' and 'unhealthy' diets, can cause an increase in the plasma level of TMAO. The gut itself is a site of significant oxidative production of TMAO. Most importantly, our findings reconcile contradictory data on TMAO. There was no direct association of plasma TMAO and the extent of atherosclerosis, both in mice and humans. However, using a mouse model of plaque instability we demonstrated an association of TMAO plasma levels with atherosclerotic plaque instability. The latter confirms TMAO as being a marker of cardiovascular risk.

Indexed as

Diet, HealthyGastrointestinal MicrobiomePlaque, AtheroscleroticAnimal FeedAnimalsAtherosclerosisBacteriaBiomarkersCarotid Artery DiseasesCholineCoronary Artery DiseaseDietary FiberDisease Models, AnimalDysbiosisHeart Disease Risk FactorsHumansBiomarkersCholineDietary FiberMethylaminesReceptors, LDLtrimethyloxamineAtherosclerosisBacterial microbiomeTMAOUnstable plaque

Identifiers

PMID32267921
PMCPMC8599768
OpenAlexW3014566317

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.