CoChat
Sign Up
Cited by 84Acute Ischemic Stroke ManagementGut microbiota and healthAbdominal vascular conditions and treatments

Serum levels of Trimethylamine-N-oxide in patients with ischemic stroke

Open access
Rexidamu, Maimaiti, Li, Hongmei, Jin, Haiyan, Huang, Jiankang·2019·Bioscience Reports
DOI 10.1042/bsr20190515PMC PMC6579976
Open this paper in CoChat — free account

Abstract

Objective: Accumulating evidence suggests that Trimethylamine-N-oxide (TMAO), a gut microbial metabolite, is implicated in the pathogenesis of many cardiovascular diseases. The aim of the present study was to investigate the serum levels of TMAO in Chinese patients with ischemic stroke. Method: In the present study, 255 consecutive patients with first-ever acute ischemic stroke and 255 age and gender-matched healthy volunteers were included for testing serum TMAO. Stroke severity was determined by the NIH Stroke Scale (NIHSS). The stroke severity was dichotomized as minor (NIHSS ≤ 5) and moderate-to-high clinical severity (NIHSS > 6). Results: The serum levels of TMAO in stroke ranged from 0.5 to 18.3 μM, with a median value of 5.8 (interquartile range (IQR), 3.3–10.0) μM, which was higher than in those controls (3.9; IQR, 2.6–6.1 μM). The median level of TMAO in those patients was significantly lower than in those moderate-to-high stroke patients (4.1 μM [IQR, 2.8–6.2] vs. 9.1 μM [5.1–11.0]; P<0.001). In univariate and multivariable models, the unadjusted risk of moderate-to-high stroke was increased by 31% (odds ratio (OR) = 1.31 [95% confidence interval (CI): 1.21–1.42], P<0.001) and 22% (OR = 1.22; 95% CI = 1.08–1.32; P<0.001), when TMAO was increased each by 1 μM. Based on the receiver operating characteristic (ROC) curve, the optimal cut-off value of serum level of TMAO as an indicator for screening of moderate-to-high stroke was estimated to be 6.6 μM, which yielded a sensitivity of 69.3 % and a specificity of 79.0%, with the area under the curve at 0.750 (95% CI, 0.687–0.812). Conclusions: Higher TMAO levels were associated with increased risk of first ischemic stroke and worse neurological deficit in Chinese patients.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1042/bsr20190515

Cites

12 of 12 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Previous studies have determined an association between TMAO from dietary choline or lecithin and stroke.

    “Although, to our knowledge, no trials have examined the effect of α-GPC on stroke, previous studies have determined the association between TMAO from dietary choline or lecithin and stroke.15,16,23”

    From Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years (2021) · cites this paper as [23]

    The Introduction says TMAO is produced from dietary choline, and the Conclusions report an association between higher TMAO levels and first ischemic stroke in Chinese patients. The paper does not mention lecithin or establish that the TMAO measured in its patients came from either dietary source; the Discussion notes that dietary intake before sampling was unknown. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Patients with ischemic stroke had higher levels of TMAO, suggesting that higher TMAO levels were associated with an increased risk of the first stroke.

    “Another case-control study also reported that patients with ischemic stroke had higher levels of TMAO, suggesting that higher TMAO levels were associated with an increased risk of the first stroke.23”

    From Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years (2021) · cites this paper as [23]

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

Flagged first, then by citations

Research works printed but not linked: 27

  1. [1]Tang W.H.W., Wang Z., Li X.S. (2017) Increased trimethylamine N-oxide portends high mortality risk independent of glycemic control in patients with type 2 diabetes mellitus. Clin. Chem. 63, 297– 306 10.1373/clinchem.2016.263640 27864387 PMC5659115 · DOI
  2. [2]Wang Z., Klipfell E., Bennett B.J., Koeth R., Levison B.S., Dugar B. (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57– 63 10.1038/nature09922 21475195 PMC3086762 · DOI · Paper page
  3. [4]Lang D.H., Yeung C.K., Peter R.M., Ibarra C., Gasser R., Itagaki K. (1998) Isoform specificity of trimethylamine N-oxygenation by human flavin-containing monooxygenase (FMO) and P450 enzymes: selective catalysis by FMO3. Biochem. Pharmacol. 56, 1005– 1012 10.1016/S0006-2952(98)00218-4 9776311 · DOI · Paper page
  4. [5]Troseid M., Ueland T., Hov J.R., Svardal A., Gregersen I., Dahl C.P. (2015) Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J. Intern. Med. 277, 717– 726 10.1111/joim.12328 25382824 · DOI · Paper page
  5. [6]Tang W.H.W., Wang Z., Fan Y. (2014) Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J. Am. Coll. Cardiol. 64, 1908– 1914 10.1016/j.jacc.2014.02.617 25444145 PMC4254529 · DOI · Paper page
  6. [7]Suzuki T., Heaney L.M., Jones D.J.L. (2017) Trimethylamine N-oxide and risk stratification after acute myocardial infarction. Clin. Chem. 63, 420– 428 10.1373/clinchem.2016.264853 28062632 · DOI
  7. [9]Zheng L., Zheng J., Xie Y. (2019) Serum gut microbe-dependent trimethylamine N-oxide improves the prediction of future cardiovascular disease in a community-based general population. Atherosclerosis 280, 126– 131 10.1016/j.atherosclerosis.2018.11.010 30508691 · DOI
  8. [10]Zhu W., Gregory J.C., Org E. (2016) Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165, 111– 124 10.1016/j.cell.2016.02.011 26972052 PMC4862743 · DOI · Paper page
  9. [12]Sheng Z., Tan Y., Liu C. (2019) Relation of circulating trimethylamine N-oxide with coronary atherosclerotic burden in patients With ST-segment elevation myocardial infarction. Am. J. Cardiol. 123, 894– 898 10.1016/j.amjcard.2018.12.018 30594289 · DOI
  10. [13]Haghikia A., Li X.S., Liman T.G. (2018) 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. 38, 2225– 2235 10.1161/ATVBAHA.118.311023 29976769 PMC6202215 · DOI
  11. [14]Hatano S. (1976) Experience from a multicentre stroke register: a preliminary report. Bull. World Health Organ. 54, 541– 553 1088404 PMC2366492
  12. [15]Tu W.J., Dong X., Zhao S.J., Yang D.G. and Chen H. (2013) Prognostic value of plasma neuroendocrine biomarkers in patients with acute ischemic stroke. J. Neuroendocrinol. 25, 771– 778 10.1111/jne.12052 23701638 · DOI
  13. [16]Brott T., Adams H.P. Jr, Olinger C.P., Marler J.R., Barsanl W.G., Biller J. (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20, 864– 870 10.1161/01.STR.20.7.864 2749846 · DOI
  14. [17]Buck B.H., Liebeskind D.S., Saver J.L., Bang O.Y., Starkman S., Ali L.K. (2007) Association of higher serum calcium levels with smaller infarct volumes in acute ischemic stroke. Arch. Neurol. 64, 1287– 1291 10.1001/archneur.64.9.1287 17846267 · DOI
  15. [18]Tu W.J., Qiu H.C., Cao J.L. (2018) Circulating serum retinoic acid for prediction of mortality in ischemic stroke. Neurology 92, e1678– e1687 10.1212/WNL.0000000000007261 30850446 · DOI
  16. [19]Wang Z., Tang W.H., Buffa J.A., Fu X., Britt E.B., Koeth R.A. (2014) Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur. Heart J. 35, 904– 910 10.1093/eurheartj/ehu002 24497336 PMC3977137 · DOI · Paper page
  17. [20]Daubail B., Jacquin A., Guilland J.C. (2013) Serum 25‐hydroxyvitamin D predicts severity and prognosis in stroke patients. Eur. J. Neurol. 20, 57– 61 10.1111/j.1468-1331.2012.03758.x 22632854 · DOI
  18. [22]Winek K., Engel O., Koduah P., Heimesaat M.M., Fischer A., Bereswill S. (2016) Depletion of cultivatable gut microbiota by broad-spectrum antibiotic pretreatment worsens outcome after murine stroke. Stroke 47, 1354– 1363 10.1161/STROKEAHA.115.011800 27056982 PMC4839545 · DOI
  19. [24]Liang Z., Dong Z., Guo M. (2018) Trimethylamine N‐oxide as a risk marker for ischemic stroke in patients with atrial fibrillation. J. Biochem. Mol. Toxicol. e22246, 10.1102/JBT.22246 30370581 · DOI
  20. [25]Nie J., Xie L., Zhao B. (2018) Serum trimethylamine N-oxide concentration is positively associated with first stroke in hypertensive patients. Stroke 49, 2021– 2028 10.1161/STROKEAHA.118.021997 30354996 · DOI · Paper page
  21. [27]Senthong V., Li X.S., Hudec T. (2016) Plasma trimethylamine N-oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with atherosclerotic burden. J. Am. Coll. Cardiol. 67, 2620– 2628 10.1016/j.jacc.2016.03.546 27256833 PMC4893167 · DOI · Paper page
  22. [29]Qi J., You T., Li J., Pan T., Xiang L., Han Y. (2018) Circulating trimethylamine N‐oxide and the risk of cardiovascular diseases: a systematic review and meta‐analysis of 11 prospective cohort studies. J. Cell. Mol. Med. 22, 185– 194 10.1111/jcmm.13307 28782886 PMC5742728 · DOI · Paper page
  23. [30]Meyer K.A., Benton T.Z., Bennett B.J. (2016) Microbiota‐dependent metabolite trimethylamine N‐oxide and coronary artery calcium in the coronary artery risk development in young adults study (CARDIA). J. Am. Heart Assoc. 5, e003970 10.1161/JAHA.116.003970 27792658 PMC5121500 · DOI
  24. [32]Yamashiro K., Tanaka R., Urabe T., Ueno Y., Yamashiro Y., Nomoto K. (2017) Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLoS ONE 12, e0171521 10.1371/journal.pone.0171521 28166278 PMC5293236 · DOI
  25. [33]Kelly J.R., Kennedy P.J., Cryan J.F., Dinan T.G., Clarke G. and Hyland N.P. (2015) Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell Neurosci. 9, 392 10.3389/fncel.2015.00392 26528128 PMC4604320 · DOI · Paper page
  26. [34]Nagatomo Y. and Tang W.H. (2015) Intersections between microbiome and heart failure: revisiting the gut hypothesis. J. Card. Fail. 21, 973– 980 10.1016/j.cardfail.2015.09.017 26435097 PMC4666782 · DOI · Paper page
  27. [35]Adrie C., Parlato M., Salmi L., Adib-Conquy M., Bical O., Deleuze P. (2015) Bacterial translocation and plasma cytokines during transcatheter and open-heart aortic valve implantation. Shock 43, 62– 67 10.1097/SHK.0000000000000262 25202829 · DOI

Cited by

Sorted by citations

Authors
Rexidamu, M., Li, H., Jin, H., & Huang, J.
Affiliations
  • Department of Neurology, Kashgar Prefecture Second People’s Hospital, Kashgar, Xinjiang Uygur Autonomous Region, China
  • Shanghai Jiao Tong University (CN)
Corresponding author
Huang, Jiankang
ORCID
Venue
Bioscience Reports
Publisher
Portland Press Ltd.
Published
2019-06
Volume
39
Issue
6
ISSN
  • 0144-8463 (ISSN-L)
  • 1573-4935
DOI
10.1042/bsr20190515
PMC
PMC6579976
OpenAlex
W2947117332
Cited by
84
References
12
Citations by year
2026: 5 · 2025: 7 · 2024: 12 · 2023: 23 · 2022: 19 · 2021: 7 · 2020: 10 · 2019: 1
FWCI
7.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioscience Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Surgery › Abdominal vascular conditions and treatments
Keywords
trimethylamine N-oxide, ischemic stroke, gut microbiota metabolites, stroke severity, serum biomarkers, stroke risk prediction, neurological deficit, Chinese patients, stroke screening
MeSH terms
Aged, Brain Ischemia, Female, Humans, Male, Methylamines, Middle Aged, Risk Factors, Stroke

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