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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 55, Issue 2


Intra-individual variation of plasma trimethylamine-N-oxide (TMAO), betaine and choline over 1 year

Tilman Kühn
  • Corresponding author
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Phone: +49 6221 42 3184, Fax: +49 6221 42 2203
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sabine Rohrmann
  • Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Disorn Sookthai / Theron Johnson / Verena Katzke / Rudolf Kaaks / Arnold von Eckardstein / Daniel Müller
Published Online: 2016-07-22 | DOI: https://doi.org/10.1515/cclm-2016-0374



Circulating trimethylamine-N-oxide (TMAO) has been implicated in the development of cardiovascular and chronic kidney diseases (CKD). However, while higher TMAO levels have been associated with increased risks of cardiovascular or renal events in first prospective studies, it remained unclear how much plasma TMAO concentrations vary over time.


We measured fasting plasma levels of TMAO and two of its precursors, betaine and choline by LC-MS, in two samples of 100 participants of the European Investigation into Cancer and Nutrition (EPIC)-Heidelberg study (age range: 47–80 years, 50% female) that were collected 1 year apart, and assessed their intra-individual variation by Spearman’s correlation coefficients (ρ).


Correlations of metabolite concentrations over 1 year were at ρ=0.29 (p=0.003) for TMAO, ρ=0.81 (p<0.001) for betaine, and ρ=0.61 (p<0.001) for choline. Plasma levels of TMAO were not significantly associated with food intake, lifestyle factors, or routine biochemistry parameters such as C-reactive protein (CRP), low-density lipoprotein (LDL)-cholesterol, or creatinine.


In contrast to fasting plasma concentrations of betaine and choline, concentrations of TMAO were more strongly affected by intra-individual variation over 1 year in adults from the general population. The modest correlation of TMAO levels over time should be considered when interpreting associations between TMAO levels and disease endpoints.

This article offers supplementary material which is provided at the end of the article.

Keywords: betaine; choline; intra-individual variation; TMAO


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About the article

Received: 2016-04-29

Accepted: 2016-06-23

Published Online: 2016-07-22

Published in Print: 2017-02-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: The EPIC-Heidelberg study was sponsored by the German Federal Ministry of Education and Research (Grant No. 01ER0809) and the German Cancer Research Center (DKFZ). The present study was further supported by the Helmholtz Association of German Research Centres (Portfolio Theme: Metabolic Dysfunction).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 55, Issue 2, Pages 261–268, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2016-0374.

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