Evidence map›Paper›PMID 34020444›Full record

ArticleThe American journal of clinical nutrition2021

Associations of circulating choline and its related metabolites with cardiometabolic biomarkers: an international pooled analysis.

Xiong-Fei Pan, Jae Jeong Yang, Xiao-Ou Shu, Steven C Moore, Nicholette D Palmer, Marta Guasch-Ferré, David M Herrington, Sei Harada, Heather Eliassen, Thomas J Wang and 18 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The American journal of clinical nutrition, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02328677 (ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
8.6field-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.

NCT02328677 recruitingnot on this map

ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis

TypeobservationalSponsorUniversity of UtahRan2007 to 2030Enrolled5,000ConditionsColorectal Cancer
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Article
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  5. Article
  6. Metabolomic Insights Into the Impact of a Maternal Western-Style Diet and Leptin Supplementation During Suckling on Adult Rat Offspring.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  7. Review
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  16. Characteristics of Cancer Epidemiology Studies That Employ Metabolomics: A Scoping Review.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023
    Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 14 institutions in 5 countries.

Xiong-Fei PanDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-9350-9230
Jae Jeong YangDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Steven C MooreDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Marta Guasch-FerréDepartment of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-8525-1404
David M HerringtonSection on Cardiology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Sei HaradaDepartment of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
Heather EliassenDepartment of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
Thomas J WangDivision of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Robert E GersztenBroad Institute of Harvard and Massachusetts Institute of Technology and Cardiovascular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID 0000-0001-8330-4293
Ioanna TzoulakiDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.ORCID 0000-0002-4275-9328
Ibrahim KaramanDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.ORCID 0000-0001-9341-8155
Paul ElliottDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.ORCID 0000-0002-7511-5684
Huilian ZhuDepartment of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.
Lynne E WagenknechtPublic Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Hui CaiDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Qiuyin CaiDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Charles E MatthewsDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Cristina MenniDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Katie A MeyerDepartment of Nutrition and Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
Loren P LipworthDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Jennifer OseDepartment of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA.
Cornelia M UlrichDepartment of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
Danxia YuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Vanderbilt University Medical Center · USNational Cancer Institute · USWake Forest University · USHarvard University · USUK Dementia Research Institute · GBUniversity of Utah · USBroad Institute · USBrown Foundation · USKeio University · JPKing's College London · GBSouthwestern Medical Center · USSun Yat-sen University · CNUniversity of Ioannina · GRUniversity of North Carolina at Chapel Hill · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Life Course Cancer Epidemiology Cohort in WomenU01CA176726 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 2018 to 2025
$22.4M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Southern Community Cohort StudyU01CA202979 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLOT, WILLIAM J., SHRUBSOLE, MARTHA J. · 2016 to 2025
$22.0M
SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTERN01HC95159 · NHLBI · UNIVERSITY OF WASHINGTON · PI KRONMAL, RICHARD A · 2007 to 2014
$19.6M
Transdisciplinary Team Science in Colorectal Cancer Prognosis: the ColoCare StudyU01CA206110 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jane C. Figueiredo, Christopher I Li · 2016 to 2026
$18.6M
Physical Activity, Energy Balance, and CancerZIACP010197 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI ALBANES, DEMETRIUS · 2009 to 2025
$17.5M
Genomic and Proteomic Architecture of AtherosclerosisR01HL111362 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HERRINGTON, DAVID MCLEOD · 2012 to 2021
$17.2M
Cancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0M
British Heart Foundation MR/M016560/1Department of Health HPRU-2012-10141Medical Research Council MR/L01341X/1Medical Research Council MR/M016560/1Medical Research Council MR/R023484/1NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA067262NCI NIH HHS U01 CA049449NCI NIH HHS U01 CA067262NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA176726NCI NIH HHS U01 CA202979NCI NIH HHS U01 CA206110NCI NIH HHS UM1 CA173640NCI NIH HHS UM1 CA176726NCI NIH HHS UM1 CA182910NCI NIH HHS UM1 CA186107NHLBI NIH HHS HHSN268201300008CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201600001CNHLBI NIH HHS HHSN268201600002CNHLBI NIH HHS HHSN268201600003CNHLBI NIH HHS HHSN268201600004CNHLBI NIH HHS HHSN268201600018CNHLBI NIH HHS HHSN268201800003INHLBI NIH HHS HHSN268201800004INHLBI NIH HHS HHSN268201800005INHLBI NIH HHS HHSN268201800006INHLBI NIH HHS HHSN268201800007INHLBI NIH HHS K01 HL127159NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N01HC95159NHLBI NIH HHS N01HC95160NHLBI NIH HHS N01HC95161NHLBI NIH HHS N01HC95162NHLBI NIH HHS N01HC95163NHLBI NIH HHS N01HC95164NHLBI NIH HHS N01HC95165NHLBI NIH HHS N01HC95166NHLBI NIH HHS N01HC95167NHLBI NIH HHS N01HC95168NHLBI NIH HHS R01 HL060944NHLBI NIH HHS R01 HL111362NHLBI NIH HHS R01 HL133932NHLBI NIH HHS R01 HL149779NHLBI NIH HHS R21 HL140375NHLBI NIH HHS UL1-TR-000040NIDDK NIH HHS R01 DK108159NIDDK NIH HHS R01 DK118062Wellcome TrustWellcome Trust 212904/Z/18/Z
6 · The paper itself

Abstract

backgroundCholine is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear.

objectiveWe examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants.

methodsThe cross-sectional analyses included 32,853 participants from 17 studies, who were free of cancer, cardiovascular diseases, chronic kidney diseases, and inflammatory bowel disease. In each study, metabolites and biomarkers were log-transformed and standardized by means and SDs, and linear regression coefficients (β) and 95% CIs were estimated with adjustments for potential confounders. Study-specific results were combined by random-effects meta-analyses. A false discovery rate <0.05 was considered significant.

resultsWe observed moderate positive associations of circulating choline, carnitine, and DMG with creatinine [β (95% CI): 0.136 (0.084, 0.188), 0.106 (0.045, 0.168), and 0.128 (0.087, 0.169), respectively, for each SD increase in biomarkers on the log scale], carnitine with triglycerides (β = 0.076; 95% CI: 0.042, 0.109), homocysteine (β = 0.064; 95% CI: 0.033, 0.095), and LDL cholesterol (β = 0.055; 95% CI: 0.013, 0.096), DMG with homocysteine (β = 0.068; 95% CI: 0.023, 0.114), insulin (β = 0.068; 95% CI: 0.043, 0.093), and IL-6 (β = 0.060; 95% CI: 0.027, 0.094), but moderate inverse associations of betaine with triglycerides (β = -0.146; 95% CI: -0.188, -0.104), insulin (β = -0.106; 95% CI: -0.130, -0.082), homocysteine (β = -0.097; 95% CI: -0.149, -0.045), and total cholesterol (β = -0.074; 95% CI: -0.102, -0.047). In the whole pooled population, no dietary factor was associated with circulating choline; red meat intake was associated with circulating carnitine [β = 0.092 (0.042, 0.142) for a 1 serving/d increase], whereas plant protein was associated with circulating betaine [β = 0.249 (0.110, 0.388) for a 5% energy increase]. Demographics, lifestyle, and metabolic disease history showed differential associations with these metabolites.

conclusionsCirculating choline, carnitine, and DMG were associated with unfavorable cardiometabolic risk profiles, whereas circulating betaine was associated with a favorable cardiometabolic risk profile. Future prospective studies are needed to examine the associations of these metabolites with incident cardiovascular events.

Indexed as

BetaineBiomarkersCardiovascular DiseasesCarnitineCholineCreatinineCross-Sectional StudiesDietHumansSarcosineBetaineBiomarkersCarnitineCholineCreatininedimethylglycineSarcosinebetainebiomarkerscardiometabolic diseasecarnitinecholinedimethylglycine

Identifiers

PMID34020444
PMCPMC8408854
OpenAlexW3161979973

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Registered trials

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.