Evidence map›Paper›PMID 32055828›Full record

ArticleThe American journal of clinical nutrition2020

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.

Benjamin C Fu, Meredith A J Hullar, Timothy W Randolph, Adrian A Franke, Kristine R Monroe, Iona Cheng, Lynne R Wilkens, John A Shepherd, Margaret M Madeleine, Loïc Le Marchand and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of clinical nutrition, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 3 pooled it
11.4field-weighted citation impact, top 1% 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

113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
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  8. Gut microbes · 2026
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53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 1 country.

Benjamin C FuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Meredith A J HullarPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Timothy W RandolphPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Adrian A FrankeEpidemiology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
Kristine R MonroeDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
Iona ChengDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Lynne R WilkensEpidemiology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
John A ShepherdEpidemiology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
Margaret M MadeleinePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Loïc Le MarchandEpidemiology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
Unhee LimEpidemiology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
Johanna W LampePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
University of Hawaiʻi at Mānoa · USFred Hutch Cancer Center · USHarvard University · USUniversity of California, San Francisco · USUniversity of Southern California · USUniversity of Washington · US

Funding

University of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Xin Chen · 1996 to 2026
$56.2M
Recruitment and Data CollectionP01CA168530 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI LE MARCHAND, LOIC · 2012 to 2016
$19.9M
Training Program in Cancer EpidemiologyT32CA009001 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI A. Heather Eliassen, Meir Stampfer · 1985 to 2026
$17.3M
Contributing Factors and Consequences of Cancer Health DisparitiesT32CA094880 · NCI · UNIVERSITY OF WASHINGTON · PI Christopher I Li, AMANDA IRENE PHIPPS · 2017 to 2026
$3.7M
TMAO, the Gut Microbiome, and Colorectal Cancer Risk in the Multiethnic CohortR01CA204368 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI LAMPE, JOHANNA W, LIM, UNHEE · 2016 to 2019
$1.3M
FHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600k
NCI NIH HHS P01 CA168530NCI NIH HHS P30 CA071789NCI NIH HHS R01 CA204368NCI NIH HHS T32 CA009001NCI NIH HHS T32 CA094880NIH HHS S10 OD020069
6 · The paper itself

Abstract

backgroundTrimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well understood and few human studies have investigated microbes involved in its production.

objectivesOur study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO.

methodsWe conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60-77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1-V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution.

resultsMedian (IQR) concentration of plasma TMAO was 3.05 μmol/L (2.10-4.60 μmol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate < 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter smithii.

conclusionsPlasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways.

Indexed as

Gastrointestinal MicrobiomeAdiposityAgedBacteriaBetaineBiomarkersCardiovascular DiseasesCarnitineCholineCohort StudiesCross-Sectional StudiesFemaleHumansMaleMethylaminesMiddle AgedBetaineBiomarkersCarnitineCholineMethylaminestrimethyloxaminebetainebiomarkerscardiometaboliccarnitinecholineinflammationmicrobiomeTMAO

Identifiers

PMID32055828
PMCPMC7266689
OpenAlexW3005948968

What OpenQuestion holds

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Registered trials

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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.