Component

Trimethylamine N-oxide / TMAO

Trimethylamine N-oxide / TMAO. Species, exposure and limitations are retained in each linked claim.

7 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. In male ApoE-null mice expressing human CETP, carnitine raised TMAO but higher TMAO correlated with smaller aortic lesions across treatment groups.

    Trimethylamine N-oxide / TMAO → Mouse atherosclerotic lesions during carnitine exposure, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Twelve-week carnitine and/or methimazole study; hCETP-expressing ApoE-null mice.
    limitations
    The inverse correlation does not establish TMAO protection; genotype, sex and co-treatment differ.
    nutrient_topic
    L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
    plain_language
    Another mouse model did not show the same adverse relationship.
    primary_references
    L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26584136/ · DOI 10.1016/j.atherosclerosis.2015.10.108

    L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 418–424

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Twelve-week carnitine and/or methimazole study; hCETP-expressing ApoE-null mice. · source_derived_draft · unverified_draft

    ## l-carnitine-mouse-atheroma-inverse Another mouse model did not show the same adverse relationship. In male ApoE-null mice expressing human CETP, carnitine raised TMAO but higher TMAO correlated with smaller aortic lesions across treatment groups. Model: Twelve-week carnitine and/or methimazole study; hCETP-expressing ApoE-null mice. Limitations: The inverse correlation does not establish TMAO protection; genotype, sex and co-treatment differ. Evidence access: Primary abstract L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26584136/ · DOI 10.1016/j.atherosclerosis.2015.10.108
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. FMO1 also oxidized TMA in the comparison, with FMO3 showing about tenfold higher specific activity.

    Human flavin-containing monooxygenase 1 / FMO1 → Trimethylamine / TMA source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"}
    experimental_model
    Recombinant FMO comparison, mouse manipulation and human expression analyses
    exposure
    FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing
    limitations
    Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human recombinant FMO1 assay
    plain_language
    The related enzymes differed quantitatively in this preparation.
    primary_references
    [choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
    tissue_or_cell_type
    Hepatic TMA oxidation

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1127–1138

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FMO comparison, mouse manipulation and human expression analyses · source_derived_draft · unverified_draft

    ### choline-fmo1-tmao FMO1 also oxidized TMA in the comparison, with FMO3 showing about tenfold higher specific activity. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related enzymes differed quantitatively in this preparation. organism: Human recombinant FMO1 assay tissue_or_cell_type: Hepatic TMA oxidation experimental_model: Recombinant FMO comparison, mouse manipulation and human expression analyses limitations: Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species. exposure: FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing evidence_span: {"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"} [choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
    Complete structured claim and evidence

  2. The enzyme comparison demonstrated FMO3-mediated oxidation of TMA to TMAO.

    Human flavin-containing monooxygenase 3 → Trimethylamine / TMA source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"}
    experimental_model
    Recombinant FMO comparison, mouse manipulation and human expression analyses
    exposure
    FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing
    limitations
    Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human recombinant FMO3 assay
    plain_language
    The liver-side enzyme processes a product generated by microbial metabolism.
    primary_references
    [choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
    tissue_or_cell_type
    Hepatic TMA oxidation

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1114–1125

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FMO comparison, mouse manipulation and human expression analyses · source_derived_draft · unverified_draft

    ### choline-fmo3-tmao The enzyme comparison demonstrated FMO3-mediated oxidation of TMA to TMAO. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver-side enzyme processes a product generated by microbial metabolism. organism: Human recombinant FMO3 assay tissue_or_cell_type: Hepatic TMA oxidation experimental_model: Recombinant FMO comparison, mouse manipulation and human expression analyses limitations: Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species. exposure: FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing evidence_span: {"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"} [choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
    Complete structured claim and evidence

  3. Chronic carnitine exposure increased microbial gamma-butyrobetaine-to-TMA conversion; baseline labeled TMAO generation was greater in omnivores.

    L-Carnitine → Human gut microbial gamma-butyrobetaine-to-TMA conversion source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human isotope challenges before/after at least two months of supplementation.
    limitations
    A metabolite-production study does not prove cardiovascular events from a given supplement dose.
    nutrient_topic
    L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
    plain_language
    The response depends partly on microbial adaptation and diet.
    primary_references
    l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601

    L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 354–360

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human isotope challenges before/after at least two months of supplementation. · source_derived_draft · unverified_draft

    ## l-carnitine-microbial-induction The response depends partly on microbial adaptation and diet. Chronic carnitine exposure increased microbial gamma-butyrobetaine-to-TMA conversion; baseline labeled TMAO generation was greater in omnivores. Model: Human isotope challenges before/after at least two months of supplementation. Limitations: A metabolite-production study does not prove cardiovascular events from a given supplement dose. Evidence access: Primary abstract l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30530985/ · DOI 10.1172/JCI94601
    Complete structured claim and evidence

  4. Chronic dietary carnitine increased atherosclerosis in the studied mice; concurrent microbial suppression prevented that increase.

    L-Carnitine → Mouse atherosclerotic lesions during carnitine exposure, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Atherosclerosis-prone mice; dietary intervention with microbiota suppression comparison.
    limitations
    Human cohort associations in the same paper are not randomized supplement effects.
    nutrient_topic
    L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
    plain_language
    One mouse study linked carnitine metabolism to more arterial lesions.
    primary_references
    Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23563705/ · DOI 10.1038/nm.3145

    L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 410–416

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Atherosclerosis-prone mice; dietary intervention with microbiota suppression comparison. · source_derived_draft · unverified_draft

    ## l-carnitine-mouse-atheroma-increase One mouse study linked carnitine metabolism to more arterial lesions. Chronic dietary carnitine increased atherosclerosis in the studied mice; concurrent microbial suppression prevented that increase. Model: Atherosclerosis-prone mice; dietary intervention with microbiota suppression comparison. Limitations: Human cohort associations in the same paper are not randomized supplement effects. Evidence access: Primary abstract Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23563705/ · DOI 10.1038/nm.3145
    Complete structured claim and evidence

  5. Adding E. timonensis to defined microbial communities in gnotobiotic mice completed carnitine-to-TMA conversion, raised TMAO and enhanced thrombosis after arterial injury.

    Emergencia timonensis → Gnotobiotic mouse arterial-injury thrombosis potential source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Gnotobiotic mouse transplantation with defined communities.
    limitations
    Not a human clinical-event trial.
    nutrient_topic
    L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
    plain_language
    A microbial addition tested a downstream vascular consequence.
    primary_references
    The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34949826/ · DOI 10.1038/s41564-021-01010-x

    L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 402–408

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Gnotobiotic mouse transplantation with defined communities. · source_derived_draft · unverified_draft

    ## l-carnitine-mouse-microbial-thrombosis A microbial addition tested a downstream vascular consequence. Adding E. timonensis to defined microbial communities in gnotobiotic mice completed carnitine-to-TMA conversion, raised TMAO and enhanced thrombosis after arterial injury. Model: Gnotobiotic mouse transplantation with defined communities. Limitations: Not a human clinical-event trial. Evidence access: Primary abstract The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34949826/ · DOI 10.1038/s41564-021-01010-x
    Complete structured claim and evidence

  6. Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion.

    Berberine → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"}
    experimental_model
    Choline tracer, microbial culture, microbiome transfer and atherosclerosis models
    exposure
    Choline-supplemented chow and berberine; deuterated choline tracing
    limitations
    Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.
    nutrient_topic
    Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
    organism
    C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia
    plain_language
    A microbial change was linked to a circulating metabolite in animals.
    primary_references
    [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
    tissue_or_cell_type
    Microbial choline metabolism

    Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1091–1102

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft

    ### berberine-tmao-mice Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A microbial change was linked to a circulating metabolite in animals. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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