Component

Circulating trimethylamine N-oxide concentration

Circulating trimethylamine N-oxide concentration. Species, exposure and limitations are retained in each linked claim.

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

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. The highest versus lowest TMAO quartile was associated with a three-year event hazard ratio of 2.54 (95% CI 1.96–3.28) in the angiography cohort.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"}
    experimental_model
    Human isotope challenge with antibiotics plus a separate observational cohort
    exposure
    Two eggs plus d9-PC before/after antibiotics; three-year event follow-up
    limitations
    The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human
    plain_language
    A blood marker predicted risk in this clinical cohort; that alone does not prove a dietary cause.
    primary_references
    [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
    tissue_or_cell_type
    Healthy challenge participants; 4007 angiography patients in the outcome cohort

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1166–1177

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope challenge with antibiotics plus a separate observational cohort · source_derived_draft · unverified_draft

    ### choline-tmao-event-association The highest versus lowest TMAO quartile was associated with a three-year event hazard ratio of 2.54 (95% CI 1.96–3.28) in the angiography cohort. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blood marker predicted risk in this clinical cohort; that alone does not prove a dietary cause. organism: Human tissue_or_cell_type: Healthy challenge participants; 4007 angiography patients in the outcome cohort experimental_model: Human isotope challenge with antibiotics plus a separate observational cohort limitations: The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events. exposure: Two eggs plus d9-PC before/after antibiotics; three-year event follow-up evidence_span: {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"} [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
    Complete structured claim and evidence

What acts on it

  1. Antibiotics suppressed challenge-associated TMAO, which reappeared after antibiotic withdrawal.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"}
    experimental_model
    Human isotope challenge with antibiotics plus a separate observational cohort
    exposure
    Two eggs plus d9-PC before/after antibiotics; three-year event follow-up
    limitations
    A mechanistic research intervention, not a recommendation to use antibiotics to manage TMAO.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human
    plain_language
    The challenge response depended on intestinal microbes.
    primary_references
    [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
    tissue_or_cell_type
    Healthy challenge participants; 4007 angiography patients in the outcome cohort

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1153–1164

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope challenge with antibiotics plus a separate observational cohort · source_derived_draft · unverified_draft

    ### choline-antibiotics-tmao Antibiotics suppressed challenge-associated TMAO, which reappeared after antibiotic withdrawal. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The challenge response depended on intestinal microbes. organism: Human tissue_or_cell_type: Healthy challenge participants; 4007 angiography patients in the outcome cohort experimental_model: Human isotope challenge with antibiotics plus a separate observational cohort limitations: A mechanistic research intervention, not a recommendation to use antibiotics to manage TMAO. exposure: Two eggs plus d9-PC before/after antibiotics; three-year event follow-up evidence_span: {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"} [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
    Complete structured claim and evidence
  2. All three bitartrate-containing arms increased fasting TMAO, p<0.0001.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
    experimental_model
    Five-arm randomized four-week choline-form intervention
    exposure
    Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
    limitations
    Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human
    plain_language
    Free-choline salt supplementation raised this marker in the trial.
    primary_references
    [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
    tissue_or_cell_type
    82 healthy volunteers with normal renal function

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1179–1190

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft

    ### choline-bitartrate-tmao All three bitartrate-containing arms increased fasting TMAO, p<0.0001. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free-choline salt supplementation raised this marker in the trial. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
    Complete structured claim and evidence
  3. Four eggs daily did not significantly raise fasting TMAO, p=0.28.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
    experimental_model
    Five-arm randomized four-week choline-form intervention
    exposure
    Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
    limitations
    Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human
    plain_language
    The food intervention did not reproduce the salt-supplement result.
    primary_references
    [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
    tissue_or_cell_type
    82 healthy volunteers with normal renal function

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1205–1216

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft

    ### choline-eggs-tmao-null Four eggs daily did not significantly raise fasting TMAO, p=0.28. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The food intervention did not reproduce the salt-supplement result. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
    Complete structured claim and evidence
  4. PC supplements did not significantly raise fasting TMAO, p=0.27.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
    experimental_model
    Five-arm randomized four-week choline-form intervention
    exposure
    Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
    limitations
    Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human
    plain_language
    A phospholipid form behaved differently from bitartrate in this setting.
    primary_references
    [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
    tissue_or_cell_type
    82 healthy volunteers with normal renal function

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1231–1242

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft

    ### choline-pc-tmao-null PC supplements did not significantly raise fasting TMAO, p=0.27. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A phospholipid form behaved differently from bitartrate in this setting. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
    Complete structured claim and evidence
  5. The challenge produced time-dependent increases in TMAO and its d9-labeled isotopologue.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"}
    experimental_model
    Human isotope challenge with antibiotics plus a separate observational cohort
    exposure
    Two eggs plus d9-PC before/after antibiotics; three-year event follow-up
    limitations
    The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events.
    nutrient_topic
    Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
    organism
    Human
    plain_language
    A label on dietary PC appeared in the downstream microbial-host product.
    primary_references
    [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
    tissue_or_cell_type
    Healthy challenge participants; 4007 angiography patients in the outcome cohort

    Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1140–1151

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope challenge with antibiotics plus a separate observational cohort · source_derived_draft · unverified_draft

    ### choline-pc-tmao-tracing The challenge produced time-dependent increases in TMAO and its d9-labeled isotopologue. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A label on dietary PC appeared in the downstream microbial-host product. organism: Human tissue_or_cell_type: Healthy challenge participants; 4007 angiography patients in the outcome cohort experimental_model: Human isotope challenge with antibiotics plus a separate observational cohort limitations: The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events. exposure: Two eggs plus d9-PC before/after antibiotics; three-year event follow-up evidence_span: {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"} [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
    Complete structured claim and evidence
  6. Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion.

    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.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards