Component

Endoxifen / 4-hydroxy-N-desmethyltamoxifen

Endoxifen / 4-hydroxy-N-desmethyltamoxifen. Species, exposure and limitations are retained in each linked claim.

4 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

Where it participates (unsigned role)

  1. Plasma endoxifen was lower with BR-DIM than placebo in women taking tamoxifen.

    3,3'-Diindolylmethane / DIM → Plasma endoxifen concentration source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/28560655.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28", "start_char": 0, "end_char": 1823, "text_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28"}
    experimental_model
    Randomized double-blind placebo-controlled trial
    exposure
    BR-DIM 150 mg twice daily for 12 months
    limitations
    Biomarker and pharmacokinetic endpoints, not recurrence or survival. The causal enzyme mechanism and effect on tamoxifen clinical benefit were not determined.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    130 women prescribed tamoxifen; 98 completed
    plain_language
    This interaction was measured in people; its effect on cancer outcomes was not established.
    primary_references
    [dim-p28560655] A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. (2017). https://pubmed.ncbi.nlm.nih.gov/28560655/ DOI: 10.1007/s10549-017-4292-7
    tissue_or_cell_type
    Estrogen biomarkers and tamoxifen metabolites

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1052–1063

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

    ### dim-endoxifen-lower Plasma endoxifen was lower with BR-DIM than placebo in women taking tamoxifen. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This interaction was measured in people; its effect on cancer outcomes was not established. organism: 130 women prescribed tamoxifen; 98 completed tissue_or_cell_type: Estrogen biomarkers and tamoxifen metabolites experimental_model: Randomized double-blind placebo-controlled trial limitations: Biomarker and pharmacokinetic endpoints, not recurrence or survival. The causal enzyme mechanism and effect on tamoxifen clinical benefit were not determined. exposure: BR-DIM 150 mg twice daily for 12 months evidence_span: {"source_cache": "artifacts/dim-research/28560655.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28", "start_char": 0, "end_char": 1823, "text_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28"} [dim-p28560655] A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. (2017). https://pubmed.ncbi.nlm.nih.gov/28560655/ DOI: 10.1007/s10549-017-4292-7
    Complete structured claim and evidence

  2. Conversion of N-desmethyltamoxifen to endoxifen was catalyzed by CYP2D6 in the tested system.

    Human cytochrome P450 2D6 → N-Desmethyltamoxifen source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"}
    experimental_model
    Kinetic, inhibition and recombinant-enzyme pathway mapping
    exposure
    Therapeutically relevant substrate concentrations
    limitations
    Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    Human liver microsomes and expressed CYPs
    plain_language
    The key activation step cannot be replaced by the statement that CYP1A2 is induced.
    primary_references
    [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
    tissue_or_cell_type
    Sequential tamoxifen metabolism

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1000–1011

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic, inhibition and recombinant-enzyme pathway mapping · source_derived_draft · unverified_draft

    ### dim-tamoxifen-endoxifen Conversion of N-desmethyltamoxifen to endoxifen was catalyzed by CYP2D6 in the tested system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The key activation step cannot be replaced by the statement that CYP1A2 is induced. organism: Human liver microsomes and expressed CYPs tissue_or_cell_type: Sequential tamoxifen metabolism experimental_model: Kinetic, inhibition and recombinant-enzyme pathway mapping limitations: Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes. exposure: Therapeutically relevant substrate concentrations evidence_span: {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"} [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
    Complete structured claim and evidence

  3. Endoxifen AUC fell 12.4% with curcumin plus piperine, p=0.02.

    Curcumin plus piperine regimen → Human endoxifen plasma exposure source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/curcumin-research/30909366.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527", "start_char": 0, "end_char": 1407, "text_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527"}
    experimental_model
    Within-patient pharmacokinetic comparison in tamoxifen-treated breast cancer patients
    exposure
    Tamoxifen 20-30 mg/day; curcumin 1200 mg three times/day, with or without piperine 10 mg three times/day
    limitations
    Small pharmacokinetic study, not a cancer recurrence trial. Piperine has independent effects; a particular CYP mechanism was not established.
    nutrient_topic
    Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin
    organism
    Homo sapiens
    plain_language
    The combination reduced exposure to tamoxifen's active metabolite.
    primary_references
    [curcumin-p30909366] Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen. (2019). https://pubmed.ncbi.nlm.nih.gov/30909366/ DOI: 10.3390/cancers11030403
    tissue_or_cell_type
    Plasma drug and metabolite AUC

    Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 970–981

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-patient pharmacokinetic comparison in tamoxifen-treated breast cancer patients · source_derived_draft · unverified_draft

    ### curcumin-endoxifen-combination Endoxifen AUC fell 12.4% with curcumin plus piperine, p=0.02. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combination reduced exposure to tamoxifen's active metabolite. organism: Homo sapiens tissue_or_cell_type: Plasma drug and metabolite AUC experimental_model: Within-patient pharmacokinetic comparison in tamoxifen-treated breast cancer patients limitations: Small pharmacokinetic study, not a cancer recurrence trial. Piperine has independent effects; a particular CYP mechanism was not established. exposure: Tamoxifen 20-30 mg/day; curcumin 1200 mg three times/day, with or without piperine 10 mg three times/day evidence_span: {"source_cache": "artifacts/curcumin-research/30909366.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527", "start_char": 0, "end_char": 1407, "text_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527"} [curcumin-p30909366] Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen. (2019). https://pubmed.ncbi.nlm.nih.gov/30909366/ DOI: 10.3390/cancers11030403
    Complete structured claim and evidence

  4. Endoxifen AUC was 7.7% lower with curcumin alone; the confidence interval crossed zero and p=0.07.

    Curcumin → Human endoxifen plasma exposure source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/curcumin-research/30909366.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527", "start_char": 0, "end_char": 1407, "text_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527"}
    experimental_model
    Within-patient pharmacokinetic comparison in tamoxifen-treated breast cancer patients
    exposure
    Tamoxifen 20-30 mg/day; curcumin 1200 mg three times/day, with or without piperine 10 mg three times/day
    limitations
    Small pharmacokinetic study, not a cancer recurrence trial. Piperine has independent effects; a particular CYP mechanism was not established.
    nutrient_topic
    Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin
    organism
    Homo sapiens
    plain_language
    The curcumin-only result suggested a decrease but was not conventionally significant.
    primary_references
    [curcumin-p30909366] Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen. (2019). https://pubmed.ncbi.nlm.nih.gov/30909366/ DOI: 10.3390/cancers11030403
    tissue_or_cell_type
    Plasma drug and metabolite AUC

    Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 957–968

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-patient pharmacokinetic comparison in tamoxifen-treated breast cancer patients · source_derived_draft · unverified_draft

    ### curcumin-endoxifen-curcumin Endoxifen AUC was 7.7% lower with curcumin alone; the confidence interval crossed zero and p=0.07. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The curcumin-only result suggested a decrease but was not conventionally significant. organism: Homo sapiens tissue_or_cell_type: Plasma drug and metabolite AUC experimental_model: Within-patient pharmacokinetic comparison in tamoxifen-treated breast cancer patients limitations: Small pharmacokinetic study, not a cancer recurrence trial. Piperine has independent effects; a particular CYP mechanism was not established. exposure: Tamoxifen 20-30 mg/day; curcumin 1200 mg three times/day, with or without piperine 10 mg three times/day evidence_span: {"source_cache": "artifacts/curcumin-research/30909366.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527", "start_char": 0, "end_char": 1407, "text_sha256": "43a5c2635c9fef8a31967689115b6152e81cf7d4d0f1687ffae113684c89d527"} [curcumin-p30909366] Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen. (2019). https://pubmed.ncbi.nlm.nih.gov/30909366/ DOI: 10.3390/cancers11030403
    Complete structured claim and evidence

In the sources

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