Nutrient chapter

3,3'-Diindolylmethane / DIM

DIM is a dietary indole compound formed from indole-3-carbinol. Its receptor, enzyme, hormone and drug effects depend on dose, timing, tissue and formulation. Laboratory induction does not prove a clinical interaction with every CYP substrate; reduced tamoxifen metabolites have been measured in a randomized trial. DIM is not an established essential nutrient.

109 recorded mechanisms · 2 availability situations · 5 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

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
DIM increased CYP1A2 mRNA dose-dependently, with induction also reflected in protein measurements.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 1A2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"}
experimental_model
Quantitative gene expression and protein assessment
exposure
DIM 10-50 micromolar
limitations
Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes
plain_language
This establishes a mechanism to investigate drug interactions, not their clinical size.
primary_references
[dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
tissue_or_cell_type
CYP and phase-II enzyme expression
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 389–400
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative gene expression and protein assessment · source_derived_draft · unverified_draft
### dim-hepatocyte-cyp1a2 DIM increased CYP1A2 mRNA dose-dependently, with induction also reflected in protein measurements. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This establishes a mechanism to investigate drug interactions, not their clinical size. organism: Primary human hepatocytes tissue_or_cell_type: CYP and phase-II enzyme expression experimental_model: Quantitative gene expression and protein assessment limitations: Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people. exposure: DIM 10-50 micromolar evidence_span: {"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"} [dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
Complete structured claim and evidence
DIM increased CYP1A1 mRNA dose-dependently, with induction also reflected in protein measurements.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 1A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"}
experimental_model
Quantitative gene expression and protein assessment
exposure
DIM 10-50 micromolar
limitations
Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes
plain_language
The cell increases the amount of one drug-processing enzyme.
primary_references
[dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
tissue_or_cell_type
CYP and phase-II enzyme expression
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 376–387
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative gene expression and protein assessment · source_derived_draft · unverified_draft
### dim-hepatocyte-cyp1a1 DIM increased CYP1A1 mRNA dose-dependently, with induction also reflected in protein measurements. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell increases the amount of one drug-processing enzyme. organism: Primary human hepatocytes tissue_or_cell_type: CYP and phase-II enzyme expression experimental_model: Quantitative gene expression and protein assessment limitations: Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people. exposure: DIM 10-50 micromolar evidence_span: {"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"} [dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
Complete structured claim and evidence
DIM directly inhibited CYP1A2 catalytic activity in the tested enzyme assay.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 1A2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"}
experimental_model
Pretreatment versus cotreatment, adduct and recombinant-enzyme assays
exposure
DIM pretreatment for 48 hours; direct catalytic assays separately
limitations
Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes and human enzyme preparations
plain_language
Direct enzyme inhibition can oppose a slower increase in enzyme production.
primary_references
[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
tissue_or_cell_type
Aflatoxin metabolism and CYP catalytic activity
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 441–452
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pretreatment versus cotreatment, adduct and recombinant-enzyme assays · source_derived_draft · unverified_draft
### dim-cyp1a2-direct-inhibition DIM directly inhibited CYP1A2 catalytic activity in the tested enzyme assay. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direct enzyme inhibition can oppose a slower increase in enzyme production. organism: Primary human hepatocytes and human enzyme preparations tissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity experimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays limitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs. exposure: DIM pretreatment for 48 hours; direct catalytic assays separately evidence_span: {"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"} [dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
Complete structured claim and evidence
DIM activated human PXR-dependent CYP3A4 promoter transcription.
3,3'-Diindolylmethane / DIM → Human pregnane X receptor / SXR / PXR / NR1I2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
A second receptor connects DIM to another drug-metabolism pathway.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 493–504
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-pxr-activation DIM activated human PXR-dependent CYP3A4 promoter transcription. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second receptor connects DIM to another drug-metabolism pathway. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
DIM increased MDR1/ABCB1 expression in a PXR-dependent manner.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
The same exposure can change a transporter as well as an enzyme.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 519–530
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-pxr-abcb1 DIM increased MDR1/ABCB1 expression in a PXR-dependent manner. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure can change a transporter as well as an enzyme. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
CYP1A2 contributed to clozapine demethylation.
Human cytochrome P450 1A2 → Clozapine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/9384460.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6", "start_char": 0, "end_char": 1794, "text_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6"}
experimental_model
Recombinant enzymes, antibodies and human liver microsomes
exposure
Enzyme-specific inhibition and metabolite formation
limitations
Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP enzymes
plain_language
Clozapine shares an enzyme that DIM can induce in laboratory systems; its response to DIM was not measured.
primary_references
[dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x
tissue_or_cell_type
Clozapine oxidation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 662–673
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzymes, antibodies and human liver microsomes · source_derived_draft · unverified_draft
### dim-clozapine-1a2 CYP1A2 contributed to clozapine demethylation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Clozapine shares an enzyme that DIM can induce in laboratory systems; its response to DIM was not measured. organism: Human CYP enzymes tissue_or_cell_type: Clozapine oxidation experimental_model: Recombinant enzymes, antibodies and human liver microsomes limitations: Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction. exposure: Enzyme-specific inhibition and metabolite formation evidence_span: {"source_cache": "artifacts/dim-research/9384460.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6", "start_char": 0, "end_char": 1794, "text_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6"} [dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x
Complete structured claim and evidence
CYP1A2 was the predominant tested catalyst of tizanidine metabolism.
Human cytochrome P450 1A2 → Tizanidine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/14998432.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa9fa0887ce5587c5c1894fd10a4afa651eac8220683d06745675a72f3e1ba2f", "start_char": 0, "end_char": 1208, "text_sha256": "fa9fa0887ce5587c5c1894fd10a4afa651eac8220683d06745675a72f3e1ba2f"}
experimental_model
Human microsomes and recombinant CYP comparison
exposure
NADPH-dependent substrate consumption and selective inhibition
limitations
Enzyme phenotyping; not a trial of DIM with tizanidine.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP enzymes
plain_language
Tizanidine has a strong pathway connection, while the size and direction of a DIM interaction remain unmeasured.
primary_references
[dim-p14998432] Tizanidine is mainly metabolized by cytochrome p450 1A2 in vitro. (2004). https://pubmed.ncbi.nlm.nih.gov/14998432/ DOI: 10.1046/j.1365-2125.2003.02028.x
tissue_or_cell_type
Tizanidine metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 779–790
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and recombinant CYP comparison · source_derived_draft · unverified_draft
### dim-tizanidine-1a2 CYP1A2 was the predominant tested catalyst of tizanidine metabolism. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Tizanidine has a strong pathway connection, while the size and direction of a DIM interaction remain unmeasured. organism: Human CYP enzymes tissue_or_cell_type: Tizanidine metabolism experimental_model: Human microsomes and recombinant CYP comparison limitations: Enzyme phenotyping; not a trial of DIM with tizanidine. exposure: NADPH-dependent substrate consumption and selective inhibition evidence_span: {"source_cache": "artifacts/dim-research/14998432.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa9fa0887ce5587c5c1894fd10a4afa651eac8220683d06745675a72f3e1ba2f", "start_char": 0, "end_char": 1208, "text_sha256": "fa9fa0887ce5587c5c1894fd10a4afa651eac8220683d06745675a72f3e1ba2f"} [dim-p14998432] Tizanidine is mainly metabolized by cytochrome p450 1A2 in vitro. (2004). https://pubmed.ncbi.nlm.nih.gov/14998432/ DOI: 10.1046/j.1365-2125.2003.02028.x
Complete structured claim and evidence
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
I3C increased caffeine-probed CYP1A2 activity in 94% of participants in the phase I study.
Indole-3-carbinol / I3C → Human cytochrome P450 1A2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/16103443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4", "start_char": 0, "end_char": 1706, "text_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4"}
experimental_model
Phase I placebo run-in and dose escalation
exposure
I3C 400 mg/day then 800 mg/day for four weeks each
limitations
The administered compound was I3C, not DIM. Multiple acid-condensation products and nonrandomized sequential periods prevent assigning the observed fold change specifically to DIM.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
17 women at elevated breast-cancer risk
plain_language
There is human evidence for the precursor, but it must not be silently relabeled as a DIM trial.
primary_references
[dim-p16103443] A phase I study of indole-3-carbinol in women: tolerability and effects. (2005). https://pubmed.ncbi.nlm.nih.gov/16103443/ DOI: 10.1158/1055-9965.epi-05-0121
tissue_or_cell_type
Caffeine CYP1A2 phenotype and estrogen metabolites
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1026–1037
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase I placebo run-in and dose escalation · source_derived_draft · unverified_draft
### dim-i3c-human-1a2 I3C increased caffeine-probed CYP1A2 activity in 94% of participants in the phase I study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: There is human evidence for the precursor, but it must not be silently relabeled as a DIM trial. organism: 17 women at elevated breast-cancer risk tissue_or_cell_type: Caffeine CYP1A2 phenotype and estrogen metabolites experimental_model: Phase I placebo run-in and dose escalation limitations: The administered compound was I3C, not DIM. Multiple acid-condensation products and nonrandomized sequential periods prevent assigning the observed fold change specifically to DIM. exposure: I3C 400 mg/day then 800 mg/day for four weeks each evidence_span: {"source_cache": "artifacts/dim-research/16103443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4", "start_char": 0, "end_char": 1706, "text_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4"} [dim-p16103443] A phase I study of indole-3-carbinol in women: tolerability and effects. (2005). https://pubmed.ncbi.nlm.nih.gov/16103443/ DOI: 10.1158/1055-9965.epi-05-0121
Complete structured claim and evidence
DIM at 10 micromolar increased proliferation in estrogen-deprived breast-cancer cells; an ERalpha antagonist blocked the response.
3,3'-Diindolylmethane / DIM → Cell proliferation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}
experimental_model
Gene expression, chromatin, inhibitors and growth assays
exposure
DIM 10 versus 50 micromolar; estradiol absent
limitations
The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human MCF-7 and T47D cells
plain_language
A growth-promoting response appeared under one defined hormonal condition.
primary_references
[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
tissue_or_cell_type
ERalpha and proliferation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 610–621
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft
### dim-eralpha-proliferation DIM at 10 micromolar increased proliferation in estrogen-deprived breast-cancer cells; an ERalpha antagonist blocked the response. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A growth-promoting response appeared under one defined hormonal condition. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
Complete structured claim and evidence
POR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization.
Human POR Y181D variant → Human cytochrome P450 1A2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/dim-research/19884324.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214", "start_char": 0, "end_char": 1738, "text_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214"}
experimental_model
Recombinant protein and engineered bacterial coexpression
exposure
POR mutation and added FMN
limitations
In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human POR Y181D and human CYP1A2 in engineered systems
plain_language
Inducing an enzyme is not enough if its electron-supply machinery fails.
primary_references
[dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445
tissue_or_cell_type
FMN-dependent electron transfer
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 272–283
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein and engineered bacterial coexpression · source_derived_draft · unverified_draft
### dim-por-fmn-loss POR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inducing an enzyme is not enough if its electron-supply machinery fails. organism: Human POR Y181D and human CYP1A2 in engineered systems tissue_or_cell_type: FMN-dependent electron transfer experimental_model: Recombinant protein and engineered bacterial coexpression limitations: In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction. exposure: POR mutation and added FMN evidence_span: {"source_cache": "artifacts/dim-research/19884324.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214", "start_char": 0, "end_char": 1738, "text_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214"} [dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445
Complete structured claim and evidence
Aqueous acid converted I3C into a mixture containing DIM and several higher oligomers.
Indole-3-carbinol / I3C → 3,3'-Diindolylmethane / DIM source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/1643248.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0e674dfc9369a32cb568674108ab6ecd17d2068f2b53fab579ec963d6d15a7e7", "start_char": 0, "end_char": 1580, "text_sha256": "0e674dfc9369a32cb568674108ab6ecd17d2068f2b53fab579ec963d6d15a7e7"}
experimental_model
Acid-catalyzed reaction and HPLC product identification
exposure
I3C in aqueous acid; pH and concentration varied
limitations
A chemical model produces several products; reported yields are not human absorption or conversion fractions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Cell-free chemical system
plain_language
DIM is one product of precursor chemistry; it is not the whole mixture produced from I3C.
primary_references
[dim-p1643248] Oligomerization of indole-3-carbinol in aqueous acid. (1992). https://pubmed.ncbi.nlm.nih.gov/1643248/ DOI: 10.1021/tx00026a007
tissue_or_cell_type
Gastric-acid approximation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 155–166
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acid-catalyzed reaction and HPLC product identification · source_derived_draft · unverified_draft
### dim-i3c-condensation Aqueous acid converted I3C into a mixture containing DIM and several higher oligomers. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: DIM is one product of precursor chemistry; it is not the whole mixture produced from I3C. organism: Cell-free chemical system tissue_or_cell_type: Gastric-acid approximation experimental_model: Acid-catalyzed reaction and HPLC product identification limitations: A chemical model produces several products; reported yields are not human absorption or conversion fractions. exposure: I3C in aqueous acid; pH and concentration varied evidence_span: {"source_cache": "artifacts/dim-research/1643248.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0e674dfc9369a32cb568674108ab6ecd17d2068f2b53fab579ec963d6d15a7e7", "start_char": 0, "end_char": 1580, "text_sha256": "0e674dfc9369a32cb568674108ab6ecd17d2068f2b53fab579ec963d6d15a7e7"} [dim-p1643248] Oligomerization of indole-3-carbinol in aqueous acid. (1992). https://pubmed.ncbi.nlm.nih.gov/1643248/ DOI: 10.1021/tx00026a007
Complete structured claim and evidence
DIM was detected after oral I3C, whereas parent I3C was not detected by the plasma assay.
Indole-3-carbinol / I3C → 3,3'-Diindolylmethane / DIM source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/17164373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298", "start_char": 0, "end_char": 1606, "text_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298"}
experimental_model
Phase I single- and repeated-dose pharmacokinetics
exposure
I3C single doses 400-1200 mg and repeated-dose follow-up
limitations
I3C intervention, not purified DIM. Assay detection limits and interindividual variation matter.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Women given I3C
plain_language
The compound swallowed differed from the compound measured in blood.
primary_references
[dim-p17164373] Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. (2006). https://pubmed.ncbi.nlm.nih.gov/17164373/ DOI: 10.1158/1055-9965.epi-06-0396
tissue_or_cell_type
Plasma I3C and condensation products
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 168–179
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase I single- and repeated-dose pharmacokinetics · source_derived_draft · unverified_draft
### dim-i3c-dim-blood DIM was detected after oral I3C, whereas parent I3C was not detected by the plasma assay. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The compound swallowed differed from the compound measured in blood. organism: Women given I3C tissue_or_cell_type: Plasma I3C and condensation products experimental_model: Phase I single- and repeated-dose pharmacokinetics limitations: I3C intervention, not purified DIM. Assay detection limits and interindividual variation matter. exposure: I3C single doses 400-1200 mg and repeated-dose follow-up evidence_span: {"source_cache": "artifacts/dim-research/17164373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298", "start_char": 0, "end_char": 1606, "text_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298"} [dim-p17164373] Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. (2006). https://pubmed.ncbi.nlm.nih.gov/17164373/ DOI: 10.1158/1055-9965.epi-06-0396
Complete structured claim and evidence
Mean DIM peak concentration rose from 61 to 607 ng/mL between 400 and 1000 mg I3C, with no further increase at 1200 mg and substantial individual variation.
Indole-3-carbinol / I3C → Plasma DIM exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/17164373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298", "start_char": 0, "end_char": 1606, "text_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298"}
experimental_model
Phase I single- and repeated-dose pharmacokinetics
exposure
I3C single doses 400-1200 mg and repeated-dose follow-up
limitations
I3C intervention, not purified DIM. Assay detection limits and interindividual variation matter.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Women given I3C
plain_language
Exposure did not continue rising proportionally as the precursor dose increased.
primary_references
[dim-p17164373] Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. (2006). https://pubmed.ncbi.nlm.nih.gov/17164373/ DOI: 10.1158/1055-9965.epi-06-0396
tissue_or_cell_type
Plasma I3C and condensation products
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 181–192
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase I single- and repeated-dose pharmacokinetics · source_derived_draft · unverified_draft
### dim-i3c-pk-nonlinear Mean DIM peak concentration rose from 61 to 607 ng/mL between 400 and 1000 mg I3C, with no further increase at 1200 mg and substantial individual variation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Exposure did not continue rising proportionally as the precursor dose increased. organism: Women given I3C tissue_or_cell_type: Plasma I3C and condensation products experimental_model: Phase I single- and repeated-dose pharmacokinetics limitations: I3C intervention, not purified DIM. Assay detection limits and interindividual variation matter. exposure: I3C single doses 400-1200 mg and repeated-dose follow-up evidence_span: {"source_cache": "artifacts/dim-research/17164373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298", "start_char": 0, "end_char": 1606, "text_sha256": "610f95545a8b0fa523b17baa7798c2936b9af5bc789257b3fc98bb0aae2bc298"} [dim-p17164373] Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. (2006). https://pubmed.ncbi.nlm.nih.gov/17164373/ DOI: 10.1158/1055-9965.epi-06-0396
Complete structured claim and evidence
Mean peak DIM concentrations were 32, 104 and 108 ng/mL after the reported 100, 200 and 300 mg doses, respectively.
3,3'-Diindolylmethane / DIM → Plasma DIM exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/18843002.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c", "start_char": 0, "end_char": 1513, "text_sha256": "c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c"}
experimental_model
Single ascending-dose randomized pharmacokinetic study
exposure
Absorption-enhanced BR-DIM; small dose cohorts
limitations
Formulation-specific, small single-dose cohorts; not a universal safe dose, long-term safety threshold or clinical-efficacy study.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Healthy nonsmoking drug-free adults
plain_language
Doubling a dose did not reliably double blood exposure.
primary_references
[dim-p18843002] Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. (2008). https://pubmed.ncbi.nlm.nih.gov/18843002/ DOI: 10.1158/1055-9965.epi-08-0520
tissue_or_cell_type
Plasma DIM
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 194–205
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single ascending-dose randomized pharmacokinetic study · source_derived_draft · unverified_draft
### dim-dim-pk Mean peak DIM concentrations were 32, 104 and 108 ng/mL after the reported 100, 200 and 300 mg doses, respectively. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Doubling a dose did not reliably double blood exposure. organism: Healthy nonsmoking drug-free adults tissue_or_cell_type: Plasma DIM experimental_model: Single ascending-dose randomized pharmacokinetic study limitations: Formulation-specific, small single-dose cohorts; not a universal safe dose, long-term safety threshold or clinical-efficacy study. exposure: Absorption-enhanced BR-DIM; small dose cohorts evidence_span: {"source_cache": "artifacts/dim-research/18843002.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c", "start_char": 0, "end_char": 1513, "text_sha256": "c6685bdd57ec7598e6a1fbbbe46f4c8708e0a9a700ed19ebbbc5e35a84c3c60c"} [dim-p18843002] Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. (2008). https://pubmed.ncbi.nlm.nih.gov/18843002/ DOI: 10.1158/1055-9965.epi-08-0520
Complete structured claim and evidence
Two monohydroxylated and one dihydroxylated DIM products appeared in human plasma and urine.
3,3'-Diindolylmethane / DIM → Hydroxylated DIM metabolites, mixed analytical pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"}
experimental_model
Human serial plasma/urine mass spectrometry and reporter assays
exposure
Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule
limitations
Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Seven adults; mouse Hepa1 reporter cells
plain_language
The body changes DIM into additional molecules that need their own records.
primary_references
[dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
tissue_or_cell_type
DIM metabolism and metabolite signaling
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 207–218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human serial plasma/urine mass spectrometry and reporter assays · source_derived_draft · unverified_draft
### dim-dim-hydroxylation Two monohydroxylated and one dihydroxylated DIM products appeared in human plasma and urine. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body changes DIM into additional molecules that need their own records. organism: Seven adults; mouse Hepa1 reporter cells tissue_or_cell_type: DIM metabolism and metabolite signaling experimental_model: Human serial plasma/urine mass spectrometry and reporter assays limitations: Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response. exposure: Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule evidence_span: {"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"} [dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
Complete structured claim and evidence
Glucuronide conjugates of hydroxylated DIM products were detected in human samples.
Hydroxylated DIM metabolites, mixed analytical pool → DIM-derived glucuronide conjugates, mixed analytical pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"}
experimental_model
Human serial plasma/urine mass spectrometry and reporter assays
exposure
Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule
limitations
Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Seven adults; mouse Hepa1 reporter cells
plain_language
A second processing step attaches a conjugating group; parent DIM alone misses this pool.
primary_references
[dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
tissue_or_cell_type
DIM metabolism and metabolite signaling
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 220–231
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human serial plasma/urine mass spectrometry and reporter assays · source_derived_draft · unverified_draft
### dim-dim-glucuronidation Glucuronide conjugates of hydroxylated DIM products were detected in human samples. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second processing step attaches a conjugating group; parent DIM alone misses this pool. organism: Seven adults; mouse Hepa1 reporter cells tissue_or_cell_type: DIM metabolism and metabolite signaling experimental_model: Human serial plasma/urine mass spectrometry and reporter assays limitations: Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response. exposure: Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule evidence_span: {"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"} [dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
Complete structured claim and evidence
Sulfate conjugates of hydroxylated DIM products were detected in human samples.
Hydroxylated DIM metabolites, mixed analytical pool → DIM-derived sulfate conjugates, mixed analytical pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"}
experimental_model
Human serial plasma/urine mass spectrometry and reporter assays
exposure
Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule
limitations
Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Seven adults; mouse Hepa1 reporter cells
plain_language
Sulfur-containing conjugation is another handling route; its presence does not demonstrate sulfate depletion.
primary_references
[dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
tissue_or_cell_type
DIM metabolism and metabolite signaling
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 233–244
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human serial plasma/urine mass spectrometry and reporter assays · source_derived_draft · unverified_draft
### dim-dim-sulfation Sulfate conjugates of hydroxylated DIM products were detected in human samples. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sulfur-containing conjugation is another handling route; its presence does not demonstrate sulfate depletion. organism: Seven adults; mouse Hepa1 reporter cells tissue_or_cell_type: DIM metabolism and metabolite signaling experimental_model: Human serial plasma/urine mass spectrometry and reporter assays limitations: Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response. exposure: Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule evidence_span: {"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"} [dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
Complete structured claim and evidence
The identified 2-oxo-DIM product showed greater potency and efficacy than parent DIM in a Hepa1 AhR reporter assay.
2-Oxo-DIM / 3-((1H-indol-3-yl)methyl)indolin-2-one → Mouse aryl hydrocarbon receptor / Ahr source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"}
experimental_model
Human serial plasma/urine mass spectrometry and reporter assays
exposure
Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule
limitations
Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Seven adults; mouse Hepa1 reporter cells
plain_language
A metabolite can signal more strongly than the compound that produced it.
primary_references
[dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
tissue_or_cell_type
DIM metabolism and metabolite signaling
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 246–257
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human serial plasma/urine mass spectrometry and reporter assays · source_derived_draft · unverified_draft
### dim-dim-metabolite-ahr The identified 2-oxo-DIM product showed greater potency and efficacy than parent DIM in a Hepa1 AhR reporter assay. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A metabolite can signal more strongly than the compound that produced it. organism: Seven adults; mouse Hepa1 reporter cells tissue_or_cell_type: DIM metabolism and metabolite signaling experimental_model: Human serial plasma/urine mass spectrometry and reporter assays limitations: Small mixed-sex sample. Product label mass and measured DIM content differ. Some metabolite structures were tentative; reporter activity was not a clinical response. exposure: Two BR-DIM 150 capsules nightly for one week; measured 45.3 mg DIM per capsule evidence_span: {"source_cache": "artifacts/dim-research/34035125.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff", "start_char": 0, "end_char": 2514, "text_sha256": "0df37954db1da2ae488edb763e1397977b65d206cdd52269a5a882b62e8748ff"} [dim-p34035125] 3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans. (2021). https://pubmed.ncbi.nlm.nih.gov/34035125/ DOI: 10.1124/dmd.120.000346
Complete structured claim and evidence
The CYP1A2 structure places its ligand above the heme prosthetic group.
Human cytochrome P450 1A2 → Heme source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/17311915.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318", "start_char": 0, "end_char": 1400, "text_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318"}
experimental_model
X-ray crystallography
exposure
Alpha-naphthoflavone-bound structure at 1.95 angstrom resolution
limitations
Structural enzyme requirement; not proof that DIM depletes iron or that iron supplementation changes DIM response.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Purified human CYP1A2
plain_language
The induced enzyme still needs its iron-containing catalytic machinery.
primary_references
[dim-p17311915] Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. (2007). https://pubmed.ncbi.nlm.nih.gov/17311915/ DOI: 10.1074/jbc.m611692200
tissue_or_cell_type
Catalytic pocket
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 259–270
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography · source_derived_draft · unverified_draft
### dim-cyp1a2-heme The CYP1A2 structure places its ligand above the heme prosthetic group. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced enzyme still needs its iron-containing catalytic machinery. organism: Purified human CYP1A2 tissue_or_cell_type: Catalytic pocket experimental_model: X-ray crystallography limitations: Structural enzyme requirement; not proof that DIM depletes iron or that iron supplementation changes DIM response. exposure: Alpha-naphthoflavone-bound structure at 1.95 angstrom resolution evidence_span: {"source_cache": "artifacts/dim-research/17311915.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318", "start_char": 0, "end_char": 1400, "text_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318"} [dim-p17311915] Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. (2007). https://pubmed.ncbi.nlm.nih.gov/17311915/ DOI: 10.1074/jbc.m611692200
Complete structured claim and evidence
Added FMN restored CYP1A2 ethoxyresorufin activity in POR Y181D membranes to 37% of the wild-type system.
Flavin mononucleotide → CYP1A2 catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/dim-research/19884324.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214", "start_char": 0, "end_char": 1738, "text_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214"}
experimental_model
Recombinant protein and engineered bacterial coexpression
exposure
POR mutation and added FMN
limitations
In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human POR Y181D and human CYP1A2 in engineered systems
plain_language
A specific cofactor-binding defect could be partly rescued in the assay.
primary_references
[dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445
tissue_or_cell_type
FMN-dependent electron transfer
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 285–296
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein and engineered bacterial coexpression · source_derived_draft · unverified_draft
### dim-por-fmn-rescue Added FMN restored CYP1A2 ethoxyresorufin activity in POR Y181D membranes to 37% of the wild-type system. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A specific cofactor-binding defect could be partly rescued in the assay. organism: Human POR Y181D and human CYP1A2 in engineered systems tissue_or_cell_type: FMN-dependent electron transfer experimental_model: Recombinant protein and engineered bacterial coexpression limitations: In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction. exposure: POR mutation and added FMN evidence_span: {"source_cache": "artifacts/dim-research/19884324.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214", "start_char": 0, "end_char": 1738, "text_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214"} [dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445
Complete structured claim and evidence
DIM bound AhR and promoted rapid nuclear AhR-complex formation in MCF-7 cells.
3,3'-Diindolylmethane / DIM → Human aryl hydrocarbon receptor / AHR source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/9771935.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799", "start_char": 0, "end_char": 1556, "text_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799"}
experimental_model
Ligand binding, nuclear complex, transcription and growth assays
exposure
DIM 10-50 micromolar in cells; rodent dosing separately
limitations
Preclinical evidence. Estrogen exposure, tissue and concentrations affect the response; no human cancer-treatment efficacy established.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human MCF-7 cells and rat mammary-tumor model
plain_language
A receptor can relay the exposure to changes in gene regulation.
primary_references
[dim-p9771935] Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. (1998). https://pubmed.ncbi.nlm.nih.gov/9771935/ DOI: 10.1093/carcin/19.9.1631
tissue_or_cell_type
AhR and estrogen-responsive signaling
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 298–309
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, nuclear complex, transcription and growth assays · source_derived_draft · unverified_draft
### dim-ahr-binding DIM bound AhR and promoted rapid nuclear AhR-complex formation in MCF-7 cells. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor can relay the exposure to changes in gene regulation. organism: Human MCF-7 cells and rat mammary-tumor model tissue_or_cell_type: AhR and estrogen-responsive signaling experimental_model: Ligand binding, nuclear complex, transcription and growth assays limitations: Preclinical evidence. Estrogen exposure, tissue and concentrations affect the response; no human cancer-treatment efficacy established. exposure: DIM 10-50 micromolar in cells; rodent dosing separately evidence_span: {"source_cache": "artifacts/dim-research/9771935.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799", "start_char": 0, "end_char": 1556, "text_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799"} [dim-p9771935] Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. (1998). https://pubmed.ncbi.nlm.nih.gov/9771935/ DOI: 10.1093/carcin/19.9.1631
Complete structured claim and evidence
DIM inhibited estradiol-induced MCF-7 proliferation in the tested estrogen-stimulated system.
3,3'-Diindolylmethane / DIM → Cell proliferation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/9771935.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799", "start_char": 0, "end_char": 1556, "text_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799"}
experimental_model
Ligand binding, nuclear complex, transcription and growth assays
exposure
DIM 10-50 micromolar in cells; rodent dosing separately
limitations
Preclinical evidence. Estrogen exposure, tissue and concentrations affect the response; no human cancer-treatment efficacy established.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human MCF-7 cells and rat mammary-tumor model
plain_language
Its effect depended on the hormonal conditions being tested.
primary_references
[dim-p9771935] Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. (1998). https://pubmed.ncbi.nlm.nih.gov/9771935/ DOI: 10.1093/carcin/19.9.1631
tissue_or_cell_type
AhR and estrogen-responsive signaling
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 311–322
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, nuclear complex, transcription and growth assays · source_derived_draft · unverified_draft
### dim-estrogen-growth-inhibition DIM inhibited estradiol-induced MCF-7 proliferation in the tested estrogen-stimulated system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Its effect depended on the hormonal conditions being tested. organism: Human MCF-7 cells and rat mammary-tumor model tissue_or_cell_type: AhR and estrogen-responsive signaling experimental_model: Ligand binding, nuclear complex, transcription and growth assays limitations: Preclinical evidence. Estrogen exposure, tissue and concentrations affect the response; no human cancer-treatment efficacy established. exposure: DIM 10-50 micromolar in cells; rodent dosing separately evidence_span: {"source_cache": "artifacts/dim-research/9771935.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799", "start_char": 0, "end_char": 1556, "text_sha256": "2f0967e62f0757c6ff4e68f7f7f673b6ba12ec581cbc7bd5c5594bdbf1964799"} [dim-p9771935] Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. (1998). https://pubmed.ncbi.nlm.nih.gov/9771935/ DOI: 10.1093/carcin/19.9.1631
Complete structured claim and evidence
DIM partly inhibited TCDD-induced CYP1A1 transcription and strongly reduced the induced EROD activity in T47D cells.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 1A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/8866829.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f", "start_char": 0, "end_char": 1403, "text_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f"}
experimental_model
Receptor competition, reporter and enzyme assays
exposure
DIM alone up to 31 micromolar or with TCDD
limitations
Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human T47D breast-cancer cells
plain_language
Binding the same receptor can produce a weaker signal and reduce another ligand response.
primary_references
[dim-p8866829] Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8866829/ DOI: 10.1016/0006-2952(96)00060-3
tissue_or_cell_type
AhR-mediated CYP1A1 response
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 324–335
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor competition, reporter and enzyme assays · source_derived_draft · unverified_draft
### dim-ahr-partial-antagonism DIM partly inhibited TCDD-induced CYP1A1 transcription and strongly reduced the induced EROD activity in T47D cells. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding the same receptor can produce a weaker signal and reduce another ligand response. organism: Human T47D breast-cancer cells tissue_or_cell_type: AhR-mediated CYP1A1 response experimental_model: Receptor competition, reporter and enzyme assays limitations: Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type. exposure: DIM alone up to 31 micromolar or with TCDD evidence_span: {"source_cache": "artifacts/dim-research/8866829.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f", "start_char": 0, "end_char": 1403, "text_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f"} [dim-p8866829] Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8866829/ DOI: 10.1016/0006-2952(96)00060-3
Complete structured claim and evidence
DIM alone did not significantly induce CYP1A1 mRNA or EROD activity at concentrations up to 31 micromolar in this T47D system.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 1A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/8866829.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f", "start_char": 0, "end_char": 1403, "text_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f"}
experimental_model
Receptor competition, reporter and enzyme assays
exposure
DIM alone up to 31 micromolar or with TCDD
limitations
Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human T47D breast-cancer cells
plain_language
The induction result is not universal across cell types and exposures.
primary_references
[dim-p8866829] Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8866829/ DOI: 10.1016/0006-2952(96)00060-3
tissue_or_cell_type
AhR-mediated CYP1A1 response
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 337–348
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor competition, reporter and enzyme assays · source_derived_draft · unverified_draft
### dim-t47d-induction-null DIM alone did not significantly induce CYP1A1 mRNA or EROD activity at concentrations up to 31 micromolar in this T47D system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induction result is not universal across cell types and exposures. organism: Human T47D breast-cancer cells tissue_or_cell_type: AhR-mediated CYP1A1 response experimental_model: Receptor competition, reporter and enzyme assays limitations: Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type. exposure: DIM alone up to 31 micromolar or with TCDD evidence_span: {"source_cache": "artifacts/dim-research/8866829.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f", "start_char": 0, "end_char": 1403, "text_sha256": "b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f"} [dim-p8866829] Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8866829/ DOI: 10.1016/0006-2952(96)00060-3
Complete structured claim and evidence
DIM increased CYP1A2 protein in cultured human liver slices.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 1A2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/9741959.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47", "start_char": 0, "end_char": 1338, "text_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47"}
experimental_model
Precision-cut liver-slice induction and immunoblotting
exposure
DIM 50 micromolar for 72 hours
limitations
Ex-vivo exposure; not a measured oral DIM effect on a patient drug concentration. Four donors showed variable responses.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human donor liver slices
plain_language
Human liver tissue can make more of this enzyme after DIM exposure.
primary_references
[dim-p9741959] 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. (1998). https://pubmed.ncbi.nlm.nih.gov/9741959/ DOI: 10.1080/004982598239227
tissue_or_cell_type
CYP1A proteins and catalytic assays
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 350–361
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Precision-cut liver-slice induction and immunoblotting · source_derived_draft · unverified_draft
### dim-liver-cyp1a2 DIM increased CYP1A2 protein in cultured human liver slices. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human liver tissue can make more of this enzyme after DIM exposure. organism: Human donor liver slices tissue_or_cell_type: CYP1A proteins and catalytic assays experimental_model: Precision-cut liver-slice induction and immunoblotting limitations: Ex-vivo exposure; not a measured oral DIM effect on a patient drug concentration. Four donors showed variable responses. exposure: DIM 50 micromolar for 72 hours evidence_span: {"source_cache": "artifacts/dim-research/9741959.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47", "start_char": 0, "end_char": 1338, "text_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47"} [dim-p9741959] 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. (1998). https://pubmed.ncbi.nlm.nih.gov/9741959/ DOI: 10.1080/004982598239227
Complete structured claim and evidence
The same liver-slice experiment found little effect of DIM on CYP3A4 protein.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 3A4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/9741959.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47", "start_char": 0, "end_char": 1338, "text_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47"}
experimental_model
Precision-cut liver-slice induction and immunoblotting
exposure
DIM 50 micromolar for 72 hours
limitations
Ex-vivo exposure; not a measured oral DIM effect on a patient drug concentration. Four donors showed variable responses.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human donor liver slices
plain_language
A result for one CYP family cannot simply be assigned to another.
primary_references
[dim-p9741959] 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. (1998). https://pubmed.ncbi.nlm.nih.gov/9741959/ DOI: 10.1080/004982598239227
tissue_or_cell_type
CYP1A proteins and catalytic assays
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 363–374
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Precision-cut liver-slice induction and immunoblotting · source_derived_draft · unverified_draft
### dim-liver-cyp3a4-null The same liver-slice experiment found little effect of DIM on CYP3A4 protein. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A result for one CYP family cannot simply be assigned to another. organism: Human donor liver slices tissue_or_cell_type: CYP1A proteins and catalytic assays experimental_model: Precision-cut liver-slice induction and immunoblotting limitations: Ex-vivo exposure; not a measured oral DIM effect on a patient drug concentration. Four donors showed variable responses. exposure: DIM 50 micromolar for 72 hours evidence_span: {"source_cache": "artifacts/dim-research/9741959.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47", "start_char": 0, "end_char": 1338, "text_sha256": "11eec60fad1ec0e18085a59f90fa3237235bb0614b5ee2b29058757e3b45ba47"} [dim-p9741959] 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. (1998). https://pubmed.ncbi.nlm.nih.gov/9741959/ DOI: 10.1080/004982598239227
Complete structured claim and evidence
DIM increased NQO1 expression about 4.5-fold at 50 micromolar in the hepatocyte experiment.
3,3'-Diindolylmethane / DIM → Human NAD(P)H quinone dehydrogenase 1 / NQO1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"}
experimental_model
Quantitative gene expression and protein assessment
exposure
DIM 10-50 micromolar
limitations
Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes
plain_language
DIM also changed a quinone-handling enzyme already connected to other nutrients.
primary_references
[dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
tissue_or_cell_type
CYP and phase-II enzyme expression
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 402–413
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative gene expression and protein assessment · source_derived_draft · unverified_draft
### dim-hepatocyte-nqo1 DIM increased NQO1 expression about 4.5-fold at 50 micromolar in the hepatocyte experiment. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: DIM also changed a quinone-handling enzyme already connected to other nutrients. organism: Primary human hepatocytes tissue_or_cell_type: CYP and phase-II enzyme expression experimental_model: Quantitative gene expression and protein assessment limitations: Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people. exposure: DIM 10-50 micromolar evidence_span: {"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"} [dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
Complete structured claim and evidence
No significant GSTA1 transcriptional increase was detected in the phytochemical comparisons including DIM.
3,3'-Diindolylmethane / DIM → Human glutathione S-transferase A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"}
experimental_model
Quantitative gene expression and protein assessment
exposure
DIM 10-50 micromolar
limitations
Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes
plain_language
An enzyme response does not imply that every detoxification pathway rises together.
primary_references
[dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
tissue_or_cell_type
CYP and phase-II enzyme expression
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 415–426
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative gene expression and protein assessment · source_derived_draft · unverified_draft
### dim-hepatocyte-gsta1-null No significant GSTA1 transcriptional increase was detected in the phytochemical comparisons including DIM. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme response does not imply that every detoxification pathway rises together. organism: Primary human hepatocytes tissue_or_cell_type: CYP and phase-II enzyme expression experimental_model: Quantitative gene expression and protein assessment limitations: Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people. exposure: DIM 10-50 micromolar evidence_span: {"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"} [dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481
Complete structured claim and evidence
DIM directly inhibited CYP1A1 catalytic activity in the tested enzyme assay.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 1A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"}
experimental_model
Pretreatment versus cotreatment, adduct and recombinant-enzyme assays
exposure
DIM pretreatment for 48 hours; direct catalytic assays separately
limitations
Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes and human enzyme preparations
plain_language
Direct enzyme inhibition can oppose a slower increase in enzyme production.
primary_references
[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
tissue_or_cell_type
Aflatoxin metabolism and CYP catalytic activity
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 428–439
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pretreatment versus cotreatment, adduct and recombinant-enzyme assays · source_derived_draft · unverified_draft
### dim-cyp1a1-direct-inhibition DIM directly inhibited CYP1A1 catalytic activity in the tested enzyme assay. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direct enzyme inhibition can oppose a slower increase in enzyme production. organism: Primary human hepatocytes and human enzyme preparations tissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity experimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays limitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs. exposure: DIM pretreatment for 48 hours; direct catalytic assays separately evidence_span: {"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"} [dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
Complete structured claim and evidence
DIM directly inhibited CYP3A4 catalytic activity in the tested enzyme assay.
3,3'-Diindolylmethane / DIM → Human cytochrome P450 3A4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"}
experimental_model
Pretreatment versus cotreatment, adduct and recombinant-enzyme assays
exposure
DIM pretreatment for 48 hours; direct catalytic assays separately
limitations
Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes and human enzyme preparations
plain_language
Direct enzyme inhibition can oppose a slower increase in enzyme production.
primary_references
[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
tissue_or_cell_type
Aflatoxin metabolism and CYP catalytic activity
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 454–465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pretreatment versus cotreatment, adduct and recombinant-enzyme assays · source_derived_draft · unverified_draft
### dim-cyp3a4-direct-inhibition DIM directly inhibited CYP3A4 catalytic activity in the tested enzyme assay. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direct enzyme inhibition can oppose a slower increase in enzyme production. organism: Primary human hepatocytes and human enzyme preparations tissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity experimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays limitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs. exposure: DIM pretreatment for 48 hours; direct catalytic assays separately evidence_span: {"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"} [dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
Complete structured claim and evidence
DIM pretreatment increased aflatoxin B1-DNA adduct formation in human hepatocytes.
3,3'-Diindolylmethane / DIM → Aflatoxin B1-derived DNA adduct formation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"}
experimental_model
Pretreatment versus cotreatment, adduct and recombinant-enzyme assays
exposure
DIM pretreatment for 48 hours; direct catalytic assays separately
limitations
Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes and human enzyme preparations
plain_language
More metabolism can activate a harmful compound rather than make it harmless.
primary_references
[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
tissue_or_cell_type
Aflatoxin metabolism and CYP catalytic activity
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 467–478
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pretreatment versus cotreatment, adduct and recombinant-enzyme assays · source_derived_draft · unverified_draft
### dim-aflatoxin-adducts DIM pretreatment increased aflatoxin B1-DNA adduct formation in human hepatocytes. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: More metabolism can activate a harmful compound rather than make it harmless. organism: Primary human hepatocytes and human enzyme preparations tissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity experimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays limitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs. exposure: DIM pretreatment for 48 hours; direct catalytic assays separately evidence_span: {"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"} [dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
Complete structured claim and evidence
The authors linked the DIM-associated adduct increase to CYP1A2 induction and/or GSTM1 downregulation.
Human cytochrome P450 1A2 → Aflatoxin B1-derived DNA adduct formation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"}
experimental_model
Pretreatment versus cotreatment, adduct and recombinant-enzyme assays
exposure
DIM pretreatment for 48 hours; direct catalytic assays separately
limitations
Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Primary human hepatocytes and human enzyme preparations
plain_language
Competing activation and conjugation routes may explain the net effect.
primary_references
[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
tissue_or_cell_type
Aflatoxin metabolism and CYP catalytic activity
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 480–491
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pretreatment versus cotreatment, adduct and recombinant-enzyme assays · source_derived_draft · unverified_draft
### dim-aflatoxin-explanation The authors linked the DIM-associated adduct increase to CYP1A2 induction and/or GSTM1 downregulation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Competing activation and conjugation routes may explain the net effect. organism: Primary human hepatocytes and human enzyme preparations tissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity experimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays limitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs. exposure: DIM pretreatment for 48 hours; direct catalytic assays separately evidence_span: {"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"} [dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206
Complete structured claim and evidence
DIM increased CYP3A4 expression in a PXR-dependent manner.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human cytochrome P450 3A4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
CYP3A4 belongs in this map alongside CYP1A2.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 506–517
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-pxr-cyp3a4 DIM increased CYP3A4 expression in a PXR-dependent manner. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP3A4 belongs in this map alongside CYP1A2. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
DIM reduced intracellular accumulation of the MDR1 substrate rhodamine 123 in the transport experiment.
3,3'-Diindolylmethane / DIM → Rhodamine 123 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
A tracer supported increased efflux; it did not measure every drug.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 532–543
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-abcb1-efflux DIM reduced intracellular accumulation of the MDR1 substrate rhodamine 123 in the transport experiment. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A tracer supported increased efflux; it did not measure every drug. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
PXR knockdown or inhibition attenuated DIM-induced CYP3A4 expression.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human cytochrome P450 3A4 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
The response weakened when a required signaling component was blocked.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 545–556
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-pxr-loss-cyp3a4 PXR knockdown or inhibition attenuated DIM-induced CYP3A4 expression. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response weakened when a required signaling component was blocked. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human P-glycoprotein / ABCB1 / MDR1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"}
experimental_model
Promoter reporters, expression, knockdown and transport assays
exposure
DIM exposure with PXR inhibition or knockdown controls
limitations
Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human hepatocytes and intestinal cell models
plain_language
The response weakened when a required signaling component was blocked.
primary_references
[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
tissue_or_cell_type
PXR-regulated CYP3A4 and ABCB1
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 558–569
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Promoter reporters, expression, knockdown and transport assays · source_derived_draft · unverified_draft
### dim-pxr-loss-abcb1 PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response weakened when a required signaling component was blocked. organism: Human hepatocytes and intestinal cell models tissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1 experimental_model: Promoter reporters, expression, knockdown and transport assays limitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions. exposure: DIM exposure with PXR inhibition or knockdown controls evidence_span: {"source_cache": "artifacts/dim-research/25542144.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d", "start_char": 0, "end_char": 1440, "text_sha256": "426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d"} [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015
Complete structured claim and evidence
DIM activated ERbeta target transcription without detectable binding to ERbeta in the study.
3,3'-Diindolylmethane / DIM → Human estrogen receptor beta / ESR2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20160136.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5", "start_char": 0, "end_char": 1134, "text_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5"}
experimental_model
Reporter, binding, chromatin and coactivator-silencing assays
exposure
DIM and SRC-2 silencing
limitations
Subtype-selective response in this system; other studies find ERalpha responses under other hormonal and concentration conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human receptor-expressing cell systems
plain_language
Receptor-dependent signaling need not mean that DIM directly occupies the hormone-binding site.
primary_references
[dim-p20160136] Selective activation of estrogen receptor-beta target genes by 3,3'-diindolylmethane. (2010). https://pubmed.ncbi.nlm.nih.gov/20160136/ DOI: 10.1210/en.2009-1028
tissue_or_cell_type
ERbeta transcription
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 571–582
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter, binding, chromatin and coactivator-silencing assays · source_derived_draft · unverified_draft
### dim-erbeta-activation DIM activated ERbeta target transcription without detectable binding to ERbeta in the study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Receptor-dependent signaling need not mean that DIM directly occupies the hormone-binding site. organism: Human receptor-expressing cell systems tissue_or_cell_type: ERbeta transcription experimental_model: Reporter, binding, chromatin and coactivator-silencing assays limitations: Subtype-selective response in this system; other studies find ERalpha responses under other hormonal and concentration conditions. exposure: DIM and SRC-2 silencing evidence_span: {"source_cache": "artifacts/dim-research/20160136.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5", "start_char": 0, "end_char": 1134, "text_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5"} [dim-p20160136] Selective activation of estrogen receptor-beta target genes by 3,3'-diindolylmethane. (2010). https://pubmed.ncbi.nlm.nih.gov/20160136/ DOI: 10.1210/en.2009-1028
Complete structured claim and evidence
DIM promoted ERbeta recruitment of SRC-2 at regulatory elements; SRC-2 silencing inhibited target-gene activation.
3,3'-Diindolylmethane / DIM → Nuclear receptor coactivator 2 / TIF2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20160136.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5", "start_char": 0, "end_char": 1134, "text_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5"}
experimental_model
Reporter, binding, chromatin and coactivator-silencing assays
exposure
DIM and SRC-2 silencing
limitations
Subtype-selective response in this system; other studies find ERalpha responses under other hormonal and concentration conditions.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human receptor-expressing cell systems
plain_language
A separate coactivator was required for the transcriptional response.
primary_references
[dim-p20160136] Selective activation of estrogen receptor-beta target genes by 3,3'-diindolylmethane. (2010). https://pubmed.ncbi.nlm.nih.gov/20160136/ DOI: 10.1210/en.2009-1028
tissue_or_cell_type
ERbeta transcription
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 584–595
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter, binding, chromatin and coactivator-silencing assays · source_derived_draft · unverified_draft
### dim-src2-recruitment DIM promoted ERbeta recruitment of SRC-2 at regulatory elements; SRC-2 silencing inhibited target-gene activation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate coactivator was required for the transcriptional response. organism: Human receptor-expressing cell systems tissue_or_cell_type: ERbeta transcription experimental_model: Reporter, binding, chromatin and coactivator-silencing assays limitations: Subtype-selective response in this system; other studies find ERalpha responses under other hormonal and concentration conditions. exposure: DIM and SRC-2 silencing evidence_span: {"source_cache": "artifacts/dim-research/20160136.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5", "start_char": 0, "end_char": 1134, "text_sha256": "558ee877330aede2675ccccdef5e31debf9824e00a1eaaacb1e7fe385d45b8e5"} [dim-p20160136] Selective activation of estrogen receptor-beta target genes by 3,3'-diindolylmethane. (2010). https://pubmed.ncbi.nlm.nih.gov/20160136/ DOI: 10.1210/en.2009-1028
Complete structured claim and evidence
DIM at 10 micromolar activated ERalpha-regulated transcription in the absence of estradiol.
3,3'-Diindolylmethane / DIM → Human estrogen receptor alpha / ESR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}
experimental_model
Gene expression, chromatin, inhibitors and growth assays
exposure
DIM 10 versus 50 micromolar; estradiol absent
limitations
The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human MCF-7 and T47D cells
plain_language
DIM cannot be described as a universal estrogen blocker.
primary_references
[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
tissue_or_cell_type
ERalpha and proliferation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 597–608
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft
### dim-eralpha-activation DIM at 10 micromolar activated ERalpha-regulated transcription in the absence of estradiol. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: DIM cannot be described as a universal estrogen blocker. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
Complete structured claim and evidence
The PKA signaling pathway participated in DIM-mediated ERalpha activation.
Protein kinase A → Human estrogen receptor alpha / ESR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}
experimental_model
Gene expression, chromatin, inhibitors and growth assays
exposure
DIM 10 versus 50 micromolar; estradiol absent
limitations
The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human MCF-7 and T47D cells
plain_language
A kinase pathway connected exposure to receptor signaling.
primary_references
[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
tissue_or_cell_type
ERalpha and proliferation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 623–634
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft
### dim-pka-eralpha The PKA signaling pathway participated in DIM-mediated ERalpha activation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase pathway connected exposure to receptor signaling. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
Complete structured claim and evidence
DIM at 50 micromolar inhibited proliferation in contrast with the lower-concentration response.
3,3'-Diindolylmethane / DIM → Cell proliferation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"}
experimental_model
Gene expression, chromatin, inhibitors and growth assays
exposure
DIM 10 versus 50 micromolar; estradiol absent
limitations
The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human MCF-7 and T47D cells
plain_language
Direction changed with concentration within the same experimental study.
primary_references
[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
tissue_or_cell_type
ERalpha and proliferation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 636–647
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene expression, chromatin, inhibitors and growth assays · source_derived_draft · unverified_draft
### dim-higher-dose-growth-inhibition DIM at 50 micromolar inhibited proliferation in contrast with the lower-concentration response. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direction changed with concentration within the same experimental study. organism: Human MCF-7 and T47D cells tissue_or_cell_type: ERalpha and proliferation experimental_model: Gene expression, chromatin, inhibitors and growth assays limitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter. exposure: DIM 10 versus 50 micromolar; estradiol absent evidence_span: {"source_cache": "artifacts/dim-research/25048790.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17", "start_char": 0, "end_char": 1824, "text_sha256": "3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17"} [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524
Complete structured claim and evidence
DIM produced overlapping AHR- and ERalpha-associated regulatory patterns, with preferential AHR recruitment to ERalpha targets when both receptors were activated.
Human aryl hydrocarbon receptor / AHR → Human estrogen receptor alpha / ESR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/37834026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443", "start_char": 0, "end_char": 1593, "text_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443"}
experimental_model
ChIP sequencing and transcriptomics
exposure
DIM, estradiol, TCDD and resveratrol comparisons
limitations
Genome-wide cell-model binding and transcription; no patient efficacy or universal receptor hierarchy established.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human MCF-7 cells
plain_language
Two receptors can cooperate on a response instead of acting as isolated switches.
primary_references
[dim-p37834026] Resveratrol and 3,3'-Diindolylmethane Differentially Regulate Aryl Hydrocarbon Receptor and Estrogen Receptor Alpha Activity through Multiple Transcriptomic Targets in MCF-7 Human Breast Cancer Cells. (2023). https://pubmed.ncbi.nlm.nih.gov/37834026/ DOI: 10.3390/ijms241914578
tissue_or_cell_type
AhR-ERalpha co-regulation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 649–660
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ChIP sequencing and transcriptomics · source_derived_draft · unverified_draft
### dim-ahr-er-crosstalk DIM produced overlapping AHR- and ERalpha-associated regulatory patterns, with preferential AHR recruitment to ERalpha targets when both receptors were activated. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two receptors can cooperate on a response instead of acting as isolated switches. organism: Human MCF-7 cells tissue_or_cell_type: AhR-ERalpha co-regulation experimental_model: ChIP sequencing and transcriptomics limitations: Genome-wide cell-model binding and transcription; no patient efficacy or universal receptor hierarchy established. exposure: DIM, estradiol, TCDD and resveratrol comparisons evidence_span: {"source_cache": "artifacts/dim-research/37834026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443", "start_char": 0, "end_char": 1593, "text_sha256": "b0f6f8f6c7fd2b3a09e9dd39b50c5e692c9bcca9b0119ab32475aff0685d2443"} [dim-p37834026] Resveratrol and 3,3'-Diindolylmethane Differentially Regulate Aryl Hydrocarbon Receptor and Estrogen Receptor Alpha Activity through Multiple Transcriptomic Targets in MCF-7 Human Breast Cancer Cells. (2023). https://pubmed.ncbi.nlm.nih.gov/37834026/ DOI: 10.3390/ijms241914578
Complete structured claim and evidence
CYP3A4 contributed to clozapine demethylation and N-oxidation.
Human cytochrome P450 3A4 → Clozapine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/9384460.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6", "start_char": 0, "end_char": 1794, "text_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6"}
experimental_model
Recombinant enzymes, antibodies and human liver microsomes
exposure
Enzyme-specific inhibition and metabolite formation
limitations
Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP enzymes
plain_language
Clozapine has more than one relevant route.
primary_references
[dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x
tissue_or_cell_type
Clozapine oxidation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 675–686
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzymes, antibodies and human liver microsomes · source_derived_draft · unverified_draft
### dim-clozapine-3a4 CYP3A4 contributed to clozapine demethylation and N-oxidation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Clozapine has more than one relevant route. organism: Human CYP enzymes tissue_or_cell_type: Clozapine oxidation experimental_model: Recombinant enzymes, antibodies and human liver microsomes limitations: Identifies metabolic routes, not a trial of DIM with clozapine. Do not infer a dose change or magnitude of interaction. exposure: Enzyme-specific inhibition and metabolite formation evidence_span: {"source_cache": "artifacts/dim-research/9384460.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6", "start_char": 0, "end_char": 1794, "text_sha256": "eb481193bb0d7564d728a25a9ddd63678e8234e628edca3f13ece910770279b6"} [dim-p9384460] The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. (1997). https://pubmed.ncbi.nlm.nih.gov/9384460/ DOI: 10.1046/j.1365-2125.1997.t01-1-00605.x
Complete structured claim and evidence
Caffeine-derived CYP1A2 indices correlated with clozapine clearance in the 14-person study.
CYP1A2 catalytic activity → Plasma clozapine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/7893591.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d568c4f2cdf1fc2d58f2ea22e395a7d7813cef2b1433fe25da51a2c40df5c545", "start_char": 0, "end_char": 849, "text_sha256": "d568c4f2cdf1fc2d58f2ea22e395a7d7813cef2b1433fe25da51a2c40df5c545"}
experimental_model
Clinical caffeine phenotyping and prior clozapine exposure
exposure
Caffeine test related to single-dose clozapine kinetics
limitations
Correlation supports enzyme relevance; no DIM administration or prediction of an individual clinical effect.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
14 healthy adults
plain_language
Enzyme activity was linked to drug handling in people, separately from any DIM exposure.
primary_references
[dim-p7893591] Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. (1994). https://pubmed.ncbi.nlm.nih.gov/7893591/ DOI: 10.1111/j.1365-2125.1994.tb04385.x
tissue_or_cell_type
CYP1A2 phenotype and clozapine disposition
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 688–699
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical caffeine phenotyping and prior clozapine exposure · source_derived_draft · unverified_draft
### dim-clozapine-phenotype Caffeine-derived CYP1A2 indices correlated with clozapine clearance in the 14-person study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Enzyme activity was linked to drug handling in people, separately from any DIM exposure. organism: 14 healthy adults tissue_or_cell_type: CYP1A2 phenotype and clozapine disposition experimental_model: Clinical caffeine phenotyping and prior clozapine exposure limitations: Correlation supports enzyme relevance; no DIM administration or prediction of an individual clinical effect. exposure: Caffeine test related to single-dose clozapine kinetics evidence_span: {"source_cache": "artifacts/dim-research/7893591.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d568c4f2cdf1fc2d58f2ea22e395a7d7813cef2b1433fe25da51a2c40df5c545", "start_char": 0, "end_char": 849, "text_sha256": "d568c4f2cdf1fc2d58f2ea22e395a7d7813cef2b1433fe25da51a2c40df5c545"} [dim-p7893591] Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. (1994). https://pubmed.ncbi.nlm.nih.gov/7893591/ DOI: 10.1111/j.1365-2125.1994.tb04385.x
Complete structured claim and evidence
CYP1A2 played a major role in olanzapine 7-hydroxylation and also contributed to N-demethylation.
Human cytochrome P450 1A2 → 7-Hydroxyolanzapine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"}
experimental_model
Human liver microsomes and recombinant enzyme phenotyping
exposure
Metabolite-specific assays including albumin effects
limitations
In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP, FMO and UGT enzymes
plain_language
This independently identified route also contributes to olanzapine handling.
primary_references
[dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
tissue_or_cell_type
Olanzapine oxidation and conjugation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 701–712
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver microsomes and recombinant enzyme phenotyping · source_derived_draft · unverified_draft
### dim-olanzapine-1a2 CYP1A2 played a major role in olanzapine 7-hydroxylation and also contributed to N-demethylation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified route also contributes to olanzapine handling. organism: Human CYP, FMO and UGT enzymes tissue_or_cell_type: Olanzapine oxidation and conjugation experimental_model: Human liver microsomes and recombinant enzyme phenotyping limitations: In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone. exposure: Metabolite-specific assays including albumin effects evidence_span: {"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"} [dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
Complete structured claim and evidence
UGT1A4 played a major role in olanzapine 10-N-glucuronide formation.
Human UDP-glucuronosyltransferase 1A4 → Olanzapine 10-N-glucuronide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"}
experimental_model
Human liver microsomes and recombinant enzyme phenotyping
exposure
Metabolite-specific assays including albumin effects
limitations
In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP, FMO and UGT enzymes
plain_language
This independently identified route also contributes to olanzapine handling.
primary_references
[dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
tissue_or_cell_type
Olanzapine oxidation and conjugation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 714–725
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver microsomes and recombinant enzyme phenotyping · source_derived_draft · unverified_draft
### dim-olanzapine-ugt UGT1A4 played a major role in olanzapine 10-N-glucuronide formation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified route also contributes to olanzapine handling. organism: Human CYP, FMO and UGT enzymes tissue_or_cell_type: Olanzapine oxidation and conjugation experimental_model: Human liver microsomes and recombinant enzyme phenotyping limitations: In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone. exposure: Metabolite-specific assays including albumin effects evidence_span: {"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"} [dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
Complete structured claim and evidence
FMO3 played a major role in olanzapine N-oxide formation.
Human flavin-containing monooxygenase 3 → Olanzapine N-oxide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"}
experimental_model
Human liver microsomes and recombinant enzyme phenotyping
exposure
Metabolite-specific assays including albumin effects
limitations
In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP, FMO and UGT enzymes
plain_language
This independently identified route also contributes to olanzapine handling.
primary_references
[dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
tissue_or_cell_type
Olanzapine oxidation and conjugation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 727–738
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver microsomes and recombinant enzyme phenotyping · source_derived_draft · unverified_draft
### dim-olanzapine-fmo FMO3 played a major role in olanzapine N-oxide formation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified route also contributes to olanzapine handling. organism: Human CYP, FMO and UGT enzymes tissue_or_cell_type: Olanzapine oxidation and conjugation experimental_model: Human liver microsomes and recombinant enzyme phenotyping limitations: In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone. exposure: Metabolite-specific assays including albumin effects evidence_span: {"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"} [dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
Complete structured claim and evidence
CYP2C8 made a substantial contribution to olanzapine N-demethylation in the tested assays.
Human cytochrome P450 2C8 → N-Desmethylolanzapine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"}
experimental_model
Human liver microsomes and recombinant enzyme phenotyping
exposure
Metabolite-specific assays including albumin effects
limitations
In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP, FMO and UGT enzymes
plain_language
This independently identified route also contributes to olanzapine handling.
primary_references
[dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
tissue_or_cell_type
Olanzapine oxidation and conjugation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 740–751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver microsomes and recombinant enzyme phenotyping · source_derived_draft · unverified_draft
### dim-olanzapine-2c8 CYP2C8 made a substantial contribution to olanzapine N-demethylation in the tested assays. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified route also contributes to olanzapine handling. organism: Human CYP, FMO and UGT enzymes tissue_or_cell_type: Olanzapine oxidation and conjugation experimental_model: Human liver microsomes and recombinant enzyme phenotyping limitations: In-vitro relative contributions; no DIM coadministration. Multiple routes limit prediction from CYP1A2 alone. exposure: Metabolite-specific assays including albumin effects evidence_span: {"source_cache": "artifacts/dim-research/26329789.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543", "start_char": 0, "end_char": 1657, "text_sha256": "1f2f35be434034ef4788653d084a6b184b1b5a109d445591c4fd0fc94b36e543"} [dim-p26329789] In Vitro Characterization of the Human Liver Microsomal Kinetics and Reaction Phenotyping of Olanzapine Metabolism. (2015). https://pubmed.ncbi.nlm.nih.gov/26329789/ DOI: 10.1124/dmd.115.064790
Complete structured claim and evidence
Median concentration-to-dose ratio was 6.0 in smokers versus 10.1 nmol/L/mg in nonsmokers.
Exposure to cigarette smoking → Dose-normalized serum olanzapine concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/37841771.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f6834b6adcdbbdf02999b1bc5f567b8c0873f393d9b0e80127c887ab8054247", "start_char": 0, "end_char": 1698, "text_sha256": "1f6834b6adcdbbdf02999b1bc5f567b8c0873f393d9b0e80127c887ab8054247"}
experimental_model
Cross-sectional therapeutic-concentration study
exposure
37 smokers; comparison with nonsmokers
limitations
Observed smoking association, not randomized DIM exposure; confounding and individual variability remain.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
58 outpatients with schizophrenia
plain_language
Smoking had a measured association; equal effects from DIM are not established.
primary_references
[dim-p37841771] Association of smoking cigarettes, age, and sex with serum concentrations of olanzapine in patients with schizophrenia. (2023). https://pubmed.ncbi.nlm.nih.gov/37841771/ DOI: 10.11613/bm.2023.030702
tissue_or_cell_type
Dose-normalized olanzapine concentrations
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 753–764
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cross-sectional therapeutic-concentration study · source_derived_draft · unverified_draft
### dim-olanzapine-smoking Median concentration-to-dose ratio was 6.0 in smokers versus 10.1 nmol/L/mg in nonsmokers. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Smoking had a measured association; equal effects from DIM are not established. organism: 58 outpatients with schizophrenia tissue_or_cell_type: Dose-normalized olanzapine concentrations experimental_model: Cross-sectional therapeutic-concentration study limitations: Observed smoking association, not randomized DIM exposure; confounding and individual variability remain. exposure: 37 smokers; comparison with nonsmokers evidence_span: {"source_cache": "artifacts/dim-research/37841771.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f6834b6adcdbbdf02999b1bc5f567b8c0873f393d9b0e80127c887ab8054247", "start_char": 0, "end_char": 1698, "text_sha256": "1f6834b6adcdbbdf02999b1bc5f567b8c0873f393d9b0e80127c887ab8054247"} [dim-p37841771] Association of smoking cigarettes, age, and sex with serum concentrations of olanzapine in patients with schizophrenia. (2023). https://pubmed.ncbi.nlm.nih.gov/37841771/ DOI: 10.11613/bm.2023.030702
Complete structured claim and evidence
CYP1A2 catalyzed theophylline demethylation and hydroxylation, with high affinity and the highest tested intrinsic clearance to dimethyluric acid.
Human cytochrome P450 1A2 → Theophylline source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/7619675.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb", "start_char": 0, "end_char": 1842, "text_sha256": "0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb"}
experimental_model
Recombinant human enzyme kinetics
exposure
Multiple substrate concentrations
limitations
Substrate concentration changed relative contributions. Not a DIM-theophylline study or an individual dosing rule.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP isoforms expressed in lymphoblastoid cells
plain_language
Theophylline is a relevant substrate to investigate, but DIM-induced concentration changes were not measured.
primary_references
[dim-p7619675] Metabolism of theophylline by cDNA-expressed human cytochromes P-450. (1995). https://pubmed.ncbi.nlm.nih.gov/7619675/ DOI: 10.1111/j.1365-2125.1995.tb04455.x
tissue_or_cell_type
Theophylline metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 766–777
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme kinetics · source_derived_draft · unverified_draft
### dim-theophylline-1a2 CYP1A2 catalyzed theophylline demethylation and hydroxylation, with high affinity and the highest tested intrinsic clearance to dimethyluric acid. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Theophylline is a relevant substrate to investigate, but DIM-induced concentration changes were not measured. organism: Human CYP isoforms expressed in lymphoblastoid cells tissue_or_cell_type: Theophylline metabolism experimental_model: Recombinant human enzyme kinetics limitations: Substrate concentration changed relative contributions. Not a DIM-theophylline study or an individual dosing rule. exposure: Multiple substrate concentrations evidence_span: {"source_cache": "artifacts/dim-research/7619675.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb", "start_char": 0, "end_char": 1842, "text_sha256": "0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb"} [dim-p7619675] Metabolism of theophylline by cDNA-expressed human cytochromes P-450. (1995). https://pubmed.ncbi.nlm.nih.gov/7619675/ DOI: 10.1111/j.1365-2125.1995.tb04455.x
Complete structured claim and evidence
CYP1A2 catalyzed duloxetine metabolism in the in-vitro experiments.
Human cytochrome P450 1A2 → Duloxetine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/18307373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149", "start_char": 0, "end_char": 2879, "text_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149"}
experimental_model
Enzyme phenotyping and clinical drug-interaction studies
exposure
Fluvoxamine with oral or intravenous duloxetine
limitations
The clinical exposure change was caused by fluvoxamine, not DIM. The study tests inhibition, not the inverse size of induction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human enzyme systems and healthy adults
plain_language
A shared enzyme is a reason to investigate an interaction, not proof DIM lowers the drug level.
primary_references
[dim-p18307373] In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. (2008). https://pubmed.ncbi.nlm.nih.gov/18307373/ DOI: 10.2165/00003088-200847030-00005
tissue_or_cell_type
Duloxetine metabolism and exposure
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 792–803
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme phenotyping and clinical drug-interaction studies · source_derived_draft · unverified_draft
### dim-duloxetine-1a2 CYP1A2 catalyzed duloxetine metabolism in the in-vitro experiments. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shared enzyme is a reason to investigate an interaction, not proof DIM lowers the drug level. organism: Human enzyme systems and healthy adults tissue_or_cell_type: Duloxetine metabolism and exposure experimental_model: Enzyme phenotyping and clinical drug-interaction studies limitations: The clinical exposure change was caused by fluvoxamine, not DIM. The study tests inhibition, not the inverse size of induction. exposure: Fluvoxamine with oral or intravenous duloxetine evidence_span: {"source_cache": "artifacts/dim-research/18307373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149", "start_char": 0, "end_char": 2879, "text_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149"} [dim-p18307373] In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. (2008). https://pubmed.ncbi.nlm.nih.gov/18307373/ DOI: 10.2165/00003088-200847030-00005
Complete structured claim and evidence
Fluvoxamine increased oral duloxetine AUC by 460% and peak concentration by 141% in the clinical study.
Fluvoxamine → Plasma duloxetine exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/18307373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149", "start_char": 0, "end_char": 2879, "text_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149"}
experimental_model
Enzyme phenotyping and clinical drug-interaction studies
exposure
Fluvoxamine with oral or intravenous duloxetine
limitations
The clinical exposure change was caused by fluvoxamine, not DIM. The study tests inhibition, not the inverse size of induction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human enzyme systems and healthy adults
plain_language
Blocking metabolism increased exposure; this measured result must not be relabeled as a DIM study.
primary_references
[dim-p18307373] In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. (2008). https://pubmed.ncbi.nlm.nih.gov/18307373/ DOI: 10.2165/00003088-200847030-00005
tissue_or_cell_type
Duloxetine metabolism and exposure
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 805–816
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme phenotyping and clinical drug-interaction studies · source_derived_draft · unverified_draft
### dim-duloxetine-inhibition Fluvoxamine increased oral duloxetine AUC by 460% and peak concentration by 141% in the clinical study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking metabolism increased exposure; this measured result must not be relabeled as a DIM study. organism: Human enzyme systems and healthy adults tissue_or_cell_type: Duloxetine metabolism and exposure experimental_model: Enzyme phenotyping and clinical drug-interaction studies limitations: The clinical exposure change was caused by fluvoxamine, not DIM. The study tests inhibition, not the inverse size of induction. exposure: Fluvoxamine with oral or intravenous duloxetine evidence_span: {"source_cache": "artifacts/dim-research/18307373.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149", "start_char": 0, "end_char": 2879, "text_sha256": "2705ee887855e9dbe738ece57d4ad9d4b3d8cc0d67de45e63c01497a4a215149"} [dim-p18307373] In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. (2008). https://pubmed.ncbi.nlm.nih.gov/18307373/ DOI: 10.2165/00003088-200847030-00005
Complete structured claim and evidence
CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation.
Human cytochrome P450 1A2 → Melatonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/11317475.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d", "start_char": 0, "end_char": 1580, "text_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d"}
experimental_model
Human microsomes, expressed enzymes and inhibition assays
exposure
Substrate range 1-1000 micromolar
limitations
In-vitro pathway identification; no DIM coadministration, sleep outcome or proof that DIM lowers nighttime melatonin.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human liver CYP systems
plain_language
Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge.
primary_references
[dim-p11317475] Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. (2001). https://pubmed.ncbi.nlm.nih.gov/11317475/ DOI: 10.1007/s002280000245
tissue_or_cell_type
Melatonin 6-hydroxylation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 818–829
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes, expressed enzymes and inhibition assays · source_derived_draft · unverified_draft
### dim-melatonin-1a2 CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge. organism: Human liver CYP systems tissue_or_cell_type: Melatonin 6-hydroxylation experimental_model: Human microsomes, expressed enzymes and inhibition assays limitations: In-vitro pathway identification; no DIM coadministration, sleep outcome or proof that DIM lowers nighttime melatonin. exposure: Substrate range 1-1000 micromolar evidence_span: {"source_cache": "artifacts/dim-research/11317475.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d", "start_char": 0, "end_char": 1580, "text_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d"} [dim-p11317475] Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. (2001). https://pubmed.ncbi.nlm.nih.gov/11317475/ DOI: 10.1007/s002280000245
Complete structured claim and evidence
The paraxanthine-to-caffeine ratio was used to phenotype CYP1A2 during smoking cessation.
Human cytochrome P450 1A2 → Caffeine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/15289794.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2", "start_char": 0, "end_char": 1753, "text_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2"}
experimental_model
Repeated caffeine phenotyping after smoking cessation
exposure
Abrupt cessation after run-in; repeated 148-mg caffeine probe doses
limitations
Smoking-cessation kinetics cannot be assigned to starting or stopping DIM. Clinical dose management requires drug-specific monitoring.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
12 heavy smokers
plain_language
Caffeine provides a measurable probe of enzyme activity.
primary_references
[dim-p15289794] Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. (2004). https://pubmed.ncbi.nlm.nih.gov/15289794/ DOI: 10.1016/j.clpt.2004.04.003
tissue_or_cell_type
CYP1A2 activity and caffeine clearance
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 831–842
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Repeated caffeine phenotyping after smoking cessation · source_derived_draft · unverified_draft
### dim-caffeine-1a2 The paraxanthine-to-caffeine ratio was used to phenotype CYP1A2 during smoking cessation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Caffeine provides a measurable probe of enzyme activity. organism: 12 heavy smokers tissue_or_cell_type: CYP1A2 activity and caffeine clearance experimental_model: Repeated caffeine phenotyping after smoking cessation limitations: Smoking-cessation kinetics cannot be assigned to starting or stopping DIM. Clinical dose management requires drug-specific monitoring. exposure: Abrupt cessation after run-in; repeated 148-mg caffeine probe doses evidence_span: {"source_cache": "artifacts/dim-research/15289794.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2", "start_char": 0, "end_char": 1753, "text_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2"} [dim-p15289794] Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. (2004). https://pubmed.ncbi.nlm.nih.gov/15289794/ DOI: 10.1016/j.clpt.2004.04.003
Complete structured claim and evidence
Caffeine clearance fell by 36.1% after cessation; the fitted half-life of CYP1A2 activity decline was 38.6 hours.
Cessation of cigarette smoking → Caffeine clearance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/15289794.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2", "start_char": 0, "end_char": 1753, "text_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2"}
experimental_model
Repeated caffeine phenotyping after smoking cessation
exposure
Abrupt cessation after run-in; repeated 148-mg caffeine probe doses
limitations
Smoking-cessation kinetics cannot be assigned to starting or stopping DIM. Clinical dose management requires drug-specific monitoring.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
12 heavy smokers
plain_language
Stopping an established inducer can raise exposure to its substrates, but these numbers describe smoking.
primary_references
[dim-p15289794] Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. (2004). https://pubmed.ncbi.nlm.nih.gov/15289794/ DOI: 10.1016/j.clpt.2004.04.003
tissue_or_cell_type
CYP1A2 activity and caffeine clearance
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 844–855
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Repeated caffeine phenotyping after smoking cessation · source_derived_draft · unverified_draft
### dim-smoking-cessation Caffeine clearance fell by 36.1% after cessation; the fitted half-life of CYP1A2 activity decline was 38.6 hours. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stopping an established inducer can raise exposure to its substrates, but these numbers describe smoking. organism: 12 heavy smokers tissue_or_cell_type: CYP1A2 activity and caffeine clearance experimental_model: Repeated caffeine phenotyping after smoking cessation limitations: Smoking-cessation kinetics cannot be assigned to starting or stopping DIM. Clinical dose management requires drug-specific monitoring. exposure: Abrupt cessation after run-in; repeated 148-mg caffeine probe doses evidence_span: {"source_cache": "artifacts/dim-research/15289794.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2", "start_char": 0, "end_char": 1753, "text_sha256": "90eb96e72afdbbb53c322c2be9a34e5aa523c27f2fd0995a8eb224e2ec6e35e2"} [dim-p15289794] Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. (2004). https://pubmed.ncbi.nlm.nih.gov/15289794/ DOI: 10.1016/j.clpt.2004.04.003
Complete structured claim and evidence
Nicotine patches did not significantly change caffeine pharmacokinetics or metabolite formation in the crossover study.
Nicotine → Caffeine clearance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/21599724.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940", "start_char": 0, "end_char": 537, "text_sha256": "2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940"}
experimental_model
Randomized crossover nicotine-patch study; full-text extract
exposure
42 mg/day transdermal nicotine or placebo; caffeine probe on day eight
limitations
Nicotine-only exposure differs from smoke exposure; this short study does not test every tissue or nicotine product.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
12 healthy smokers abstinent from tobacco during study
plain_language
Smoking and nicotine alone are not interchangeable CYP1A2 exposures.
primary_references
[dim-p21599724] Effect of nicotine on cytochrome P450 1A2 activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21599724/ DOI: 10.1111/j.1365-2125.2011.04023.x
tissue_or_cell_type
Caffeine-based hepatic CYP1A2 phenotyping
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 857–868
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover nicotine-patch study; full-text extract · source_derived_draft · unverified_draft
### dim-nicotine-not-smoke Nicotine patches did not significantly change caffeine pharmacokinetics or metabolite formation in the crossover study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Smoking and nicotine alone are not interchangeable CYP1A2 exposures. organism: 12 healthy smokers abstinent from tobacco during study tissue_or_cell_type: Caffeine-based hepatic CYP1A2 phenotyping experimental_model: Randomized crossover nicotine-patch study; full-text extract limitations: Nicotine-only exposure differs from smoke exposure; this short study does not test every tissue or nicotine product. exposure: 42 mg/day transdermal nicotine or placebo; caffeine probe on day eight evidence_span: {"source_cache": "artifacts/dim-research/21599724.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940", "start_char": 0, "end_char": 537, "text_sha256": "2a31ba5c71ba785b8fc6cdec21ed2dfa37686cb6d44dbf22616b0ab9b585a940"} [dim-p21599724] Effect of nicotine on cytochrome P450 1A2 activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21599724/ DOI: 10.1111/j.1365-2125.2011.04023.x
Complete structured claim and evidence
CYP1A2 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.
Human cytochrome P450 1A2 → Ramelteon source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20478852.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e", "start_char": 0, "end_char": 1696, "text_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e"}
experimental_model
Microsomal metabolism and drug-interaction prediction
exposure
CYP1A2, CYP2C19 and CYP3A4 assays
limitations
In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human liver and intestinal microsomes
plain_language
Ramelteon has several metabolic routes; none here measures a DIM interaction.
primary_references
[dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009
tissue_or_cell_type
Ramelteon metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 870–881
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal metabolism and drug-interaction prediction · source_derived_draft · unverified_draft
### dim-ramelteon-cyp1a2 CYP1A2 catalyzed ramelteon metabolism in the tested microsomal/recombinant system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ramelteon has several metabolic routes; none here measures a DIM interaction. organism: Human liver and intestinal microsomes tissue_or_cell_type: Ramelteon metabolism experimental_model: Microsomal metabolism and drug-interaction prediction limitations: In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction. exposure: CYP1A2, CYP2C19 and CYP3A4 assays evidence_span: {"source_cache": "artifacts/dim-research/20478852.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e", "start_char": 0, "end_char": 1696, "text_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e"} [dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009
Complete structured claim and evidence
CYP2C19 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.
Human cytochrome P450 2C19 → Ramelteon source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20478852.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e", "start_char": 0, "end_char": 1696, "text_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e"}
experimental_model
Microsomal metabolism and drug-interaction prediction
exposure
CYP1A2, CYP2C19 and CYP3A4 assays
limitations
In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human liver and intestinal microsomes
plain_language
Ramelteon has several metabolic routes; none here measures a DIM interaction.
primary_references
[dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009
tissue_or_cell_type
Ramelteon metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 883–894
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal metabolism and drug-interaction prediction · source_derived_draft · unverified_draft
### dim-ramelteon-cyp2c19 CYP2C19 catalyzed ramelteon metabolism in the tested microsomal/recombinant system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ramelteon has several metabolic routes; none here measures a DIM interaction. organism: Human liver and intestinal microsomes tissue_or_cell_type: Ramelteon metabolism experimental_model: Microsomal metabolism and drug-interaction prediction limitations: In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction. exposure: CYP1A2, CYP2C19 and CYP3A4 assays evidence_span: {"source_cache": "artifacts/dim-research/20478852.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e", "start_char": 0, "end_char": 1696, "text_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e"} [dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009
Complete structured claim and evidence
CYP3A4 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.
Human cytochrome P450 3A4 → Ramelteon source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20478852.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e", "start_char": 0, "end_char": 1696, "text_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e"}
experimental_model
Microsomal metabolism and drug-interaction prediction
exposure
CYP1A2, CYP2C19 and CYP3A4 assays
limitations
In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human liver and intestinal microsomes
plain_language
Ramelteon has several metabolic routes; none here measures a DIM interaction.
primary_references
[dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009
tissue_or_cell_type
Ramelteon metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 896–907
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal metabolism and drug-interaction prediction · source_derived_draft · unverified_draft
### dim-ramelteon-cyp3a4 CYP3A4 catalyzed ramelteon metabolism in the tested microsomal/recombinant system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ramelteon has several metabolic routes; none here measures a DIM interaction. organism: Human liver and intestinal microsomes tissue_or_cell_type: Ramelteon metabolism experimental_model: Microsomal metabolism and drug-interaction prediction limitations: In-vitro estimated shares vary by pathway and model. Fluvoxamine inhibits multiple routes; its large interaction cannot be inverted into a DIM prediction. exposure: CYP1A2, CYP2C19 and CYP3A4 assays evidence_span: {"source_cache": "artifacts/dim-research/20478852.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e", "start_char": 0, "end_char": 1696, "text_sha256": "0b04ad3560e6db88e29df6793283d7571c2e7bba1d499b30a5675e49bc17434e"} [dim-p20478852] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. (2010). https://pubmed.ncbi.nlm.nih.gov/20478852/ DOI: 10.1124/dmd.110.034009
Complete structured claim and evidence
CYP1A2 contributed prominently to propranolol N-desisopropylation.
Human cytochrome P450 1A2 → Propranolol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/7640150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247", "start_char": 0, "end_char": 2428, "text_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247"}
experimental_model
Human microsomes and recombinant enzyme phenotyping
exposure
N-desisopropylation versus ring hydroxylation
limitations
Route- and enantiomer-specific biochemistry; total propranolol exposure cannot be predicted from one route.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP isoforms
plain_language
This is one route through a drug with several clearance mechanisms.
primary_references
[dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. (1995). https://pubmed.ncbi.nlm.nih.gov/7640150/ DOI: 10.1111/j.1365-2125.1995.tb04472.x
tissue_or_cell_type
Propranolol enantiomer metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 909–920
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and recombinant enzyme phenotyping · source_derived_draft · unverified_draft
### dim-propranolol-1a2 CYP1A2 contributed prominently to propranolol N-desisopropylation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is one route through a drug with several clearance mechanisms. organism: Human CYP isoforms tissue_or_cell_type: Propranolol enantiomer metabolism experimental_model: Human microsomes and recombinant enzyme phenotyping limitations: Route- and enantiomer-specific biochemistry; total propranolol exposure cannot be predicted from one route. exposure: N-desisopropylation versus ring hydroxylation evidence_span: {"source_cache": "artifacts/dim-research/7640150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247", "start_char": 0, "end_char": 2428, "text_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247"} [dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. (1995). https://pubmed.ncbi.nlm.nih.gov/7640150/ DOI: 10.1111/j.1365-2125.1995.tb04472.x
Complete structured claim and evidence
CYP2D6 was a major catalyst of propranolol ring 4-hydroxylation.
Human cytochrome P450 2D6 → Propranolol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/7640150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247", "start_char": 0, "end_char": 2428, "text_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247"}
experimental_model
Human microsomes and recombinant enzyme phenotyping
exposure
N-desisopropylation versus ring hydroxylation
limitations
Route- and enantiomer-specific biochemistry; total propranolol exposure cannot be predicted from one route.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP isoforms
plain_language
A separate enzyme supports a different transformation of the same drug.
primary_references
[dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. (1995). https://pubmed.ncbi.nlm.nih.gov/7640150/ DOI: 10.1111/j.1365-2125.1995.tb04472.x
tissue_or_cell_type
Propranolol enantiomer metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 922–933
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and recombinant enzyme phenotyping · source_derived_draft · unverified_draft
### dim-propranolol-2d6 CYP2D6 was a major catalyst of propranolol ring 4-hydroxylation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate enzyme supports a different transformation of the same drug. organism: Human CYP isoforms tissue_or_cell_type: Propranolol enantiomer metabolism experimental_model: Human microsomes and recombinant enzyme phenotyping limitations: Route- and enantiomer-specific biochemistry; total propranolol exposure cannot be predicted from one route. exposure: N-desisopropylation versus ring hydroxylation evidence_span: {"source_cache": "artifacts/dim-research/7640150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247", "start_char": 0, "end_char": 2428, "text_sha256": "368198090ed645914a14e9d365b48030bcfd8a67e4d5bc4f9f6d1476e8340247"} [dim-p7640150] Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2. (1995). https://pubmed.ncbi.nlm.nih.gov/7640150/ DOI: 10.1111/j.1365-2125.1995.tb04472.x
Complete structured claim and evidence
CYP1A1 contributed to ondansetron metabolism in the studied human systems.
Human cytochrome P450 1A1 → Ondansetron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"}
experimental_model
Human microsomes and individually expressed enzymes
exposure
Enzyme-specific inhibitors and radiolabeled substrate
limitations
CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP systems
plain_language
A substrate list alone omits other routes that can limit a single-enzyme interaction.
primary_references
[dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
tissue_or_cell_type
Ondansetron oxidation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 935–946
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and individually expressed enzymes · source_derived_draft · unverified_draft
### dim-ondansetron-cyp1a1 CYP1A1 contributed to ondansetron metabolism in the studied human systems. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A substrate list alone omits other routes that can limit a single-enzyme interaction. organism: Human CYP systems tissue_or_cell_type: Ondansetron oxidation experimental_model: Human microsomes and individually expressed enzymes limitations: CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect. exposure: Enzyme-specific inhibitors and radiolabeled substrate evidence_span: {"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"} [dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
Complete structured claim and evidence
CYP1A2 contributed to ondansetron metabolism in the studied human systems.
Human cytochrome P450 1A2 → Ondansetron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"}
experimental_model
Human microsomes and individually expressed enzymes
exposure
Enzyme-specific inhibitors and radiolabeled substrate
limitations
CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP systems
plain_language
A substrate list alone omits other routes that can limit a single-enzyme interaction.
primary_references
[dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
tissue_or_cell_type
Ondansetron oxidation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 948–959
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and individually expressed enzymes · source_derived_draft · unverified_draft
### dim-ondansetron-cyp1a2 CYP1A2 contributed to ondansetron metabolism in the studied human systems. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A substrate list alone omits other routes that can limit a single-enzyme interaction. organism: Human CYP systems tissue_or_cell_type: Ondansetron oxidation experimental_model: Human microsomes and individually expressed enzymes limitations: CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect. exposure: Enzyme-specific inhibitors and radiolabeled substrate evidence_span: {"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"} [dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
Complete structured claim and evidence
CYP2D6 contributed to ondansetron metabolism in the studied human systems.
Human cytochrome P450 2D6 → Ondansetron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"}
experimental_model
Human microsomes and individually expressed enzymes
exposure
Enzyme-specific inhibitors and radiolabeled substrate
limitations
CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP systems
plain_language
A substrate list alone omits other routes that can limit a single-enzyme interaction.
primary_references
[dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
tissue_or_cell_type
Ondansetron oxidation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 961–972
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and individually expressed enzymes · source_derived_draft · unverified_draft
### dim-ondansetron-cyp2d6 CYP2D6 contributed to ondansetron metabolism in the studied human systems. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A substrate list alone omits other routes that can limit a single-enzyme interaction. organism: Human CYP systems tissue_or_cell_type: Ondansetron oxidation experimental_model: Human microsomes and individually expressed enzymes limitations: CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect. exposure: Enzyme-specific inhibitors and radiolabeled substrate evidence_span: {"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"} [dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
Complete structured claim and evidence
The CYP3A subfamily contributed to ondansetron metabolism in the studied human systems.
Human CYP3A subfamily, isoform unresolved → Ondansetron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"}
experimental_model
Human microsomes and individually expressed enzymes
exposure
Enzyme-specific inhibitors and radiolabeled substrate
limitations
CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human CYP systems
plain_language
A substrate list alone omits other routes that can limit a single-enzyme interaction.
primary_references
[dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
tissue_or_cell_type
Ondansetron oxidation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 974–985
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and individually expressed enzymes · source_derived_draft · unverified_draft
### dim-ondansetron-cyp3a-subfamily The CYP3A subfamily contributed to ondansetron metabolism in the studied human systems. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A substrate list alone omits other routes that can limit a single-enzyme interaction. organism: Human CYP systems tissue_or_cell_type: Ondansetron oxidation experimental_model: Human microsomes and individually expressed enzymes limitations: CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect. exposure: Enzyme-specific inhibitors and radiolabeled substrate evidence_span: {"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"} [dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5
Complete structured claim and evidence
CYP3A4/5 catalyzed formation of N-desmethyltamoxifen, the quantitatively major initial pathway.
Human cytochrome P450 3A4 → Tamoxifen 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 route to active metabolites begins with several linked transformations.
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 987–998
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-3a4 CYP3A4/5 catalyzed formation of N-desmethyltamoxifen, the quantitatively major initial pathway. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The route to active metabolites begins with several linked transformations. 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
CYP2D6 and other CYPs formed 4-hydroxytamoxifen through a smaller initial route.
Human cytochrome P450 2D6 → Tamoxifen 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
Parent-drug removal and active-metabolite formation can move differently.
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 1013–1024
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-4oh CYP2D6 and other CYPs formed 4-hydroxytamoxifen through a smaller initial route. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Parent-drug removal and active-metabolite formation can move differently. 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
I3C increased the urinary 2-to-16-alpha-hydroxyestrone ratio without significant changes in the reported serum hormones.
Indole-3-carbinol / I3C → Urinary 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/16103443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4", "start_char": 0, "end_char": 1706, "text_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4"}
experimental_model
Phase I placebo run-in and dose escalation
exposure
I3C 400 mg/day then 800 mg/day for four weeks each
limitations
The administered compound was I3C, not DIM. Multiple acid-condensation products and nonrandomized sequential periods prevent assigning the observed fold change specifically to DIM.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
17 women at elevated breast-cancer risk
plain_language
Changing metabolite proportions is different from lowering every circulating hormone.
primary_references
[dim-p16103443] A phase I study of indole-3-carbinol in women: tolerability and effects. (2005). https://pubmed.ncbi.nlm.nih.gov/16103443/ DOI: 10.1158/1055-9965.epi-05-0121
tissue_or_cell_type
Caffeine CYP1A2 phenotype and estrogen metabolites
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1039–1050
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase I placebo run-in and dose escalation · source_derived_draft · unverified_draft
### dim-i3c-ratio I3C increased the urinary 2-to-16-alpha-hydroxyestrone ratio without significant changes in the reported serum hormones. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing metabolite proportions is different from lowering every circulating hormone. organism: 17 women at elevated breast-cancer risk tissue_or_cell_type: Caffeine CYP1A2 phenotype and estrogen metabolites experimental_model: Phase I placebo run-in and dose escalation limitations: The administered compound was I3C, not DIM. Multiple acid-condensation products and nonrandomized sequential periods prevent assigning the observed fold change specifically to DIM. exposure: I3C 400 mg/day then 800 mg/day for four weeks each evidence_span: {"source_cache": "artifacts/dim-research/16103443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4", "start_char": 0, "end_char": 1706, "text_sha256": "ece0ac1a0c31053cdc1ec3eefbf9c78887018e0eddf2db36c3a1a07c998e15c4"} [dim-p16103443] A phase I study of indole-3-carbinol in women: tolerability and effects. (2005). https://pubmed.ncbi.nlm.nih.gov/16103443/ DOI: 10.1158/1055-9965.epi-05-0121
Complete structured claim and evidence
BR-DIM reduced plasma 4-hydroxytamoxifen compared with placebo.
3,3'-Diindolylmethane / DIM → Plasma 4-hydroxytamoxifen 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
A second active metabolite also fell.
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 1065–1076
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-4oh-tam-lower BR-DIM reduced plasma 4-hydroxytamoxifen compared with placebo. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second active metabolite also fell. 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
BR-DIM reduced plasma N-desmethyltamoxifen compared with placebo.
3,3'-Diindolylmethane / DIM → Plasma N-desmethyltamoxifen 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
The precursor pool for endoxifen also changed.
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 1078–1089
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-ndesmethyl-lower BR-DIM reduced plasma N-desmethyltamoxifen compared with placebo. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor pool for endoxifen also changed. 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
BR-DIM increased the urinary 2/16-alpha-hydroxyestrone ratio relative to placebo.
3,3'-Diindolylmethane / DIM → Urinary 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio 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
A ratio changed; calling one estrogen universally good and another bad would go beyond the trial.
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 1091–1102
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-estrogen-ratio BR-DIM increased the urinary 2/16-alpha-hydroxyestrone ratio relative to placebo. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A ratio changed; calling one estrogen universally good and another bad would go beyond the trial. 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
Serum SHBG increased more with BR-DIM than placebo.
3,3'-Diindolylmethane / DIM → Human sex hormone-binding globulin / SHBG 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
A hormone-binding protein changed independently of the drug metabolites.
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 1104–1115
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-shbg Serum SHBG increased more with BR-DIM than placebo. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A hormone-binding protein changed independently of the drug metabolites. 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
Breast density measured by mammography or MRI did not change with BR-DIM in the trial.
3,3'-Diindolylmethane / DIM → Breast density measured by mammography or MRI 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
The biomarker changes did not establish a change in this tissue outcome.
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 1117–1128
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-breast-density-null Breast density measured by mammography or MRI did not change with BR-DIM in the trial. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The biomarker changes did not establish a change in this tissue outcome. 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
DIM was detected in prostate tissue from 26 of 28 evaluable men, with a mean of 14.2 ng/g.
3,3'-Diindolylmethane / DIM → Prostatic DIM concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/27069550.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e", "start_char": 0, "end_char": 1626, "text_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e"}
experimental_model
Pre-prostatectomy tissue and biomarker study
exposure
Absorption-enhanced DIM 225 mg twice daily for at least 14 days
limitations
Uncontrolled preoperative study. Tissue detection and altered localization do not establish tumor control, survival benefit or testosterone lowering.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
28 evaluable men with localized prostate cancer
plain_language
A tissue measurement showed delivery under this formulation and regimen.
primary_references
[dim-p27069550] Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients. (2016). https://pubmed.ncbi.nlm.nih.gov/27069550/
tissue_or_cell_type
Prostate DIM, androgen-receptor localization and PSA
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1130–1141
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pre-prostatectomy tissue and biomarker study · source_derived_draft · unverified_draft
### dim-prostate-delivery DIM was detected in prostate tissue from 26 of 28 evaluable men, with a mean of 14.2 ng/g. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A tissue measurement showed delivery under this formulation and regimen. organism: 28 evaluable men with localized prostate cancer tissue_or_cell_type: Prostate DIM, androgen-receptor localization and PSA experimental_model: Pre-prostatectomy tissue and biomarker study limitations: Uncontrolled preoperative study. Tissue detection and altered localization do not establish tumor control, survival benefit or testosterone lowering. exposure: Absorption-enhanced DIM 225 mg twice daily for at least 14 days evidence_span: {"source_cache": "artifacts/dim-research/27069550.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e", "start_char": 0, "end_char": 1626, "text_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e"} [dim-p27069550] Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients. (2016). https://pubmed.ncbi.nlm.nih.gov/27069550/
Complete structured claim and evidence
After treatment, 96% of evaluable patients showed androgen-receptor nuclear exclusion, compared with none in pretreatment biopsies.
3,3'-Diindolylmethane / DIM → Androgen receptor nuclear localization source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/27069550.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e", "start_char": 0, "end_char": 1626, "text_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e"}
experimental_model
Pre-prostatectomy tissue and biomarker study
exposure
Absorption-enhanced DIM 225 mg twice daily for at least 14 days
limitations
Uncontrolled preoperative study. Tissue detection and altered localization do not establish tumor control, survival benefit or testosterone lowering.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
28 evaluable men with localized prostate cancer
plain_language
A receptor changed location; this was not a randomized efficacy comparison.
primary_references
[dim-p27069550] Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients. (2016). https://pubmed.ncbi.nlm.nih.gov/27069550/
tissue_or_cell_type
Prostate DIM, androgen-receptor localization and PSA
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1143–1154
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pre-prostatectomy tissue and biomarker study · source_derived_draft · unverified_draft
### dim-ar-exclusion After treatment, 96% of evaluable patients showed androgen-receptor nuclear exclusion, compared with none in pretreatment biopsies. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor changed location; this was not a randomized efficacy comparison. organism: 28 evaluable men with localized prostate cancer tissue_or_cell_type: Prostate DIM, androgen-receptor localization and PSA experimental_model: Pre-prostatectomy tissue and biomarker study limitations: Uncontrolled preoperative study. Tissue detection and altered localization do not establish tumor control, survival benefit or testosterone lowering. exposure: Absorption-enhanced DIM 225 mg twice daily for at least 14 days evidence_span: {"source_cache": "artifacts/dim-research/27069550.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e", "start_char": 0, "end_char": 1626, "text_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e"} [dim-p27069550] Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients. (2016). https://pubmed.ncbi.nlm.nih.gov/27069550/
Complete structured claim and evidence
PSA declined in 71% of evaluable patients during the preoperative study.
3,3'-Diindolylmethane / DIM → Serum prostate-specific antigen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/27069550.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e", "start_char": 0, "end_char": 1626, "text_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e"}
experimental_model
Pre-prostatectomy tissue and biomarker study
exposure
Absorption-enhanced DIM 225 mg twice daily for at least 14 days
limitations
Uncontrolled preoperative study. Tissue detection and altered localization do not establish tumor control, survival benefit or testosterone lowering.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
28 evaluable men with localized prostate cancer
plain_language
An uncontrolled marker change cannot establish cancer prevention or treatment benefit.
primary_references
[dim-p27069550] Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients. (2016). https://pubmed.ncbi.nlm.nih.gov/27069550/
tissue_or_cell_type
Prostate DIM, androgen-receptor localization and PSA
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1156–1167
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pre-prostatectomy tissue and biomarker study · source_derived_draft · unverified_draft
### dim-psa-change PSA declined in 71% of evaluable patients during the preoperative study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: An uncontrolled marker change cannot establish cancer prevention or treatment benefit. organism: 28 evaluable men with localized prostate cancer tissue_or_cell_type: Prostate DIM, androgen-receptor localization and PSA experimental_model: Pre-prostatectomy tissue and biomarker study limitations: Uncontrolled preoperative study. Tissue detection and altered localization do not establish tumor control, survival benefit or testosterone lowering. exposure: Absorption-enhanced DIM 225 mg twice daily for at least 14 days evidence_span: {"source_cache": "artifacts/dim-research/27069550.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e", "start_char": 0, "end_char": 1626, "text_sha256": "7048d2f449ad8c31af0eb9e89b956d9d1dcebb0f74e1a4d0eabcc3635314053e"} [dim-p27069550] Anti-androgenic activity of absorption-enhanced 3, 3'-diindolylmethane in prostatectomy patients. (2016). https://pubmed.ncbi.nlm.nih.gov/27069550/
Complete structured claim and evidence
CIN2+ occurred in 9% on DIM versus 12% on placebo, RR 0.7 with 95% CI 0.4-1.2.
3,3'-Diindolylmethane / DIM → Cervical intraepithelial neoplasia grade 2 or worse source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/22075942.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617", "start_char": 0, "end_char": 1631, "text_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617"}
experimental_model
Double-blind randomized placebo-controlled trial
exposure
Oral DIM 150 mg/day for six months
limitations
No demonstrated HPV/cytology benefit; CIN2+ estimates were imprecise. Not evidence that a supplement replaces screening or lesion treatment.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
551 women available for analysis
plain_language
The confidence interval did not establish a reduction in this endpoint.
primary_references
[dim-p22075942] Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22075942/ DOI: 10.1038/bjc.2011.496
tissue_or_cell_type
Low-grade cervical abnormalities and HPV
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1169–1180
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### dim-cervical-cin2 CIN2+ occurred in 9% on DIM versus 12% on placebo, RR 0.7 with 95% CI 0.4-1.2. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The confidence interval did not establish a reduction in this endpoint. organism: 551 women available for analysis tissue_or_cell_type: Low-grade cervical abnormalities and HPV experimental_model: Double-blind randomized placebo-controlled trial limitations: No demonstrated HPV/cytology benefit; CIN2+ estimates were imprecise. Not evidence that a supplement replaces screening or lesion treatment. exposure: Oral DIM 150 mg/day for six months evidence_span: {"source_cache": "artifacts/dim-research/22075942.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617", "start_char": 0, "end_char": 1631, "text_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617"} [dim-p22075942] Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22075942/ DOI: 10.1038/bjc.2011.496
Complete structured claim and evidence
Among baseline HPV-positive women, 69% on DIM versus 61% on placebo remained positive at six months, RR 1.1 with 95% CI 0.9-1.4.
3,3'-Diindolylmethane / DIM → Persistence of HPV positivity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/22075942.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617", "start_char": 0, "end_char": 1631, "text_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617"}
experimental_model
Double-blind randomized placebo-controlled trial
exposure
Oral DIM 150 mg/day for six months
limitations
No demonstrated HPV/cytology benefit; CIN2+ estimates were imprecise. Not evidence that a supplement replaces screening or lesion treatment.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
551 women available for analysis
plain_language
This trial did not demonstrate improved HPV clearance.
primary_references
[dim-p22075942] Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22075942/ DOI: 10.1038/bjc.2011.496
tissue_or_cell_type
Low-grade cervical abnormalities and HPV
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1182–1193
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft
### dim-hpv-null Among baseline HPV-positive women, 69% on DIM versus 61% on placebo remained positive at six months, RR 1.1 with 95% CI 0.9-1.4. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This trial did not demonstrate improved HPV clearance. organism: 551 women available for analysis tissue_or_cell_type: Low-grade cervical abnormalities and HPV experimental_model: Double-blind randomized placebo-controlled trial limitations: No demonstrated HPV/cytology benefit; CIN2+ estimates were imprecise. Not evidence that a supplement replaces screening or lesion treatment. exposure: Oral DIM 150 mg/day for six months evidence_span: {"source_cache": "artifacts/dim-research/22075942.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617", "start_char": 0, "end_char": 1631, "text_sha256": "a48e14708d6ab188e676830826bab1afebc6d3eecf8c80e533963f3ab67a7617"} [dim-p22075942] Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22075942/ DOI: 10.1038/bjc.2011.496
Complete structured claim and evidence
The pilot study found no statistically significant difference between DIM and placebo on its reported outcomes.
3,3'-Diindolylmethane / DIM → Regression of cervical intraepithelial lesions source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/19939441.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba95e25bccf862a414ecb9d5b54d2c95f19d76f5c2bc5cb5176ec31e635c5777", "start_char": 0, "end_char": 2504, "text_sha256": "ba95e25bccf862a414ecb9d5b54d2c95f19d76f5c2bc5cb5176ec31e635c5777"}
experimental_model
Randomized placebo-controlled pilot trial
exposure
Oral DIM approximately 2 mg/kg/day for 12 weeks
limitations
Incomplete follow-up biopsies and improvement in both arms; no statistically significant group difference.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
64 women enrolled; 60 available for analysis
plain_language
Improvement within a treated group is not proof that the treatment caused it.
primary_references
[dim-p19939441] Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. (2010). https://pubmed.ncbi.nlm.nih.gov/19939441/ DOI: 10.1016/j.ygyno.2009.10.060
tissue_or_cell_type
Biopsy-confirmed CIN2/3
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1195–1206
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled pilot trial · source_derived_draft · unverified_draft
### dim-cervical-pilot-null The pilot study found no statistically significant difference between DIM and placebo on its reported outcomes. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improvement within a treated group is not proof that the treatment caused it. organism: 64 women enrolled; 60 available for analysis tissue_or_cell_type: Biopsy-confirmed CIN2/3 experimental_model: Randomized placebo-controlled pilot trial limitations: Incomplete follow-up biopsies and improvement in both arms; no statistically significant group difference. exposure: Oral DIM approximately 2 mg/kg/day for 12 weeks evidence_span: {"source_cache": "artifacts/dim-research/19939441.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba95e25bccf862a414ecb9d5b54d2c95f19d76f5c2bc5cb5176ec31e635c5777", "start_char": 0, "end_char": 2504, "text_sha256": "ba95e25bccf862a414ecb9d5b54d2c95f19d76f5c2bc5cb5176ec31e635c5777"} [dim-p19939441] Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. (2010). https://pubmed.ncbi.nlm.nih.gov/19939441/ DOI: 10.1016/j.ygyno.2009.10.060
Complete structured claim and evidence
DIM delayed the BaP peak and lowered its peak plasma concentration in the microdose study.
3,3'-Diindolylmethane / DIM → Benzo[a]pyrene source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/36642108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384", "start_char": 0, "end_char": 1801, "text_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384"}
experimental_model
Within-person human dietary intervention and radiotracer microdose
exposure
Seven days of BR-DIM or Brussels sprouts before 50-ng radiolabeled BaP
limitations
Microdose kinetics with large individual variation. Lower plasma radiocarbon does not establish less DNA damage or reduced human cancer risk.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Small adult volunteer cohort
plain_language
A compound can change absorption timing without proving that enzyme detoxification increased.
primary_references
[dim-p36642108] Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts. (2023). https://pubmed.ncbi.nlm.nih.gov/36642108/ DOI: 10.1016/j.taap.2023.116377
tissue_or_cell_type
Benzo[a]pyrene absorption and metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1208–1219
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person human dietary intervention and radiotracer microdose · source_derived_draft · unverified_draft
### dim-bap-kinetics DIM delayed the BaP peak and lowered its peak plasma concentration in the microdose study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A compound can change absorption timing without proving that enzyme detoxification increased. organism: Small adult volunteer cohort tissue_or_cell_type: Benzo[a]pyrene absorption and metabolism experimental_model: Within-person human dietary intervention and radiotracer microdose limitations: Microdose kinetics with large individual variation. Lower plasma radiocarbon does not establish less DNA damage or reduced human cancer risk. exposure: Seven days of BR-DIM or Brussels sprouts before 50-ng radiolabeled BaP evidence_span: {"source_cache": "artifacts/dim-research/36642108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384", "start_char": 0, "end_char": 1801, "text_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384"} [dim-p36642108] Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts. (2023). https://pubmed.ncbi.nlm.nih.gov/36642108/ DOI: 10.1016/j.taap.2023.116377
Complete structured claim and evidence
DIM and Brussels-sprout interventions reduced total plasma-recovered BaP-related radiocarbon by 56-67% relative to the non-intervention condition.
3,3'-Diindolylmethane / DIM → Total BaP-related plasma radiocarbon signal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/36642108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384", "start_char": 0, "end_char": 1801, "text_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384"}
experimental_model
Within-person human dietary intervention and radiotracer microdose
exposure
Seven days of BR-DIM or Brussels sprouts before 50-ng radiolabeled BaP
limitations
Microdose kinetics with large individual variation. Lower plasma radiocarbon does not establish less DNA damage or reduced human cancer risk.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Small adult volunteer cohort
plain_language
Parent compound and combined metabolites were distinct measurements.
primary_references
[dim-p36642108] Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts. (2023). https://pubmed.ncbi.nlm.nih.gov/36642108/ DOI: 10.1016/j.taap.2023.116377
tissue_or_cell_type
Benzo[a]pyrene absorption and metabolism
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1221–1232
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person human dietary intervention and radiotracer microdose · source_derived_draft · unverified_draft
### dim-bap-total DIM and Brussels-sprout interventions reduced total plasma-recovered BaP-related radiocarbon by 56-67% relative to the non-intervention condition. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Parent compound and combined metabolites were distinct measurements. organism: Small adult volunteer cohort tissue_or_cell_type: Benzo[a]pyrene absorption and metabolism experimental_model: Within-person human dietary intervention and radiotracer microdose limitations: Microdose kinetics with large individual variation. Lower plasma radiocarbon does not establish less DNA damage or reduced human cancer risk. exposure: Seven days of BR-DIM or Brussels sprouts before 50-ng radiolabeled BaP evidence_span: {"source_cache": "artifacts/dim-research/36642108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384", "start_char": 0, "end_char": 1801, "text_sha256": "93b6510deeea8915ef7bd506c9b7d1d83b8d4b417f3e8194cbb9b33a89233384"} [dim-p36642108] Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts. (2023). https://pubmed.ncbi.nlm.nih.gov/36642108/ DOI: 10.1016/j.taap.2023.116377
Complete structured claim and evidence
DIM activated Nrf2-dependent transcription in mouse fibroblasts, whereas I3C did not in the tested conditions.
3,3'-Diindolylmethane / DIM → Mouse Nrf2 / Nfe2l2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"}
experimental_model
Reporter and gene/protein expression experiments
exposure
DIM compared with I3C and sulforaphane
limitations
Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Mouse NIH3T3 fibroblasts
plain_language
A chemical conversion changed signaling activity in this model.
primary_references
[dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
tissue_or_cell_type
Nrf2-regulated defense genes
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1234–1245
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and gene/protein expression experiments · source_derived_draft · unverified_draft
### dim-mouse-nrf2 DIM activated Nrf2-dependent transcription in mouse fibroblasts, whereas I3C did not in the tested conditions. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A chemical conversion changed signaling activity in this model. organism: Mouse NIH3T3 fibroblasts tissue_or_cell_type: Nrf2-regulated defense genes experimental_model: Reporter and gene/protein expression experiments limitations: Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion. exposure: DIM compared with I3C and sulforaphane evidence_span: {"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"} [dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
Complete structured claim and evidence
DIM increased HO-1 mRNA and protein in the mouse fibroblast study.
3,3'-Diindolylmethane / DIM → Mouse heme oxygenase 1 / Hmox1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"}
experimental_model
Reporter and gene/protein expression experiments
exposure
DIM compared with I3C and sulforaphane
limitations
Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Mouse NIH3T3 fibroblasts
plain_language
This downstream enzyme is recorded separately from the Nrf2 regulator.
primary_references
[dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
tissue_or_cell_type
Nrf2-regulated defense genes
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1247–1258
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and gene/protein expression experiments · source_derived_draft · unverified_draft
### dim-nrf2-mouse-hmox1 DIM increased HO-1 mRNA and protein in the mouse fibroblast study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This downstream enzyme is recorded separately from the Nrf2 regulator. organism: Mouse NIH3T3 fibroblasts tissue_or_cell_type: Nrf2-regulated defense genes experimental_model: Reporter and gene/protein expression experiments limitations: Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion. exposure: DIM compared with I3C and sulforaphane evidence_span: {"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"} [dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
Complete structured claim and evidence
DIM increased NQO1 mRNA and protein in the mouse fibroblast study.
3,3'-Diindolylmethane / DIM → Mouse NAD(P)H quinone dehydrogenase 1 / Nqo1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"}
experimental_model
Reporter and gene/protein expression experiments
exposure
DIM compared with I3C and sulforaphane
limitations
Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Mouse NIH3T3 fibroblasts
plain_language
This downstream enzyme is recorded separately from the Nrf2 regulator.
primary_references
[dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
tissue_or_cell_type
Nrf2-regulated defense genes
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1260–1271
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and gene/protein expression experiments · source_derived_draft · unverified_draft
### dim-nrf2-mouse-nqo1 DIM increased NQO1 mRNA and protein in the mouse fibroblast study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This downstream enzyme is recorded separately from the Nrf2 regulator. organism: Mouse NIH3T3 fibroblasts tissue_or_cell_type: Nrf2-regulated defense genes experimental_model: Reporter and gene/protein expression experiments limitations: Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion. exposure: DIM compared with I3C and sulforaphane evidence_span: {"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"} [dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
Complete structured claim and evidence
DIM increased gamma-glutamylcysteine synthetase mRNA and protein in the mouse fibroblast study.
3,3'-Diindolylmethane / DIM → Glutathione-synthesis gene expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"}
experimental_model
Reporter and gene/protein expression experiments
exposure
DIM compared with I3C and sulforaphane
limitations
Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Mouse NIH3T3 fibroblasts
plain_language
This downstream enzyme is recorded separately from the Nrf2 regulator.
primary_references
[dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
tissue_or_cell_type
Nrf2-regulated defense genes
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1273–1284
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and gene/protein expression experiments · source_derived_draft · unverified_draft
### dim-nrf2-glutathione-synthesis-gene-expression DIM increased gamma-glutamylcysteine synthetase mRNA and protein in the mouse fibroblast study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This downstream enzyme is recorded separately from the Nrf2 regulator. organism: Mouse NIH3T3 fibroblasts tissue_or_cell_type: Nrf2-regulated defense genes experimental_model: Reporter and gene/protein expression experiments limitations: Mouse cells; transcriptional induction does not establish clinical antioxidant benefit or nutrient repletion. exposure: DIM compared with I3C and sulforaphane evidence_span: {"source_cache": "artifacts/dim-research/21615272.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8", "start_char": 0, "end_char": 737, "text_sha256": "1ae26f09db419c2cd095519c3326616a14343b52e23a71e7994a4aed764ab1b8"} [dim-p21615272] 3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts. (2011). https://pubmed.ncbi.nlm.nih.gov/21615272/ DOI: 10.3109/10715762.2011.571683
Complete structured claim and evidence
DIM treatment reduced AHR in the tested lung-cancer models.
3,3'-Diindolylmethane / DIM → Human aryl hydrocarbon receptor / AHR source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}
experimental_model
Cell perturbation and xenograft experiments
exposure
DIM; NRF2 overexpression and pharmacological rescue controls
limitations
Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human non-small-cell lung-cancer cells and mouse xenografts
plain_language
A particular tumor context showed suppression of this defense/signaling component.
primary_references
[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
tissue_or_cell_type
Ferroptosis and AHR/NRF2/GPX4
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1286–1297
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft
### dim-nsclc-ahr DIM treatment reduced AHR in the tested lung-cancer models. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A particular tumor context showed suppression of this defense/signaling component. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
Complete structured claim and evidence
DIM treatment reduced NRF2 in the tested lung-cancer models.
3,3'-Diindolylmethane / DIM → Human Nrf2 / NFE2L2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}
experimental_model
Cell perturbation and xenograft experiments
exposure
DIM; NRF2 overexpression and pharmacological rescue controls
limitations
Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human non-small-cell lung-cancer cells and mouse xenografts
plain_language
A particular tumor context showed suppression of this defense/signaling component.
primary_references
[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
tissue_or_cell_type
Ferroptosis and AHR/NRF2/GPX4
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1299–1310
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft
### dim-nsclc-nfe2l2 DIM treatment reduced NRF2 in the tested lung-cancer models. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A particular tumor context showed suppression of this defense/signaling component. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
Complete structured claim and evidence
DIM treatment reduced GPX4 in the tested lung-cancer models.
3,3'-Diindolylmethane / DIM → GPX4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}
experimental_model
Cell perturbation and xenograft experiments
exposure
DIM; NRF2 overexpression and pharmacological rescue controls
limitations
Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human non-small-cell lung-cancer cells and mouse xenografts
plain_language
A particular tumor context showed suppression of this defense/signaling component.
primary_references
[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
tissue_or_cell_type
Ferroptosis and AHR/NRF2/GPX4
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1312–1323
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft
### dim-nsclc-gpx4 DIM treatment reduced GPX4 in the tested lung-cancer models. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A particular tumor context showed suppression of this defense/signaling component. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
Complete structured claim and evidence
DIM lowered cellular GSH in the lung-cancer experiments.
3,3'-Diindolylmethane / DIM → Cellular reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}
experimental_model
Cell perturbation and xenograft experiments
exposure
DIM; NRF2 overexpression and pharmacological rescue controls
limitations
Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human non-small-cell lung-cancer cells and mouse xenografts
plain_language
Glutathione availability changed in these cells, not as a demonstrated whole-body nutrient deficiency.
primary_references
[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
tissue_or_cell_type
Ferroptosis and AHR/NRF2/GPX4
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1325–1336
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft
### dim-nsclc-gsh DIM lowered cellular GSH in the lung-cancer experiments. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione availability changed in these cells, not as a demonstrated whole-body nutrient deficiency. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
Complete structured claim and evidence
DIM increased measured cellular ferrous iron in the lung-cancer experiments.
3,3'-Diindolylmethane / DIM → Ferrous iron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}
experimental_model
Cell perturbation and xenograft experiments
exposure
DIM; NRF2 overexpression and pharmacological rescue controls
limitations
Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human non-small-cell lung-cancer cells and mouse xenografts
plain_language
Iron-dependent cell-death chemistry connects to the same canonical iron node.
primary_references
[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
tissue_or_cell_type
Ferroptosis and AHR/NRF2/GPX4
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1338–1349
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft
### dim-nsclc-iron DIM increased measured cellular ferrous iron in the lung-cancer experiments. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-dependent cell-death chemistry connects to the same canonical iron node. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
Complete structured claim and evidence
DIM induced ferroptosis that could be reversed by ferrostatin-1, NAC or the tested AHR antagonist; NRF2 overexpression also reversed it.
3,3'-Diindolylmethane / DIM → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}
experimental_model
Cell perturbation and xenograft experiments
exposure
DIM; NRF2 overexpression and pharmacological rescue controls
limitations
Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human non-small-cell lung-cancer cells and mouse xenografts
plain_language
Perturbation controls helped connect the response to specific defenses.
primary_references
[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
tissue_or_cell_type
Ferroptosis and AHR/NRF2/GPX4
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1351–1362
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft
### dim-nsclc-ferroptosis DIM induced ferroptosis that could be reversed by ferrostatin-1, NAC or the tested AHR antagonist; NRF2 overexpression also reversed it. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Perturbation controls helped connect the response to specific defenses. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
Complete structured claim and evidence
DIM promoted proteasomal depletion of HDAC1 in the colon-cancer study.
3,3'-Diindolylmethane / DIM → Human histone deacetylase 1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"}
experimental_model
Protein degradation and cell-cycle studies
exposure
DIM; proteasome-mediated protein depletion
limitations
Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human colon-cancer cells and xenografts
plain_language
This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site.
primary_references
[dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
tissue_or_cell_type
Class I HDAC regulation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1364–1375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein degradation and cell-cycle studies · source_derived_draft · unverified_draft
### dim-hdac-hdac1 DIM promoted proteasomal depletion of HDAC1 in the colon-cancer study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site. organism: Human colon-cancer cells and xenografts tissue_or_cell_type: Class I HDAC regulation experimental_model: Protein degradation and cell-cycle studies limitations: Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site. exposure: DIM; proteasome-mediated protein depletion evidence_span: {"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"} [dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
Complete structured claim and evidence
DIM promoted proteasomal depletion of HDAC2 in the colon-cancer study.
3,3'-Diindolylmethane / DIM → Human histone deacetylase 2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"}
experimental_model
Protein degradation and cell-cycle studies
exposure
DIM; proteasome-mediated protein depletion
limitations
Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human colon-cancer cells and xenografts
plain_language
This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site.
primary_references
[dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
tissue_or_cell_type
Class I HDAC regulation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1377–1388
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein degradation and cell-cycle studies · source_derived_draft · unverified_draft
### dim-hdac-hdac2 DIM promoted proteasomal depletion of HDAC2 in the colon-cancer study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site. organism: Human colon-cancer cells and xenografts tissue_or_cell_type: Class I HDAC regulation experimental_model: Protein degradation and cell-cycle studies limitations: Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site. exposure: DIM; proteasome-mediated protein depletion evidence_span: {"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"} [dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
Complete structured claim and evidence
DIM promoted proteasomal depletion of HDAC3 in the colon-cancer study.
3,3'-Diindolylmethane / DIM → Human histone deacetylase 3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"}
experimental_model
Protein degradation and cell-cycle studies
exposure
DIM; proteasome-mediated protein depletion
limitations
Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human colon-cancer cells and xenografts
plain_language
This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site.
primary_references
[dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
tissue_or_cell_type
Class I HDAC regulation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1390–1401
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein degradation and cell-cycle studies · source_derived_draft · unverified_draft
### dim-hdac-hdac3 DIM promoted proteasomal depletion of HDAC3 in the colon-cancer study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site. organism: Human colon-cancer cells and xenografts tissue_or_cell_type: Class I HDAC regulation experimental_model: Protein degradation and cell-cycle studies limitations: Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site. exposure: DIM; proteasome-mediated protein depletion evidence_span: {"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"} [dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
Complete structured claim and evidence
DIM promoted proteasomal depletion of HDAC8 in the colon-cancer study.
3,3'-Diindolylmethane / DIM → Human histone deacetylase 8 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"}
experimental_model
Protein degradation and cell-cycle studies
exposure
DIM; proteasome-mediated protein depletion
limitations
Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human colon-cancer cells and xenografts
plain_language
This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site.
primary_references
[dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
tissue_or_cell_type
Class I HDAC regulation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1403–1414
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein degradation and cell-cycle studies · source_derived_draft · unverified_draft
### dim-hdac-hdac8 DIM promoted proteasomal depletion of HDAC8 in the colon-cancer study. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mechanism removes an epigenetic regulatory protein rather than merely blocking its active site. organism: Human colon-cancer cells and xenografts tissue_or_cell_type: Class I HDAC regulation experimental_model: Protein degradation and cell-cycle studies limitations: Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site. exposure: DIM; proteasome-mediated protein depletion evidence_span: {"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"} [dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
Complete structured claim and evidence
Class I HDAC depletion was accompanied by increased p21/p27 expression and G2 cell-cycle arrest.
3,3'-Diindolylmethane / DIM → Cell-cycle arrest in G2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"}
experimental_model
Protein degradation and cell-cycle studies
exposure
DIM; proteasome-mediated protein depletion
limitations
Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human colon-cancer cells and xenografts
plain_language
Changing chromatin regulators connected to cell-cycle control.
primary_references
[dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
tissue_or_cell_type
Class I HDAC regulation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1416–1427
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein degradation and cell-cycle studies · source_derived_draft · unverified_draft
### dim-hdac-cycle Class I HDAC depletion was accompanied by increased p21/p27 expression and G2 cell-cycle arrest. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing chromatin regulators connected to cell-cycle control. organism: Human colon-cancer cells and xenografts tissue_or_cell_type: Class I HDAC regulation experimental_model: Protein degradation and cell-cycle studies limitations: Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site. exposure: DIM; proteasome-mediated protein depletion evidence_span: {"source_cache": "artifacts/dim-research/20068155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9", "start_char": 0, "end_char": 862, "text_sha256": "bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9"} [dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924
Complete structured claim and evidence
DIM rapidly activated ATM and enhanced ATM-linked DNA-damage-response signaling in the studied cell system.
3,3'-Diindolylmethane / DIM → Human ATM kinase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/24127581.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc", "start_char": 0, "end_char": 1379, "text_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc"}
experimental_model
Cell signaling and rodent radiation experiments
exposure
Submicromolar cell exposures and multidose rodent DIM schedules
limitations
No human radioprotection trial. Lack of protection in tested tumor xenografts cannot establish safety with all radiotherapy or cancer types.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Cultured cells and irradiated rodents; breast-tumor xenografts separately
plain_language
The compound also affected a DNA-damage sensor.
primary_references
[dim-p24127581] DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. (2013). https://pubmed.ncbi.nlm.nih.gov/24127581/ DOI: 10.1073/pnas.1308206110
tissue_or_cell_type
ATM-mediated damage response
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1429–1440
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell signaling and rodent radiation experiments · source_derived_draft · unverified_draft
### dim-atm-response DIM rapidly activated ATM and enhanced ATM-linked DNA-damage-response signaling in the studied cell system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The compound also affected a DNA-damage sensor. organism: Cultured cells and irradiated rodents; breast-tumor xenografts separately tissue_or_cell_type: ATM-mediated damage response experimental_model: Cell signaling and rodent radiation experiments limitations: No human radioprotection trial. Lack of protection in tested tumor xenografts cannot establish safety with all radiotherapy or cancer types. exposure: Submicromolar cell exposures and multidose rodent DIM schedules evidence_span: {"source_cache": "artifacts/dim-research/24127581.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc", "start_char": 0, "end_char": 1379, "text_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc"} [dim-p24127581] DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. (2013). https://pubmed.ncbi.nlm.nih.gov/24127581/ DOI: 10.1073/pnas.1308206110
Complete structured claim and evidence
DIM protected cultured cells and rodents against irradiation under the tested schedules; tested breast-cancer xenografts were not protected.
3,3'-Diindolylmethane / DIM → Cell survival after ionizing radiation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/24127581.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc", "start_char": 0, "end_char": 1379, "text_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc"}
experimental_model
Cell signaling and rodent radiation experiments
exposure
Submicromolar cell exposures and multidose rodent DIM schedules
limitations
No human radioprotection trial. Lack of protection in tested tumor xenografts cannot establish safety with all radiotherapy or cancer types.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Cultured cells and irradiated rodents; breast-tumor xenografts separately
plain_language
Protection of one model does not establish protection or safety in every tissue.
primary_references
[dim-p24127581] DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. (2013). https://pubmed.ncbi.nlm.nih.gov/24127581/ DOI: 10.1073/pnas.1308206110
tissue_or_cell_type
ATM-mediated damage response
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1442–1453
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell signaling and rodent radiation experiments · source_derived_draft · unverified_draft
### dim-radiation-survival DIM protected cultured cells and rodents against irradiation under the tested schedules; tested breast-cancer xenografts were not protected. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection of one model does not establish protection or safety in every tissue. organism: Cultured cells and irradiated rodents; breast-tumor xenografts separately tissue_or_cell_type: ATM-mediated damage response experimental_model: Cell signaling and rodent radiation experiments limitations: No human radioprotection trial. Lack of protection in tested tumor xenografts cannot establish safety with all radiotherapy or cancer types. exposure: Submicromolar cell exposures and multidose rodent DIM schedules evidence_span: {"source_cache": "artifacts/dim-research/24127581.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc", "start_char": 0, "end_char": 1379, "text_sha256": "6e938b73271132ed6dc4ed9f3a4d7bb6cf85fd3071df159c17c9fcef93b901fc"} [dim-p24127581] DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. (2013). https://pubmed.ncbi.nlm.nih.gov/24127581/ DOI: 10.1073/pnas.1308206110
Complete structured claim and evidence
DIM increased STIM1 expression and supported store-operated calcium entry in the experimental muscle model.
3,3'-Diindolylmethane / DIM → Mouse stromal interaction molecule 1 / Stim1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/42308990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb", "start_char": 0, "end_char": 2803, "text_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb"}
experimental_model
Dexamethasone atrophy and aging-model experiments
exposure
DIM in experimental atrophy/aging models
limitations
2026 preclinical study, not a human sarcopenia trial. Mouse STIM1 stays distinct from the human selenium-linked STIM1 record.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Mouse muscle, mouse C2C12 myotubes and C. elegans
plain_language
Calcium signaling is another network connection, with species kept explicit.
primary_references
[dim-p42308990] 3,3'-Diindolylmethane ameliorates muscle atrophy by modulating mitochondrial function and calcium homeostasis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308990/ DOI: 10.1016/j.phymed.2026.158409
tissue_or_cell_type
Mitochondrial function and store-operated calcium entry
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1455–1466
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dexamethasone atrophy and aging-model experiments · source_derived_draft · unverified_draft
### dim-mouse-stim1 DIM increased STIM1 expression and supported store-operated calcium entry in the experimental muscle model. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium signaling is another network connection, with species kept explicit. organism: Mouse muscle, mouse C2C12 myotubes and C. elegans tissue_or_cell_type: Mitochondrial function and store-operated calcium entry experimental_model: Dexamethasone atrophy and aging-model experiments limitations: 2026 preclinical study, not a human sarcopenia trial. Mouse STIM1 stays distinct from the human selenium-linked STIM1 record. exposure: DIM in experimental atrophy/aging models evidence_span: {"source_cache": "artifacts/dim-research/42308990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb", "start_char": 0, "end_char": 2803, "text_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb"} [dim-p42308990] 3,3'-Diindolylmethane ameliorates muscle atrophy by modulating mitochondrial function and calcium homeostasis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308990/ DOI: 10.1016/j.phymed.2026.158409
Complete structured claim and evidence
DIM limited the loss of mitochondrial membrane potential and excessive ROS generation in the atrophy models.
3,3'-Diindolylmethane / DIM → Inner mitochondrial membrane potential source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/42308990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb", "start_char": 0, "end_char": 2803, "text_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb"}
experimental_model
Dexamethasone atrophy and aging-model experiments
exposure
DIM in experimental atrophy/aging models
limitations
2026 preclinical study, not a human sarcopenia trial. Mouse STIM1 stays distinct from the human selenium-linked STIM1 record.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Mouse muscle, mouse C2C12 myotubes and C. elegans
plain_language
Mitochondrial measurements improved in this preclinical setting.
primary_references
[dim-p42308990] 3,3'-Diindolylmethane ameliorates muscle atrophy by modulating mitochondrial function and calcium homeostasis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308990/ DOI: 10.1016/j.phymed.2026.158409
tissue_or_cell_type
Mitochondrial function and store-operated calcium entry
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1468–1479
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dexamethasone atrophy and aging-model experiments · source_derived_draft · unverified_draft
### dim-muscle-mito DIM limited the loss of mitochondrial membrane potential and excessive ROS generation in the atrophy models. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial measurements improved in this preclinical setting. organism: Mouse muscle, mouse C2C12 myotubes and C. elegans tissue_or_cell_type: Mitochondrial function and store-operated calcium entry experimental_model: Dexamethasone atrophy and aging-model experiments limitations: 2026 preclinical study, not a human sarcopenia trial. Mouse STIM1 stays distinct from the human selenium-linked STIM1 record. exposure: DIM in experimental atrophy/aging models evidence_span: {"source_cache": "artifacts/dim-research/42308990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb", "start_char": 0, "end_char": 2803, "text_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb"} [dim-p42308990] 3,3'-Diindolylmethane ameliorates muscle atrophy by modulating mitochondrial function and calcium homeostasis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308990/ DOI: 10.1016/j.phymed.2026.158409
Complete structured claim and evidence
DIM attenuated dexamethasone-induced myotube and mouse muscle atrophy and improved mouse grip-strength measures.
3,3'-Diindolylmethane / DIM → Muscle atrophy source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/42308990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb", "start_char": 0, "end_char": 2803, "text_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb"}
experimental_model
Dexamethasone atrophy and aging-model experiments
exposure
DIM in experimental atrophy/aging models
limitations
2026 preclinical study, not a human sarcopenia trial. Mouse STIM1 stays distinct from the human selenium-linked STIM1 record.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Mouse muscle, mouse C2C12 myotubes and C. elegans
plain_language
This is a candidate mechanism to test in humans, not an established treatment.
primary_references
[dim-p42308990] 3,3'-Diindolylmethane ameliorates muscle atrophy by modulating mitochondrial function and calcium homeostasis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308990/ DOI: 10.1016/j.phymed.2026.158409
tissue_or_cell_type
Mitochondrial function and store-operated calcium entry
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1481–1492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dexamethasone atrophy and aging-model experiments · source_derived_draft · unverified_draft
### dim-muscle-atrophy DIM attenuated dexamethasone-induced myotube and mouse muscle atrophy and improved mouse grip-strength measures. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is a candidate mechanism to test in humans, not an established treatment. organism: Mouse muscle, mouse C2C12 myotubes and C. elegans tissue_or_cell_type: Mitochondrial function and store-operated calcium entry experimental_model: Dexamethasone atrophy and aging-model experiments limitations: 2026 preclinical study, not a human sarcopenia trial. Mouse STIM1 stays distinct from the human selenium-linked STIM1 record. exposure: DIM in experimental atrophy/aging models evidence_span: {"source_cache": "artifacts/dim-research/42308990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb", "start_char": 0, "end_char": 2803, "text_sha256": "4bd26fd33c370df293346c5680820459a885a7545286d92c9e1c27220d41f2cb"} [dim-p42308990] 3,3'-Diindolylmethane ameliorates muscle atrophy by modulating mitochondrial function and calcium homeostasis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308990/ DOI: 10.1016/j.phymed.2026.158409
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens protein
plain_language
POR carries a FAD cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 407–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fad Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FAD cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens protein
plain_language
POR carries a FMN cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 422–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fmn Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FMN cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.
NADPH-cytochrome P450 oxidoreductase / POR → Human vitamin D 25-hydroxylase / CYP2R1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Figure 2C; Methods 2.3 and reconstitution assays.
experimental_model
Purified enzyme and phospholipid-vesicle reconstitution
exposure
0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C.
limitations
Assay optimum is not a tissue expression target or a vitamin dosing requirement.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens proteins
plain_language
CYP2R1 needs an electron-supplying partner.
primary_references
[cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
tissue_or_cell_type
reconstituted membrane
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 392–405
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme and phospholipid-vesicle reconstitution · source_derived_draft · unverified_draft
### vd-act-por-support Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2R1 needs an electron-supplying partner. organism: Homo sapiens proteins tissue_or_cell_type: reconstituted membrane experimental_model: Purified enzyme and phospholipid-vesicle reconstitution limitations: Assay optimum is not a tissue expression target or a vitamin dosing requirement. exposure: 0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C. cross_nutrient: true evidence_location: Primary Figure 2C; Methods 2.3 and reconstitution assays. nutrient: Vitamin D2 and D3 [cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
Complete structured claim and evidence
Vitamin K2 bound and activated human SXR and induced its CYP3A4 target gene in the tested system.
Vitamin K2 / menaquinone family → Human pregnane X receptor / SXR / PXR / NR1I2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"}
experimental_model
Ligand binding, gene expression and receptor-null mouse cells
exposure
Vitamin K2 exposure and receptor deficiency
limitations
Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human osteosarcoma cells and mouse calvarial cells
plain_language
K2 can have a receptor-signaling role separate from protein carboxylation.
primary_references
[k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200
tissue_or_cell_type
SXR/PXR transcription
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 695–706
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, gene expression and receptor-null mouse cells · source_derived_draft · unverified_draft
### k2-k2-sxr Vitamin K2 bound and activated human SXR and induced its CYP3A4 target gene in the tested system. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: K2 can have a receptor-signaling role separate from protein carboxylation. organism: Human osteosarcoma cells and mouse calvarial cells tissue_or_cell_type: SXR/PXR transcription experimental_model: Ligand binding, gene expression and receptor-null mouse cells limitations: Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue. exposure: Vitamin K2 exposure and receptor deficiency evidence_span: {"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"} [k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200
Complete structured claim and evidence
NQO1 protein and enzyme activity increased after lipoic-acid treatment in HL-60 cells.
Lipoic acid → Human NAD(P)H quinone dehydrogenase 1 / NQO1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"}
experimental_model
Human HL-60 leukemia cell biochemical study
exposure
Alpha-lipoic-acid exposure
limitations
Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line
plain_language
The response included more activity of a specific quinone-processing enzyme.
primary_references
[ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071
tissue_or_cell_type
HL-60 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 884–895
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HL-60 leukemia cell biochemical study · source_derived_draft · unverified_draft
### ala-hl60-nqo1 NQO1 protein and enzyme activity increased after lipoic-acid treatment in HL-60 cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response included more activity of a specific quinone-processing enzyme. organism: Human cell line tissue_or_cell_type: HL-60 cells experimental_model: Human HL-60 leukemia cell biochemical study limitations: Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit. exposure: Alpha-lipoic-acid exposure evidence_span: {"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"} [ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071
Complete structured claim and evidence
Boric acid increased NQO1 mRNA at measured time points within 1–4 hours in human DU-145 cells.
Boric acid / orthoboric acid / B(OH)3 → Human NAD(P)H quinone dehydrogenase 1 / NQO1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/boron-research/30196486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a", "start_char": 0, "end_char": 2006, "text_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a"}
experimental_model
PERK knockout comparison, immunofluorescence and quantitative PCR
exposure
10 µM boric acid; 1–6 hour comparisons
limitations
Knockout dependence in mouse fibroblasts is separate from human tumor-cell transcription. Increased GCLC mRNA is not a measured increase in glutathione synthesis or clinical antioxidant benefit.
nutrient_topic
Boron research collection; topical membership is not evidence of a direct dietary effect. · Boron
organism
Human
plain_language
The cells increased instructions for NQO1; this does not measure the protein’s activity or a health benefit.
primary_references
[boron-p30196486] Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status. (2019). https://pubmed.ncbi.nlm.nih.gov/30196486/ DOI: 10.1007/s12011-018-1498-4
tissue_or_cell_type
DU-145 prostate cancer cell culture
Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 547–558
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PERK knockout comparison, immunofluorescence and quantitative PCR · source_derived_draft · unverified_draft
### boron-nqo1-transcription Boric acid increased NQO1 mRNA at measured time points within 1–4 hours in human DU-145 cells. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells increased instructions for NQO1; this does not measure the protein’s activity or a health benefit. organism: Human tissue_or_cell_type: DU-145 prostate cancer cell culture experimental_model: PERK knockout comparison, immunofluorescence and quantitative PCR limitations: Knockout dependence in mouse fibroblasts is separate from human tumor-cell transcription. Increased GCLC mRNA is not a measured increase in glutathione synthesis or clinical antioxidant benefit. exposure: 10 µM boric acid; 1–6 hour comparisons evidence_span: {"source_cache": "artifacts/boron-research/30196486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a", "start_char": 0, "end_char": 2006, "text_sha256": "e220df5fb0f9b8653035f7a144259ce66778467a7a72acbf7cd7d113f8b6030a"} [boron-p30196486] Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status. (2019). https://pubmed.ncbi.nlm.nih.gov/30196486/ DOI: 10.1007/s12011-018-1498-4
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

More CYP protein cannot replace a defective electron supplier

Condition: machinery_impairment · Human POR Y181D with compromised FMN binding

Normal role: POR supplies electrons that support CYP1A2 catalysis.

Recorded consequence: Reduced CYP1A2 activity in engineered membranes, partly restored by added FMN.

Scope: Human proteins expressed in bacteria; not a DIM deficiency syndrome

A receptor is needed for part of the DIM response

Condition: machinery_impairment · PXR genetic knockdown or pharmacological inhibition

Normal role: PXR links DIM exposure to CYP3A4 and ABCB1 expression.

Recorded consequence: Attenuation of the induced expression response.

Scope: Human cell models; experimental receptor impairment, not dietary DIM deficiency

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which DIM metabolites dominate signaling in each human tissue at supplement exposures?Human hydroxylated/conjugated products and reporter activity are demonstrated, but many structures, tissue concentrations and clinical contributions remain incompletely characterized.
Does the measured reduction in tamoxifen metabolites reduce prevention or treatment benefit, and by which mechanism?The randomized DIM trial measured lower endoxifen and other metabolites, but did not measure recurrence/survival or identify the responsible enzyme/transport step. Do not assign the finding specifically to CYP1A2.
Which hormonal and cellular contexts determine whether DIM promotes or suppresses growth and antioxidant defenses?Dose, estradiol background, receptor/coactivator expression, cell type and metabolite exposure differ. Opposite results under different conditions are preserved as context rather than automatically called contradictions.
Is a dietary DIM requirement or deficiency syndrome established?No essential requirement or DIM-deficiency syndrome is established by the curated research. Experimental POR or PXR impairment is not a shortage of dietary DIM.
How much does a specified DIM formulation change CYP1A2 activity and each listed drug exposure in people?The direct evidence assembled here is human-cell induction, substrate studies and a tamoxifen clinical trial. NCT00392652 registered a DIM probe-cocktail study, completed with 14 participants, but the registry had no posted results when checked on 2026-09-17. Registration is not an observed induction result. No drug-level or caffeine-dose adjustment is derived here.
Does starting or stopping DIM produce a clinically important change in clozapine, olanzapine, theophylline, tizanidine, duloxetine, melatonin, caffeine, ramelteon, propranolol or ondansetron?These drugs are independently indexed and their metabolic routes retained. Their DIM-specific direction and magnitude remain unestablished in the curated evidence; induction, inhibition, alternative routes and exposure all matter.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

3,3'-Diindolylmethane / DIM

The mechanisms

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

DIM increased CYP1A2 mRNA dose-dependently, with induction also reflected in protein measurements.

DIM increased CYP1A1 mRNA dose-dependently, with induction also reflected in protein measurements.

DIM directly inhibited CYP1A2 catalytic activity in the tested enzyme assay.

DIM activated human PXR-dependent CYP3A4 promoter transcription.

DIM increased MDR1/ABCB1 expression in a PXR-dependent manner.

CYP1A2 contributed to clozapine demethylation.

CYP1A2 was the predominant tested catalyst of tizanidine metabolism.

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

I3C increased caffeine-probed CYP1A2 activity in 94% of participants in the phase I study.

DIM at 10 micromolar increased proliferation in estrogen-deprived breast-cancer cells; an ERalpha antagonist blocked the response.

POR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization.

Aqueous acid converted I3C into a mixture containing DIM and several higher oligomers.

DIM was detected after oral I3C, whereas parent I3C was not detected by the plasma assay.

Mean DIM peak concentration rose from 61 to 607 ng/mL between 400 and 1000 mg I3C, with no further increase at 1200 mg and substantial individual variation.

Mean peak DIM concentrations were 32, 104 and 108 ng/mL after the reported 100, 200 and 300 mg doses, respectively.

Two monohydroxylated and one dihydroxylated DIM products appeared in human plasma and urine.

Glucuronide conjugates of hydroxylated DIM products were detected in human samples.

Sulfate conjugates of hydroxylated DIM products were detected in human samples.

The identified 2-oxo-DIM product showed greater potency and efficacy than parent DIM in a Hepa1 AhR reporter assay.

The CYP1A2 structure places its ligand above the heme prosthetic group.

Added FMN restored CYP1A2 ethoxyresorufin activity in POR Y181D membranes to 37% of the wild-type system.

DIM bound AhR and promoted rapid nuclear AhR-complex formation in MCF-7 cells.

DIM inhibited estradiol-induced MCF-7 proliferation in the tested estrogen-stimulated system.

DIM partly inhibited TCDD-induced CYP1A1 transcription and strongly reduced the induced EROD activity in T47D cells.

DIM alone did not significantly induce CYP1A1 mRNA or EROD activity at concentrations up to 31 micromolar in this T47D system.

DIM increased CYP1A2 protein in cultured human liver slices.

The same liver-slice experiment found little effect of DIM on CYP3A4 protein.

DIM increased NQO1 expression about 4.5-fold at 50 micromolar in the hepatocyte experiment.

No significant GSTA1 transcriptional increase was detected in the phytochemical comparisons including DIM.

DIM directly inhibited CYP1A1 catalytic activity in the tested enzyme assay.

DIM directly inhibited CYP3A4 catalytic activity in the tested enzyme assay.

DIM pretreatment increased aflatoxin B1-DNA adduct formation in human hepatocytes.

The authors linked the DIM-associated adduct increase to CYP1A2 induction and/or GSTM1 downregulation.

DIM increased CYP3A4 expression in a PXR-dependent manner.

DIM reduced intracellular accumulation of the MDR1 substrate rhodamine 123 in the transport experiment.

PXR knockdown or inhibition attenuated DIM-induced CYP3A4 expression.

PXR knockdown or inhibition attenuated DIM-induced ABCB1 expression.

DIM activated ERbeta target transcription without detectable binding to ERbeta in the study.

DIM promoted ERbeta recruitment of SRC-2 at regulatory elements; SRC-2 silencing inhibited target-gene activation.

DIM at 10 micromolar activated ERalpha-regulated transcription in the absence of estradiol.

The PKA signaling pathway participated in DIM-mediated ERalpha activation.

DIM at 50 micromolar inhibited proliferation in contrast with the lower-concentration response.

DIM produced overlapping AHR- and ERalpha-associated regulatory patterns, with preferential AHR recruitment to ERalpha targets when both receptors were activated.

CYP3A4 contributed to clozapine demethylation and N-oxidation.

Caffeine-derived CYP1A2 indices correlated with clozapine clearance in the 14-person study.

CYP1A2 played a major role in olanzapine 7-hydroxylation and also contributed to N-demethylation.

UGT1A4 played a major role in olanzapine 10-N-glucuronide formation.

FMO3 played a major role in olanzapine N-oxide formation.

CYP2C8 made a substantial contribution to olanzapine N-demethylation in the tested assays.

Median concentration-to-dose ratio was 6.0 in smokers versus 10.1 nmol/L/mg in nonsmokers.

CYP1A2 catalyzed theophylline demethylation and hydroxylation, with high affinity and the highest tested intrinsic clearance to dimethyluric acid.

CYP1A2 catalyzed duloxetine metabolism in the in-vitro experiments.

Fluvoxamine increased oral duloxetine AUC by 460% and peak concentration by 141% in the clinical study.

CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation.

The paraxanthine-to-caffeine ratio was used to phenotype CYP1A2 during smoking cessation.

Caffeine clearance fell by 36.1% after cessation; the fitted half-life of CYP1A2 activity decline was 38.6 hours.

Nicotine patches did not significantly change caffeine pharmacokinetics or metabolite formation in the crossover study.

CYP1A2 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.

CYP2C19 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.

CYP3A4 catalyzed ramelteon metabolism in the tested microsomal/recombinant system.

CYP1A2 contributed prominently to propranolol N-desisopropylation.

CYP2D6 was a major catalyst of propranolol ring 4-hydroxylation.

CYP1A1 contributed to ondansetron metabolism in the studied human systems.

CYP1A2 contributed to ondansetron metabolism in the studied human systems.

CYP2D6 contributed to ondansetron metabolism in the studied human systems.

The CYP3A subfamily contributed to ondansetron metabolism in the studied human systems.

CYP3A4/5 catalyzed formation of N-desmethyltamoxifen, the quantitatively major initial pathway.

CYP2D6 and other CYPs formed 4-hydroxytamoxifen through a smaller initial route.

I3C increased the urinary 2-to-16-alpha-hydroxyestrone ratio without significant changes in the reported serum hormones.

BR-DIM reduced plasma 4-hydroxytamoxifen compared with placebo.

BR-DIM reduced plasma N-desmethyltamoxifen compared with placebo.

BR-DIM increased the urinary 2/16-alpha-hydroxyestrone ratio relative to placebo.

Serum SHBG increased more with BR-DIM than placebo.

Breast density measured by mammography or MRI did not change with BR-DIM in the trial.

DIM was detected in prostate tissue from 26 of 28 evaluable men, with a mean of 14.2 ng/g.

After treatment, 96% of evaluable patients showed androgen-receptor nuclear exclusion, compared with none in pretreatment biopsies.

PSA declined in 71% of evaluable patients during the preoperative study.