Olanzapine

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Patient blood comparison within a mainly mechanistic animal study.

limitations

Not evidence that supplementation improves cognition in these patients.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A human blood observation accompanied the mouse work.

primary_references

Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

trigger_kind

biomarker_context Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 432–438

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Patient blood comparison within a mainly mechanistic animal study. · source_derived_draft · unverified_draft

## ergothioneine-olanzapine-human-marker A human blood observation accompanied the mouse work. The study also found lower blood ergothioneine in olanzapine-treated patients. Model: Patient blood comparison within a mainly mechanistic animal study. Limitations: Not evidence that supplementation improves cognition in these patients. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse treatment, multi-omics and microbiota-transplant experiments.

limitations

Association among microbial taxa and metabolite levels does not resolve every biosynthetic flux.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A medicine-associated ecosystem change coincided with a lower pool.

primary_references

Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

trigger_kind

biomarker_context Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 424–430

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse treatment, multi-omics and microbiota-transplant experiments. · source_derived_draft · unverified_draft

## ergothioneine-olanzapine-mouse-pool A medicine-associated ecosystem change coincided with a lower pool. Chronic olanzapine treatment in mice reduced blood and brain ergothioneine alongside altered microbiota and cognitive deficits. Model: Mouse treatment, multi-omics and microbiota-transplant experiments. Limitations: Association among microbial taxa and metabolite levels does not resolve every biosynthetic flux. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

evidence_access

Primary full text

experimental_model

Purified human DDO drug concentration-response assay.

limitations

Biochemical potency is not proof of clinically relevant brain inhibition or a reason to change treatment.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Two drugs differed at a D-aspartate-clearing enzyme.

primary_references

Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 264–270

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human DDO drug concentration-response assay. · source_derived_draft · unverified_draft

## d-aspartate-olanzapine-human-ddo Two drugs differed at a D-aspartate-clearing enzyme. Olanzapine inhibited recombinant human DDO at an IC50 near 23 micromolar under both 4 and 100 micromolar FAD conditions; clozapine did not inhibit the tested enzyme. Model: Purified human DDO drug concentration-response assay. Limitations: Biochemical potency is not proof of clinically relevant brain inhibition or a reason to change treatment. Evidence access: Primary full text Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

evidence_access

Primary full text

experimental_model

Mouse microdialysis 24 hours after the final injection.

limitations

Knockouts already differ at baseline. This does not prove the pathway mediates clinical antipsychotic efficacy.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Removing the enzyme removed this drug-associated increment in the mouse experiment.

primary_references

Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 280–286

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse microdialysis 24 hours after the final injection. · source_derived_draft · unverified_draft

## d-aspartate-olanzapine-mouse-dependence Removing the enzyme removed this drug-associated increment in the mouse experiment. Four weeks of olanzapine at 5 mg/kg/day intraperitoneally increased prefrontal extracellular D-aspartate and glutamate in wild-type mice; the increments were absent in Ddo-knockout mice. Model: Mouse microdialysis 24 hours after the final injection. Limitations: Knockouts already differ at baseline. This does not prove the pathway mediates clinical antipsychotic efficacy. Evidence access: Primary full text Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

evidence_span

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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

evidence_span

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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

evidence_span

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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

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

evidence_span

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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

evidence_access

Primary full text

experimental_model

Recombinant mouse versus human DDO assays.

limitations

This is not an observed dietary riboflavin-drug interaction in people.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Cofactor conditions altered the mouse drug-enzyme interaction.

primary_references

Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 272–278

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant mouse versus human DDO assays. · source_derived_draft · unverified_draft

## d-aspartate-olanzapine-fad-species Cofactor conditions altered the mouse drug-enzyme interaction. Lowering assay FAD from 100 to 4 micromolar shifted olanzapine IC50 at mouse DDO from about 5.6 to 1.4 micromolar; the human enzyme did not show this potency shift. Model: Recombinant mouse versus human DDO assays. Limitations: This is not an observed dietary riboflavin-drug interaction in people. Evidence access: Primary full text Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288