Component

Dietary (3R,3-prime-R)-zeaxanthin

Dietary (3R,3-prime-R)-zeaxanthin. Species, exposure and limitations are retained in each linked claim.

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

How nutrients influence it

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

How nutrients reach it in more than one step

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

Tracing routes…

What it does

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

Recorded relationships

What it acts on

  1. Free zeaxanthin increased ABCG5 protein expression in Caco-2 cells.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    The cell increased a transporter subunit; actual zeaxanthin efflux was not established.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 691–702

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-abcg5-expression Free zeaxanthin increased ABCG5 protein expression in Caco-2 cells. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell increased a transporter subunit; actual zeaxanthin efflux was not established. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  2. Dose-normalized bioavailability was 40% lower at 10 mg than at 1 mg.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/14985215.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88", "start_char": 0, "end_char": 1830, "text_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88"}
    experimental_model
    Repeated-dose plasma kinetic study
    exposure
    1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76
    limitations
    Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    20 healthy volunteers
    plain_language
    Ten times the dose did not give ten times the normalized response.
    primary_references
    [zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. (2004). https://pubmed.ncbi.nlm.nih.gov/14985215/ DOI: 10.1093/ajcn/79.3.410
    tissue_or_cell_type
    Plasma

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 860–871

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Repeated-dose plasma kinetic study · source_derived_draft · unverified_draft

    ### zeaxanthin-dose-normalized Dose-normalized bioavailability was 40% lower at 10 mg than at 1 mg. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ten times the dose did not give ten times the normalized response. organism: 20 healthy volunteers tissue_or_cell_type: Plasma experimental_model: Repeated-dose plasma kinetic study limitations: Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses. exposure: 1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76 evidence_span: {"source_cache": "artifacts/zeaxanthin-research/14985215.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88", "start_char": 0, "end_char": 1830, "text_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88"} [zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. (2004). https://pubmed.ncbi.nlm.nih.gov/14985215/ DOI: 10.1093/ajcn/79.3.410
    Complete structured claim and evidence
  3. Zeaxanthin increased GCLC mRNA in ARPE-19 cells.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    It increased instructions for the catalytic glutathione-synthesis subunit.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 379–390

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-gclc-expression Zeaxanthin increased GCLC mRNA in ARPE-19 cells. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: It increased instructions for the catalytic glutathione-synthesis subunit. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  4. Zeaxanthin increased GCLM mRNA in ARPE-19 cells.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    The regulatory subunit also responded.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 392–403

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-gclm-expression Zeaxanthin increased GCLM mRNA in ARPE-19 cells. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The regulatory subunit also responded. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  5. Zeaxanthin increased the measured cellular glutathione pool.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    The cells accumulated more glutathione.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 431–442

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-gsh-pool Zeaxanthin increased the measured cellular glutathione pool. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells accumulated more glutathione. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  6. Zeaxanthin increased HMOX1 mRNA and protein.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    Another Nrf2-regulated defense enzyme increased.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 405–416

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-hmox1-expression Zeaxanthin increased HMOX1 mRNA and protein. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another Nrf2-regulated defense enzyme increased. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  7. No meso-zeaxanthin formation was detected over the trial sampling period.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15137922.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6410a0f5d52cf32390f90f59a7b17d2340a889f888836129f8a93482ca055be0", "start_char": 0, "end_char": 1847, "text_sha256": "6410a0f5d52cf32390f90f59a7b17d2340a889f888836129f8a93482ca055be0"}
    experimental_model
    Randomized single-blind crossover meal trial
    exposure
    5 mg free zeaxanthin equivalents as free pigment or dipalmitate in yoghurt/breakfast; 24 h sampling
    limitations
    Meal- and formulation-specific response; no proof of disease prevention or an optimal universal formulation.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    12 volunteers
    plain_language
    The study did not show rapid conversion of dietary zeaxanthin into meso-zeaxanthin.
    primary_references
    [zeaxanthin-p15137922] Comparison of plasma responses in human subjects after the ingestion of 3R,3R'-zeaxanthin dipalmitate from wolfberry (Lycium barbarum) and non-esterified 3R,3R'-zeaxanthin using chiral high-performance liquid chromatography. (2004). https://pubmed.ncbi.nlm.nih.gov/15137922/ DOI: 10.1079/bjn20041105
    tissue_or_cell_type
    Plasma response

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 808–819

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

    ### zeaxanthin-human-meso-null No meso-zeaxanthin formation was detected over the trial sampling period. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study did not show rapid conversion of dietary zeaxanthin into meso-zeaxanthin. organism: 12 volunteers tissue_or_cell_type: Plasma response experimental_model: Randomized single-blind crossover meal trial limitations: Meal- and formulation-specific response; no proof of disease prevention or an optimal universal formulation. exposure: 5 mg free zeaxanthin equivalents as free pigment or dipalmitate in yoghurt/breakfast; 24 h sampling evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15137922.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6410a0f5d52cf32390f90f59a7b17d2340a889f888836129f8a93482ca055be0", "start_char": 0, "end_char": 1847, "text_sha256": "6410a0f5d52cf32390f90f59a7b17d2340a889f888836129f8a93482ca055be0"} [zeaxanthin-p15137922] Comparison of plasma responses in human subjects after the ingestion of 3R,3R'-zeaxanthin dipalmitate from wolfberry (Lycium barbarum) and non-esterified 3R,3R'-zeaxanthin using chiral high-performance liquid chromatography. (2004). https://pubmed.ncbi.nlm.nih.gov/15137922/ DOI: 10.1079/bjn20041105
    Complete structured claim and evidence
  8. Zeaxanthin adopted a transmembrane orientation in the DMPC bilayer, with mean tilt near 40 degrees to the membrane normal.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/28852075.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02ce5ff25dc230c1de6bcb2c4e1e48e1d7f8c218f48e6817d1c697b47b319e7b", "start_char": 0, "end_char": 1275, "text_sha256": "02ce5ff25dc230c1de6bcb2c4e1e48e1d7f8c218f48e6817d1c697b47b319e7b"}
    experimental_model
    Microscopy, Raman imaging and molecular dynamics
    exposure
    Lutein and zeaxanthin orientation
    limitations
    Model-bilayer geometry is not a measurement of every human retinal membrane.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Model membrane
    plain_language
    The pigment spans the membrane rather than remaining only on its surface.
    primary_references
    [zeaxanthin-p28852075] Localization and Orientation of Xanthophylls in a Lipid Bilayer. (2017). https://pubmed.ncbi.nlm.nih.gov/28852075/ DOI: 10.1038/s41598-017-10183-7
    tissue_or_cell_type
    DMPC giant unilamellar vesicles

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 314–325

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microscopy, Raman imaging and molecular dynamics · source_derived_draft · unverified_draft

    ### zeaxanthin-membrane-orientation Zeaxanthin adopted a transmembrane orientation in the DMPC bilayer, with mean tilt near 40 degrees to the membrane normal. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pigment spans the membrane rather than remaining only on its surface. organism: Model membrane tissue_or_cell_type: DMPC giant unilamellar vesicles experimental_model: Microscopy, Raman imaging and molecular dynamics limitations: Model-bilayer geometry is not a measurement of every human retinal membrane. exposure: Lutein and zeaxanthin orientation evidence_span: {"source_cache": "artifacts/zeaxanthin-research/28852075.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02ce5ff25dc230c1de6bcb2c4e1e48e1d7f8c218f48e6817d1c697b47b319e7b", "start_char": 0, "end_char": 1275, "text_sha256": "02ce5ff25dc230c1de6bcb2c4e1e48e1d7f8c218f48e6817d1c697b47b319e7b"} [zeaxanthin-p28852075] Localization and Orientation of Xanthophylls in a Lipid Bilayer. (2017). https://pubmed.ncbi.nlm.nih.gov/28852075/ DOI: 10.1038/s41598-017-10183-7
    Complete structured claim and evidence
  9. The 3-prime-dehydrolutein time course supported its formation from zeaxanthin, without identifying the responsible enzyme.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/14985215.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88", "start_char": 0, "end_char": 1830, "text_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88"}
    experimental_model
    Repeated-dose plasma kinetic study
    exposure
    1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76
    limitations
    Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    20 healthy volunteers
    plain_language
    A circulating metabolite followed pigment intake.
    primary_references
    [zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. (2004). https://pubmed.ncbi.nlm.nih.gov/14985215/ DOI: 10.1093/ajcn/79.3.410
    tissue_or_cell_type
    Plasma

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 873–884

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Repeated-dose plasma kinetic study · source_derived_draft · unverified_draft

    ### zeaxanthin-metabolite-timecourse The 3-prime-dehydrolutein time course supported its formation from zeaxanthin, without identifying the responsible enzyme. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A circulating metabolite followed pigment intake. organism: 20 healthy volunteers tissue_or_cell_type: Plasma experimental_model: Repeated-dose plasma kinetic study limitations: Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses. exposure: 1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76 evidence_span: {"source_cache": "artifacts/zeaxanthin-research/14985215.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88", "start_char": 0, "end_char": 1830, "text_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88"} [zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. (2004). https://pubmed.ncbi.nlm.nih.gov/14985215/ DOI: 10.1093/ajcn/79.3.410
    Complete structured claim and evidence
  10. Zeaxanthin increased NQO1 mRNA and protein.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    The quinone-processing defense enzyme increased.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 418–429

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-nqo1-expression Zeaxanthin increased NQO1 mRNA and protein. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The quinone-processing defense enzyme increased. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  11. Zeaxanthin increased nuclear Nrf2 in ARPE-19 cells.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    It activated part of the cell’s own defense response.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 366–377

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-nrf2-location Zeaxanthin increased nuclear Nrf2 in ARPE-19 cells. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: It activated part of the cell’s own defense response. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  12. Daily 1 and 10 mg doses raised plasma zeaxanthin approximately four- and twentyfold, respectively.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/14985215.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88", "start_char": 0, "end_char": 1830, "text_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88"}
    experimental_model
    Repeated-dose plasma kinetic study
    exposure
    1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76
    limitations
    Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    20 healthy volunteers
    plain_language
    More intake raised blood levels, but not proportionally.
    primary_references
    [zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. (2004). https://pubmed.ncbi.nlm.nih.gov/14985215/ DOI: 10.1093/ajcn/79.3.410
    tissue_or_cell_type
    Plasma

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 847–858

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Repeated-dose plasma kinetic study · source_derived_draft · unverified_draft

    ### zeaxanthin-plasma-dose-response Daily 1 and 10 mg doses raised plasma zeaxanthin approximately four- and twentyfold, respectively. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More intake raised blood levels, but not proportionally. organism: 20 healthy volunteers tissue_or_cell_type: Plasma experimental_model: Repeated-dose plasma kinetic study limitations: Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses. exposure: 1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76 evidence_span: {"source_cache": "artifacts/zeaxanthin-research/14985215.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88", "start_char": 0, "end_char": 1830, "text_sha256": "dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88"} [zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. (2004). https://pubmed.ncbi.nlm.nih.gov/14985215/ DOI: 10.1093/ajcn/79.3.410
    Complete structured claim and evidence
  13. Pure zeaxanthin supplementation increased macular pigment, approaching a steady central peak by 24–32 weeks.

    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15326146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2", "start_char": 0, "end_char": 1572, "text_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2"}
    experimental_model
    Long-term dietary depletion followed by single-pigment repletion
    exposure
    Lifelong xanthophyll-free diet; six animals received pure zeaxanthin 2.2 mg/kg/day for 24–56 weeks
    limitations
    Extreme combined-xanthophyll depletion is not isolated human zeaxanthin deficiency or a clinical diagnostic threshold.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Rhesus macaques
    plain_language
    The tissue pigment recovered gradually after supply resumed.
    primary_references
    [zeaxanthin-p15326146] Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys. (2004). https://pubmed.ncbi.nlm.nih.gov/15326146/ DOI: 10.1167/iovs.02-1243
    tissue_or_cell_type
    Serum and macular pigment
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 899–910

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Long-term dietary depletion followed by single-pigment repletion · source_derived_draft · unverified_draft

    ### zeaxanthin-primate-repletion Pure zeaxanthin supplementation increased macular pigment, approaching a steady central peak by 24–32 weeks. Condition category: nutrient_deficiency nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tissue pigment recovered gradually after supply resumed. organism: Rhesus macaques tissue_or_cell_type: Serum and macular pigment experimental_model: Long-term dietary depletion followed by single-pigment repletion limitations: Extreme combined-xanthophyll depletion is not isolated human zeaxanthin deficiency or a clinical diagnostic threshold. exposure: Lifelong xanthophyll-free diet; six animals received pure zeaxanthin 2.2 mg/kg/day for 24–56 weeks evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15326146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2", "start_char": 0, "end_char": 1572, "text_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2"} [zeaxanthin-p15326146] Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys. (2004). https://pubmed.ncbi.nlm.nih.gov/15326146/ DOI: 10.1167/iovs.02-1243
    Complete structured claim and evidence
  14. Serum zeaxanthin rose rapidly during the first four weeks of supplementation.

    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15326146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2", "start_char": 0, "end_char": 1572, "text_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2"}
    experimental_model
    Long-term dietary depletion followed by single-pigment repletion
    exposure
    Lifelong xanthophyll-free diet; six animals received pure zeaxanthin 2.2 mg/kg/day for 24–56 weeks
    limitations
    Extreme combined-xanthophyll depletion is not isolated human zeaxanthin deficiency or a clinical diagnostic threshold.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Rhesus macaques
    plain_language
    Blood and tissue recovery followed different time courses.
    primary_references
    [zeaxanthin-p15326146] Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys. (2004). https://pubmed.ncbi.nlm.nih.gov/15326146/ DOI: 10.1167/iovs.02-1243
    tissue_or_cell_type
    Serum and macular pigment
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 912–923

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Long-term dietary depletion followed by single-pigment repletion · source_derived_draft · unverified_draft

    ### zeaxanthin-primate-serum Serum zeaxanthin rose rapidly during the first four weeks of supplementation. Condition category: nutrient_deficiency nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood and tissue recovery followed different time courses. organism: Rhesus macaques tissue_or_cell_type: Serum and macular pigment experimental_model: Long-term dietary depletion followed by single-pigment repletion limitations: Extreme combined-xanthophyll depletion is not isolated human zeaxanthin deficiency or a clinical diagnostic threshold. exposure: Lifelong xanthophyll-free diet; six animals received pure zeaxanthin 2.2 mg/kg/day for 24–56 weeks evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15326146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2", "start_char": 0, "end_char": 1572, "text_sha256": "2feb9366dc3d6fc9886076332f2e4ebc33603b94b113bc130163226845f7cea2"} [zeaxanthin-p15326146] Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys. (2004). https://pubmed.ncbi.nlm.nih.gov/15326146/ DOI: 10.1167/iovs.02-1243
    Complete structured claim and evidence
  15. The same experiment did not detect the carotenoid-dependent decrease in saturated DMPC liposomes.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/30689980.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743", "start_char": 0, "end_char": 1545, "text_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743"}
    experimental_model
    Photosensitized liposome experiment
    exposure
    Carotenoids at 0.15 mol%; toluidine-blue photosensitization
    limitations
    Measured effects depended on membrane composition; do not generalize the saturated-membrane null to all antioxidant chemistry.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Cell-free lipid systems
    plain_language
    A different membrane gave a different result.
    primary_references
    [zeaxanthin-p30689980] The effect of carotenoids on the concentration of singlet oxygen in lipid membranes. (2019). https://pubmed.ncbi.nlm.nih.gov/30689980/ DOI: 10.1016/j.bbamem.2019.01.012
    tissue_or_cell_type
    Saturated versus unsaturated lipid bilayers

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 340–351

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Photosensitized liposome experiment · source_derived_draft · unverified_draft

    ### zeaxanthin-saturated-null The same experiment did not detect the carotenoid-dependent decrease in saturated DMPC liposomes. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different membrane gave a different result. organism: Cell-free lipid systems tissue_or_cell_type: Saturated versus unsaturated lipid bilayers experimental_model: Photosensitized liposome experiment limitations: Measured effects depended on membrane composition; do not generalize the saturated-membrane null to all antioxidant chemistry. exposure: Carotenoids at 0.15 mol%; toluidine-blue photosensitization evidence_span: {"source_cache": "artifacts/zeaxanthin-research/30689980.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743", "start_char": 0, "end_char": 1545, "text_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743"} [zeaxanthin-p30689980] The effect of carotenoids on the concentration of singlet oxygen in lipid membranes. (2019). https://pubmed.ncbi.nlm.nih.gov/30689980/ DOI: 10.1016/j.bbamem.2019.01.012
    Complete structured claim and evidence
  16. ERG a- and b-wave amplitudes did not differ between supplemented and control knockout mice.

    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/30265681.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151", "start_char": 0, "end_char": 2098, "text_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151"}
    experimental_model
    RPE-specific knockout with oral supplementation
    exposure
    55–60 mg/kg/day zeaxanthin by gavage for four months
    limitations
    High-dose preventive animal model; genetic Sod2 loss is not manganese dietary deficiency, and this does not establish human AMD treatment.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Sod2-deleted mice
    plain_language
    Protection did not extend to every retinal function measure.
    primary_references
    [zeaxanthin-p30265681] Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress. (2018). https://pubmed.ncbi.nlm.nih.gov/30265681/ DOI: 10.1371/journal.pone.0203816
    tissue_or_cell_type
    Retina/RPE/choroid
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 509–520

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RPE-specific knockout with oral supplementation · source_derived_draft · unverified_draft

    ### zeaxanthin-sod2-ab-null ERG a- and b-wave amplitudes did not differ between supplemented and control knockout mice. Condition category: machinery_impairment nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection did not extend to every retinal function measure. organism: Sod2-deleted mice tissue_or_cell_type: Retina/RPE/choroid experimental_model: RPE-specific knockout with oral supplementation limitations: High-dose preventive animal model; genetic Sod2 loss is not manganese dietary deficiency, and this does not establish human AMD treatment. exposure: 55–60 mg/kg/day zeaxanthin by gavage for four months evidence_span: {"source_cache": "artifacts/zeaxanthin-research/30265681.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151", "start_char": 0, "end_char": 2098, "text_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151"} [zeaxanthin-p30265681] Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress. (2018). https://pubmed.ncbi.nlm.nih.gov/30265681/ DOI: 10.1371/journal.pone.0203816
    Complete structured claim and evidence
  17. After four months, ERG c-wave amplitude was 28% higher with zeaxanthin than in unsupplemented knockout mice.

    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/30265681.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151", "start_char": 0, "end_char": 2098, "text_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151"}
    experimental_model
    RPE-specific knockout with oral supplementation
    exposure
    55–60 mg/kg/day zeaxanthin by gavage for four months
    limitations
    High-dose preventive animal model; genetic Sod2 loss is not manganese dietary deficiency, and this does not establish human AMD treatment.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Sod2-deleted mice
    plain_language
    One measure of RPE function was better preserved.
    primary_references
    [zeaxanthin-p30265681] Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress. (2018). https://pubmed.ncbi.nlm.nih.gov/30265681/ DOI: 10.1371/journal.pone.0203816
    tissue_or_cell_type
    Retina/RPE/choroid
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 496–507

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RPE-specific knockout with oral supplementation · source_derived_draft · unverified_draft

    ### zeaxanthin-sod2-c-wave After four months, ERG c-wave amplitude was 28% higher with zeaxanthin than in unsupplemented knockout mice. Condition category: machinery_impairment nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One measure of RPE function was better preserved. organism: Sod2-deleted mice tissue_or_cell_type: Retina/RPE/choroid experimental_model: RPE-specific knockout with oral supplementation limitations: High-dose preventive animal model; genetic Sod2 loss is not manganese dietary deficiency, and this does not establish human AMD treatment. exposure: 55–60 mg/kg/day zeaxanthin by gavage for four months evidence_span: {"source_cache": "artifacts/zeaxanthin-research/30265681.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151", "start_char": 0, "end_char": 2098, "text_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151"} [zeaxanthin-p30265681] Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress. (2018). https://pubmed.ncbi.nlm.nih.gov/30265681/ DOI: 10.1371/journal.pone.0203816
    Complete structured claim and evidence
  18. Zeaxanthin reduced RPE/choroid nitrotyrosine content in the knockout model.

    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/30265681.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151", "start_char": 0, "end_char": 2098, "text_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151"}
    experimental_model
    RPE-specific knockout with oral supplementation
    exposure
    55–60 mg/kg/day zeaxanthin by gavage for four months
    limitations
    High-dose preventive animal model; genetic Sod2 loss is not manganese dietary deficiency, and this does not establish human AMD treatment.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Sod2-deleted mice
    plain_language
    A marker of oxidative injury decreased.
    primary_references
    [zeaxanthin-p30265681] Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress. (2018). https://pubmed.ncbi.nlm.nih.gov/30265681/ DOI: 10.1371/journal.pone.0203816
    tissue_or_cell_type
    Retina/RPE/choroid
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 522–533

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RPE-specific knockout with oral supplementation · source_derived_draft · unverified_draft

    ### zeaxanthin-sod2-nitrotyrosine Zeaxanthin reduced RPE/choroid nitrotyrosine content in the knockout model. Condition category: machinery_impairment nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A marker of oxidative injury decreased. organism: Sod2-deleted mice tissue_or_cell_type: Retina/RPE/choroid experimental_model: RPE-specific knockout with oral supplementation limitations: High-dose preventive animal model; genetic Sod2 loss is not manganese dietary deficiency, and this does not establish human AMD treatment. exposure: 55–60 mg/kg/day zeaxanthin by gavage for four months evidence_span: {"source_cache": "artifacts/zeaxanthin-research/30265681.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151", "start_char": 0, "end_char": 2098, "text_sha256": "656f827109394a907278c44e8d33e883c92437beea2a607e99e75ae348489151"} [zeaxanthin-p30265681] Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress. (2018). https://pubmed.ncbi.nlm.nih.gov/30265681/ DOI: 10.1371/journal.pone.0203816
    Complete structured claim and evidence
  19. Zeaxanthin decreased the detected singlet-oxygen concentration in unsaturated-lipid liposomes.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/30689980.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743", "start_char": 0, "end_char": 1545, "text_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743"}
    experimental_model
    Photosensitized liposome experiment
    exposure
    Carotenoids at 0.15 mol%; toluidine-blue photosensitization
    limitations
    Measured effects depended on membrane composition; do not generalize the saturated-membrane null to all antioxidant chemistry.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Cell-free lipid systems
    plain_language
    Protection depended on the surrounding membrane.
    primary_references
    [zeaxanthin-p30689980] The effect of carotenoids on the concentration of singlet oxygen in lipid membranes. (2019). https://pubmed.ncbi.nlm.nih.gov/30689980/ DOI: 10.1016/j.bbamem.2019.01.012
    tissue_or_cell_type
    Saturated versus unsaturated lipid bilayers

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 327–338

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Photosensitized liposome experiment · source_derived_draft · unverified_draft

    ### zeaxanthin-unsaturated-quenching Zeaxanthin decreased the detected singlet-oxygen concentration in unsaturated-lipid liposomes. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection depended on the surrounding membrane. organism: Cell-free lipid systems tissue_or_cell_type: Saturated versus unsaturated lipid bilayers experimental_model: Photosensitized liposome experiment limitations: Measured effects depended on membrane composition; do not generalize the saturated-membrane null to all antioxidant chemistry. exposure: Carotenoids at 0.15 mol%; toluidine-blue photosensitization evidence_span: {"source_cache": "artifacts/zeaxanthin-research/30689980.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743", "start_char": 0, "end_char": 1545, "text_sha256": "94c10c1ffd51016a2038f725e1e38457c47b5c929bd89f7222d8bc84a7f76743"} [zeaxanthin-p30689980] The effect of carotenoids on the concentration of singlet oxygen in lipid membranes. (2019). https://pubmed.ncbi.nlm.nih.gov/30689980/ DOI: 10.1016/j.bbamem.2019.01.012
    Complete structured claim and evidence
  20. The zeaxanthin arm showed a 1.5-line improvement in high-contrast acuity; the indexed result does not establish between-group superiority.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/22027699.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "849b03f2bf0734e12b654e662e0a15e5f347415de7b0bbabe2cdc0d7bad85e3e", "start_char": 0, "end_char": 3131, "text_sha256": "849b03f2bf0734e12b654e662e0a15e5f347415de7b0bbabe2cdc0d7bad85e3e"}
    experimental_model
    Small randomized active-comparator ZVF trial
    exposure
    One year; 8 mg zeaxanthin, 8 mg zeaxanthin plus 9 mg lutein, or 9 mg lutein comparator
    limitations
    The so-called faux placebo was active lutein. Small unequal arms, multiple outcomes and borderline tests limit claims of superiority; proposed competition was not directly tested.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    60 patients with mild-to-moderate AMD; 57 men
    plain_language
    A within-arm improvement is weaker evidence than a clear treatment comparison.
    primary_references
    [zeaxanthin-p22027699] Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973. (2011). https://pubmed.ncbi.nlm.nih.gov/22027699/ DOI: 10.1016/j.optm.2011.08.008
    tissue_or_cell_type
    Macular pigment and visual tasks

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 990–1001

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small randomized active-comparator ZVF trial · source_derived_draft · unverified_draft

    ### zeaxanthin-zvf-acuity The zeaxanthin arm showed a 1.5-line improvement in high-contrast acuity; the indexed result does not establish between-group superiority. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A within-arm improvement is weaker evidence than a clear treatment comparison. organism: 60 patients with mild-to-moderate AMD; 57 men tissue_or_cell_type: Macular pigment and visual tasks experimental_model: Small randomized active-comparator ZVF trial limitations: The so-called faux placebo was active lutein. Small unequal arms, multiple outcomes and borderline tests limit claims of superiority; proposed competition was not directly tested. exposure: One year; 8 mg zeaxanthin, 8 mg zeaxanthin plus 9 mg lutein, or 9 mg lutein comparator evidence_span: {"source_cache": "artifacts/zeaxanthin-research/22027699.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "849b03f2bf0734e12b654e662e0a15e5f347415de7b0bbabe2cdc0d7bad85e3e", "start_char": 0, "end_char": 3131, "text_sha256": "849b03f2bf0734e12b654e662e0a15e5f347415de7b0bbabe2cdc0d7bad85e3e"} [zeaxanthin-p22027699] Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973. (2011). https://pubmed.ncbi.nlm.nih.gov/22027699/ DOI: 10.1016/j.optm.2011.08.008
    Complete structured claim and evidence

What acts on it

  1. The study distinguishes GSTP1-associated zeaxanthin binding from StARD3-associated lutein binding.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/21322544.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0362dd86389ecba7d75e2628ffcd785ea404e40a709084dd5a0749a4cfb89fa", "start_char": 0, "end_char": 1825, "text_sha256": "e0362dd86389ecba7d75e2628ffcd785ea404e40a709084dd5a0749a4cfb89fa"}
    experimental_model
    Recombinant binding assays and primate retinal localization
    exposure
    Surface plasmon resonance and immunohistochemistry
    limitations
    Binding does not prove net retinal delivery or clinical benefit; localization is from monkey tissue.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    Human protein and monkey retinal tissue
    plain_language
    The two pigments have different identified binding proteins.
    primary_references
    [lutein-p21322544] Identification of StARD3 as a lutein-binding protein in the macula of the primate retina. (2011). https://pubmed.ncbi.nlm.nih.gov/21322544/ DOI: 10.1021/bi101906y
    tissue_or_cell_type
    Retina and purified protein

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 138–149

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant binding assays and primate retinal localization · source_derived_draft · unverified_draft

    ### lutein-gstp1-distinction The study distinguishes GSTP1-associated zeaxanthin binding from StARD3-associated lutein binding. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two pigments have different identified binding proteins. organism: Human protein and monkey retinal tissue tissue_or_cell_type: Retina and purified protein experimental_model: Recombinant binding assays and primate retinal localization limitations: Binding does not prove net retinal delivery or clinical benefit; localization is from monkey tissue. exposure: Surface plasmon resonance and immunohistochemistry evidence_span: {"source_cache": "artifacts/lutein-research/21322544.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0362dd86389ecba7d75e2628ffcd785ea404e40a709084dd5a0749a4cfb89fa", "start_char": 0, "end_char": 1825, "text_sha256": "e0362dd86389ecba7d75e2628ffcd785ea404e40a709084dd5a0749a4cfb89fa"} [lutein-p21322544] Identification of StARD3 as a lutein-binding protein in the macula of the primate retina. (2011). https://pubmed.ncbi.nlm.nih.gov/21322544/ DOI: 10.1021/bi101906y
    Complete structured claim and evidence
  2. HDL most effectively delivered zeaxanthin and meso-zeaxanthin; SR-BI inhibition suppressed zeaxanthin delivery.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/27538825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1db014221931676349f15dc3c5138fba122417fb49fec5de481594c72b0596f3", "start_char": 0, "end_char": 1346, "text_sha256": "1db014221931676349f15dc3c5138fba122417fb49fec5de481594c72b0596f3"}
    experimental_model
    Carotenoid delivery using isolated human lipoproteins
    exposure
    Carotenoid-loaded LDL versus HDL
    limitations
    Cell delivery ranking is not identical to circulating carriage fractions or the WHAM-chicken phenotype.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    Human ARPE-19 cells
    plain_language
    The preferred delivery route differed between pigments.
    primary_references
    [lutein-p27538825] Mechanisms of selective delivery of xanthophylls to retinal pigment epithelial cells by human lipoproteins. (2016). https://pubmed.ncbi.nlm.nih.gov/27538825/ DOI: 10.1194/jlr.m070193
    tissue_or_cell_type
    Retinal pigment epithelial model

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 645–656

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carotenoid delivery using isolated human lipoproteins · source_derived_draft · unverified_draft

    ### lutein-hdl-z-delivery HDL most effectively delivered zeaxanthin and meso-zeaxanthin; SR-BI inhibition suppressed zeaxanthin delivery. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The preferred delivery route differed between pigments. organism: Human ARPE-19 cells tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Carotenoid delivery using isolated human lipoproteins limitations: Cell delivery ranking is not identical to circulating carriage fractions or the WHAM-chicken phenotype. exposure: Carotenoid-loaded LDL versus HDL evidence_span: {"source_cache": "artifacts/lutein-research/27538825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1db014221931676349f15dc3c5138fba122417fb49fec5de481594c72b0596f3", "start_char": 0, "end_char": 1346, "text_sha256": "1db014221931676349f15dc3c5138fba122417fb49fec5de481594c72b0596f3"} [lutein-p27538825] Mechanisms of selective delivery of xanthophylls to retinal pigment epithelial cells by human lipoproteins. (2016). https://pubmed.ncbi.nlm.nih.gov/27538825/ DOI: 10.1194/jlr.m070193
    Complete structured claim and evidence
  3. After dipalmitate exposure, about 80.8% of cell-associated zeaxanthin species were free zeaxanthin.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    Most of the measured intracellular pigment was de-esterified.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 665–676

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-ester-free-product After dipalmitate exposure, about 80.8% of cell-associated zeaxanthin species were free zeaxanthin. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Most of the measured intracellular pigment was de-esterified. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  4. GSTA1 showed only low-affinity xanthophyll binding in the comparison.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15355982.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92", "start_char": 0, "end_char": 1907, "text_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92"}
    experimental_model
    Human macular protein purification and recombinant binding
    exposure
    Equilibrium binding and immunocytochemistry
    limitations
    Binding affinity is assay-specific and does not quantify uptake or clinical benefit.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human tissue/proteins
    plain_language
    Membership in the GST family does not guarantee selective binding.
    primary_references
    [zeaxanthin-p15355982] Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. (2004). https://pubmed.ncbi.nlm.nih.gov/15355982/ DOI: 10.1074/jbc.m405334200
    tissue_or_cell_type
    Macula and purified proteins

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 236–247

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human macular protein purification and recombinant binding · source_derived_draft · unverified_draft

    ### zeaxanthin-gsta1-low GSTA1 showed only low-affinity xanthophyll binding in the comparison. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Membership in the GST family does not guarantee selective binding. organism: Human tissue/proteins tissue_or_cell_type: Macula and purified proteins experimental_model: Human macular protein purification and recombinant binding limitations: Binding affinity is assay-specific and does not quantify uptake or clinical benefit. exposure: Equilibrium binding and immunocytochemistry evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15355982.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92", "start_char": 0, "end_char": 1907, "text_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92"} [zeaxanthin-p15355982] Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. (2004). https://pubmed.ncbi.nlm.nih.gov/15355982/ DOI: 10.1074/jbc.m405334200
    Complete structured claim and evidence
  5. GSTM1 showed only low-affinity xanthophyll binding in the comparison.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15355982.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92", "start_char": 0, "end_char": 1907, "text_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92"}
    experimental_model
    Human macular protein purification and recombinant binding
    exposure
    Equilibrium binding and immunocytochemistry
    limitations
    Binding affinity is assay-specific and does not quantify uptake or clinical benefit.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human tissue/proteins
    plain_language
    Different GST proteins have different binding behavior.
    primary_references
    [zeaxanthin-p15355982] Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. (2004). https://pubmed.ncbi.nlm.nih.gov/15355982/ DOI: 10.1074/jbc.m405334200
    tissue_or_cell_type
    Macula and purified proteins

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 249–260

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human macular protein purification and recombinant binding · source_derived_draft · unverified_draft

    ### zeaxanthin-gstm1-low GSTM1 showed only low-affinity xanthophyll binding in the comparison. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different GST proteins have different binding behavior. organism: Human tissue/proteins tissue_or_cell_type: Macula and purified proteins experimental_model: Human macular protein purification and recombinant binding limitations: Binding affinity is assay-specific and does not quantify uptake or clinical benefit. exposure: Equilibrium binding and immunocytochemistry evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15355982.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92", "start_char": 0, "end_char": 1907, "text_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92"} [zeaxanthin-p15355982] Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. (2004). https://pubmed.ncbi.nlm.nih.gov/15355982/ DOI: 10.1074/jbc.m405334200
    Complete structured claim and evidence
  6. Purified recombinant GSTP1 bound dietary zeaxanthin with apparent Kd 0.33 micromolar.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15355982.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92", "start_char": 0, "end_char": 1907, "text_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92"}
    experimental_model
    Human macular protein purification and recombinant binding
    exposure
    Equilibrium binding and immunocytochemistry
    limitations
    Binding affinity is assay-specific and does not quantify uptake or clinical benefit.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human tissue/proteins
    plain_language
    A retinal binding protein selectively holds dietary zeaxanthin.
    primary_references
    [zeaxanthin-p15355982] Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. (2004). https://pubmed.ncbi.nlm.nih.gov/15355982/ DOI: 10.1074/jbc.m405334200
    tissue_or_cell_type
    Macula and purified proteins

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 210–221

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human macular protein purification and recombinant binding · source_derived_draft · unverified_draft

    ### zeaxanthin-gstp1-binding Purified recombinant GSTP1 bound dietary zeaxanthin with apparent Kd 0.33 micromolar. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A retinal binding protein selectively holds dietary zeaxanthin. organism: Human tissue/proteins tissue_or_cell_type: Macula and purified proteins experimental_model: Human macular protein purification and recombinant binding limitations: Binding affinity is assay-specific and does not quantify uptake or clinical benefit. exposure: Equilibrium binding and immunocytochemistry evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15355982.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92", "start_char": 0, "end_char": 1907, "text_sha256": "6365b1d54aafda71be4dbf6c8e5252fa6ce0af3b808d9af6fe07c37ae188ea92"} [zeaxanthin-p15355982] Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. (2004). https://pubmed.ncbi.nlm.nih.gov/15355982/ DOI: 10.1074/jbc.m405334200
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Ten-year analysis by original L+Z assignment gave late-AMD HR 0.91 (95% CI 0.84–0.99).

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/35653117.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb", "start_char": 0, "end_char": 3155, "text_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb"}
    experimental_model
    Ten-year epidemiologic follow-up of randomized AREDS2 assignments
    exposure
    Original randomization followed by common AREDS2 supplementation for everyone
    limitations
    Not ten years of continuously separated randomized treatment; same cohort, additional follow-up.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    3882 original participants
    plain_language
    A modest long-term association favored original assignment.
    primary_references
    [lutein-p35653117] Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. (2022). https://pubmed.ncbi.nlm.nih.gov/35653117/ DOI: 10.1001/jamaophthalmol.2022.1640
    tissue_or_cell_type
    Late AMD and lung cancer

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 788–799

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-year epidemiologic follow-up of randomized AREDS2 assignments · source_derived_draft · unverified_draft

    ### lutein-areds-longterm Ten-year analysis by original L+Z assignment gave late-AMD HR 0.91 (95% CI 0.84–0.99). Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: A modest long-term association favored original assignment. organism: 3882 original participants tissue_or_cell_type: Late AMD and lung cancer experimental_model: Ten-year epidemiologic follow-up of randomized AREDS2 assignments limitations: Not ten years of continuously separated randomized treatment; same cohort, additional follow-up. exposure: Original randomization followed by common AREDS2 supplementation for everyone evidence_span: {"source_cache": "artifacts/lutein-research/35653117.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb", "start_char": 0, "end_char": 3155, "text_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb"} [lutein-p35653117] Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. (2022). https://pubmed.ncbi.nlm.nih.gov/35653117/ DOI: 10.1001/jamaophthalmol.2022.1640
    Complete structured claim and evidence
  2. L+Z assignment had lung-cancer OR 1.15 (95% CI 0.79–1.66), without a significant increase.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/35653117.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb", "start_char": 0, "end_char": 3155, "text_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb"}
    experimental_model
    Ten-year epidemiologic follow-up of randomized AREDS2 assignments
    exposure
    Original randomization followed by common AREDS2 supplementation for everyone
    limitations
    Not ten years of continuously separated randomized treatment; same cohort, additional follow-up.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    3882 original participants
    plain_language
    The beta-carotene signal was not demonstrated for the pair.
    primary_references
    [lutein-p35653117] Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. (2022). https://pubmed.ncbi.nlm.nih.gov/35653117/ DOI: 10.1001/jamaophthalmol.2022.1640
    tissue_or_cell_type
    Late AMD and lung cancer

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 801–812

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-year epidemiologic follow-up of randomized AREDS2 assignments · source_derived_draft · unverified_draft

    ### lutein-areds-longterm-lung-null L+Z assignment had lung-cancer OR 1.15 (95% CI 0.79–1.66), without a significant increase. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The beta-carotene signal was not demonstrated for the pair. organism: 3882 original participants tissue_or_cell_type: Late AMD and lung cancer experimental_model: Ten-year epidemiologic follow-up of randomized AREDS2 assignments limitations: Not ten years of continuously separated randomized treatment; same cohort, additional follow-up. exposure: Original randomization followed by common AREDS2 supplementation for everyone evidence_span: {"source_cache": "artifacts/lutein-research/35653117.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb", "start_char": 0, "end_char": 3155, "text_sha256": "66ae960c242e18fe246c623e055e94d52a638b6ac6330f8a85208a58d52c13cb"} [lutein-p35653117] Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. (2022). https://pubmed.ncbi.nlm.nih.gov/35653117/ DOI: 10.1001/jamaophthalmol.2022.1640
    Complete structured claim and evidence
  3. Primary L+Z versus placebo comparison gave HR 0.90 (98.7% CI 0.76–1.07; P=0.12).

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/23644932.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1bd379926e56d7243222c2ef69d6367b74aede2b02faabfb77fadcbadf95008f", "start_char": 0, "end_char": 3037, "text_sha256": "1bd379926e56d7243222c2ef69d6367b74aede2b02faabfb77fadcbadf95008f"}
    experimental_model
    AREDS2 phase 3 factorial randomized trial
    exposure
    Lutein 10 mg + zeaxanthin 2 mg daily; background AREDS formula; median five years
    limitations
    Combination and background treatment prevent attribution to lutein alone; primary contrast differs from replacement and main-effects analyses. Published correction 10.1001/jama.2013.6403 changes the Table 3 lung-neoplasm row label and Table 4 lung-neoplasm entries. These records use the indexed abstract and do not reproduce the uncorrected Table 4. Correction: https://jamanetwork.com/journals/jama/fullarticle/1710434 .
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    4203 adults aged 50–85 at elevated AMD progression risk
    plain_language
    Adding the pair did not meet the primary statistical threshold.
    primary_references
    [lutein-p23644932] Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. (2013). https://pubmed.ncbi.nlm.nih.gov/23644932/ DOI: 10.1001/jama.2013.4997
    tissue_or_cell_type
    Eyes with large drusen and/or fellow-eye advanced AMD

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 723–734

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AREDS2 phase 3 factorial randomized trial · source_derived_draft · unverified_draft

    ### lutein-areds-primary-null Primary L+Z versus placebo comparison gave HR 0.90 (98.7% CI 0.76–1.07; P=0.12). Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding the pair did not meet the primary statistical threshold. organism: 4203 adults aged 50–85 at elevated AMD progression risk tissue_or_cell_type: Eyes with large drusen and/or fellow-eye advanced AMD experimental_model: AREDS2 phase 3 factorial randomized trial limitations: Combination and background treatment prevent attribution to lutein alone; primary contrast differs from replacement and main-effects analyses. Published correction 10.1001/jama.2013.6403 changes the Table 3 lung-neoplasm row label and Table 4 lung-neoplasm entries. These records use the indexed abstract and do not reproduce the uncorrected Table 4. Correction: https://jamanetwork.com/journals/jama/fullarticle/1710434 . exposure: Lutein 10 mg + zeaxanthin 2 mg daily; background AREDS formula; median five years evidence_span: {"source_cache": "artifacts/lutein-research/23644932.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1bd379926e56d7243222c2ef69d6367b74aede2b02faabfb77fadcbadf95008f", "start_char": 0, "end_char": 3037, "text_sha256": "1bd379926e56d7243222c2ef69d6367b74aede2b02faabfb77fadcbadf95008f"} [lutein-p23644932] Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. (2013). https://pubmed.ncbi.nlm.nih.gov/23644932/ DOI: 10.1001/jama.2013.4997
    Complete structured claim and evidence
  4. Central geographic atrophy HR was 0.94 (95% CI 0.70–1.26), without a significant difference.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/24310343.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72", "start_char": 0, "end_char": 2419, "text_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72"}
    experimental_model
    Exploratory secondary analyses of AREDS2
    exposure
    L+Z 10/2 mg; direct comparison with beta-carotene on AREDS background
    limitations
    Exploratory contrasts and different confidence thresholds do not contradict the prespecified primary analysis.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    Same AREDS2 cohort, not an independent replication
    plain_language
    The same comparison did not show benefit for every subtype.
    primary_references
    [lutein-p24310343] Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. (2014). https://pubmed.ncbi.nlm.nih.gov/24310343/ DOI: 10.1001/jamaophthalmol.2013.7376
    tissue_or_cell_type
    Late AMD subtypes

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 775–786

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Exploratory secondary analyses of AREDS2 · source_derived_draft · unverified_draft

    ### lutein-areds-replacement-atrophy-null Central geographic atrophy HR was 0.94 (95% CI 0.70–1.26), without a significant difference. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same comparison did not show benefit for every subtype. organism: Same AREDS2 cohort, not an independent replication tissue_or_cell_type: Late AMD subtypes experimental_model: Exploratory secondary analyses of AREDS2 limitations: Exploratory contrasts and different confidence thresholds do not contradict the prespecified primary analysis. exposure: L+Z 10/2 mg; direct comparison with beta-carotene on AREDS background evidence_span: {"source_cache": "artifacts/lutein-research/24310343.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72", "start_char": 0, "end_char": 2419, "text_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72"} [lutein-p24310343] Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. (2014). https://pubmed.ncbi.nlm.nih.gov/24310343/ DOI: 10.1001/jamaophthalmol.2013.7376
    Complete structured claim and evidence
  5. Exploratory L+Z versus beta-carotene comparison gave late-AMD HR 0.82 (95% CI 0.69–0.96).

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/24310343.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72", "start_char": 0, "end_char": 2419, "text_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72"}
    experimental_model
    Exploratory secondary analyses of AREDS2
    exposure
    L+Z 10/2 mg; direct comparison with beta-carotene on AREDS background
    limitations
    Exploratory contrasts and different confidence thresholds do not contradict the prespecified primary analysis.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    Same AREDS2 cohort, not an independent replication
    plain_language
    Replacement comparison favored the xanthophyll pair.
    primary_references
    [lutein-p24310343] Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. (2014). https://pubmed.ncbi.nlm.nih.gov/24310343/ DOI: 10.1001/jamaophthalmol.2013.7376
    tissue_or_cell_type
    Late AMD subtypes

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 749–760

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Exploratory secondary analyses of AREDS2 · source_derived_draft · unverified_draft

    ### lutein-areds-replacement-late Exploratory L+Z versus beta-carotene comparison gave late-AMD HR 0.82 (95% CI 0.69–0.96). Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacement comparison favored the xanthophyll pair. organism: Same AREDS2 cohort, not an independent replication tissue_or_cell_type: Late AMD subtypes experimental_model: Exploratory secondary analyses of AREDS2 limitations: Exploratory contrasts and different confidence thresholds do not contradict the prespecified primary analysis. exposure: L+Z 10/2 mg; direct comparison with beta-carotene on AREDS background evidence_span: {"source_cache": "artifacts/lutein-research/24310343.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72", "start_char": 0, "end_char": 2419, "text_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72"} [lutein-p24310343] Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. (2014). https://pubmed.ncbi.nlm.nih.gov/24310343/ DOI: 10.1001/jamaophthalmol.2013.7376
    Complete structured claim and evidence
  6. The corresponding neovascular-AMD HR was 0.78 (95% CI 0.64–0.94).

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/24310343.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72", "start_char": 0, "end_char": 2419, "text_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72"}
    experimental_model
    Exploratory secondary analyses of AREDS2
    exposure
    L+Z 10/2 mg; direct comparison with beta-carotene on AREDS background
    limitations
    Exploratory contrasts and different confidence thresholds do not contradict the prespecified primary analysis.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    Same AREDS2 cohort, not an independent replication
    plain_language
    The subtype result favored the pair for neovascular AMD.
    primary_references
    [lutein-p24310343] Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. (2014). https://pubmed.ncbi.nlm.nih.gov/24310343/ DOI: 10.1001/jamaophthalmol.2013.7376
    tissue_or_cell_type
    Late AMD subtypes

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 762–773

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Exploratory secondary analyses of AREDS2 · source_derived_draft · unverified_draft

    ### lutein-areds-replacement-neovascular The corresponding neovascular-AMD HR was 0.78 (95% CI 0.64–0.94). Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The subtype result favored the pair for neovascular AMD. organism: Same AREDS2 cohort, not an independent replication tissue_or_cell_type: Late AMD subtypes experimental_model: Exploratory secondary analyses of AREDS2 limitations: Exploratory contrasts and different confidence thresholds do not contradict the prespecified primary analysis. exposure: L+Z 10/2 mg; direct comparison with beta-carotene on AREDS background evidence_span: {"source_cache": "artifacts/lutein-research/24310343.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72", "start_char": 0, "end_char": 2419, "text_sha256": "617cbda47a00c8fc552395a255003b013afa72aca6640c5c2e49d2b4caf09a72"} [lutein-p24310343] Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. (2014). https://pubmed.ncbi.nlm.nih.gov/24310343/ DOI: 10.1001/jamaophthalmol.2013.7376
    Complete structured claim and evidence
  7. In the lowest dietary L+Z quintile, cataract-surgery HR was 0.68 (95% CI 0.48–0.96; P=0.03).

    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/lutein-research/23645227.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32", "start_char": 0, "end_char": 2245, "text_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32"}
    experimental_model
    AREDS2 cataract secondary outcome and dietary subgroup analysis
    exposure
    L+Z 10/2 mg daily; median 4.7 years
    limitations
    Lowest-intake subgroup is not a clinical deficiency diagnosis; overall and subgroup results must stay separate.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    3159 participants phakic in at least one eye
    plain_language
    A subgroup with lower intake had a favorable estimate.
    primary_references
    [lutein-p23645227] Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. (2013). https://pubmed.ncbi.nlm.nih.gov/23645227/ DOI: 10.1001/jamaophthalmol.2013.4412
    tissue_or_cell_type
    6027 study eyes
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 827–838

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AREDS2 cataract secondary outcome and dietary subgroup analysis · source_derived_draft · unverified_draft

    ### lutein-cataract-low-intake In the lowest dietary L+Z quintile, cataract-surgery HR was 0.68 (95% CI 0.48–0.96; P=0.03). Condition category: biomarker_context nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: A subgroup with lower intake had a favorable estimate. organism: 3159 participants phakic in at least one eye tissue_or_cell_type: 6027 study eyes experimental_model: AREDS2 cataract secondary outcome and dietary subgroup analysis limitations: Lowest-intake subgroup is not a clinical deficiency diagnosis; overall and subgroup results must stay separate. exposure: L+Z 10/2 mg daily; median 4.7 years evidence_span: {"source_cache": "artifacts/lutein-research/23645227.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32", "start_char": 0, "end_char": 2245, "text_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32"} [lutein-p23645227] Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. (2013). https://pubmed.ncbi.nlm.nih.gov/23645227/ DOI: 10.1001/jamaophthalmol.2013.4412
    Complete structured claim and evidence
  8. Overall cataract-surgery HR was 0.96 (95% CI 0.84–1.10; P=0.54).

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/23645227.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32", "start_char": 0, "end_char": 2245, "text_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32"}
    experimental_model
    AREDS2 cataract secondary outcome and dietary subgroup analysis
    exposure
    L+Z 10/2 mg daily; median 4.7 years
    limitations
    Lowest-intake subgroup is not a clinical deficiency diagnosis; overall and subgroup results must stay separate.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    3159 participants phakic in at least one eye
    plain_language
    The trial did not show an overall cataract-surgery benefit.
    primary_references
    [lutein-p23645227] Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. (2013). https://pubmed.ncbi.nlm.nih.gov/23645227/ DOI: 10.1001/jamaophthalmol.2013.4412
    tissue_or_cell_type
    6027 study eyes

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 814–825

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AREDS2 cataract secondary outcome and dietary subgroup analysis · source_derived_draft · unverified_draft

    ### lutein-cataract-overall-null Overall cataract-surgery HR was 0.96 (95% CI 0.84–1.10; P=0.54). Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial did not show an overall cataract-surgery benefit. organism: 3159 participants phakic in at least one eye tissue_or_cell_type: 6027 study eyes experimental_model: AREDS2 cataract secondary outcome and dietary subgroup analysis limitations: Lowest-intake subgroup is not a clinical deficiency diagnosis; overall and subgroup results must stay separate. exposure: L+Z 10/2 mg daily; median 4.7 years evidence_span: {"source_cache": "artifacts/lutein-research/23645227.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32", "start_char": 0, "end_char": 2245, "text_sha256": "3e75988c75dde9e6525246ae68335c49c03c31f02c7419dcf74110966b7dce32"} [lutein-p23645227] Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. (2013). https://pubmed.ncbi.nlm.nih.gov/23645227/ DOI: 10.1001/jamaophthalmol.2013.4412
    Complete structured claim and evidence
  9. L+Z produced no significant difference in yearly cognitive composite change: 0.03 (99% CI −0.14 to 0.19; P=0.66).

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/26305649.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6b4498bace6ac4564fae52aef2f95e564154631bdfa1e19b02fa6878043dbe72", "start_char": 0, "end_char": 2936, "text_sha256": "6b4498bace6ac4564fae52aef2f95e564154631bdfa1e19b02fa6878043dbe72"}
    experimental_model
    AREDS2 ancillary randomized cognitive study
    exposure
    L+Z 10/2 mg daily; five-year study on background nutrient formulas
    limitations
    Cognitive outcome, not a direct brain-lutein assay; no attribution to isolated lutein.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    3501 tested older participants at AMD risk
    plain_language
    The large older-adult study did not show cognitive benefit.
    primary_references
    [lutein-p26305649] Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26305649/ DOI: 10.1001/jama.2015.9677
    tissue_or_cell_type
    Telephone cognitive test battery

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 892–903

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AREDS2 ancillary randomized cognitive study · source_derived_draft · unverified_draft

    ### lutein-cognition-areds-null L+Z produced no significant difference in yearly cognitive composite change: 0.03 (99% CI −0.14 to 0.19; P=0.66). Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The large older-adult study did not show cognitive benefit. organism: 3501 tested older participants at AMD risk tissue_or_cell_type: Telephone cognitive test battery experimental_model: AREDS2 ancillary randomized cognitive study limitations: Cognitive outcome, not a direct brain-lutein assay; no attribution to isolated lutein. exposure: L+Z 10/2 mg daily; five-year study on background nutrient formulas evidence_span: {"source_cache": "artifacts/lutein-research/26305649.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6b4498bace6ac4564fae52aef2f95e564154631bdfa1e19b02fa6878043dbe72", "start_char": 0, "end_char": 2936, "text_sha256": "6b4498bace6ac4564fae52aef2f95e564154631bdfa1e19b02fa6878043dbe72"} [lutein-p26305649] Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26305649/ DOI: 10.1001/jama.2015.9677
    Complete structured claim and evidence
  10. L+Z improved the tested chromatic-contrast threshold versus placebo.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"}
    experimental_model
    Randomized double-blind placebo-controlled visual-performance study
    exposure
    Lutein 10 mg + zeaxanthin 2 mg daily for one year
    limitations
    Combined intervention; improved task performance is not evidence of AMD prevention or treatment.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    115 young healthy adults
    plain_language
    Participants detected the test contrast better.
    primary_references
    [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    tissue_or_cell_type
    Serum, macular pigment and visual tasks

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 866–877

    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 visual-performance study · source_derived_draft · unverified_draft

    ### lutein-contrast-improvement L+Z improved the tested chromatic-contrast threshold versus placebo. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: Participants detected the test contrast better. organism: 115 young healthy adults tissue_or_cell_type: Serum, macular pigment and visual tasks experimental_model: Randomized double-blind placebo-controlled visual-performance study limitations: Combined intervention; improved task performance is not evidence of AMD prevention or treatment. exposure: Lutein 10 mg + zeaxanthin 2 mg daily for one year evidence_span: {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"} [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    Complete structured claim and evidence
  11. The high-egg salad meal increased lutein/zeaxanthin lipoprotein AUC about four- to fivefold versus salad without egg.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/26016861.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c275d8263df6d127f722fc47b45e9bc513c6d871653afbc878bc50a911b1df55", "start_char": 0, "end_char": 2045, "text_sha256": "c275d8263df6d127f722fc47b45e9bc513c6d871653afbc878bc50a911b1df55"}
    experimental_model
    Randomized three-meal crossover trial
    exposure
    Salad plus 0, 75 or 150 g scrambled whole eggs; ten-hour sampling
    limitations
    Eggs supplied both fat and carotenoids; the experiment does not isolate a choline effect. Published erratum 10.3945/ajcn.115.120956 corrects an author affiliation to Department of Nutrition Science; it does not change the trial outcomes. Correction: https://doi.org/10.3945/ajcn.115.120956 .
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    16 healthy young men
    plain_language
    The whole-food meal increased carotenoid appearance in blood.
    primary_references
    [lutein-p26016861] Effects of egg consumption on carotenoid absorption from co-consumed, raw vegetables. (2015). https://pubmed.ncbi.nlm.nih.gov/26016861/ DOI: 10.3945/ajcn.115.111062
    tissue_or_cell_type
    Post-meal triglyceride-rich lipoproteins

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 593–604

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized three-meal crossover trial · source_derived_draft · unverified_draft

    ### lutein-egg-matrix The high-egg salad meal increased lutein/zeaxanthin lipoprotein AUC about four- to fivefold versus salad without egg. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The whole-food meal increased carotenoid appearance in blood. organism: 16 healthy young men tissue_or_cell_type: Post-meal triglyceride-rich lipoproteins experimental_model: Randomized three-meal crossover trial limitations: Eggs supplied both fat and carotenoids; the experiment does not isolate a choline effect. Published erratum 10.3945/ajcn.115.120956 corrects an author affiliation to Department of Nutrition Science; it does not change the trial outcomes. Correction: https://doi.org/10.3945/ajcn.115.120956 . exposure: Salad plus 0, 75 or 150 g scrambled whole eggs; ten-hour sampling evidence_span: {"source_cache": "artifacts/lutein-research/26016861.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c275d8263df6d127f722fc47b45e9bc513c6d871653afbc878bc50a911b1df55", "start_char": 0, "end_char": 2045, "text_sha256": "c275d8263df6d127f722fc47b45e9bc513c6d871653afbc878bc50a911b1df55"} [lutein-p26016861] Effects of egg consumption on carotenoid absorption from co-consumed, raw vegetables. (2015). https://pubmed.ncbi.nlm.nih.gov/26016861/ DOI: 10.3945/ajcn.115.111062
    Complete structured claim and evidence
  12. Glare disability did not improve significantly in the treated group despite correlation with pigment density.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"}
    experimental_model
    Randomized double-blind placebo-controlled visual-performance study
    exposure
    Lutein 10 mg + zeaxanthin 2 mg daily for one year
    limitations
    Combined intervention; improved task performance is not evidence of AMD prevention or treatment.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    115 young healthy adults
    plain_language
    A biomarker correlation did not guarantee a treatment effect.
    primary_references
    [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    tissue_or_cell_type
    Serum, macular pigment and visual tasks

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 879–890

    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 visual-performance study · source_derived_draft · unverified_draft

    ### lutein-glare-null Glare disability did not improve significantly in the treated group despite correlation with pigment density. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: A biomarker correlation did not guarantee a treatment effect. organism: 115 young healthy adults tissue_or_cell_type: Serum, macular pigment and visual tasks experimental_model: Randomized double-blind placebo-controlled visual-performance study limitations: Combined intervention; improved task performance is not evidence of AMD prevention or treatment. exposure: Lutein 10 mg + zeaxanthin 2 mg daily for one year evidence_span: {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"} [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    Complete structured claim and evidence
  13. The equal-ratio meso-zeaxanthin, zeaxanthin and lutein mixture quenched more singlet oxygen than each individual pigment at the same total concentration.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/20678467.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aaf88f567941ed16adb101981a218960bbd8ae3cfe0919868de63462e7c7be01", "start_char": 0, "end_char": 989, "text_sha256": "aaf88f567941ed16adb101981a218960bbd8ae3cfe0919868de63462e7c7be01"}
    experimental_model
    EPR of donor eye tissue and solution quenching assays
    exposure
    White-light challenge and equal-total-concentration carotenoid comparisons
    limitations
    Solution mixture effects do not establish an optimal oral ratio or clinical benefit; exogenous pigment addition differs from delivery in a living eye.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    Postmortem human tissue and cell-free systems
    plain_language
    The three pigments worked better together in this solution experiment.
    primary_references
    [lutein-p20678467] Studies on the singlet oxygen scavenging mechanism of human macular pigment. (2010). https://pubmed.ncbi.nlm.nih.gov/20678467/ DOI: 10.1016/j.abb.2010.07.024
    tissue_or_cell_type
    Macula, RPE/choroid and carotenoid solutions

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 229–240

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · EPR of donor eye tissue and solution quenching assays · source_derived_draft · unverified_draft

    ### lutein-mixture-quenching The equal-ratio meso-zeaxanthin, zeaxanthin and lutein mixture quenched more singlet oxygen than each individual pigment at the same total concentration. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: The three pigments worked better together in this solution experiment. organism: Postmortem human tissue and cell-free systems tissue_or_cell_type: Macula, RPE/choroid and carotenoid solutions experimental_model: EPR of donor eye tissue and solution quenching assays limitations: Solution mixture effects do not establish an optimal oral ratio or clinical benefit; exogenous pigment addition differs from delivery in a living eye. exposure: White-light challenge and equal-total-concentration carotenoid comparisons evidence_span: {"source_cache": "artifacts/lutein-research/20678467.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aaf88f567941ed16adb101981a218960bbd8ae3cfe0919868de63462e7c7be01", "start_char": 0, "end_char": 989, "text_sha256": "aaf88f567941ed16adb101981a218960bbd8ae3cfe0919868de63462e7c7be01"} [lutein-p20678467] Studies on the singlet oxygen scavenging mechanism of human macular pigment. (2010). https://pubmed.ncbi.nlm.nih.gov/20678467/ DOI: 10.1016/j.abb.2010.07.024
    Complete structured claim and evidence
  14. L+Z increased macular pigment optical density versus placebo at all measured eccentricities.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"}
    experimental_model
    Randomized double-blind placebo-controlled visual-performance study
    exposure
    Lutein 10 mg + zeaxanthin 2 mg daily for one year
    limitations
    Combined intervention; improved task performance is not evidence of AMD prevention or treatment.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    115 young healthy adults
    plain_language
    More pigment was measured in the macula.
    primary_references
    [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    tissue_or_cell_type
    Serum, macular pigment and visual tasks

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 840–851

    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 visual-performance study · source_derived_draft · unverified_draft

    ### lutein-mpod-increase L+Z increased macular pigment optical density versus placebo at all measured eccentricities. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: More pigment was measured in the macula. organism: 115 young healthy adults tissue_or_cell_type: Serum, macular pigment and visual tasks experimental_model: Randomized double-blind placebo-controlled visual-performance study limitations: Combined intervention; improved task performance is not evidence of AMD prevention or treatment. exposure: Lutein 10 mg + zeaxanthin 2 mg daily for one year evidence_span: {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"} [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    Complete structured claim and evidence
  15. L+Z improved photostress recovery time versus placebo.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"}
    experimental_model
    Randomized double-blind placebo-controlled visual-performance study
    exposure
    Lutein 10 mg + zeaxanthin 2 mg daily for one year
    limitations
    Combined intervention; improved task performance is not evidence of AMD prevention or treatment.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    115 young healthy adults
    plain_language
    Vision recovered faster after the experimental bright flash.
    primary_references
    [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    tissue_or_cell_type
    Serum, macular pigment and visual tasks

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 853–864

    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 visual-performance study · source_derived_draft · unverified_draft

    ### lutein-photostress-improvement L+Z improved photostress recovery time versus placebo. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vision recovered faster after the experimental bright flash. organism: 115 young healthy adults tissue_or_cell_type: Serum, macular pigment and visual tasks experimental_model: Randomized double-blind placebo-controlled visual-performance study limitations: Combined intervention; improved task performance is not evidence of AMD prevention or treatment. exposure: Lutein 10 mg + zeaxanthin 2 mg daily for one year evidence_span: {"source_cache": "artifacts/lutein-research/25468896.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3", "start_char": 0, "end_char": 2007, "text_sha256": "01231d6577e7c30e79a74525772191092df003b42344095a53faf0279f138ac3"} [lutein-p25468896] A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. (2014). https://pubmed.ncbi.nlm.nih.gov/25468896/ DOI: 10.1167/iovs.14-15573
    Complete structured claim and evidence
  16. The young-adult trial reported improved visual memory associated with supplementation.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/lutein-research/29135938.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f60146e188d1a3093c572c3f637ebd659184f72727a75b35afd265b5ef0be71b", "start_char": 21132, "end_char": 25480, "text_sha256": "02d9398a25880c0ead3b3ef0ed91d12a98f837a8c8f89c141986dd926e1010a8"}
    experimental_model
    Small randomized double-masked placebo-controlled trial with biomarker-response analyses
    exposure
    Lutein 10 mg + zeaxanthin 2 mg daily for one year
    limitations
    Small unequal groups and multiple outcomes; attention/reasoning findings depended on pigment-response analysis. MPOD does not directly measure brain tissue.
    nutrient_topic
    Lutein research collection; topical membership is not evidence of a direct dietary effect. · Lutein
    organism
    51 analyzable healthy adults aged 18–30; 37 active and 14 placebo
    plain_language
    A small study found a benefit on a specific memory task.
    primary_references
    [lutein-p29135938] Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults. (2017). https://pubmed.ncbi.nlm.nih.gov/29135938/ DOI: 10.3390/nu9111246
    tissue_or_cell_type
    Cognitive testing and retinal pigment measurement

    Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 905–916

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small randomized double-masked placebo-controlled trial with biomarker-response analyses · source_derived_draft · unverified_draft

    ### lutein-young-memory The young-adult trial reported improved visual memory associated with supplementation. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small study found a benefit on a specific memory task. organism: 51 analyzable healthy adults aged 18–30; 37 active and 14 placebo tissue_or_cell_type: Cognitive testing and retinal pigment measurement experimental_model: Small randomized double-masked placebo-controlled trial with biomarker-response analyses limitations: Small unequal groups and multiple outcomes; attention/reasoning findings depended on pigment-response analysis. MPOD does not directly measure brain tissue. exposure: Lutein 10 mg + zeaxanthin 2 mg daily for one year evidence_span: {"source_cache": "artifacts/lutein-research/29135938.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f60146e188d1a3093c572c3f637ebd659184f72727a75b35afd265b5ef0be71b", "start_char": 21132, "end_char": 25480, "text_sha256": "02d9398a25880c0ead3b3ef0ed91d12a98f837a8c8f89c141986dd926e1010a8"} [lutein-p29135938] Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults. (2017). https://pubmed.ncbi.nlm.nih.gov/29135938/ DOI: 10.3390/nu9111246
    Complete structured claim and evidence
  17. J-aggregated dipalmitate gave a 23% higher AUC estimate than H-aggregated free pigment, with P=0.064.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/29185931.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3db71b8dc1b111c999db31427237d2296afb9024060396a63b2b2bc4d9bbcd37", "start_char": 0, "end_char": 1785, "text_sha256": "3db71b8dc1b111c999db31427237d2296afb9024060396a63b2b2bc4d9bbcd37"}
    experimental_model
    Randomized two-way crossover and simulated digestion
    exposure
    10 mg free-zeaxanthin equivalents in H-aggregated free or J-aggregated dipalmitate formulations
    limitations
    The 23% higher AUC estimate had P=0.064 and did not meet 0.05; aggregation and esterification changed together.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    16 human participants and in vitro digestion
    plain_language
    The estimate favored one formulation, but statistical uncertainty remained.
    primary_references
    [zeaxanthin-p29185931] Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study. (2017). https://pubmed.ncbi.nlm.nih.gov/29185931/ DOI: 10.1017/s0007114517002653
    tissue_or_cell_type
    TAG-rich lipoprotein response

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 821–832

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized two-way crossover and simulated digestion · source_derived_draft · unverified_draft

    ### zeaxanthin-aggregation-trend J-aggregated dipalmitate gave a 23% higher AUC estimate than H-aggregated free pigment, with P=0.064. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The estimate favored one formulation, but statistical uncertainty remained. organism: 16 human participants and in vitro digestion tissue_or_cell_type: TAG-rich lipoprotein response experimental_model: Randomized two-way crossover and simulated digestion limitations: The 23% higher AUC estimate had P=0.064 and did not meet 0.05; aggregation and esterification changed together. exposure: 10 mg free-zeaxanthin equivalents in H-aggregated free or J-aggregated dipalmitate formulations evidence_span: {"source_cache": "artifacts/zeaxanthin-research/29185931.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3db71b8dc1b111c999db31427237d2296afb9024060396a63b2b2bc4d9bbcd37", "start_char": 0, "end_char": 1785, "text_sha256": "3db71b8dc1b111c999db31427237d2296afb9024060396a63b2b2bc4d9bbcd37"} [zeaxanthin-p29185931] Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study. (2017). https://pubmed.ncbi.nlm.nih.gov/29185931/ DOI: 10.1017/s0007114517002653
    Complete structured claim and evidence
  18. At 2 mM, ascorbate exacerbated phototoxicity; zeaxanthin or alpha-tocopherol partly ameliorated it.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"}
    experimental_model
    Retinaldehyde-liposome photosensitization with cells
    exposure
    4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate
    limitations
    Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cells and unsaturated liposomes
    plain_language
    A higher concentration changed the interaction.
    primary_references
    [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132
    tissue_or_cell_type
    RPE injury model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 951–962

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

    ### zeaxanthin-ascorbate-high At 2 mM, ascorbate exacerbated phototoxicity; zeaxanthin or alpha-tocopherol partly ameliorated it. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher concentration changed the interaction. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132
    Complete structured claim and evidence
  19. Adding 0.5 mM ascorbate to the combination raised viability to approximately 69%.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"}
    experimental_model
    Retinaldehyde-liposome photosensitization with cells
    exposure
    4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate
    limitations
    Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cells and unsaturated liposomes
    plain_language
    Vitamin C added protection under this condition.
    primary_references
    [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132
    tissue_or_cell_type
    RPE injury model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 938–949

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

    ### zeaxanthin-ascorbate-low Adding 0.5 mM ascorbate to the combination raised viability to approximately 69%. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C added protection under this condition. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132
    Complete structured claim and evidence
  20. The vitamin E–zeaxanthin combination did not prevent the deleterious high-ascorbate effect in the rose-bengal model.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/22924673.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177", "start_char": 0, "end_char": 1415, "text_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177"}
    experimental_model
    Rose-bengal photosensitization with antioxidant combinations
    exposure
    Visible-light exposures; ascorbate 0.35–1.4 mM with lipophilic antioxidants
    limitations
    Different photosensitizer and exposure duration from the retinaldehyde study; do not treat this as a universal contradiction or dietary safety threshold.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cells
    plain_language
    Protection had limits under a different light challenge.
    primary_references
    [zeaxanthin-p22924673] Concentration dependence of vitamin C in combinations with vitamin E and zeaxanthin on light-induced toxicity to retinal pigment epithelial cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22924673/ DOI: 10.1111/j.1751-1097.2012.01228.x
    tissue_or_cell_type
    Cultured RPE model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 964–975

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rose-bengal photosensitization with antioxidant combinations · source_derived_draft · unverified_draft

    ### zeaxanthin-ascorbate-rescue-limit The vitamin E–zeaxanthin combination did not prevent the deleterious high-ascorbate effect in the rose-bengal model. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection had limits under a different light challenge. organism: Human ARPE-19 cells tissue_or_cell_type: Cultured RPE model experimental_model: Rose-bengal photosensitization with antioxidant combinations limitations: Different photosensitizer and exposure duration from the retinaldehyde study; do not treat this as a universal contradiction or dietary safety threshold. exposure: Visible-light exposures; ascorbate 0.35–1.4 mM with lipophilic antioxidants evidence_span: {"source_cache": "artifacts/zeaxanthin-research/22924673.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177", "start_char": 0, "end_char": 1415, "text_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177"} [zeaxanthin-p22924673] Concentration dependence of vitamin C in combinations with vitamin E and zeaxanthin on light-induced toxicity to retinal pigment epithelial cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22924673/ DOI: 10.1111/j.1751-1097.2012.01228.x
    Complete structured claim and evidence
  21. BSO abolished zeaxanthin-associated protection of cell viability and mitochondrial membrane potential.

    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    Pigment supply did not overcome the blocked glutathione response.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 457–468

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-bso-failure BSO abolished zeaxanthin-associated protection of cell viability and mitochondrial membrane potential. Condition category: machinery_impairment nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pigment supply did not overcome the blocked glutathione response. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  22. Combined zeaxanthin and alpha-tocopherol raised viability from about 26% to 63% in the tested model.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"}
    experimental_model
    Retinaldehyde-liposome photosensitization with cells
    exposure
    4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate
    limitations
    Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cells and unsaturated liposomes
    plain_language
    The pair protected cells against this defined light challenge.
    primary_references
    [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132
    tissue_or_cell_type
    RPE injury model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 925–936

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

    ### zeaxanthin-c-e-z-protection Combined zeaxanthin and alpha-tocopherol raised viability from about 26% to 63% in the tested model. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pair protected cells against this defined light challenge. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132
    Complete structured claim and evidence
  23. Nystatin-sensitive uptake supported a caveolae/lipid-raft-related route for zeaxanthin micelles.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    A second endocytic route contributed in the assay.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 769–780

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-caveolae-route Nystatin-sensitive uptake supported a caveolae/lipid-raft-related route for zeaxanthin micelles. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second endocytic route contributed in the assay. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  24. CD36 supported zeaxanthin uptake in the transfected-cell experiment.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"}
    experimental_model
    SPR and transporter overexpression
    exposure
    SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers
    limitations
    The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human proteins in HEK-293T cells and donor eye tissue
    plain_language
    Another lipid transporter supplied an entry route.
    primary_references
    [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
    tissue_or_cell_type
    Recombinant receptors and HEK-293T cells

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 613–624

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SPR and transporter overexpression · source_derived_draft · unverified_draft

    ### zeaxanthin-cd36-uptake CD36 supported zeaxanthin uptake in the transfected-cell experiment. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another lipid transporter supplied an entry route. organism: Human proteins in HEK-293T cells and donor eye tissue tissue_or_cell_type: Recombinant receptors and HEK-293T cells experimental_model: SPR and transporter overexpression limitations: The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial. exposure: SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers evidence_span: {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"} [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
    Complete structured claim and evidence
  25. The 13-cis xanthophyll configuration produced a stronger oxygen-penetration barrier than all-trans in the model membranes.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/37578906.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b71f2d30f62ae7c00c7b92d32de4b216af85bfcffb9ff3b467cb02e2fb0ba12", "start_char": 0, "end_char": 1038, "text_sha256": "0b71f2d30f62ae7c00c7b92d32de4b216af85bfcffb9ff3b467cb02e2fb0ba12"}
    experimental_model
    Fluorescence lifetime imaging and EPR oximetry
    exposure
    All-trans versus 13-cis xanthophyll configurations
    limitations
    Retinal regulatory implications are proposed; assay oxygen permeability is not a clinical photoprotection endpoint.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Cell-free lipid vesicles
    plain_language
    Pigment configuration changed how oxygen entered the membrane.
    primary_references
    [zeaxanthin-p37578906] How Do Xanthophylls Protect Lipid Membranes from Oxidative Damage? (2023). https://pubmed.ncbi.nlm.nih.gov/37578906/ DOI: 10.1021/acs.jpclett.3c01374
    tissue_or_cell_type
    Model lipid membranes

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 353–364

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fluorescence lifetime imaging and EPR oximetry · source_derived_draft · unverified_draft

    ### zeaxanthin-cis-oxygen-barrier The 13-cis xanthophyll configuration produced a stronger oxygen-penetration barrier than all-trans in the model membranes. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pigment configuration changed how oxygen entered the membrane. organism: Cell-free lipid vesicles tissue_or_cell_type: Model lipid membranes experimental_model: Fluorescence lifetime imaging and EPR oximetry limitations: Retinal regulatory implications are proposed; assay oxygen permeability is not a clinical photoprotection endpoint. exposure: All-trans versus 13-cis xanthophyll configurations evidence_span: {"source_cache": "artifacts/zeaxanthin-research/37578906.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b71f2d30f62ae7c00c7b92d32de4b216af85bfcffb9ff3b467cb02e2fb0ba12", "start_char": 0, "end_char": 1038, "text_sha256": "0b71f2d30f62ae7c00c7b92d32de4b216af85bfcffb9ff3b467cb02e2fb0ba12"} [zeaxanthin-p37578906] How Do Xanthophylls Protect Lipid Membranes from Oxidative Damage? (2023). https://pubmed.ncbi.nlm.nih.gov/37578906/ DOI: 10.1021/acs.jpclett.3c01374
    Complete structured claim and evidence
  26. Dynasore-sensitive uptake supported a clathrin-related route for zeaxanthin micelles.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    Cells could take up the formulation through an endocytic route.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 756–767

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-clathrin-route Dynasore-sensitive uptake supported a clathrin-related route for zeaxanthin micelles. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells could take up the formulation through an endocytic route. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  27. Zeaxanthin dipalmitate did not significantly increase ABCG5 expression in the comparison.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    Free and esterified pigment produced different expression responses.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 704–715

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-ester-abcg5-null Zeaxanthin dipalmitate did not significantly increase ABCG5 expression in the comparison. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free and esterified pigment produced different expression responses. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  28. Monoesters were detected in cells and basolateral medium after dipalmitate exposure.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    Some ester-linked pigment also crossed this model.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 678–689

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-ester-mono-product Monoesters were detected in cells and basolateral medium after dipalmitate exposure. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some ester-linked pigment also crossed this model. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  29. Ezetimibe reduced free-zeaxanthin uptake in the Caco-2 inhibitor experiment.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    The drug reduced uptake in cells; clinical importance remains unknown.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 743–754

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-ezetimibe-uptake Ezetimibe reduced free-zeaxanthin uptake in the Caco-2 inhibitor experiment. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug reduced uptake in cells; clinical importance remains unknown. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  30. The GSTP1–zeaxanthin protective effect did not require glutathione in this liposome experiment.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"}
    experimental_model
    Lipid-peroxyl radical challenge in liposomes
    exposure
    AAPH or AMVN challenge; dietary and meso zeaxanthin
    limitations
    Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Cell-free system with human GSTP1
    plain_language
    This binding-related effect persisted without glutathione.
    primary_references
    [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    tissue_or_cell_type
    Egg-yolk phosphatidylcholine liposomes

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 288–299

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lipid-peroxyl radical challenge in liposomes · source_derived_draft · unverified_draft

    ### zeaxanthin-gsh-independent The GSTP1–zeaxanthin protective effect did not require glutathione in this liposome experiment. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This binding-related effect persisted without glutathione. organism: Cell-free system with human GSTP1 tissue_or_cell_type: Egg-yolk phosphatidylcholine liposomes experimental_model: Lipid-peroxyl radical challenge in liposomes limitations: Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination. exposure: AAPH or AMVN challenge; dietary and meso zeaxanthin evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"} [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    Complete structured claim and evidence
  31. GSTP1 association increased resistance of zeaxanthin diastereomers to chemical degradation.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"}
    experimental_model
    Lipid-peroxyl radical challenge in liposomes
    exposure
    AAPH or AMVN challenge; dietary and meso zeaxanthin
    limitations
    Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Cell-free system with human GSTP1
    plain_language
    The protein helped preserve the pigments during oxidation.
    primary_references
    [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    tissue_or_cell_type
    Egg-yolk phosphatidylcholine liposomes

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 275–286

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lipid-peroxyl radical challenge in liposomes · source_derived_draft · unverified_draft

    ### zeaxanthin-gstp1-stability GSTP1 association increased resistance of zeaxanthin diastereomers to chemical degradation. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protein helped preserve the pigments during oxidation. organism: Cell-free system with human GSTP1 tissue_or_cell_type: Egg-yolk phosphatidylcholine liposomes experimental_model: Lipid-peroxyl radical challenge in liposomes limitations: Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination. exposure: AAPH or AMVN challenge; dietary and meso zeaxanthin evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"} [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    Complete structured claim and evidence
  32. GSTP1-bound dietary zeaxanthin synergistically inhibited peroxidation induced by either radical generator.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"}
    experimental_model
    Lipid-peroxyl radical challenge in liposomes
    exposure
    AAPH or AMVN challenge; dietary and meso zeaxanthin
    limitations
    Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Cell-free system with human GSTP1
    plain_language
    Binding enhanced protection of the test membrane.
    primary_references
    [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    tissue_or_cell_type
    Egg-yolk phosphatidylcholine liposomes

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 262–273

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lipid-peroxyl radical challenge in liposomes · source_derived_draft · unverified_draft

    ### zeaxanthin-gstp1-synergy GSTP1-bound dietary zeaxanthin synergistically inhibited peroxidation induced by either radical generator. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding enhanced protection of the test membrane. organism: Cell-free system with human GSTP1 tissue_or_cell_type: Egg-yolk phosphatidylcholine liposomes experimental_model: Lipid-peroxyl radical challenge in liposomes limitations: Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination. exposure: AAPH or AMVN challenge; dietary and meso zeaxanthin evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"} [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    Complete structured claim and evidence
  33. HDL increased zeaxanthin uptake mediated by the tested SRB proteins.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"}
    experimental_model
    SPR and transporter overexpression
    exposure
    SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers
    limitations
    The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human proteins in HEK-293T cells and donor eye tissue
    plain_language
    The carrier and receptor worked together in this model.
    primary_references
    [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
    tissue_or_cell_type
    Recombinant receptors and HEK-293T cells

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 626–637

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SPR and transporter overexpression · source_derived_draft · unverified_draft

    ### zeaxanthin-hdl-delivery HDL increased zeaxanthin uptake mediated by the tested SRB proteins. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier and receptor worked together in this model. organism: Human proteins in HEK-293T cells and donor eye tissue tissue_or_cell_type: Recombinant receptors and HEK-293T cells experimental_model: SPR and transporter overexpression limitations: The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial. exposure: SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers evidence_span: {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"} [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
    Complete structured claim and evidence
  34. EIPA treatment did not significantly inhibit uptake of the tested zeaxanthin micelles.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    This inhibition test did not support a major macropinocytosis contribution.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 782–793

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-macropinocytosis-null EIPA treatment did not significantly inhibit uptake of the tested zeaxanthin micelles. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inhibition test did not support a major macropinocytosis contribution. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  35. GSTP1-bound meso-zeaxanthin was more protective than bound dietary zeaxanthin in this assay.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"}
    experimental_model
    Lipid-peroxyl radical challenge in liposomes
    exposure
    AAPH or AMVN challenge; dietary and meso zeaxanthin
    limitations
    Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Cell-free system with human GSTP1
    plain_language
    The two stereoisomers were not identical in this comparison.
    primary_references
    [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    tissue_or_cell_type
    Egg-yolk phosphatidylcholine liposomes

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 301–312

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lipid-peroxyl radical challenge in liposomes · source_derived_draft · unverified_draft

    ### zeaxanthin-meso-bound-protection GSTP1-bound meso-zeaxanthin was more protective than bound dietary zeaxanthin in this assay. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two stereoisomers were not identical in this comparison. organism: Cell-free system with human GSTP1 tissue_or_cell_type: Egg-yolk phosphatidylcholine liposomes experimental_model: Lipid-peroxyl radical challenge in liposomes limitations: Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination. exposure: AAPH or AMVN challenge; dietary and meso zeaxanthin evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"} [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002
    Complete structured claim and evidence
  36. The diacetate micromicelle formulation raised serum zeaxanthin more than the other active formulations.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/32824736.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5e70eca7c596aeb48b7f1cfccb9af65134926ab26737bc67e3594e4453d09f4", "start_char": 0, "end_char": 1173, "text_sha256": "c5e70eca7c596aeb48b7f1cfccb9af65134926ab26737bc67e3594e4453d09f4"}
    experimental_model
    Randomized double-blind placebo-controlled formulation trial
    exposure
    Six months; free pigments in sunflower/omega-3 oil versus mixed diacetate micromicelles
    limitations
    Combined delivery and ester changes prevent attribution to esterification alone; serum response is not a retinal outcome.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    81 healthy volunteers
    plain_language
    How the pigments were packaged changed their blood response.
    primary_references
    [zeaxanthin-p32824736] The Impact of Formulation on Lutein, Zeaxanthin, and meso-Zeaxanthin Bioavailability: A Randomised Double-Blind Placebo-Controlled Study. (2020). https://pubmed.ncbi.nlm.nih.gov/32824736/ DOI: 10.3390/antiox9080767
    tissue_or_cell_type
    Fasting serum carotenoids

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 834–845

    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 formulation trial · source_derived_draft · unverified_draft

    ### zeaxanthin-micromicelles The diacetate micromicelle formulation raised serum zeaxanthin more than the other active formulations. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: How the pigments were packaged changed their blood response. organism: 81 healthy volunteers tissue_or_cell_type: Fasting serum carotenoids experimental_model: Randomized double-blind placebo-controlled formulation trial limitations: Combined delivery and ester changes prevent attribution to esterification alone; serum response is not a retinal outcome. exposure: Six months; free pigments in sunflower/omega-3 oil versus mixed diacetate micromicelles evidence_span: {"source_cache": "artifacts/zeaxanthin-research/32824736.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5e70eca7c596aeb48b7f1cfccb9af65134926ab26737bc67e3594e4453d09f4", "start_char": 0, "end_char": 1173, "text_sha256": "c5e70eca7c596aeb48b7f1cfccb9af65134926ab26737bc67e3594e4453d09f4"} [zeaxanthin-p32824736] The Impact of Formulation on Lutein, Zeaxanthin, and meso-Zeaxanthin Bioavailability: A Randomised Double-Blind Placebo-Controlled Study. (2020). https://pubmed.ncbi.nlm.nih.gov/32824736/ DOI: 10.3390/antiox9080767
    Complete structured claim and evidence
  37. Ezetimibe-sensitive uptake supported NPC1L1 involvement in free-zeaxanthin uptake.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    The cholesterol-uptake pathway contributed in intestinal cells.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 639–650

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-npc1l1-uptake Ezetimibe-sensitive uptake supported NPC1L1 involvement in free-zeaxanthin uptake. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cholesterol-uptake pathway contributed in intestinal cells. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  38. Nrf2 knockdown suppressed zeaxanthin-induced glutathione accumulation.

    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    Adding pigment could not fully replace the missing regulatory machinery.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 444–455

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-nrf2-failure Nrf2 knockdown suppressed zeaxanthin-induced glutathione accumulation. Condition category: machinery_impairment nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding pigment could not fully replace the missing regulatory machinery. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  39. LY294002 blocked zeaxanthin-associated survival protection; U0126 did not show the same effect.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}
    experimental_model
    Cell challenge with siRNA and pathway inhibitors
    exposure
    Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors
    limitations
    Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human ARPE-19 cell line
    plain_language
    Activating a pathway and needing it for protection are different tests.
    primary_references
    [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    tissue_or_cell_type
    Retinal pigment epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 470–481

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

    ### zeaxanthin-pi3k-block LY294002 blocked zeaxanthin-associated survival protection; U0126 did not show the same effect. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activating a pathway and needing it for protection are different tests. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190
    Complete structured claim and evidence
  40. SCARB2/LIMP-II supported zeaxanthin uptake in the same comparison.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"}
    experimental_model
    SPR and transporter overexpression
    exposure
    SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers
    limitations
    The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human proteins in HEK-293T cells and donor eye tissue
    plain_language
    A separate scavenger receptor also transported the pigment.
    primary_references
    [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
    tissue_or_cell_type
    Recombinant receptors and HEK-293T cells

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 600–611

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SPR and transporter overexpression · source_derived_draft · unverified_draft

    ### zeaxanthin-scarb2-uptake SCARB2/LIMP-II supported zeaxanthin uptake in the same comparison. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate scavenger receptor also transported the pigment. organism: Human proteins in HEK-293T cells and donor eye tissue tissue_or_cell_type: Recombinant receptors and HEK-293T cells experimental_model: SPR and transporter overexpression limitations: The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial. exposure: SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers evidence_span: {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"} [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
    Complete structured claim and evidence
  41. BLT-1-sensitive uptake supported SR-BI involvement in free-zeaxanthin uptake.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"}
    experimental_model
    Micelle uptake, transporter inhibition and protein-expression assays
    exposure
    Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe
    limitations
    Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human Caco-2 monolayers
    plain_language
    The shared carotenoid transporter contributed here too.
    primary_references
    [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    tissue_or_cell_type
    Intestinal epithelial model

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 652–663

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Micelle uptake, transporter inhibition and protein-expression assays · source_derived_draft · unverified_draft

    ### zeaxanthin-srbi-intestinal BLT-1-sensitive uptake supported SR-BI involvement in free-zeaxanthin uptake. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared carotenoid transporter contributed here too. organism: Human Caco-2 monolayers tissue_or_cell_type: Intestinal epithelial model experimental_model: Micelle uptake, transporter inhibition and protein-expression assays limitations: Inhibitors support pathway involvement rather than exclusivity. Protein-expression changes do not prove efflux; a cell model cannot establish clinical drug spacing. exposure: Free and dipalmitate xanthophyll micelles; BLT-1 and ezetimibe evidence_span: {"source_cache": "artifacts/zeaxanthin-research/42123990.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4", "start_char": 0, "end_char": 1803, "text_sha256": "c0b42011e7f16c3fe60d599d489d01e4b3098db9ad04856d26aca10008e995f4"} [zeaxanthin-p42123990] Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model. (2026). https://pubmed.ncbi.nlm.nih.gov/42123990/ DOI: 10.3390/nu18091389
    Complete structured claim and evidence
  42. SR-BI supported zeaxanthin uptake in the transfected-cell experiment.

    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"}
    experimental_model
    SPR and transporter overexpression
    exposure
    SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers
    limitations
    The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial.
    nutrient_topic
    Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin
    organism
    Human proteins in HEK-293T cells and donor eye tissue
    plain_language
    A shared lipid receptor can deliver zeaxanthin.
    primary_references
    [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
    tissue_or_cell_type
    Recombinant receptors and HEK-293T cells

    Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 587–598

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SPR and transporter overexpression · source_derived_draft · unverified_draft

    ### zeaxanthin-srbi-uptake SR-BI supported zeaxanthin uptake in the transfected-cell experiment. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shared lipid receptor can deliver zeaxanthin. organism: Human proteins in HEK-293T cells and donor eye tissue tissue_or_cell_type: Recombinant receptors and HEK-293T cells experimental_model: SPR and transporter overexpression limitations: The study used SCARB2/LIMP-II (methods reagent AF1966), not the similarly named SCARB1 splice variant SR-BII. Reagent identity: https://www.rndsystems.com/products/human-limpii-sr-b2-antibody_af1966 . Transporter overexpression is not an oral absorption trial. exposure: SR-BI, SCARB2/LIMP-II and CD36; HDL or LDL carriers evidence_span: {"source_cache": "artifacts/zeaxanthin-research/28947101.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2", "start_char": 0, "end_char": 1330, "text_sha256": "8899547af674d9bc7acc413d58c440726a1469ca705aa82bc5dafd5c89aadcc2"} [zeaxanthin-p28947101] All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. (2017). https://pubmed.ncbi.nlm.nih.gov/28947101/ DOI: 10.1016/j.abb.2017.09.013
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    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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