Component

Human thiamine transporter 2 / SLC19A3

Human plasma membrane transporter for free thiamine.

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

Read recorded mechanisms Open recursive mind map

How nutrients influence it

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

How nutrients reach it in more than one step

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

Tracing routes…

What it does

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

Recorded relationships

What it acts on

  1. SLC19A3-directed siRNA reduced carrier-mediated Caco-2 thiamine uptake by 48%.

    Human thiamine transporter 2 / SLC19A3 → Intestinal free-thiamine uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence-scope
    Small-intestinal membranes; Caco-2 cells
    evidence_locator
    Single-transporter siRNA experiment
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/said-2004-intestinal-transport-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1710}]
    experimental_model
    Native human enterocyte membranes and polarized Caco-2 cells; imaging, immunoblotting and siRNA.
    exposure
    Experimental siRNA knockdown; not nutritional deficiency.
    limitations
    Overlapping contributions are not additive clinical percentages.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Removing transporter 2 also reduced B1 entry.
    primary_references
    [said-2004-intestinal-transport] Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine (2004). https://pubmed.ncbi.nlm.nih.gov/14615284/ DOI: 10.1152/ajpgi.00361.2003
    tissue_or_cell_type
    Small-intestinal membranes; Caco-2 cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 223–236

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Native human enterocyte membranes and polarized Caco-2 cells; imaging, immunoblotting and siRNA. · source_derived_draft · unverified_draft

    ### b1-slc19a3-caco2-silencing SLC19A3-directed siRNA reduced carrier-mediated Caco-2 thiamine uptake by 48%. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing transporter 2 also reduced B1 entry. organism: Homo sapiens tissue_or_cell_type: Small-intestinal membranes; Caco-2 cells experimental_model: Native human enterocyte membranes and polarized Caco-2 cells; imaging, immunoblotting and siRNA. limitations: Overlapping contributions are not additive clinical percentages. evidence_locator: Single-transporter siRNA experiment exposure: Experimental siRNA knockdown; not nutritional deficiency. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/said-2004-intestinal-transport-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1710}] evidence-scope: Small-intestinal membranes; Caco-2 cells [said-2004-intestinal-transport] Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine (2004). https://pubmed.ncbi.nlm.nih.gov/14615284/ DOI: 10.1152/ajpgi.00361.2003
    Complete structured claim and evidence

  2. SLC19A3 protein was detected in human enterocyte brush-border membranes, with no basolateral signal.

    Human thiamine transporter 2 / SLC19A3 → Intestinal epithelium source_derived_draftungraded
    Experimental context and source evidence
    evidence-scope
    Small-intestinal membranes; Caco-2 cells
    evidence_locator
    Native membrane Western blots; polarized Caco-2 imaging
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/said-2004-intestinal-transport-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1710}]
    experimental_model
    Native human enterocyte membranes and polarized Caco-2 cells; imaging, immunoblotting and siRNA.
    limitations
    Localization alone does not measure net absorption.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    The transporter sits on the intestinal surface facing the lumen.
    primary_references
    [said-2004-intestinal-transport] Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine (2004). https://pubmed.ncbi.nlm.nih.gov/14615284/ DOI: 10.1152/ajpgi.00361.2003
    spatial_context
    Apical brush-border membrane.
    tissue_or_cell_type
    Small-intestinal membranes; Caco-2 cells

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 193–206

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Native human enterocyte membranes and polarized Caco-2 cells; imaging, immunoblotting and siRNA. · source_derived_draft · unverified_draft

    ### b1-slc19a3-enterocyte-apical SLC19A3 protein was detected in human enterocyte brush-border membranes, with no basolateral signal. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter sits on the intestinal surface facing the lumen. organism: Homo sapiens tissue_or_cell_type: Small-intestinal membranes; Caco-2 cells experimental_model: Native human enterocyte membranes and polarized Caco-2 cells; imaging, immunoblotting and siRNA. limitations: Localization alone does not measure net absorption. evidence_locator: Native membrane Western blots; polarized Caco-2 imaging spatial_context: Apical brush-border membrane. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/said-2004-intestinal-transport-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1710}] evidence-scope: Small-intestinal membranes; Caco-2 cells [said-2004-intestinal-transport] Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine (2004). https://pubmed.ncbi.nlm.nih.gov/14615284/ DOI: 10.1152/ajpgi.00361.2003
    Complete structured claim and evidence

  3. SLC19A3 expression did not enhance folic-acid uptake in the assay that detected increased thiamine uptake.

    Human thiamine transporter 2 / SLC19A3 → Cellular folic acid uptake source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    SLC19-family relatedness does not establish folate-thiamine competition at SLC19A3.
    evidence-scope
    HeLa cells
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/rajgopal-2001-slc19a3-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1133}]
    experimental_model
    Transient human SLC19A3 transfection in HeLa cells.
    limitations
    Tested folic acid; does not exclude every folate species.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Related vitamin transporters need not carry the same nutrient.
    primary_references
    [rajgopal-2001-slc19a3] SLC19A3 encodes a second thiamine transporter ThTr2 (2001). https://pubmed.ncbi.nlm.nih.gov/11731220/ DOI: 10.1016/S0925-4439(01)00073-4
    tissue_or_cell_type
    HeLa cells

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 178–191

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient human SLC19A3 transfection in HeLa cells. · source_derived_draft · unverified_draft

    ### b1-slc19a3-folate-specificity SLC19A3 expression did not enhance folic-acid uptake in the assay that detected increased thiamine uptake. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Related vitamin transporters need not carry the same nutrient. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: Transient human SLC19A3 transfection in HeLa cells. limitations: Tested folic acid; does not exclude every folate species. cross_nutrient: SLC19-family relatedness does not establish folate-thiamine competition at SLC19A3. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/rajgopal-2001-slc19a3-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1133}] evidence_locator: Abstract evidence-scope: HeLa cells [rajgopal-2001-slc19a3] SLC19A3 encodes a second thiamine transporter ThTr2 (2001). https://pubmed.ncbi.nlm.nih.gov/11731220/ DOI: 10.1016/S0925-4439(01)00073-4
    Complete structured claim and evidence

  4. SLC19A3-transfected HeLa cells accumulated more radiolabeled thiamine than vector controls.

    Human thiamine transporter 2 / SLC19A3 → Cellular free-thiamine uptake source_derived_draftungraded
    Experimental context and source evidence
    evidence-scope
    HeLa cells
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/rajgopal-2001-slc19a3-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1133}]
    experimental_model
    Transient human SLC19A3 transfection in HeLa cells.
    limitations
    Heterologous expression; contribution varies across tissues.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    A second human membrane transporter imports free B1.
    primary_references
    [rajgopal-2001-slc19a3] SLC19A3 encodes a second thiamine transporter ThTr2 (2001). https://pubmed.ncbi.nlm.nih.gov/11731220/ DOI: 10.1016/S0925-4439(01)00073-4
    tissue_or_cell_type
    HeLa cells
    transport_direction
    Extracellular medium to cell interior.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 163–176

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient human SLC19A3 transfection in HeLa cells. · source_derived_draft · unverified_draft

    ### b1-slc19a3-free-thiamine-uptake SLC19A3-transfected HeLa cells accumulated more radiolabeled thiamine than vector controls. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second human membrane transporter imports free B1. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: Transient human SLC19A3 transfection in HeLa cells. limitations: Heterologous expression; contribution varies across tissues. transport_direction: Extracellular medium to cell interior. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/rajgopal-2001-slc19a3-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1133}] evidence_locator: Abstract evidence-scope: HeLa cells [rajgopal-2001-slc19a3] SLC19A3 encodes a second thiamine transporter ThTr2 (2001). https://pubmed.ncbi.nlm.nih.gov/11731220/ DOI: 10.1016/S0925-4439(01)00073-4
    Complete structured claim and evidence

  5. Wild-type SLC19A3 did not confer detectable biotin uptake, whereas the SLC5A6 positive control did.

    Human thiamine transporter 2 / SLC19A3 → Cellular biotin uptake source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Distinguishes thiamine transport from biotin transport; no shared-substrate mechanism demonstrated.
    evidence-scope
    Caco-2 and MDCK epithelial models
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}]
    experimental_model
    Human transporter constructs in epithelial cell lines; uptake and surface targeting.
    limitations
    Tested cell models; clinical biotin-response mechanism remains unresolved.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Human proteins in human and canine cell lines
    plain_language
    The name biotin-responsive disease does not make SLC19A3 a biotin carrier.
    primary_references
    [subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006
    tissue_or_cell_type
    Caco-2 and MDCK epithelial models

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 294–307

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter constructs in epithelial cell lines; uptake and surface targeting. · source_derived_draft · unverified_draft

    ### b1-slc19a3-not-biotin-transporter Wild-type SLC19A3 did not confer detectable biotin uptake, whereas the SLC5A6 positive control did. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The name biotin-responsive disease does not make SLC19A3 a biotin carrier. organism: Human proteins in human and canine cell lines tissue_or_cell_type: Caco-2 and MDCK epithelial models experimental_model: Human transporter constructs in epithelial cell lines; uptake and surface targeting. limitations: Tested cell models; clinical biotin-response mechanism remains unresolved. cross_nutrient: Distinguishes thiamine transport from biotin transport; no shared-substrate mechanism demonstrated. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}] evidence_locator: Abstract evidence-scope: Caco-2 and MDCK epithelial models [subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006
    Complete structured claim and evidence

  6. Human SLC19A3 expression increased pyridoxine uptake at pH 5.5; transport favored acidic over neutral/basic conditions.

    Human thiamine transporter 2 / SLC19A3 → Cellular pyridoxine uptake source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    A pH-dependent shared transport route links B1 and the pyridoxine form of B6.
    evidence-scope
    Cultured epithelial cells
    evidence_locator
    Figures 1-3, 6 and 9
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/yamashiro-2020-pyridoxine-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1718}]
    experimental_model
    Human transporter constructs in MDCKII/HEK293 cells; radiotracer uptake at pH 5.5.
    extracellular-pH
    5.5
    limitations
    No systemic B6 transport fraction or supplementation benefit established.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Human proteins; canine and human cell hosts
    plain_language
    The B1 carrier can also carry one B6 form under acidic conditions.
    primary_references
    [yamashiro-2020-pyridoxine] pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7863892/ DOI: 10.1074/jbc.RA120.013610
    tissue_or_cell_type
    Cultured epithelial cells

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 631–645

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter constructs in MDCKII/HEK293 cells; radiotracer uptake at pH 5.5. · source_derived_draft · unverified_draft

    ### b1-slc19a3-pyridoxine-transport Human SLC19A3 expression increased pyridoxine uptake at pH 5.5; transport favored acidic over neutral/basic conditions. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B1 carrier can also carry one B6 form under acidic conditions. organism: Human proteins; canine and human cell hosts tissue_or_cell_type: Cultured epithelial cells experimental_model: Human transporter constructs in MDCKII/HEK293 cells; radiotracer uptake at pH 5.5. limitations: No systemic B6 transport fraction or supplementation benefit established. cross_nutrient: A pH-dependent shared transport route links B1 and the pyridoxine form of B6. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/yamashiro-2020-pyridoxine-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1718}] evidence_locator: Figures 1-3, 6 and 9 extracellular-pH: 5.5 evidence-scope: Cultured epithelial cells [yamashiro-2020-pyridoxine] pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7863892/ DOI: 10.1074/jbc.RA120.013610
    Complete structured claim and evidence

  7. Electronic health record analysis suggested that thiamine laboratory values are reduced in individuals receiving prescription drugs that significantly inhibit ThTR-2, particularly in vulnerable populations such as individuals with alcoholism.

    Human thiamine transporter 2 / SLC19A3 → Plasma thiamine concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/31764942.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b", "start_char": 0, "end_char": 1829, "text_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b"}
    experimental_model
    High-throughput screen of 1360 compounds, in-silico modelling and electronic health record analysis
    exposure
    Inhibition kinetics with IC50 values and predicted intestinal concentrations
    limitations
    A screen plus a records analysis, not a trial. The trial termination cited as motivation involved a different, more potent inhibitor.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human transporter and human health records
    plain_language
    In real records, people on these drugs had lower vitamin B1, most of all those already at risk.
    primary_references
    [metformin-p31764942] Drug-nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR-2 (SLC19A3). (2020). https://pubmed.ncbi.nlm.nih.gov/31764942/ DOI: 10.1093/ajcn/nqz255
    tissue_or_cell_type
    Intestinal thiamine absorption
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1334–1345

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-throughput screen of 1360 compounds, in-silico modelling and electronic health record analysis · source_derived_draft · unverified_draft

    ### metformin-thtr2-records-signal Electronic health record analysis suggested that thiamine laboratory values are reduced in individuals receiving prescription drugs that significantly inhibit ThTR-2, particularly in vulnerable populations such as individuals with alcoholism. Condition category: biomarker_context nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: In real records, people on these drugs had lower vitamin B1, most of all those already at risk. organism: Human transporter and human health records tissue_or_cell_type: Intestinal thiamine absorption experimental_model: High-throughput screen of 1360 compounds, in-silico modelling and electronic health record analysis limitations: A screen plus a records analysis, not a trial. The trial termination cited as motivation involved a different, more potent inhibitor. exposure: Inhibition kinetics with IC50 values and predicted intestinal concentrations evidence_span: {"source_cache": "artifacts/metformin-research/31764942.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b", "start_char": 0, "end_char": 1829, "text_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b"} [metformin-p31764942] Drug-nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR-2 (SLC19A3). (2020). https://pubmed.ncbi.nlm.nih.gov/31764942/ DOI: 10.1093/ajcn/nqz255
    Complete structured claim and evidence

  8. Species differences in the substrate specificity of THTR-2 between the human and mouse orthologues were observed.

    Human thiamine transporter 2 / SLC19A3 → Mouse thiamine transporter 2 / Slc19a3 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/metformin-research/26528626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9", "start_char": 0, "end_char": 1436, "text_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9"}
    experimental_model
    Transporter uptake assays in cells expressing human THTR-1 and THTR-2
    exposure
    Metformin against thiamine uptake by SLC19A2 and SLC19A3
    limitations
    In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human transporters, with mouse orthologue comparison
    plain_language
    The mouse version of this carrier does not behave like the human one.
    primary_references
    [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501
    tissue_or_cell_type
    Small-intestinal absorption

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1308–1319

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter uptake assays in cells expressing human THTR-1 and THTR-2 · source_derived_draft · unverified_draft

    ### metformin-thtr2-species-difference Species differences in the substrate specificity of THTR-2 between the human and mouse orthologues were observed. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The mouse version of this carrier does not behave like the human one. organism: Human transporters, with mouse orthologue comparison tissue_or_cell_type: Small-intestinal absorption experimental_model: Transporter uptake assays in cells expressing human THTR-1 and THTR-2 limitations: In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status. exposure: Metformin against thiamine uptake by SLC19A2 and SLC19A3 evidence_span: {"source_cache": "artifacts/metformin-research/26528626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9", "start_char": 0, "end_char": 1436, "text_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9"} [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501
    Complete structured claim and evidence

  9. Human THTR-2 (SLC19A3), highly expressed in the small intestine, transported metformin with a Km of 1.15 mM, whereas THTR-1 did not.

    Human thiamine transporter 2 / SLC19A3 → Metformin source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/metformin-research/26528626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9", "start_char": 0, "end_char": 1436, "text_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9"}
    experimental_model
    Transporter uptake assays in cells expressing human THTR-1 and THTR-2
    exposure
    Metformin against thiamine uptake by SLC19A2 and SLC19A3
    limitations
    In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human transporters, with mouse orthologue comparison
    plain_language
    The vitamin B1 transporter in the gut also carries the drug.
    primary_references
    [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501
    tissue_or_cell_type
    Small-intestinal absorption
    transport_effect
    raises Intestinal THTR-2 transported metformin with a Km of 1.15 mM, which is absorption.
    transport_pool
    the enterocyte interior Intestinal THTR-2 transported metformin with a Km of 1.15 mM, which is absorption.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1282–1293

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter uptake assays in cells expressing human THTR-1 and THTR-2 · source_derived_draft · unverified_draft

    ### metformin-thtr2-transports-metformin Human THTR-2 (SLC19A3), highly expressed in the small intestine, transported metformin with a Km of 1.15 mM, whereas THTR-1 did not. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The vitamin B1 transporter in the gut also carries the drug. organism: Human transporters, with mouse orthologue comparison tissue_or_cell_type: Small-intestinal absorption experimental_model: Transporter uptake assays in cells expressing human THTR-1 and THTR-2 limitations: In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status. exposure: Metformin against thiamine uptake by SLC19A2 and SLC19A3 evidence_span: {"source_cache": "artifacts/metformin-research/26528626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9", "start_char": 0, "end_char": 1436, "text_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9"} [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501
    Complete structured claim and evidence

What acts on it

  1. SLC19A3 mRNA fell 53% and THTR-2 protein 83% under high glucose.

    D-glucose → Human thiamine transporter 2 / SLC19A3 source_derived_draftungraded
    Experimental context and source evidence
    curation_topic
    thiamine · Thiamine (vitamin B1)
    experimental_condition
    5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_contrast
    {"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Transporter abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.
    experimental_model
    Human primary proximal-tubule epithelial cells; 5-day culture
    limitations
    Cell culture; does not by itself establish patient-level thiamine loss.
    primary_references
    Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

    Diabetes cascade: targeted primary-source supplement · lines 21–21

    See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft

    SLC19A3 mRNA fell 53% and THTR-2 protein 83% under high glucose. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Cell culture; does not by itself establish patient-level thiamine loss. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
    Complete structured claim and evidence

  2. Phosphorylated thiamine derivatives stabilized purified human SLC19A3 less strongly than free thiamine in binding assays.

    Thiamine diphosphate → Human thiamine transporter 2 / SLC19A3 source_derived_draftungraded
    Experimental context and source evidence
    evidence-scope
    Purified membrane protein
    evidence_locator
    Results: cryo-EM structures; Supplementary Figure 1a
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/PMC11447181.txt", "start_char": 9508, "end_char": 11196}]
    experimental_model
    Recombinant human SLC19A3 from Expi293F; cryo-EM and thermal-shift binding assays.
    limitations
    Thermal stabilization is not a direct transport-rate measurement.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Adding phosphates changes how B1 fits this cell-surface carrier.
    primary_references
    [gabriel-2024-slc19a3-structure] Structural basis of thiamine transport and drug recognition by SLC19A3 (2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC11447181/ DOI: 10.1038/s41467-024-52872-8
    tissue_or_cell_type
    Purified membrane protein

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 588–600

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SLC19A3 from Expi293F; cryo-EM and thermal-shift binding assays. · source_derived_draft · unverified_draft

    ### b1-slc19a3-phosphorylation-binding-boundary Phosphorylated thiamine derivatives stabilized purified human SLC19A3 less strongly than free thiamine in binding assays. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding phosphates changes how B1 fits this cell-surface carrier. organism: Homo sapiens tissue_or_cell_type: Purified membrane protein experimental_model: Recombinant human SLC19A3 from Expi293F; cryo-EM and thermal-shift binding assays. limitations: Thermal stabilization is not a direct transport-rate measurement. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC11447181.txt", "start_char": 9508, "end_char": 11196}] evidence_locator: Results: cryo-EM structures; Supplementary Figure 1a evidence-scope: Purified membrane protein [gabriel-2024-slc19a3-structure] Structural basis of thiamine transport and drug recognition by SLC19A3 (2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC11447181/ DOI: 10.1038/s41467-024-52872-8
    Complete structured claim and evidence

  3. Goldenseal extract inhibited THTR2-mediated metformin transport in transfected cells.

    Goldenseal extract, composition specified by study → Human thiamine transporter 2 / SLC19A3 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"}
    experimental_model
    Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics
    exposure
    Goldenseal extract and isolated berberine or hydrastine were tested separately
    limitations
    Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured.
    nutrient_topic
    Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
    organism
    Human transporters in HEK293 cells; mice
    plain_language
    The mixture and each transporter remain separate database entries.
    primary_references
    [berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
    tissue_or_cell_type
    Intestinal uptake

    Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 909–920

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics · source_derived_draft · unverified_draft

    ### berberine-goldenseal-slc19a3 Goldenseal extract inhibited THTR2-mediated metformin transport in transfected cells. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mixture and each transporter remain separate database entries. organism: Human transporters in HEK293 cells; mice tissue_or_cell_type: Intestinal uptake experimental_model: Transporter-expressing cells and oral-versus-intravenous mouse pharmacokinetics limitations: Extract potency was normalized to berberine content but does not mean berberine alone caused the effect. Transported probe was metformin, so thiamine depletion was not measured. exposure: Goldenseal extract and isolated berberine or hydrastine were tested separately evidence_span: {"source_cache": "artifacts/berberine-research/37562957.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646", "start_char": 0, "end_char": 2598, "text_sha256": "3d19a5ed2d4ef8f98675f7932f2ea70d6848fc1105362f39681e1c595e204646"} [berberine-p37562957] Goldenseal-Mediated Inhibition of Intestinal Uptake Transporters Decreases Metformin Systemic Exposure in Mice. (2023). https://pubmed.ncbi.nlm.nih.gov/37562957/ DOI: 10.1124/dmd.123.001360
    Complete structured claim and evidence

  4. Of 1360 screened compounds, 146 inhibited ThTR-2, and several oral drugs including metformin were predicted to reach intestinal concentrations that may result in ThTR-2-mediated drug-nutrient interactions.

    Metformin → Human thiamine transporter 2 / SLC19A3 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/31764942.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b", "start_char": 0, "end_char": 1829, "text_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b"}
    experimental_model
    High-throughput screen of 1360 compounds, in-silico modelling and electronic health record analysis
    exposure
    Inhibition kinetics with IC50 values and predicted intestinal concentrations
    limitations
    A screen plus a records analysis, not a trial. The trial termination cited as motivation involved a different, more potent inhibitor.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human transporter and human health records
    plain_language
    Among many drugs tested, this one is expected to reach gut levels high enough to matter.
    primary_references
    [metformin-p31764942] Drug-nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR-2 (SLC19A3). (2020). https://pubmed.ncbi.nlm.nih.gov/31764942/ DOI: 10.1093/ajcn/nqz255
    tissue_or_cell_type
    Intestinal thiamine absorption
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1321–1332

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-throughput screen of 1360 compounds, in-silico modelling and electronic health record analysis · source_derived_draft · unverified_draft

    ### metformin-thtr2-drug-screen Of 1360 screened compounds, 146 inhibited ThTR-2, and several oral drugs including metformin were predicted to reach intestinal concentrations that may result in ThTR-2-mediated drug-nutrient interactions. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Among many drugs tested, this one is expected to reach gut levels high enough to matter. organism: Human transporter and human health records tissue_or_cell_type: Intestinal thiamine absorption experimental_model: High-throughput screen of 1360 compounds, in-silico modelling and electronic health record analysis limitations: A screen plus a records analysis, not a trial. The trial termination cited as motivation involved a different, more potent inhibitor. exposure: Inhibition kinetics with IC50 values and predicted intestinal concentrations evidence_span: {"source_cache": "artifacts/metformin-research/31764942.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b", "start_char": 0, "end_char": 1829, "text_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b"} [metformin-p31764942] Drug-nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR-2 (SLC19A3). (2020). https://pubmed.ncbi.nlm.nih.gov/31764942/ DOI: 10.1093/ajcn/nqz255
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. High glucose reduced apical-to-basolateral thiamine transport across proximal-tubule monolayers by 37%.

    D-glucose → Human proximal-tubule thiamine reabsorption source_derived_draftungraded
    Experimental context and source evidence
    curation_topic
    thiamine · Thiamine (vitamin B1)
    experimental_condition
    5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_contrast
    {"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Directional thiamine transport", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.
    experimental_model
    Human primary proximal-tubule epithelial cells; 5-day culture
    limitations
    Transport assay; transporter-expression changes accompany the effect without proving exclusive mediation.
    primary_references
    Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

    Diabetes cascade: targeted primary-source supplement · lines 24–24

    See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft

    High glucose reduced apical-to-basolateral thiamine transport across proximal-tubule monolayers by 37%. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Transport assay; transporter-expression changes accompany the effect without proving exclusive mediation. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
    Complete structured claim and evidence

  2. After 28 days of experimental biotin depletion, leukocyte SLC19A3 RNA was 33% of baseline in seven adults.

    Biotin → SLC19A3 RNA abundance source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    cross_nutrient
    Human biotin availability was associated with SLC19A3 expression; functional B1 deficiency was not established.
    depleted-nutrient
    Biotin · Biotin
    evidence-scope
    Blood leukocytes
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/vlasova-2005-biotin-slc19a3-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1488}]
    experimental_model
    Seven evaluable adults before and after 28 days of an egg-white biotin-depleting diet.
    limitations
    No transporter protein, thiamine uptake or CNS endpoint measured.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Low biotin changed expression of a B1-transporter gene.
    primary_references
    [vlasova-2005-biotin-slc19a3] Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood (2005). https://pubmed.ncbi.nlm.nih.gov/15623830/ DOI: 10.1093/jn/135.1.42
    tissue_or_cell_type
    Blood leukocytes
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 309–323

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven evaluable adults before and after 28 days of an egg-white biotin-depleting diet. · source_derived_draft · unverified_draft

    ### b1-biotin-depletion-slc19a3-rna After 28 days of experimental biotin depletion, leukocyte SLC19A3 RNA was 33% of baseline in seven adults. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low biotin changed expression of a B1-transporter gene. organism: Homo sapiens tissue_or_cell_type: Blood leukocytes experimental_model: Seven evaluable adults before and after 28 days of an egg-white biotin-depleting diet. limitations: No transporter protein, thiamine uptake or CNS endpoint measured. cross_nutrient: Human biotin availability was associated with SLC19A3 expression; functional B1 deficiency was not established. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/vlasova-2005-biotin-slc19a3-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1488}] evidence_locator: Abstract depleted-nutrient: Biotin evidence-scope: Blood leukocytes [vlasova-2005-biotin-slc19a3] Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood (2005). https://pubmed.ncbi.nlm.nih.gov/15623830/ DOI: 10.1093/jn/135.1.42
    Complete structured claim and evidence

  3. G23V abolished detectable SLC19A3 thiamine transport without preventing cell-surface targeting.

    Human SLC19A3 G23V variant → Cellular free-thiamine uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence-scope
    Caco-2 and MDCK epithelial models
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}]
    experimental_model
    Human transporter constructs in epithelial cell lines; uptake and surface targeting.
    limitations
    Expression assay, not direct brain flux.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Human proteins in human and canine cell lines
    plain_language
    A correctly positioned transporter can still fail to move B1.
    primary_references
    [subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006
    tissue_or_cell_type
    Caco-2 and MDCK epithelial models
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 266–278

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter constructs in epithelial cell lines; uptake and surface targeting. · source_derived_draft · unverified_draft

    ### b1-slc19a3-g23v-transport G23V abolished detectable SLC19A3 thiamine transport without preventing cell-surface targeting. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A correctly positioned transporter can still fail to move B1. organism: Human proteins in human and canine cell lines tissue_or_cell_type: Caco-2 and MDCK epithelial models experimental_model: Human transporter constructs in epithelial cell lines; uptake and surface targeting. limitations: Expression assay, not direct brain flux. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}] evidence_locator: Abstract evidence-scope: Caco-2 and MDCK epithelial models [subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006
    Complete structured claim and evidence

  4. Family mapping identified recessive SLC19A3 variants in the disorder then called biotin-responsive basal ganglia disease.

    SLC19A3 basal ganglia disease genotypes → SLC19A3 basal ganglia disease phenotype source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence-scope
    Clinical genetics
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/zeng-2005-slc19a3-genetics-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1170}]
    experimental_model
    Affected families; linkage mapping and sequence analysis.
    limitations
    Clinical response to biotin does not identify its molecular action.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Inherited B1-transporter defects can cause severe neurological disease.
    primary_references
    [zeng-2005-slc19a3-genetics] Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3 (2005). https://pubmed.ncbi.nlm.nih.gov/15871139/ DOI: 10.1086/431216
    tissue_or_cell_type
    Clinical genetics
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 325–337

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected families; linkage mapping and sequence analysis. · source_derived_draft · unverified_draft

    ### b1-slc19a3-inherited-basal-ganglia Family mapping identified recessive SLC19A3 variants in the disorder then called biotin-responsive basal ganglia disease. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited B1-transporter defects can cause severe neurological disease. organism: Homo sapiens tissue_or_cell_type: Clinical genetics experimental_model: Affected families; linkage mapping and sequence analysis. limitations: Clinical response to biotin does not identify its molecular action. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/zeng-2005-slc19a3-genetics-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1170}] evidence_locator: Abstract evidence-scope: Clinical genetics [zeng-2005-slc19a3-genetics] Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3 (2005). https://pubmed.ncbi.nlm.nih.gov/15871139/ DOI: 10.1086/431216
    Complete structured claim and evidence

  5. T422A abolished detectable SLC19A3 thiamine transport without preventing cell-surface targeting.

    Human SLC19A3 T422A variant → Cellular free-thiamine uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence-scope
    Caco-2 and MDCK epithelial models
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}]
    experimental_model
    Human transporter constructs in epithelial cell lines; uptake and surface targeting.
    limitations
    Expression assay, not direct brain flux.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Human proteins in human and canine cell lines
    plain_language
    This second disease variant disrupts transport function.
    primary_references
    [subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006
    tissue_or_cell_type
    Caco-2 and MDCK epithelial models
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 280–292

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter constructs in epithelial cell lines; uptake and surface targeting. · source_derived_draft · unverified_draft

    ### b1-slc19a3-t422a-transport T422A abolished detectable SLC19A3 thiamine transport without preventing cell-surface targeting. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This second disease variant disrupts transport function. organism: Human proteins in human and canine cell lines tissue_or_cell_type: Caco-2 and MDCK epithelial models experimental_model: Human transporter constructs in epithelial cell lines; uptake and surface targeting. limitations: Expression assay, not direct brain flux. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}] evidence_locator: Abstract evidence-scope: Caco-2 and MDCK epithelial models [subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006
    Complete structured claim and evidence

  6. Thiamine inhibited SLC19A2- and SLC19A3-mediated pyridoxine uptake in acidic-pH transfectant assays.

    Thiamine (vitamin B1) → Cellular pyridoxine uptake source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Direct B1-to-pyridoxine transport inhibition is demonstrated in vitro, with pH and exposure limitations.
    evidence-scope
    Cultured epithelial cells
    evidence_locator
    Figures 1-3, 6 and 9
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/yamashiro-2020-pyridoxine-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1718}]
    experimental_model
    Human transporter constructs in MDCKII/HEK293 cells; radiotracer uptake at pH 5.5.
    extracellular-pH
    5.5
    limitations
    Assay inhibition does not show clinical B6 deficiency from dietary thiamine.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Human proteins; canine and human cell hosts
    plain_language
    B1 reduced uptake of a B6 form in these transporter experiments.
    primary_references
    [yamashiro-2020-pyridoxine] pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7863892/ DOI: 10.1074/jbc.RA120.013610
    tissue_or_cell_type
    Cultured epithelial cells

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 647–661

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter constructs in MDCKII/HEK293 cells; radiotracer uptake at pH 5.5. · source_derived_draft · unverified_draft

    ### b1-thiamine-inhibits-pyridoxine-uptake Thiamine inhibited SLC19A2- and SLC19A3-mediated pyridoxine uptake in acidic-pH transfectant assays. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 reduced uptake of a B6 form in these transporter experiments. organism: Human proteins; canine and human cell hosts tissue_or_cell_type: Cultured epithelial cells experimental_model: Human transporter constructs in MDCKII/HEK293 cells; radiotracer uptake at pH 5.5. limitations: Assay inhibition does not show clinical B6 deficiency from dietary thiamine. cross_nutrient: Direct B1-to-pyridoxine transport inhibition is demonstrated in vitro, with pH and exposure limitations. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/yamashiro-2020-pyridoxine-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1718}] evidence_locator: Figures 1-3, 6 and 9 extracellular-pH: 5.5 evidence-scope: Cultured epithelial cells [yamashiro-2020-pyridoxine] pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7863892/ DOI: 10.1074/jbc.RA120.013610
    Complete structured claim and evidence

  7. Metformin, along with phenformin, chloroquine, verapamil, famotidine and amprolium, inhibited hTHTR-2-mediated uptake of both thiamine and metformin.

    Metformin → Intestinal free-thiamine uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/26528626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9", "start_char": 0, "end_char": 1436, "text_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9"}
    experimental_model
    Transporter uptake assays in cells expressing human THTR-1 and THTR-2
    exposure
    Metformin against thiamine uptake by SLC19A2 and SLC19A3
    limitations
    In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human transporters, with mouse orthologue comparison
    plain_language
    Because they share the carrier, the drug gets in the vitamin’s way.
    primary_references
    [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501
    tissue_or_cell_type
    Small-intestinal absorption
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1295–1306

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter uptake assays in cells expressing human THTR-1 and THTR-2 · source_derived_draft · unverified_draft

    ### metformin-metformin-inhibits-thtr2 Metformin, along with phenformin, chloroquine, verapamil, famotidine and amprolium, inhibited hTHTR-2-mediated uptake of both thiamine and metformin. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Because they share the carrier, the drug gets in the vitamin’s way. organism: Human transporters, with mouse orthologue comparison tissue_or_cell_type: Small-intestinal absorption experimental_model: Transporter uptake assays in cells expressing human THTR-1 and THTR-2 limitations: In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status. exposure: Metformin against thiamine uptake by SLC19A2 and SLC19A3 evidence_span: {"source_cache": "artifacts/metformin-research/26528626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9", "start_char": 0, "end_char": 1436, "text_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9"} [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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

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