Nutrient chapter

Thiamine (vitamin B1)

Unphosphorylated vitamin B1; substrate for TPK1.

135 recorded mechanisms · 44 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Calf intestinal alkaline phosphatase hydrolyzed ThDP and ThMP; ThDP had 53-fold higher Vmax/Km under the tested conditions.
Calf intestinal alkaline phosphatase → Thiamine phosphate ester hydrolysis source_derived_draftungraded
Experimental context and source evidence
evidence-scope
Purified intestinal enzyme
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/vovk-2002-phosphatase-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 828}]
experimental_model
Calf intestinal alkaline phosphatase; pH 8.5, 30 C; substrate kinetics.
limitations
Purified bovine enzyme; does not quantify human meal absorption.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Bos taurus
plain_language
An intestinal enzyme can remove B1 phosphate groups; the two forms react at different rates.
primary_references
[vovk-2002-phosphatase] [Relative reactivity of thiamine monophosphate and thiamine diphosphate upon interaction with alkaline phosphatase] (2002). https://pubmed.ncbi.nlm.nih.gov/12199107/
tissue_or_cell_type
Purified intestinal enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 106–118
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Calf intestinal alkaline phosphatase; pH 8.5, 30 C; substrate kinetics. · source_derived_draft · unverified_draft
### b1-phosphate-ester-hydrolysis Calf intestinal alkaline phosphatase hydrolyzed ThDP and ThMP; ThDP had 53-fold higher Vmax/Km under the tested conditions. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intestinal enzyme can remove B1 phosphate groups; the two forms react at different rates. organism: Bos taurus tissue_or_cell_type: Purified intestinal enzyme experimental_model: Calf intestinal alkaline phosphatase; pH 8.5, 30 C; substrate kinetics. limitations: Purified bovine enzyme; does not quantify human meal absorption. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/vovk-2002-phosphatase-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 828}] evidence_locator: Abstract evidence-scope: Purified intestinal enzyme [vovk-2002-phosphatase] [Relative reactivity of thiamine monophosphate and thiamine diphosphate upon interaction with alkaline phosphatase] (2002). https://pubmed.ncbi.nlm.nih.gov/12199107/
Complete structured claim and evidence
Human SLC19A2 expression increased thiamine uptake in HeLa cells, with apparent Kt 2.5 +/- 0.6 micromolar.
Human thiamine transporter 1 / SLC19A2 → 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/dutta-1999-slc19a2-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1275}]
experimental_model
Human placental cDNA expressed in HeLa cells; radiotracer uptake.
limitations
Expression-system affinity is not a blood sufficiency threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
This membrane protein brings free B1 into cells.
primary_references
[dutta-1999-slc19a2] Cloning of the human thiamine transporter, a member of the folate transporter family (1999). https://pubmed.ncbi.nlm.nih.gov/10542220/ DOI: 10.1074/jbc.274.45.31925
tissue_or_cell_type
HeLa cells
transport_direction
Extracellular medium to cell interior.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 120–133
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human placental cDNA expressed in HeLa cells; radiotracer uptake. · source_derived_draft · unverified_draft
### b1-slc19a2-free-thiamine-uptake Human SLC19A2 expression increased thiamine uptake in HeLa cells, with apparent Kt 2.5 +/- 0.6 micromolar. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This membrane protein brings free B1 into cells. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: Human placental cDNA expressed in HeLa cells; radiotracer uptake. limitations: Expression-system affinity is not a blood sufficiency threshold. transport_direction: Extracellular medium to cell interior. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/dutta-1999-slc19a2-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1275}] evidence_locator: Abstract evidence-scope: HeLa cells [dutta-1999-slc19a2] Cloning of the human thiamine transporter, a member of the folate transporter family (1999). https://pubmed.ncbi.nlm.nih.gov/10542220/ DOI: 10.1074/jbc.274.45.31925
Complete structured claim and evidence
SLC19A2-mediated uptake did not require extracellular sodium and increased with an outward proton gradient.
Human thiamine transporter 1 / SLC19A2 → 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/dutta-1999-slc19a2-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1275}]
experimental_model
Human placental cDNA expressed in HeLa cells; radiotracer uptake.
limitations
Does not establish an exact proton stoichiometry.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 entry in this assay depended on proton conditions without sodium cotransport.
primary_references
[dutta-1999-slc19a2] Cloning of the human thiamine transporter, a member of the folate transporter family (1999). https://pubmed.ncbi.nlm.nih.gov/10542220/ DOI: 10.1074/jbc.274.45.31925
tissue_or_cell_type
HeLa cells
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 135–147
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human placental cDNA expressed in HeLa cells; radiotracer uptake. · source_derived_draft · unverified_draft
### b1-slc19a2-sodium-independence SLC19A2-mediated uptake did not require extracellular sodium and increased with an outward proton gradient. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 entry in this assay depended on proton conditions without sodium cotransport. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: Human placental cDNA expressed in HeLa cells; radiotracer uptake. limitations: Does not establish an exact proton stoichiometry. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/dutta-1999-slc19a2-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1275}] evidence_locator: Abstract evidence-scope: HeLa cells [dutta-1999-slc19a2] Cloning of the human thiamine transporter, a member of the folate transporter family (1999). https://pubmed.ncbi.nlm.nih.gov/10542220/ DOI: 10.1074/jbc.274.45.31925
Complete structured claim and evidence
Two exon-2 frameshifting SLC19A2 variants were identified among four Iranian TRMA families.
SLC19A2 frameshift genotypes in TRMA families → Thiamine-responsive megaloblastic anemia syndrome 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/diaz-1999-trma-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1218}]
experimental_model
Four Iranian TRMA families; linkage and SLC19A2 sequencing.
limitations
Family genetics; individual tissue mechanisms were not directly tested.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Inherited disruption of B1 transport accompanies anemia, diabetes and deafness.
primary_references
[diaz-1999-trma] Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome (1999). https://www.nature.com/articles/ng0799_309 DOI: 10.1038/10385
tissue_or_cell_type
Clinical genetics
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 149–161
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four Iranian TRMA families; linkage and SLC19A2 sequencing. · source_derived_draft · unverified_draft
### b1-slc19a2-frameshift-trma Two exon-2 frameshifting SLC19A2 variants were identified among four Iranian TRMA families. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited disruption of B1 transport accompanies anemia, diabetes and deafness. organism: Homo sapiens tissue_or_cell_type: Clinical genetics experimental_model: Four Iranian TRMA families; linkage and SLC19A2 sequencing. limitations: Family genetics; individual tissue mechanisms were not directly tested. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/diaz-1999-trma-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1218}] evidence_locator: Abstract evidence-scope: Clinical genetics [diaz-1999-trma] Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome (1999). https://www.nature.com/articles/ng0799_309 DOI: 10.1038/10385
Complete structured claim and evidence
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
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
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
SLC19A2-directed siRNA reduced carrier-mediated Caco-2 thiamine uptake by 56%.
Human thiamine transporter 1 / SLC19A2 → 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
Knockdown fraction is assay-specific.
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 1 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 208–221
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-slc19a2-caco2-silencing SLC19A2-directed siRNA reduced carrier-mediated Caco-2 thiamine uptake by 56%. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing transporter 1 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: Knockdown fraction is assay-specific. 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
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
Slc19a3-null mice had lower thiamine uptake in isolated intestinal cells and intact loops.
Mouse Slc19a3-null genotype → Intestinal free-thiamine uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Intestine
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/reidling-2010-slc19a3-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1719}]
experimental_model
Slc19a3-null or Slc19a2-null mice versus littermates; cells, intestinal loops and expression assays.
limitations
Cannot assign the same quantitative effect to humans.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
Loss of transporter 2 reduced intestinal B1 entry in mice.
primary_references
[reidling-2010-slc19a3-knockout] Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice (2010). https://pubmed.ncbi.nlm.nih.gov/19879271/ DOI: 10.1053/j.gastro.2009.10.042
tissue_or_cell_type
Intestine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 238–250
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc19a3-null or Slc19a2-null mice versus littermates; cells, intestinal loops and expression assays. · source_derived_draft · unverified_draft
### b1-mouse-slc19a3-absorption-loss Slc19a3-null mice had lower thiamine uptake in isolated intestinal cells and intact loops. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of transporter 2 reduced intestinal B1 entry in mice. organism: Mus musculus tissue_or_cell_type: Intestine experimental_model: Slc19a3-null or Slc19a2-null mice versus littermates; cells, intestinal loops and expression assays. limitations: Cannot assign the same quantitative effect to humans. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/reidling-2010-slc19a3-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1719}] evidence_locator: Abstract evidence-scope: Intestine [reidling-2010-slc19a3-knockout] Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice (2010). https://pubmed.ncbi.nlm.nih.gov/19879271/ DOI: 10.1053/j.gastro.2009.10.042
Complete structured claim and evidence
Slc19a2-null mouse intestine increased Slc19a3 expression while thiamine uptake remained comparable to controls.
Mouse Slc19a2-null genotype → Mouse thiamine transporter 2 / Slc19a3 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Intestine
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/reidling-2010-slc19a3-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1719}]
experimental_model
Slc19a3-null or Slc19a2-null mice versus littermates; cells, intestinal loops and expression assays.
limitations
Association supports compensation; not a universal redundancy rule.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
The second transporter can compensate in this mouse tissue.
primary_references
[reidling-2010-slc19a3-knockout] Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice (2010). https://pubmed.ncbi.nlm.nih.gov/19879271/ DOI: 10.1053/j.gastro.2009.10.042
tissue_or_cell_type
Intestine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 252–264
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc19a3-null or Slc19a2-null mice versus littermates; cells, intestinal loops and expression assays. · source_derived_draft · unverified_draft
### b1-mouse-slc19a2-compensation Slc19a2-null mouse intestine increased Slc19a3 expression while thiamine uptake remained comparable to controls. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second transporter can compensate in this mouse tissue. organism: Mus musculus tissue_or_cell_type: Intestine experimental_model: Slc19a3-null or Slc19a2-null mice versus littermates; cells, intestinal loops and expression assays. limitations: Association supports compensation; not a universal redundancy rule. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/reidling-2010-slc19a3-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1719}] evidence_locator: Abstract evidence-scope: Intestine [reidling-2010-slc19a3-knockout] Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice (2010). https://pubmed.ncbi.nlm.nih.gov/19879271/ DOI: 10.1053/j.gastro.2009.10.042
Complete structured claim and evidence
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
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
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
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
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
TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction.
ATP → Thiamine (vitamin B1) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP.
curation_note
Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection.
evidence-scope
Recombinant enzyme
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}]
experimental_model
Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis.
limitations
Overall chemistry does not resolve substrate-binding order.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step.
primary_references
[onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
reaction
thiamine + ATP -> thiamine diphosphate + AMP
related_existing_claim_keys
["mg-tpk1-thiamine-to-thdp"]
tissue_or_cell_type
Recombinant enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 339–356
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. · source_derived_draft · unverified_draft
### b1-tpk1-atp-amp-stoichiometry TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. limitations: Overall chemistry does not resolve substrate-binding order. cross_nutrient: Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP. reaction: thiamine + ATP -> thiamine diphosphate + AMP related_existing_claim_keys: ["mg-tpk1-thiamine-to-thdp"] curation_note: Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}] evidence_locator: Abstract evidence-scope: Recombinant enzyme [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
D71N markedly decreased recombinant human TPK1 catalytic turnover.
Human TPK1 D71N experimental variant → Human thiamine pyrophosphokinase 1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Recombinant enzyme
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/onozuka-2003-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1438}]
experimental_model
Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis.
limitations
Engineered mutation; not an isolated clinical magnesium effect.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Disrupting an active-site residue impairs B1 activation.
primary_references
[onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
tissue_or_cell_type
Recombinant enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 358–371
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. · source_derived_draft · unverified_draft
### b1-tpk1-d71n-catalysis D71N markedly decreased recombinant human TPK1 catalytic turnover. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disrupting an active-site residue impairs B1 activation. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. limitations: Engineered mutation; not an isolated clinical magnesium effect. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/onozuka-2003-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1438}] evidence_locator: Abstract evidence-scope: Recombinant enzyme [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
Purified mouse TPK1 formed ATP and thiamine from ThDP plus AMP under high-AMP, magnesium-containing conditions.
Mouse thiamine pyrophosphokinase 1 → ATP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg dependence remains distinct from physiological net reaction direction.
evidence-scope
Recombinant enzyme
evidence_locator
Reaction definition and sections 2.2 and 3.3
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}]
experimental_model
Purified recombinant mouse TPK1; forward and reverse reactions.
limitations
High AMP/Mg requirements do not establish meaningful reverse flux in humans.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
The activation chemistry can run backward experimentally.
primary_references
[sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
tissue_or_cell_type
Recombinant enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 373–386
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant mouse TPK1; forward and reverse reactions. · source_derived_draft · unverified_draft
### b1-mouse-tpk1-reverse-reaction Purified mouse TPK1 formed ATP and thiamine from ThDP plus AMP under high-AMP, magnesium-containing conditions. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The activation chemistry can run backward experimentally. organism: Mus musculus tissue_or_cell_type: Recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reactions. limitations: High AMP/Mg requirements do not establish meaningful reverse flux in humans. cross_nutrient: Mg dependence remains distinct from physiological net reaction direction. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}] evidence_locator: Reaction definition and sections 2.2 and 3.3 evidence-scope: Recombinant enzyme [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
TPK1-deficient patients had reduced ThDP in sampled muscle and blood; blood remained low during thiamine supplementation.
Biallelic TPK1 deficiency genotypes → Cellular thiamine diphosphate content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Muscle and blood
evidence_locator
Table 2
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 13816, "end_char": 16551}]
experimental_model
Five patients from three families; muscle/blood chemistry and enzyme assays.
limitations
Small heterogeneous series; no universal blood or tissue cutoff.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Extra B1 intake does not guarantee normal cofactor production when activation machinery is impaired.
primary_references
[mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
tissue_or_cell_type
Muscle and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 388–400
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five patients from three families; muscle/blood chemistry and enzyme assays. · source_derived_draft · unverified_draft
### b1-tpk1-deficiency-thdp TPK1-deficient patients had reduced ThDP in sampled muscle and blood; blood remained low during thiamine supplementation. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra B1 intake does not guarantee normal cofactor production when activation machinery is impaired. organism: Homo sapiens tissue_or_cell_type: Muscle and blood experimental_model: Five patients from three families; muscle/blood chemistry and enzyme assays. limitations: Small heterogeneous series; no universal blood or tissue cutoff. evidence_locator: Table 2 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 13816, "end_char": 16551}] evidence-scope: Muscle and blood [mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
Complete structured claim and evidence
Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions.
Thiamine diphosphate → Pyruvate dehydrogenase complex activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Muscle and blood
evidence_locator
Figure 3; Table 1
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 12774, "end_char": 13380}]
experimental_model
Five patients from three families; muscle/blood chemistry and enzyme assays.
limitations
Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Supplying cofactor directly to the assay exposed an activation problem upstream of PDH.
primary_references
[mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
tissue_or_cell_type
Muscle and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 402–414
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five patients from three families; muscle/blood chemistry and enzyme assays. · source_derived_draft · unverified_draft
### b1-tpk1-deficiency-pdh-assay-rescue Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying cofactor directly to the assay exposed an activation problem upstream of PDH. organism: Homo sapiens tissue_or_cell_type: Muscle and blood experimental_model: Five patients from three families; muscle/blood chemistry and enzyme assays. limitations: Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy. evidence_locator: Figure 3; Table 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 12774, "end_char": 13380}] evidence-scope: Muscle and blood [mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
Complete structured claim and evidence
Human SLC25A19 proteoliposomes exchanged labeled dATP with internal ThDP or ThMP, but not free thiamine.
Human mitochondrial thiamine diphosphate transporter / SLC25A19 → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
evidence-scope
Proteoliposomes; lymphoblasts; embryonic fibroblasts
evidence_locator
Figure 6
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 12861, "end_char": 14293}]
experimental_model
Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.
limitations
Indirect exchange assay; physiological counter-substrate stoichiometry not fixed.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Human and mouse experimental systems
plain_language
The mitochondrial carrier recognizes phosphorylated B1 differently from cell-surface thiamine carriers.
primary_references
[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103
tissue_or_cell_type
Proteoliposomes; lymphoblasts; embryonic fibroblasts
transport_direction
Reconstituted membrane exchange; physiological role is mitochondrial delivery.
transport_effect
depends The reconstituted assay exchanged external dATP for internal ThDP, which is the opposite of the delivery role the record attributes to it.
transport_pool
the mitochondrial matrix The reconstituted assay exchanged external dATP for internal ThDP, which is the opposite of the delivery role the record attributes to it.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 416–429
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. · source_derived_draft · unverified_draft
### b1-slc25a19-phosphorylated-substrates Human SLC25A19 proteoliposomes exchanged labeled dATP with internal ThDP or ThMP, but not free thiamine. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial carrier recognizes phosphorylated B1 differently from cell-surface thiamine carriers. organism: Human and mouse experimental systems tissue_or_cell_type: Proteoliposomes; lymphoblasts; embryonic fibroblasts experimental_model: Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. limitations: Indirect exchange assay; physiological counter-substrate stoichiometry not fixed. evidence_locator: Figure 6 transport_direction: Reconstituted membrane exchange; physiological role is mitochondrial delivery. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 12861, "end_char": 14293}] evidence-scope: Proteoliposomes; lymphoblasts; embryonic fibroblasts [lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103
Complete structured claim and evidence
G177A patient lymphoblasts had approximately tenfold lower mitochondrial ThDP despite modestly increased cytosolic ThDP.
SLC25A19 G177A homozygous genotype → Mitochondrial thiamine diphosphate content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Patient lymphoblasts
evidence_locator
Table 1
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}]
experimental_model
Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.
limitations
Cultured lymphoblast fractions; not a plasma threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 cofactor can remain outside mitochondria when its carrier fails.
primary_references
[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103
tissue_or_cell_type
Patient lymphoblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 431–443
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. · source_derived_draft · unverified_draft
### b1-slc25a19-human-pool-separation G177A patient lymphoblasts had approximately tenfold lower mitochondrial ThDP despite modestly increased cytosolic ThDP. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 cofactor can remain outside mitochondria when its carrier fails. organism: Homo sapiens tissue_or_cell_type: Patient lymphoblasts experimental_model: Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. limitations: Cultured lymphoblast fractions; not a plasma threshold. evidence_locator: Table 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}] evidence-scope: Patient lymphoblasts [lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103
Complete structured claim and evidence
ThDP was undetectable in knockout fibroblast mitochondrial fractions while cytosolic ThDP increased.
Mouse Slc25a19-null genotype → Mitochondrial thiamine diphosphate content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Embryonic fibroblasts
evidence_locator
Table 1
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}]
experimental_model
Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.
limitations
Undetectable means below this assay detection, not proven absolute zero.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
Deleting the carrier separates cellular B1 supply from mitochondrial availability.
primary_references
[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103
tissue_or_cell_type
Embryonic fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 445–457
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. · source_derived_draft · unverified_draft
### b1-slc25a19-mouse-mito-depletion ThDP was undetectable in knockout fibroblast mitochondrial fractions while cytosolic ThDP increased. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deleting the carrier separates cellular B1 supply from mitochondrial availability. organism: Mus musculus tissue_or_cell_type: Embryonic fibroblasts experimental_model: Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. limitations: Undetectable means below this assay detection, not proven absolute zero. evidence_locator: Table 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}] evidence-scope: Embryonic fibroblasts [lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103
Complete structured claim and evidence
G125S expression reduced mitochondrial radiolabeled-ThDP uptake and transporter protein abundance relative to wild type.
Human SLC25A19 G125S variant → Mitochondrial thiamine diphosphate uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
HepG2 mitochondria
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/subramanian-2013-mitochondrial-uptake-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1750}]
experimental_model
Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells.
limitations
Lower abundance prevents assigning the entire effect to transport kinetics.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
This inherited carrier variant limits mitochondrial cofactor uptake.
primary_references
[subramanian-2013-mitochondrial-uptake] Mitochondrial Uptake of Thiamin Pyrophosphate: Physiological and Cell Biological Aspects (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3758298/ DOI: 10.1371/journal.pone.0073503
tissue_or_cell_type
HepG2 mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 459–471
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells. · source_derived_draft · unverified_draft
### b1-slc25a19-g125s-uptake G125S expression reduced mitochondrial radiolabeled-ThDP uptake and transporter protein abundance relative to wild type. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inherited carrier variant limits mitochondrial cofactor uptake. organism: Homo sapiens tissue_or_cell_type: HepG2 mitochondria experimental_model: Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells. limitations: Lower abundance prevents assigning the entire effect to transport kinetics. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2013-mitochondrial-uptake-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1750}] evidence_locator: Abstract evidence-scope: HepG2 mitochondria [subramanian-2013-mitochondrial-uptake] Mitochondrial Uptake of Thiamin Pyrophosphate: Physiological and Cell Biological Aspects (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3758298/ DOI: 10.1371/journal.pone.0073503
Complete structured claim and evidence
G125S carrier constructs retained mitochondrial targeting despite impaired uptake.
Human SLC25A19 G125S variant → Mitochondria source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
HepG2 cells
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/subramanian-2013-mitochondrial-uptake-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1750}]
experimental_model
Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells.
limitations
Imaging identifies organellar targeting; carrier is in the inner membrane, not soluble matrix.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Reaching the correct organelle does not guarantee carrier function.
primary_references
[subramanian-2013-mitochondrial-uptake] Mitochondrial Uptake of Thiamin Pyrophosphate: Physiological and Cell Biological Aspects (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3758298/ DOI: 10.1371/journal.pone.0073503
spatial_context
Mitochondrial localization of membrane carrier.
tissue_or_cell_type
HepG2 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 473–486
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells. · source_derived_draft · unverified_draft
### b1-slc25a19-g125s-targeting G125S carrier constructs retained mitochondrial targeting despite impaired uptake. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reaching the correct organelle does not guarantee carrier function. organism: Homo sapiens tissue_or_cell_type: HepG2 cells experimental_model: Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells. limitations: Imaging identifies organellar targeting; carrier is in the inner membrane, not soluble matrix. spatial_context: Mitochondrial localization of membrane carrier. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2013-mitochondrial-uptake-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1750}] evidence_locator: Abstract evidence-scope: HepG2 cells [subramanian-2013-mitochondrial-uptake] Mitochondrial Uptake of Thiamin Pyrophosphate: Physiological and Cell Biological Aspects (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3758298/ DOI: 10.1371/journal.pone.0073503
Complete structured claim and evidence
Four SLC25A19-affected patients had episodic paralysis/encephalopathy and progressive polyneuropathy with bilateral striatal necrosis.
SLC25A19 neuropathy family genotype → SLC25A19 neuropathy and striatal injury phenotype source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Neurological phenotype
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/spiegel-2009-slc25a19-neuropathy-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 774}]
experimental_model
Four patients aged 7-20; homozygosity mapping and clinical characterization.
limitations
Normal head circumference and urinary organic acids in this family do not describe every variant.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Mitochondrial B1 transport disease can present after normal early development.
primary_references
[spiegel-2009-slc25a19-neuropathy] SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis (2009). https://pubmed.ncbi.nlm.nih.gov/19798730/ DOI: 10.1002/ana.21752
tissue_or_cell_type
Neurological phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 488–500
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four patients aged 7-20; homozygosity mapping and clinical characterization. · source_derived_draft · unverified_draft
### b1-slc25a19-neuropathy-genetics Four SLC25A19-affected patients had episodic paralysis/encephalopathy and progressive polyneuropathy with bilateral striatal necrosis. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial B1 transport disease can present after normal early development. organism: Homo sapiens tissue_or_cell_type: Neurological phenotype experimental_model: Four patients aged 7-20; homozygosity mapping and clinical characterization. limitations: Normal head circumference and urinary organic acids in this family do not describe every variant. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/spiegel-2009-slc25a19-neuropathy-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 774}] evidence_locator: Abstract evidence-scope: Neurological phenotype [spiegel-2009-slc25a19-neuropathy] SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis (2009). https://pubmed.ncbi.nlm.nih.gov/19798730/ DOI: 10.1002/ana.21752
Complete structured claim and evidence
NCM460 colonocytes took up radiolabeled ThDP without prior substrate dephosphorylation; native human apical vesicles also showed carrier-mediated uptake.
Thiamine diphosphate → Colonic thiamine diphosphate uptake source_derived_draftungraded
Experimental context and source evidence
evidence-scope
Colonocytes; colonic apical membranes
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/nabokina-2012-colonic-tpp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1813}]
experimental_model
NCM460 cells and human donor colonic apical vesicles; custom tritiated ThDP.
limitations
Does not quantify systemic contribution from gut microbial B1.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Colon cells can absorb the phosphorylated B1 form directly.
primary_references
[nabokina-2012-colonic-tpp] A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3423106/ DOI: 10.1152/ajpgi.00151.2012
tissue_or_cell_type
Colonocytes; colonic apical membranes
transport_direction
Luminal/apical compartment into colonocytes.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 502–515
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NCM460 cells and human donor colonic apical vesicles; custom tritiated ThDP. · source_derived_draft · unverified_draft
### b1-colon-intact-thdp-uptake NCM460 colonocytes took up radiolabeled ThDP without prior substrate dephosphorylation; native human apical vesicles also showed carrier-mediated uptake. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Colon cells can absorb the phosphorylated B1 form directly. organism: Homo sapiens tissue_or_cell_type: Colonocytes; colonic apical membranes experimental_model: NCM460 cells and human donor colonic apical vesicles; custom tritiated ThDP. limitations: Does not quantify systemic contribution from gut microbial B1. transport_direction: Luminal/apical compartment into colonocytes. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/nabokina-2012-colonic-tpp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1813}] evidence_locator: Abstract evidence-scope: Colonocytes; colonic apical membranes [nabokina-2012-colonic-tpp] A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3423106/ DOI: 10.1152/ajpgi.00151.2012
Complete structured claim and evidence
Human SLC44A4 isoform 1 expression increased ThDP uptake in ARPE19 cells.
Human SLC44A4 isoform 1 → Colonic thiamine diphosphate uptake source_derived_draftungraded
Experimental context and source evidence
evidence-scope
ARPE19; MDCK; human colon
evidence_locator
Figure 1
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 19781, "end_char": 21596}]
experimental_model
Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging.
limitations
Heterologous uptake; host dietary contribution unmeasured.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Human constructs; human and canine host cells
plain_language
This SLC44A4 form can carry phosphorylated B1.
primary_references
[nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257
tissue_or_cell_type
ARPE19; MDCK; human colon
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 517–529
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. · source_derived_draft · unverified_draft
### b1-slc44a4-iso1-uptake Human SLC44A4 isoform 1 expression increased ThDP uptake in ARPE19 cells. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This SLC44A4 form can carry phosphorylated B1. organism: Human constructs; human and canine host cells tissue_or_cell_type: ARPE19; MDCK; human colon experimental_model: Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. limitations: Heterologous uptake; host dietary contribution unmeasured. evidence_locator: Figure 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 19781, "end_char": 21596}] evidence-scope: ARPE19; MDCK; human colon [nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257
Complete structured claim and evidence
Expressed SLC44A4 isoform 3 also supported ThDP uptake.
Human SLC44A4 isoform 3 → Colonic thiamine diphosphate uptake source_derived_draftungraded
Experimental context and source evidence
evidence-scope
ARPE19; MDCK; human colon
evidence_locator
Figure 10
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 39610, "end_char": 40292}]
experimental_model
Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging.
limitations
Not evidence for untested isoform 2.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Human constructs; human and canine host cells
plain_language
A second splice form retained transport activity.
primary_references
[nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257
tissue_or_cell_type
ARPE19; MDCK; human colon
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 531–543
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. · source_derived_draft · unverified_draft
### b1-slc44a4-iso3-uptake Expressed SLC44A4 isoform 3 also supported ThDP uptake. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second splice form retained transport activity. organism: Human constructs; human and canine host cells tissue_or_cell_type: ARPE19; MDCK; human colon experimental_model: Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. limitations: Not evidence for untested isoform 2. evidence_locator: Figure 10 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 39610, "end_char": 40292}] evidence-scope: ARPE19; MDCK; human colon [nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257
Complete structured claim and evidence
SLC44A4 isoform-1 fusion protein predominantly localized to the apical domain of polarized MDCK cells.
Human SLC44A4 isoform 1 → Intestinal epithelium source_derived_draftungraded
Experimental context and source evidence
evidence-scope
ARPE19; MDCK; human colon
evidence_locator
Figure 8
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 47362, "end_char": 48692}]
experimental_model
Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging.
limitations
Canine model expressing human protein; not direct transepithelial flux.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Human constructs; human and canine host cells
plain_language
Its membrane targeting fits entry from the gut lumen.
primary_references
[nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257
spatial_context
Apical membrane of polarized epithelial model.
tissue_or_cell_type
ARPE19; MDCK; human colon
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 545–558
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. · source_derived_draft · unverified_draft
### b1-slc44a4-apical-targeting SLC44A4 isoform-1 fusion protein predominantly localized to the apical domain of polarized MDCK cells. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Its membrane targeting fits entry from the gut lumen. organism: Human constructs; human and canine host cells tissue_or_cell_type: ARPE19; MDCK; human colon experimental_model: Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. limitations: Canine model expressing human protein; not direct transepithelial flux. evidence_locator: Figure 8 spatial_context: Apical membrane of polarized epithelial model. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 47362, "end_char": 48692}] evidence-scope: ARPE19; MDCK; human colon [nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257
Complete structured claim and evidence
Slc44a4 knockout nearly eliminated carrier-mediated colonic radiolabeled-ThDP uptake in mice.
Mouse Slc44a4-null genotype → Colonic thiamine diphosphate uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Colon
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/sabui-2024-slc44a4-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 2031}]
experimental_model
Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge.
limitations
Does not quantify human systemic B1 supply.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
The carrier accounts for most measured colonic uptake in this model.
primary_references
[sabui-2024-slc44a4-knockout] Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology (2024). https://pubmed.ncbi.nlm.nih.gov/38713615/ DOI: 10.1152/ajpgi.00065.2024
tissue_or_cell_type
Colon
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 560–572
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge. · source_derived_draft · unverified_draft
### b1-slc44a4-mouse-uptake-loss Slc44a4 knockout nearly eliminated carrier-mediated colonic radiolabeled-ThDP uptake in mice. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier accounts for most measured colonic uptake in this model. organism: Mus musculus tissue_or_cell_type: Colon experimental_model: Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge. limitations: Does not quantify human systemic B1 supply. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sabui-2024-slc44a4-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 2031}] evidence_locator: Abstract evidence-scope: Colon [sabui-2024-slc44a4-knockout] Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology (2024). https://pubmed.ncbi.nlm.nih.gov/38713615/ DOI: 10.1152/ajpgi.00065.2024
Complete structured claim and evidence
Slc44a4-null mice were more susceptible to experimental DSS colitis than wild-type littermates.
Mouse Slc44a4-null genotype → Experimental DSS colitis severity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Colon
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/sabui-2024-slc44a4-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 2031}]
experimental_model
Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge.
limitations
No isolated proof that ThDP depletion mediates the entire inflammatory effect.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
Losing the colonic carrier worsened the response to an inflammatory challenge.
primary_references
[sabui-2024-slc44a4-knockout] Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology (2024). https://pubmed.ncbi.nlm.nih.gov/38713615/ DOI: 10.1152/ajpgi.00065.2024
tissue_or_cell_type
Colon
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 574–586
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge. · source_derived_draft · unverified_draft
### b1-slc44a4-mouse-dss-susceptibility Slc44a4-null mice were more susceptible to experimental DSS colitis than wild-type littermates. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing the colonic carrier worsened the response to an inflammatory challenge. organism: Mus musculus tissue_or_cell_type: Colon experimental_model: Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge. limitations: No isolated proof that ThDP depletion mediates the entire inflammatory effect. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sabui-2024-slc44a4-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 2031}] evidence_locator: Abstract evidence-scope: Colon [sabui-2024-slc44a4-knockout] Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology (2024). https://pubmed.ncbi.nlm.nih.gov/38713615/ DOI: 10.1152/ajpgi.00065.2024
Complete structured claim and evidence
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
Rat brain mitochondria formed ThTP from ThDP and inorganic phosphate with respiratory substrates; ATP hydrolysis did not energize synthesis.
Thiamine diphosphate → Thiamine triphosphate source_derived_draftungraded
Experimental context and source evidence
evidence-scope
Brain mitochondria
evidence_locator
Results: ThTP synthesis in isolated mitochondria and energy coupling
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}]
experimental_model
Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors.
limitations
Not a demonstrated human signaling function or a TPK1 reaction.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
A third phosphate can be added to B1 using respiratory energy in this preparation.
primary_references
[gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379
reaction
ThDP + Pi <-> ThTP + water; coupled to respiratory energy
tissue_or_cell_type
Brain mitochondria
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 602–615
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. · source_derived_draft · unverified_draft
### b1-brain-thtp-from-thdp-and-pi Rat brain mitochondria formed ThTP from ThDP and inorganic phosphate with respiratory substrates; ATP hydrolysis did not energize synthesis. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A third phosphate can be added to B1 using respiratory energy in this preparation. organism: Rattus norvegicus tissue_or_cell_type: Brain mitochondria experimental_model: Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. limitations: Not a demonstrated human signaling function or a TPK1 reaction. reaction: ThDP + Pi <-> ThTP + water; coupled to respiratory energy evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}] evidence_locator: Results: ThTP synthesis in isolated mitochondria and energy coupling evidence-scope: Brain mitochondria [gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379
Complete structured claim and evidence
Depolarization or mitochondrial disruption inhibited ThTP synthesis in rat brain mitochondrial preparations.
Inner mitochondrial membrane potential → Thiamine triphosphate synthesis source_derived_draftungraded
Experimental context and source evidence
evidence-scope
Brain mitochondria
evidence_locator
Results: ThTP synthesis in isolated mitochondria and energy coupling
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}]
experimental_model
Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors.
limitations
Proton-motive-force dependence is supported; the proposed ATP-synthase identity was not definitively established.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Intact, energized mitochondria were required for this B1-phosphate reaction.
primary_references
[gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379
tissue_or_cell_type
Brain mitochondria
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 617–629
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. · source_derived_draft · unverified_draft
### b1-brain-thtp-proton-motive-dependence Depolarization or mitochondrial disruption inhibited ThTP synthesis in rat brain mitochondrial preparations. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intact, energized mitochondria were required for this B1-phosphate reaction. organism: Rattus norvegicus tissue_or_cell_type: Brain mitochondria experimental_model: Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. limitations: Proton-motive-force dependence is supported; the proposed ATP-synthase identity was not definitively established. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}] evidence_locator: Results: ThTP synthesis in isolated mitochondria and energy coupling evidence-scope: Brain mitochondria [gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379
Complete structured claim and evidence
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
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
Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP.
Human pyruvate dehydrogenase E1 → Pyruvate source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "seifert-2006-pdh-catalysis", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Recombinant human E1; transient kinetics.
limitations
Purified-system evidence; nutritional response was not tested.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made.
primary_references
[seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l
tissue_or_cell_type
Purified mitochondrial enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 663–674
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human E1; transient kinetics. · source_derived_draft · unverified_draft
### b1-pdh-pyruvate-covalent-decarboxylation Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made. organism: Homo sapiens tissue_or_cell_type: Purified mitochondrial enzyme experimental_model: Recombinant human E1; transient kinetics. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "seifert-2006-pdh-catalysis", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l
Complete structured claim and evidence
Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation.
Human pyruvate dehydrogenase E1 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested.
evidence
[{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human recombinant proteins; radiolabeled pyruvate assay.
limitations
Purified-system evidence; nutritional response was not tested.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction.
primary_references
[kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 676–688
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant proteins; radiolabeled pyruvate assay. · source_derived_draft · unverified_draft
### b1-pdh-lipoyl-acetyl-transfer Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human recombinant proteins; radiolabeled pyruvate assay. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested. nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
Complete structured claim and evidence
The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation.
Dihydrolipoyl acetyltransferase / DLAT → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1-dependent E1 and B5-derived CoA participate in different sequential steps.
evidence
[{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human DLAT cryo-EM; bacterial ligand poses used for modeling.
limitations
Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier.
primary_references
[jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357
tissue_or_cell_type
Purified catalytic core
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 690–702
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLAT cryo-EM; bacterial ligand poses used for modeling. · source_derived_draft · unverified_draft
### b1-pdh-dlat-coa-acetylation The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier. organism: Homo sapiens tissue_or_cell_type: Purified catalytic core experimental_model: Human DLAT cryo-EM; bacterial ligand poses used for modeling. limitations: Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment. evidence: [{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent E1 and B5-derived CoA participate in different sequential steps. nutrient: Thiamine (vitamin B1) [jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357
Complete structured claim and evidence
Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay.
PDH E1 phosphorylated at alpha Ser264 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Engineered human site-1-only E1; phosphorylation, ITC and kinetics.
limitations
Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner.
primary_references
[kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (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 · Engineered human site-1-only E1; phosphorylation, ITC and kinetics. · source_derived_draft · unverified_draft
### b1-pdh-phosphorylation-blocks-lipoyl-recognition Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Engineered human site-1-only E1; phosphorylation, ITC and kinetics. limitations: Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse experiment. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
Complete structured claim and evidence
Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.
DLD → Protein-bound reduced dihydrolipoyl-lysine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.
evidence
[{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human DLD crystallography with NAD+ and NADH.
limitations
Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.
primary_references
[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft
### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
Complete structured claim and evidence
Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro.
4-Phosphopantothenate → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested.
evidence
[{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Reconstituted human enzyme pathway.
limitations
Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step.
primary_references
[daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant enzymes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 731–743
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human enzyme pathway. · source_derived_draft · unverified_draft
### b1-coa-b5-downstream-biosynthesis Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzymes experimental_model: Reconstituted human enzyme pathway. limitations: Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction. evidence: [{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested. nutrient: Thiamine (vitamin B1) [daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
Recombinant human FLAD1 isoforms 1 and 2 exhibited FAD synthetase activity; isoform 2 was purified, and activity required MgCl2.
Human FAD synthetase isoform 2 → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested.
evidence
[{"paper_key": "brizio-2006-fad", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Recombinant human FLAD1 isoforms expressed in E. coli.
limitations
No tissue Mg threshold or combined B1/B2 deficiency experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes.
primary_references
[brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003
tissue_or_cell_type
Purified/expressed proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 745–757
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human FLAD1 isoforms expressed in E. coli. · source_derived_draft · unverified_draft
### b1-fad-b2-cofactor-synthesis Recombinant human FLAD1 isoforms 1 and 2 exhibited FAD synthetase activity; isoform 2 was purified, and activity required MgCl2. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes. organism: Homo sapiens tissue_or_cell_type: Purified/expressed proteins experimental_model: Recombinant human FLAD1 isoforms expressed in E. coli. limitations: No tissue Mg threshold or combined B1/B2 deficiency experiment. evidence: [{"paper_key": "brizio-2006-fad", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested. nutrient: Thiamine (vitamin B1) [brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003
Complete structured claim and evidence
The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations.
LIAS Arg249His → Human pyruvate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway.
evidence
[{"paper_key": "mayr-2011-lias", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Patient biochemical analysis.
limitations
Single patient; no proof of thiamine-treatment failure mechanism.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect.
primary_references
[mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011
tissue_or_cell_type
Muscle and cultured fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 759–771
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient biochemical analysis. · source_derived_draft · unverified_draft
### b1-lias-defect-reduces-pdh The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect. organism: Homo sapiens tissue_or_cell_type: Muscle and cultured fibroblasts experimental_model: Patient biochemical analysis. limitations: Single patient; no proof of thiamine-treatment failure mechanism. evidence: [{"paper_key": "mayr-2011-lias", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway. nutrient: Thiamine (vitamin B1) [mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011
Complete structured claim and evidence
Human BCKDH E1 decarboxylates a branched-chain alpha-ketoacid using ThDP and reductively acylates the lipoylated DBT domain.
Human branched-chain ketoacid dehydrogenase E1 → Dihydrolipoyl branched-chain transacylase / DBT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later.
evidence
[{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Recombinant human E1b and E2b lipoyl domain assays.
limitations
Purified-system evidence; nutritional response was not tested.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2.
primary_references
[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 773–785
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human E1b and E2b lipoyl domain assays. · source_derived_draft · unverified_draft
### b1-bckdh-ketoacid-acylation Human BCKDH E1 decarboxylates a branched-chain alpha-ketoacid using ThDP and reductively acylates the lipoylated DBT domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Recombinant human E1b and E2b lipoyl domain assays. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later. nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
Complete structured claim and evidence
Apo/holo human E1b structures showed that ThDP binding orders the phosphorylation loop needed to recognize the lipoylated E2b domain.
Thiamine diphosphate → Human branched-chain ketoacid dehydrogenase E1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
ThDP occupancy enables interaction with the lipoylated E2 carrier.
evidence
[{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human apo/holo E1b crystallography and lipoyl-domain binding.
limitations
Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 binding changes the enzyme shape so it can receive its lipoyl partner.
primary_references
[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 787–799
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human apo/holo E1b crystallography and lipoyl-domain binding. · source_derived_draft · unverified_draft
### b1-bckdh-thdp-orders-loop Apo/holo human E1b structures showed that ThDP binding orders the phosphorylation loop needed to recognize the lipoylated E2b domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 binding changes the enzyme shape so it can receive its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human apo/holo E1b crystallography and lipoyl-domain binding. limitations: Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response. evidence: [{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: ThDP occupancy enables interaction with the lipoylated E2 carrier. nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
Complete structured claim and evidence
ThDP reduced kinase-mediated phosphorylation of wild-type human E1b; loop-network mutations abolished this protection in the reconstituted assay.
Thiamine diphosphate → Human branched-chain ketoacid dehydrogenase E1 source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human E1b/E2b with recombinant rat BCKD kinase.
limitations
Mixed-species assay; kinase accessibility, not clinical thiamine responsiveness.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens E1/E2; Rattus norvegicus kinase
plain_language
Cofactor occupancy also affected access to a regulatory site. The result depends on an intact loop and does not show that every genetic BCKDH defect responds to B1.
primary_references
[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
tissue_or_cell_type
Purified mixed-species assay
Thiamine: mechanisms, deficiency and nutrient interactions (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 · Human E1b/E2b with recombinant rat BCKD kinase. · source_derived_draft · unverified_draft
### b1-bckdh-cofactor-limits-phosphorylation ThDP reduced kinase-mediated phosphorylation of wild-type human E1b; loop-network mutations abolished this protection in the reconstituted assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor occupancy also affected access to a regulatory site. The result depends on an intact loop and does not show that every genetic BCKDH defect responds to B1. organism: Homo sapiens E1/E2; Rattus norvegicus kinase tissue_or_cell_type: Purified mixed-species assay experimental_model: Human E1b/E2b with recombinant rat BCKD kinase. limitations: Mixed-species assay; kinase accessibility, not clinical thiamine responsiveness. evidence: [{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
Complete structured claim and evidence
Four-week thiamine-deprived rats had mean total plasma branched-chain amino acids 1.6 times control.
Thiamine (vitamin B1) → Plasma total branched-chain amino-acid concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Dietary B1 deprivation perturbed branched-chain amino-acid metabolism.
evidence
[{"paper_key": "shigematsu-1989-bcaa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Four-week dietary depletion.
limitations
Severe animal depletion; not a plasma B1 diagnostic cutoff.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Severe dietary B1 deprivation altered the circulating pool of leucine, isoleucine and valine in this rat experiment.
primary_references
[shigematsu-1989-bcaa] Branched-chain alpha-ketoacids and related acids in thiamin-deprived rats (1989). https://pubmed.ncbi.nlm.nih.gov/2760689/ DOI: 10.3177/jnsv.35.163
tissue_or_cell_type
Plasma; liver thiamine measured
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 814–826
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-week dietary depletion. · source_derived_draft · unverified_draft
### b1-deficiency-plasma-bcaa-rise Four-week thiamine-deprived rats had mean total plasma branched-chain amino acids 1.6 times control. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe dietary B1 deprivation altered the circulating pool of leucine, isoleucine and valine in this rat experiment. organism: Rattus norvegicus tissue_or_cell_type: Plasma; liver thiamine measured experimental_model: Four-week dietary depletion. limitations: Severe animal depletion; not a plasma B1 diagnostic cutoff. evidence: [{"paper_key": "shigematsu-1989-bcaa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Dietary B1 deprivation perturbed branched-chain amino-acid metabolism. nutrient: Thiamine (vitamin B1) [shigematsu-1989-bcaa] Branched-chain alpha-ketoacids and related acids in thiamin-deprived rats (1989). https://pubmed.ncbi.nlm.nih.gov/2760689/ DOI: 10.3177/jnsv.35.163
Complete structured claim and evidence
Total plasma branched-chain alpha-ketoacids were 2.7 times control after thiamine deprivation, without a significant reported correlation to liver thiamine.
Thiamine (vitamin B1) → Plasma total branched-chain alpha-ketoacid concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B1 deprivation changes metabolites of three essential amino acids.
evidence
[{"paper_key": "shigematsu-1989-bcaa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Four-week dietary depletion.
limitations
Do not infer a linear liver-thiamine/ketoacid relationship or human MSUD equivalence.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Ketoacid accumulation is compatible with impaired disposal, but this pool measurement is not a direct flux assay.
primary_references
[shigematsu-1989-bcaa] Branched-chain alpha-ketoacids and related acids in thiamin-deprived rats (1989). https://pubmed.ncbi.nlm.nih.gov/2760689/ DOI: 10.3177/jnsv.35.163
tissue_or_cell_type
Plasma; liver thiamine measured
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 828–840
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-week dietary depletion. · source_derived_draft · unverified_draft
### b1-deficiency-plasma-bcka-rise Total plasma branched-chain alpha-ketoacids were 2.7 times control after thiamine deprivation, without a significant reported correlation to liver thiamine. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ketoacid accumulation is compatible with impaired disposal, but this pool measurement is not a direct flux assay. organism: Rattus norvegicus tissue_or_cell_type: Plasma; liver thiamine measured experimental_model: Four-week dietary depletion. limitations: Do not infer a linear liver-thiamine/ketoacid relationship or human MSUD equivalence. evidence: [{"paper_key": "shigematsu-1989-bcaa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 deprivation changes metabolites of three essential amino acids. nutrient: Thiamine (vitamin B1) [shigematsu-1989-bcaa] Branched-chain alpha-ketoacids and related acids in thiamin-deprived rats (1989). https://pubmed.ncbi.nlm.nih.gov/2760689/ DOI: 10.3177/jnsv.35.163
Complete structured claim and evidence
Human recombinant OGDH reacted with 2-oxoglutarate to produce spectroscopic signals supporting a ThDP-bound post-decarboxylation enamine.
Human 2-oxoglutarate dehydrogenase E1 → OGDH-bound carboxypropylidene-ThDP enamine source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human OGDH circular dichroism and related spectroscopy.
limitations
Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants.
primary_references
[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
tissue_or_cell_type
Purified E1
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 842–853
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OGDH circular dichroism and related spectroscopy. · source_derived_draft · unverified_draft
### b1-ogdh-thdp-enamine-chemistry Human recombinant OGDH reacted with 2-oxoglutarate to produce spectroscopic signals supporting a ThDP-bound post-decarboxylation enamine. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants. organism: Homo sapiens tissue_or_cell_type: Purified E1 experimental_model: Human OGDH circular dichroism and related spectroscopy. limitations: Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
Complete structured claim and evidence
Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay.
2-Oxoglutarate dehydrogenase complex → Succinyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex.
evidence
[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Reconstituted human multienzyme assay.
limitations
NADH assay measures overall complex turnover, not every intermediate independently.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD.
primary_references
[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
tissue_or_cell_type
Purified enzyme complex
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 855–867
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human multienzyme assay. · source_derived_draft · unverified_draft
### b1-ogdh-complex-couples-succinyl-nadh Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD. organism: Homo sapiens tissue_or_cell_type: Purified enzyme complex experimental_model: Reconstituted human multienzyme assay. limitations: NADH assay measures overall complex turnover, not every intermediate independently. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex. nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
Complete structured claim and evidence
Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH.
DHTKD1 → 2-Oxoadipate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH.
evidence
[{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human recombinant component reconstitution.
limitations
Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme.
primary_references
[nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
tissue_or_cell_type
Purified complex
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 869–881
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant component reconstitution. · source_derived_draft · unverified_draft
### b1-dhtkd1-recruits-shared-dlst-dld Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme. organism: Homo sapiens tissue_or_cell_type: Purified complex experimental_model: Human recombinant component reconstitution. limitations: Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH. nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
Complete structured claim and evidence
Recombinant human DHTKD1 showed approximately 49-fold greater catalytic efficiency for 2-oxoadipate than 2-oxoglutarate in the reported assay.
DHTKD1 → 2-Oxoadipate source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human enzyme substrate-kinetic comparison.
limitations
The approximately 49-fold value belongs to this preparation and assay; it is not universal tissue selectivity.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The two B1 enzymes overlap in possible substrates, but DHTKD1 is specialized for the longer amino-acid-derived ketoacid.
primary_references
[nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 883–894
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme substrate-kinetic comparison. · source_derived_draft · unverified_draft
### b1-dhtkd1-prefers-oxoadipate Recombinant human DHTKD1 showed approximately 49-fold greater catalytic efficiency for 2-oxoadipate than 2-oxoglutarate in the reported assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two B1 enzymes overlap in possible substrates, but DHTKD1 is specialized for the longer amino-acid-derived ketoacid. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human enzyme substrate-kinetic comparison. limitations: The approximately 49-fold value belongs to this preparation and assay; it is not universal tissue selectivity. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
Complete structured claim and evidence
The human DHTKD1 dimer structure places ThDP-containing active sites at the subunit interface and reveals a pocket compatible with the longer 2-oxoadipate substrate.
DHTKD1 → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
1.9-A human DHTKD1 crystal structure.
limitations
Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable.
primary_references
[bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x
tissue_or_cell_type
Recombinant protein crystal
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 896–907
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 1.9-A human DHTKD1 crystal structure. · source_derived_draft · unverified_draft
### b1-dhtkd1-thdp-dimer-sites The human DHTKD1 dimer structure places ThDP-containing active sites at the subunit interface and reveals a pocket compatible with the longer 2-oxoadipate substrate. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable. organism: Homo sapiens tissue_or_cell_type: Recombinant protein crystal experimental_model: 1.9-A human DHTKD1 crystal structure. limitations: Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand. evidence: [{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x
Complete structured claim and evidence
Patient DHTKD1-deficient fibroblasts accumulated deuterium-labeled 2-oxoadipate from labeled lysine; wild-type DHTKD1 expression normalized the biochemical defect.
DHTKD1 → 2-Oxoadipate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
A B1-dependent enzyme connects lysine degradation to glutaryl-CoA metabolism.
evidence
[{"paper_key": "danhauser-2012-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Patient fibroblasts, isotope tracing and lentiviral complementation.
limitations
Two individuals; neurological phenotypes vary and biochemical rescue does not prove a clinical treatment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Replacing the faulty enzyme restored the tested metabolic step. The experiment identifies a machinery defect rather than a lack of dietary B1.
primary_references
[danhauser-2012-dhtkd1] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pubmed.ncbi.nlm.nih.gov/23141293/ DOI: 10.1016/j.ajhg.2012.10.006
tissue_or_cell_type
Cultured fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 909–921
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblasts, isotope tracing and lentiviral complementation. · source_derived_draft · unverified_draft
### b1-dhtkd1-patient-lysine-turnover Patient DHTKD1-deficient fibroblasts accumulated deuterium-labeled 2-oxoadipate from labeled lysine; wild-type DHTKD1 expression normalized the biochemical defect. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the faulty enzyme restored the tested metabolic step. The experiment identifies a machinery defect rather than a lack of dietary B1. organism: Homo sapiens tissue_or_cell_type: Cultured fibroblasts experimental_model: Patient fibroblasts, isotope tracing and lentiviral complementation. limitations: Two individuals; neurological phenotypes vary and biochemical rescue does not prove a clinical treatment. evidence: [{"paper_key": "danhauser-2012-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: A B1-dependent enzyme connects lysine degradation to glutaryl-CoA metabolism. nutrient: Thiamine (vitamin B1) [danhauser-2012-dhtkd1] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pubmed.ncbi.nlm.nih.gov/23141293/ DOI: 10.1016/j.ajhg.2012.10.006
Complete structured claim and evidence
The human DHTKD1 Arg715Cys variant impaired DLST interaction in recombinant complex-formation experiments.
DHTKD1 Arg715Cys → DLST source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence
[{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-59", "p-61", "p-63", "p-64"], "locator": "R715C", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Recombinant variant interaction assays.
limitations
Variant-specific assembly result; no thiamine rescue claim.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Having the B1-dependent protein is not enough if it cannot join its downstream partner.
primary_references
[bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x
tissue_or_cell_type
Purified proteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 923–934
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant variant interaction assays. · source_derived_draft · unverified_draft
### b1-dhtkd1-r715c-dlst-binding The human DHTKD1 Arg715Cys variant impaired DLST interaction in recombinant complex-formation experiments. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having the B1-dependent protein is not enough if it cannot join its downstream partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Recombinant variant interaction assays. limitations: Variant-specific assembly result; no thiamine rescue claim. evidence: [{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-59", "p-61", "p-63", "p-64"], "locator": "R715C", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x
Complete structured claim and evidence
Glutaryl-CoA inhibited human OGDH activity in reconstituted experiments, supporting possible regulatory communication from OADH-linked amino-acid degradation to the TCA cycle.
Glutaryl-CoA → Human 2-oxoglutarate dehydrogenase E1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Amino-acid catabolism and central carbon metabolism communicate through an acyl-CoA product.
evidence
[{"paper_key": "nemeria-2018-crosstalk", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Reconstituted human enzyme inhibition assays.
limitations
In vitro regulation; physiological free metabolite concentrations and net in vivo effect were not established.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A product of one B1-dependent route can restrain a different B1 enzyme in a test tube. Its importance inside tissues remains unquantified.
primary_references
[nemeria-2018-crosstalk] Evidence for functional and regulatory cross-talk between the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex and 2-oxoadipate dehydrogenase on the l-lysine, l-hydroxylysine and l-tryptophan degradation pathways from studies in vitro (2018). https://pubmed.ncbi.nlm.nih.gov/29752936/ DOI: 10.1016/j.bbabio.2018.05.001
tissue_or_cell_type
Purified complexes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 936–948
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human enzyme inhibition assays. · source_derived_draft · unverified_draft
### b1-lysine-product-inhibits-ogdh Glutaryl-CoA inhibited human OGDH activity in reconstituted experiments, supporting possible regulatory communication from OADH-linked amino-acid degradation to the TCA cycle. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A product of one B1-dependent route can restrain a different B1 enzyme in a test tube. Its importance inside tissues remains unquantified. organism: Homo sapiens tissue_or_cell_type: Purified complexes experimental_model: Reconstituted human enzyme inhibition assays. limitations: In vitro regulation; physiological free metabolite concentrations and net in vivo effect were not established. evidence: [{"paper_key": "nemeria-2018-crosstalk", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Amino-acid catabolism and central carbon metabolism communicate through an acyl-CoA product. nutrient: Thiamine (vitamin B1) [nemeria-2018-crosstalk] Evidence for functional and regulatory cross-talk between the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex and 2-oxoadipate dehydrogenase on the l-lysine, l-hydroxylysine and l-tryptophan degradation pathways from studies in vitro (2018). https://pubmed.ncbi.nlm.nih.gov/29752936/ DOI: 10.1016/j.bbabio.2018.05.001
Complete structured claim and evidence
Human TKT transfers two carbons from xylulose-5-phosphate to ribose-5-phosphate, yielding glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate.
Human transketolase → Nonoxidative pentose phosphate pathway source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-12"], "locator": "simplified reaction scheme", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Recombinant human TKT reaction analysis.
limitations
Direct reaction chemistry; indirect recycling effects on oxidative PPP flux need separate evidence.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 supports sugar rearrangement, connecting pentose and glycolytic intermediates. This reaction does not directly make NADPH.
primary_references
[mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 950–961
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TKT reaction analysis. · source_derived_draft · unverified_draft
### b1-tkt-nonoxidative-carbon-transfer Human TKT transfers two carbons from xylulose-5-phosphate to ribose-5-phosphate, yielding glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 supports sugar rearrangement, connecting pentose and glycolytic intermediates. This reaction does not directly make NADPH. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Recombinant human TKT reaction analysis. limitations: Direct reaction chemistry; indirect recycling effects on oxidative PPP flux need separate evidence. evidence: [{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-12"], "locator": "simplified reaction scheme", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955
Complete structured claim and evidence
Acid-quench NMR of human TKT identified the protonated form of the DHE-ThDP intermediate generated during the donor half-reaction.
Human transketolase → 1,2-Dihydroxyethyl-ThDP intermediate source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-31", "p-44", "p-46", "p-47"], "locator": "acid quench", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human recombinant TKT; chemical quench and NMR.
limitations
Acid quench protonates the intermediate; native enamine occupancy is inferred from trapped species.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 temporarily carries the two-carbon sugar fragment before its transfer to an acceptor; the detected acid-trapped form is distinguished from the reactive enamine.
primary_references
[mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 963–974
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant TKT; chemical quench and NMR. · source_derived_draft · unverified_draft
### b1-tkt-dhe-thdp-intermediate Acid-quench NMR of human TKT identified the protonated form of the DHE-ThDP intermediate generated during the donor half-reaction. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 temporarily carries the two-carbon sugar fragment before its transfer to an acceptor; the detected acid-trapped form is distinguished from the reactive enamine. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human recombinant TKT; chemical quench and NMR. limitations: Acid quench protonates the intermediate; native enamine occupancy is inferred from trapped species. evidence: [{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-31", "p-44", "p-46", "p-47"], "locator": "acid quench", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955
Complete structured claim and evidence
Purified rat peroxisomal HACL1 cleaved 2-hydroxy-3-methylhexadecanoyl-CoA into formyl-CoA and 2-methylpentadecanal, with activity dependent on ThDP and Mg2+.
Rat 2-hydroxyacyl-CoA lyase 1 → 2-Hydroxy-3-methylhexadecanoyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct B1/Mg dependence of a lipid-cleavage enzyme; not evidence that dietary Mg universally limits alpha oxidation.
evidence
[{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Purified rat liver lyase; defined-substrate product identification.
limitations
Defined branched substrate and rat purified enzyme; not a human deficiency experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
B1 and magnesium support a carbon-cleavage reaction in fatty-acid alpha oxidation. Here the measured products are a one-carbon CoA ester and a shortened aldehyde.
primary_references
[foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039
tissue_or_cell_type
Liver peroxisomes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 976–988
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver lyase; defined-substrate product identification. · source_derived_draft · unverified_draft
### b1-hacl1-rat-branched-cleavage Purified rat peroxisomal HACL1 cleaved 2-hydroxy-3-methylhexadecanoyl-CoA into formyl-CoA and 2-methylpentadecanal, with activity dependent on ThDP and Mg2+. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 and magnesium support a carbon-cleavage reaction in fatty-acid alpha oxidation. Here the measured products are a one-carbon CoA ester and a shortened aldehyde. organism: Rattus norvegicus tissue_or_cell_type: Liver peroxisomes experimental_model: Purified rat liver lyase; defined-substrate product identification. limitations: Defined branched substrate and rat purified enzyme; not a human deficiency experiment. evidence: [{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Direct B1/Mg dependence of a lipid-cleavage enzyme; not evidence that dietary Mg universally limits alpha oxidation. nutrient: Thiamine (vitamin B1) [foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039
Complete structured claim and evidence
Human HACL1 expression increased lyase activity in mammalian cells, and GFP fusions showed that its C-terminal sequence could direct peroxisomal localization.
Human 2-hydroxyacyl-CoA lyase 1 / HACL1 → Peroxisome source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract", "p-8"], "locator": "peroxisome targeting signal 1 variant", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human HACL1 expression and fluorescent localization constructs.
limitations
Localization and activity used expression constructs; metal-dependence measurements in this paper were on rat enzyme.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The cloned human protein is an active lyase with a peroxisomal address, distinct from ER-associated HACL2.
primary_references
[foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039
tissue_or_cell_type
Transfected mammalian cells
Thiamine: mechanisms, deficiency and nutrient interactions (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 · Human HACL1 expression and fluorescent localization constructs. · source_derived_draft · unverified_draft
### b1-hacl1-human-peroxisomal-targeting Human HACL1 expression increased lyase activity in mammalian cells, and GFP fusions showed that its C-terminal sequence could direct peroxisomal localization. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cloned human protein is an active lyase with a peroxisomal address, distinct from ER-associated HACL2. organism: Homo sapiens tissue_or_cell_type: Transfected mammalian cells experimental_model: Human HACL1 expression and fluorescent localization constructs. limitations: Localization and activity used expression constructs; metal-dependence measurements in this paper were on rat enzyme. evidence: [{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract", "p-8"], "locator": "peroxisome targeting signal 1 variant", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039
Complete structured claim and evidence
Rat liver/hepatocyte pathway experiments supported activation of 2-hydroxy-fatty acid to its CoA ester before ThDP-dependent cleavage; whole-pathway assays required ATP, CoA, Mg2+, ThDP and NAD+.
2-Hydroxystearate → 2-Hydroxystearoyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation.
evidence
[{"paper_key": "foulon-2005-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Intact/permeabilized rat hepatocytes and liver preparations.
limitations
Whole-pathway requirements cannot all be assigned to the isolated lyase.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD.
primary_references
[foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200
tissue_or_cell_type
Liver
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1003–1015
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intact/permeabilized rat hepatocytes and liver preparations. · source_derived_draft · unverified_draft
### b1-alpha-oxidation-activation-before-cleavage Rat liver/hepatocyte pathway experiments supported activation of 2-hydroxy-fatty acid to its CoA ester before ThDP-dependent cleavage; whole-pathway assays required ATP, CoA, Mg2+, ThDP and NAD+. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Intact/permeabilized rat hepatocytes and liver preparations. limitations: Whole-pathway requirements cannot all be assigned to the isolated lyase. evidence: [{"paper_key": "foulon-2005-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation. nutrient: Thiamine (vitamin B1) [foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200
Complete structured claim and evidence
Affinity-purified human HACL2 produced fatty aldehyde from 2-hydroxy-C18:0-CoA, but not the free acid, and activity depended on added ThDP.
Human 2-hydroxyacyl-CoA lyase 2 / HACL2 → 2-Hydroxystearoyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1-dependent cleavage uses a B5-derived CoA-ester substrate.
evidence
[{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "generated fatty aldehyde", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human tagged HACL2 purified from HEK293T cells.
limitations
Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA.
primary_references
[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
tissue_or_cell_type
Purified membrane-associated protein
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1017–1029
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human tagged HACL2 purified from HEK293T cells. · source_derived_draft · unverified_draft
### b1-hacl2-thdp-dependent-coa-cleavage Affinity-purified human HACL2 produced fatty aldehyde from 2-hydroxy-C18:0-CoA, but not the free acid, and activity depended on added ThDP. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA. organism: Homo sapiens tissue_or_cell_type: Purified membrane-associated protein experimental_model: Human tagged HACL2 purified from HEK293T cells. limitations: Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this experiment. evidence: [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "generated fatty aldehyde", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent cleavage uses a B5-derived CoA-ester substrate. nutrient: Thiamine (vitamin B1) [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
Complete structured claim and evidence
Tagged human HACL2 colocalized with an ER marker and partitioned into the membrane fraction in HeLa cells.
Human 2-hydroxyacyl-CoA lyase 2 / HACL2 → Endoplasmic reticulum source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-47", "p-48"], "locator": "HACL2 is an ER membrane protein", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human HACL2 immunofluorescence and fractionation.
limitations
Tagged overexpression localization.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
This B1-dependent lipid-cleavage protein is associated with ER membranes; its location differs from peroxisomal HACL1.
primary_references
[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
tissue_or_cell_type
Transfected HeLa cells
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1031–1042
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HACL2 immunofluorescence and fractionation. · source_derived_draft · unverified_draft
### b1-hacl2-er-localization Tagged human HACL2 colocalized with an ER marker and partitioned into the membrane fraction in HeLa cells. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B1-dependent lipid-cleavage protein is associated with ER membranes; its location differs from peroxisomal HACL1. organism: Homo sapiens tissue_or_cell_type: Transfected HeLa cells experimental_model: Human HACL2 immunofluorescence and fractionation. limitations: Tagged overexpression localization. evidence: [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-47", "p-48"], "locator": "HACL2 is an ER membrane protein", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
Complete structured claim and evidence
Hacl2 knockout reduced phytosphingosine-derived glycerolipid labeling more strongly than Hacl1 knockout in CHO-K1 cells.
Chinese hamster HACL2 → Phytosphingosine degradation into glycerolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence
[{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-42", "p-61"], "locator": "higher contribution of HACL2", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
CHO-K1 knockout and radiolabeled phytosphingosine tracing.
limitations
Genetic cell model; does not establish human tissue dominance or thiamine-deficiency pathology.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Cricetulus griseus
plain_language
In these hamster cells, the ER lyase made the larger contribution to disposal of this sphingoid-base-derived substrate.
primary_references
[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
tissue_or_cell_type
Ovary-derived CHO-K1 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1044–1055
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO-K1 knockout and radiolabeled phytosphingosine tracing. · source_derived_draft · unverified_draft
### b1-hamster-hacl2-phytosphingosine-flux Hacl2 knockout reduced phytosphingosine-derived glycerolipid labeling more strongly than Hacl1 knockout in CHO-K1 cells. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In these hamster cells, the ER lyase made the larger contribution to disposal of this sphingoid-base-derived substrate. organism: Cricetulus griseus tissue_or_cell_type: Ovary-derived CHO-K1 cells experimental_model: CHO-K1 knockout and radiolabeled phytosphingosine tracing. limitations: Genetic cell model; does not establish human tissue dominance or thiamine-deficiency pathology. evidence: [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-42", "p-61"], "locator": "higher contribution of HACL2", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
Complete structured claim and evidence
Added 2-hydroxypalmitate increased odd-chain phosphatidylcholine in either single Hacl knockout, but not in the Hacl1/Hacl2 double knockout.
Chinese hamster HACL1 → Odd-chain phosphatidylcholine production source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence
[{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-42", "p-53"], "locator": "such an increase was not observed", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
CHO-K1 knockout; 2-hydroxypalmitate feeding and LC-MS/MS.
limitations
Substrate-specific redundancy; does not establish equal contributions in human tissues.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Cricetulus griseus
plain_language
For an externally supplied hydroxy-fatty acid, either lyase could support the measured route; this differs from phytosphingosine-derived substrate routing.
primary_references
[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
tissue_or_cell_type
Ovary-derived CHO-K1 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1057–1068
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO-K1 knockout; 2-hydroxypalmitate feeding and LC-MS/MS. · source_derived_draft · unverified_draft
### b1-hamster-hacl-redundant-free-hydroxyacid Added 2-hydroxypalmitate increased odd-chain phosphatidylcholine in either single Hacl knockout, but not in the Hacl1/Hacl2 double knockout. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: For an externally supplied hydroxy-fatty acid, either lyase could support the measured route; this differs from phytosphingosine-derived substrate routing. organism: Cricetulus griseus tissue_or_cell_type: Ovary-derived CHO-K1 cells experimental_model: CHO-K1 knockout; 2-hydroxypalmitate feeding and LC-MS/MS. limitations: Substrate-specific redundancy; does not establish equal contributions in human tissues. evidence: [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-42", "p-53"], "locator": "such an increase was not observed", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
Complete structured claim and evidence
Before neurological signs, total high-energy phosphates were 89% of control in diencephalon and 91% in lower brainstem; after signs, 76% and 79%.
Thiamine (vitamin B1) → Brain high-energy phosphate content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
before the onset of neurological signs
experimental_model
Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs.
exposure
Pyrithiamine-induced severe thiamine deficiency in rats
limitations
Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Energy reserves fell early in two vulnerable brain regions.
primary_references
[aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006
tissue_or_cell_type
Diencephalon and lower brainstem
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1070–1082
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. · source_derived_draft · unverified_draft
### thiamine-def-regional-energy-loss Before neurological signs, total high-energy phosphates were 89% of control in diencephalon and 91% in lower brainstem; after signs, 76% and 79%. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Energy reserves fell early in two vulnerable brain regions. organism: Rattus norvegicus tissue_or_cell_type: Diencephalon and lower brainstem experimental_model: Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. limitations: Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: before the onset of neurological signs exposure: Pyrithiamine-induced severe thiamine deficiency in rats [aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006
Complete structured claim and evidence
Cerebral cortex and cerebellum showed no significant high-energy phosphate reduction in the same encephalopathic rats.
Thiamine (vitamin B1) → Brain high-energy phosphate content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
high energy phosphates were not significantly reduced
experimental_model
Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs.
exposure
Pyrithiamine-induced severe thiamine deficiency in rats
limitations
A nonsignificant result does not prove unchanged ATP in every cell or at later stages. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
A severe thiamine-deficiency model did not cause uniform energy depletion across the brain.
primary_references
[aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006
tissue_or_cell_type
Cerebral cortex and cerebellum
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1084–1096
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. · source_derived_draft · unverified_draft
### thiamine-def-regional-energy-preservation Cerebral cortex and cerebellum showed no significant high-energy phosphate reduction in the same encephalopathic rats. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A severe thiamine-deficiency model did not cause uniform energy depletion across the brain. organism: Rattus norvegicus tissue_or_cell_type: Cerebral cortex and cerebellum experimental_model: Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. limitations: A nonsignificant result does not prove unchanged ATP in every cell or at later stages. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: high energy phosphates were not significantly reduced exposure: Pyrithiamine-induced severe thiamine deficiency in rats [aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006
Complete structured claim and evidence
The potassium-induced increment in carbon-14 carbon dioxide production from labeled glucose was 50% lower in deficient rat brain slices; resting production was similar to controls.
Thiamine (vitamin B1) → Brain glucose oxidation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
under resting conditions
experimental_model
Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.
exposure
Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices
limitations
Carbon dioxide labeling measures glucose oxidation under this stimulation protocol, not whole-brain ATP directly. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
The slices could maintain resting oxidation but had less capacity to increase it when stimulated.
primary_references
[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667
tissue_or_cell_type
Brain slices
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1098–1110
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft
### thiamine-def-stimulated-glucose-oxidation The potassium-induced increment in carbon-14 carbon dioxide production from labeled glucose was 50% lower in deficient rat brain slices; resting production was similar to controls. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The slices could maintain resting oxidation but had less capacity to increase it when stimulated. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: Carbon dioxide labeling measures glucose oxidation under this stimulation protocol, not whole-brain ATP directly. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: under resting conditions exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667
Complete structured claim and evidence
The potassium-induced increment in glucose-derived carbon-14 acetylcholine was 75% lower in deficient rat brain slices.
Thiamine (vitamin B1) → Brain acetylcholine synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested.
evidence_location
Abstract
evidence_span
declined by 50 and 75%, respectively
experimental_model
Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.
exposure
Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices
limitations
This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon.
primary_references
[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667
tissue_or_cell_type
Brain slices
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1112–1125
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft
### thiamine-def-stimulated-acetylcholine-synthesis The potassium-induced increment in glucose-derived carbon-14 acetylcholine was 75% lower in deficient rat brain slices. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release. evidence_location: Abstract evidence_span: declined by 50 and 75%, respectively cross_nutrient: Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested. exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667
Complete structured claim and evidence
Brain mitochondrial state 3 respiration fell with pyruvate/malate, 2-oxoglutarate or glutamate as substrates; state 4 respiration did not change.
Thiamine (vitamin B1) → Mitochondrial ADP-stimulated respiration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
State 4 respiration did not change
experimental_model
Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates.
exposure
Low-thiamine diet plus pyrithiamine in rats
limitations
Does not demonstrate that thiamine directly forms part of the respiratory chain or that all electron-transport activity fails.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
The mitochondrial deficit depended on both substrate and respiratory state.
primary_references
[parker-1984-brain-mitochondria] Brain mitochondrial metabolism in experimental thiamine deficiency (1984). https://pubmed.ncbi.nlm.nih.gov/6493495/ DOI: 10.1212/wnl.34.11.1477
tissue_or_cell_type
Isolated brain mitochondria
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1127–1139
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates. · source_derived_draft · unverified_draft
### thiamine-def-brain-state3-respiration Brain mitochondrial state 3 respiration fell with pyruvate/malate, 2-oxoglutarate or glutamate as substrates; state 4 respiration did not change. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial deficit depended on both substrate and respiratory state. organism: Rattus norvegicus tissue_or_cell_type: Isolated brain mitochondria experimental_model: Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates. limitations: Does not demonstrate that thiamine directly forms part of the respiratory chain or that all electron-transport activity fails. evidence_location: Abstract evidence_span: State 4 respiration did not change exposure: Low-thiamine diet plus pyrithiamine in rats [parker-1984-brain-mitochondria] Brain mitochondrial metabolism in experimental thiamine deficiency (1984). https://pubmed.ncbi.nlm.nih.gov/6493495/ DOI: 10.1212/wnl.34.11.1477
Complete structured claim and evidence
Acute symptomatic rats had thalamic dialysate glutamate of 3.37 versus 0.93 micromolar in controls, with no corresponding cortical increase.
Thiamine (vitamin B1) → Extracellular brain glutamate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
precedes the appearance of histological lesions
experimental_model
Awake freely moving rats with pyrithiamine-induced deficiency; microdialysis of ventral posterior medial thalamus and contralateral frontoparietal cortex, compared with pair-fed controls.
exposure
Pyrithiamine-induced deficiency within six hours of loss of righting reflexes
limitations
Microdialysis alone cannot assign increased release versus impaired uptake or prove NMDA-mediated cell death. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Glutamate accumulated outside cells in a vulnerable region before visible tissue lesions.
primary_references
[hazell-1993-extracellular-glutamate] Cerebral vulnerability is associated with selective increase in extracellular glutamate concentration in experimental thiamine deficiency (1993). https://pubmed.ncbi.nlm.nih.gov/8103080/ DOI: 10.1111/j.1471-4159.1993.tb03635.x
tissue_or_cell_type
Ventral posterior medial thalamus versus frontoparietal cortex
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1141–1153
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Awake freely moving rats with pyrithiamine-induced deficiency; microdialysis of ventral posterior medial thalamus and contralateral frontoparietal cortex, compared with pair-fed controls. · source_derived_draft · unverified_draft
### thiamine-def-thalamic-extracellular-glutamate Acute symptomatic rats had thalamic dialysate glutamate of 3.37 versus 0.93 micromolar in controls, with no corresponding cortical increase. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutamate accumulated outside cells in a vulnerable region before visible tissue lesions. organism: Rattus norvegicus tissue_or_cell_type: Ventral posterior medial thalamus versus frontoparietal cortex experimental_model: Awake freely moving rats with pyrithiamine-induced deficiency; microdialysis of ventral posterior medial thalamus and contralateral frontoparietal cortex, compared with pair-fed controls. limitations: Microdialysis alone cannot assign increased release versus impaired uptake or prove NMDA-mediated cell death. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: precedes the appearance of histological lesions exposure: Pyrithiamine-induced deficiency within six hours of loss of righting reflexes [hazell-1993-extracellular-glutamate] Cerebral vulnerability is associated with selective increase in extracellular glutamate concentration in experimental thiamine deficiency (1993). https://pubmed.ncbi.nlm.nih.gov/8103080/ DOI: 10.1111/j.1471-4159.1993.tb03635.x
Complete structured claim and evidence
Reactive oxygen species assay signals were higher in thalamus and cortex on day 14 of pyrithiamine-assisted deficiency.
Thiamine (vitamin B1) → Brain reactive oxygen species assay signal source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract; Methods; Figure 1A
evidence_span
significantly elevated in thalamus and cortex on day 14
experimental_model
Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays.
exposure
Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex
limitations
The assay does not identify one oxidant species or its initiating enzyme; seizures can also influence the endpoint.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Late symptomatic depletion increased a marker of oxidant production in both sampled regions.
primary_references
[langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735
tissue_or_cell_type
Thalamus and cortex
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1155–1167
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. · source_derived_draft · unverified_draft
### thiamine-def-brain-ros-increase Reactive oxygen species assay signals were higher in thalamus and cortex on day 14 of pyrithiamine-assisted deficiency. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Late symptomatic depletion increased a marker of oxidant production in both sampled regions. organism: Rattus norvegicus tissue_or_cell_type: Thalamus and cortex experimental_model: Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. limitations: The assay does not identify one oxidant species or its initiating enzyme; seizures can also influence the endpoint. evidence_location: Abstract; Methods; Figure 1A evidence_span: significantly elevated in thalamus and cortex on day 14 exposure: Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex [langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735
Complete structured claim and evidence
Reduced glutathione concentrations did not change significantly in thalamus or cortex on days 13 or 14.
Thiamine (vitamin B1) → GSH source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract; Figure 1B
evidence_span
No significant changes in GSH concentration
experimental_model
Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays.
exposure
Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex
limitations
Total regional concentration does not measure glutathione turnover or subcellular redox state; no direct NADPH result is inferred.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Higher oxidant signals did not require a detectable fall in the measured glutathione pool.
primary_references
[langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735
tissue_or_cell_type
Thalamus and cortex
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1169–1181
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. · source_derived_draft · unverified_draft
### thiamine-def-glutathione-preserved-oxidant-context Reduced glutathione concentrations did not change significantly in thalamus or cortex on days 13 or 14. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher oxidant signals did not require a detectable fall in the measured glutathione pool. organism: Rattus norvegicus tissue_or_cell_type: Thalamus and cortex experimental_model: Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. limitations: Total regional concentration does not measure glutathione turnover or subcellular redox state; no direct NADPH result is inferred. evidence_location: Abstract; Figure 1B evidence_span: No significant changes in GSH concentration exposure: Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex [langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735
Complete structured claim and evidence
Focal extravascular IgG staining appeared in susceptible mouse brain regions by day 10, before obvious cell loss or hemorrhage.
Thiamine (vitamin B1) → Blood-brain barrier permeability source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Results: BBB Dysfunction; Figure 5
evidence_span
before the onset of apparent cell loss
experimental_model
Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry.
exposure
Dietary thiamine removal plus daily pyrithiamine in mice or rats
limitations
IgG localization is a permeability proxy; timing does not prove the barrier change caused later neuron death.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
A blood protein crossed the barrier before overt tissue loss was visible.
primary_references
[calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
tissue_or_cell_type
Vulnerable thalamic and related regions
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1183–1195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. · source_derived_draft · unverified_draft
### thiamine-def-bbb-igg-leak Focal extravascular IgG staining appeared in susceptible mouse brain regions by day 10, before obvious cell loss or hemorrhage. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blood protein crossed the barrier before overt tissue loss was visible. organism: Mus musculus tissue_or_cell_type: Vulnerable thalamic and related regions experimental_model: Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. limitations: IgG localization is a permeability proxy; timing does not prove the barrier change caused later neuron death. evidence_location: Results: BBB Dysfunction; Figure 5 evidence_span: before the onset of apparent cell loss exposure: Dietary thiamine removal plus daily pyrithiamine in mice or rats [calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
Complete structured claim and evidence
Thalamic microvessel endothelial NOS immunoreactivity increased after ten days of the mouse depletion protocol.
Thiamine (vitamin B1) → Mouse endothelial nitric oxide synthase / Nos3 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Results: NOS Induction; Figure 3
evidence_span
enhanced endothelial NOS immunoreactivity
experimental_model
Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry.
exposure
Dietary thiamine removal plus daily pyrithiamine in mice or rats
limitations
Immunostaining is not a direct nitric oxide flux measurement and does not establish a protective or damaging net effect.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
The blood-vessel lining increased its endothelial nitric oxide synthase signal.
primary_references
[calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
tissue_or_cell_type
Thalamic microvessel walls
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1197–1209
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. · source_derived_draft · unverified_draft
### thiamine-def-mouse-endothelial-nos3 Thalamic microvessel endothelial NOS immunoreactivity increased after ten days of the mouse depletion protocol. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood-vessel lining increased its endothelial nitric oxide synthase signal. organism: Mus musculus tissue_or_cell_type: Thalamic microvessel walls experimental_model: Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. limitations: Immunostaining is not a direct nitric oxide flux measurement and does not establish a protective or damaging net effect. evidence_location: Results: NOS Induction; Figure 3 evidence_span: enhanced endothelial NOS immunoreactivity exposure: Dietary thiamine removal plus daily pyrithiamine in mice or rats [calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
Complete structured claim and evidence
Numerous iNOS-positive macrophage-like cells appeared in mouse thalamus from day 10; this iNOS staining was not detected in rats.
Thiamine (vitamin B1) → Mouse inducible nitric oxide synthase / Nos2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Results: NOS Induction; Figure 3
evidence_span
but not in rats
experimental_model
Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry.
exposure
Dietary thiamine removal plus daily pyrithiamine in mice or rats
limitations
The authors could not reliably distinguish infiltrating macrophages from microglia; do not label all these cells as resident microglia.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
An inflammatory nitric oxide synthase signal was species-specific in this study.
primary_references
[calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
tissue_or_cell_type
Thalamic macrophage-like cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1211–1223
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. · source_derived_draft · unverified_draft
### thiamine-def-mouse-macrophagelike-nos2 Numerous iNOS-positive macrophage-like cells appeared in mouse thalamus from day 10; this iNOS staining was not detected in rats. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inflammatory nitric oxide synthase signal was species-specific in this study. organism: Mus musculus tissue_or_cell_type: Thalamic macrophage-like cells experimental_model: Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. limitations: The authors could not reliably distinguish infiltrating macrophages from microglia; do not label all these cells as resident microglia. evidence_location: Results: NOS Induction; Figure 3 evidence_span: but not in rats exposure: Dietary thiamine removal plus daily pyrithiamine in mice or rats [calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
Complete structured claim and evidence
Iron accumulated in microglia of vulnerable mouse regions from day 10; rat iron-laden microglia often clustered near vessels.
Thiamine (vitamin B1) → Iron source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Thiamine disruption accompanies altered local iron handling; iron intake, chelation and iron-repletion response were not tested.
evidence_location
Results: Ferritin, Iron, and Microglial Responses to TD; Figure 7
evidence_span
iron accumulated in microglia
experimental_model
Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry.
exposure
Dietary thiamine removal plus daily pyrithiamine in mice or rats
limitations
Histochemistry does not establish iron origin, oxidation state or that dietary iron caused injury.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus; Rattus norvegicus
plain_language
Severe depletion changed where iron was retained in the brain.
primary_references
[calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
tissue_or_cell_type
Microglia in vulnerable thalamic and geniculate regions; rat inferior colliculus
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1225–1238
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. · source_derived_draft · unverified_draft
### thiamine-def-microglial-iron-accumulation Iron accumulated in microglia of vulnerable mouse regions from day 10; rat iron-laden microglia often clustered near vessels. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe depletion changed where iron was retained in the brain. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Microglia in vulnerable thalamic and geniculate regions; rat inferior colliculus experimental_model: Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. limitations: Histochemistry does not establish iron origin, oxidation state or that dietary iron caused injury. evidence_location: Results: Ferritin, Iron, and Microglial Responses to TD; Figure 7 evidence_span: iron accumulated in microglia cross_nutrient: Thiamine disruption accompanies altered local iron handling; iron intake, chelation and iron-repletion response were not tested. exposure: Dietary thiamine removal plus daily pyrithiamine in mice or rats [calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
Complete structured claim and evidence
Ferritin staining increased in activated microglia and vessels within selectively vulnerable regions of depleted mice and rats.
Thiamine (vitamin B1) → Mammalian ferritin protein complexes source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Local iron storage changes accompany severe thiamine disruption; this is not evidence of systemic iron deficiency or overload.
evidence_location
Results: Ferritin, Iron, and Microglial Responses to TD; Figures 5-6
evidence_span
intense ferritin immunoreactivity
experimental_model
Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry.
exposure
Dietary thiamine removal plus daily pyrithiamine in mice or rats
limitations
Staining does not distinguish ferritin subunits or prove ferritin causes injury; serum ferritin was not measured.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus; Rattus norvegicus
plain_language
Iron-storage protein accumulated locally alongside the iron signal.
primary_references
[calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
tissue_or_cell_type
Vulnerable brain microglia and microvessels
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1240–1253
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. · source_derived_draft · unverified_draft
### thiamine-def-ferritin-regional-increase Ferritin staining increased in activated microglia and vessels within selectively vulnerable regions of depleted mice and rats. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-storage protein accumulated locally alongside the iron signal. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Vulnerable brain microglia and microvessels experimental_model: Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. limitations: Staining does not distinguish ferritin subunits or prove ferritin causes injury; serum ferritin was not measured. evidence_location: Results: Ferritin, Iron, and Microglial Responses to TD; Figures 5-6 evidence_span: intense ferritin immunoreactivity cross_nutrient: Local iron storage changes accompany severe thiamine disruption; this is not evidence of systemic iron deficiency or overload. exposure: Dietary thiamine removal plus daily pyrithiamine in mice or rats [calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7
Complete structured claim and evidence
Frontal-cortex EAAT1 protein was 62% lower in the five Wernicke cases than in five controls.
Thiamine (vitamin B1) → Human excitatory amino acid transporter 1 / SLC1A3 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract; Results; Figure 1
evidence_span
reduced by 62%
experimental_model
Human frontal-cortex autopsy samples: five male Wernicke encephalopathy cases with alcohol intake above 80 g/day versus five male controls below 20 g/day; immunoblotting and histology.
exposure
Neuropathologically identified Wernicke encephalopathy with heavy alcohol exposure
limitations
Does not isolate thiamine from alcohol effects, establish the initiating event, or directly measure uptake in living patients.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
An astrocyte glutamate transporter was reduced in the sampled diseased human cortex.
primary_references
[hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908
tissue_or_cell_type
Frontal cortex
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1255–1267
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human frontal-cortex autopsy samples: five male Wernicke encephalopathy cases with alcohol intake above 80 g/day versus five male controls below 20 g/day; immunoblotting and histology. · source_derived_draft · unverified_draft
### thiamine-def-human-eaat1-loss Frontal-cortex EAAT1 protein was 62% lower in the five Wernicke cases than in five controls. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An astrocyte glutamate transporter was reduced in the sampled diseased human cortex. organism: Homo sapiens tissue_or_cell_type: Frontal cortex experimental_model: Human frontal-cortex autopsy samples: five male Wernicke encephalopathy cases with alcohol intake above 80 g/day versus five male controls below 20 g/day; immunoblotting and histology. limitations: Does not isolate thiamine from alcohol effects, establish the initiating event, or directly measure uptake in living patients. evidence_location: Abstract; Results; Figure 1 evidence_span: reduced by 62% exposure: Neuropathologically identified Wernicke encephalopathy with heavy alcohol exposure [hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908
Complete structured claim and evidence
Frontal-cortex EAAT2 protein was 71% lower in the five Wernicke cases than in five controls.
Thiamine (vitamin B1) → Human excitatory amino acid transporter 2 / SLC1A2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract; Results; Figure 1
evidence_span
diminished by 71%
experimental_model
Human frontal-cortex autopsy samples: five male Wernicke encephalopathy cases with alcohol intake above 80 g/day versus five male controls below 20 g/day; immunoblotting and histology.
exposure
Neuropathologically identified Wernicke encephalopathy with heavy alcohol exposure
limitations
Does not isolate thiamine from alcohol effects, establish the initiating event, or directly measure uptake in living patients.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
An astrocyte glutamate transporter was reduced in the sampled diseased human cortex.
primary_references
[hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908
tissue_or_cell_type
Frontal cortex
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1269–1281
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human frontal-cortex autopsy samples: five male Wernicke encephalopathy cases with alcohol intake above 80 g/day versus five male controls below 20 g/day; immunoblotting and histology. · source_derived_draft · unverified_draft
### thiamine-def-human-eaat2-loss Frontal-cortex EAAT2 protein was 71% lower in the five Wernicke cases than in five controls. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An astrocyte glutamate transporter was reduced in the sampled diseased human cortex. organism: Homo sapiens tissue_or_cell_type: Frontal cortex experimental_model: Human frontal-cortex autopsy samples: five male Wernicke encephalopathy cases with alcohol intake above 80 g/day versus five male controls below 20 g/day; immunoblotting and histology. limitations: Does not isolate thiamine from alcohol effects, establish the initiating event, or directly measure uptake in living patients. evidence_location: Abstract; Results; Figure 1 evidence_span: diminished by 71% exposure: Neuropathologically identified Wernicke encephalopathy with heavy alcohol exposure [hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908
Complete structured claim and evidence
N-acetylcysteine co-treatment prevented the loss of EAAT2 protein in medial thalamus of the depleted rats.
N-Acetyl-L-cysteine → Rat excitatory amino acid transporter 2 / Slc1a2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Rat Model of TD; Results; Figures 6-7
evidence_span
NAC prevented downregulation of the transporter protein
experimental_model
Male Sprague-Dawley rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day, with or without N-acetylcysteine 163 mg/kg/day intraperitoneally; day-14 symptomatic stage; pair-fed controls.
exposure
Pyrithiamine-assisted depletion with pharmacological N-acetylcysteine co-treatment
limitations
N-acetylcysteine has multiple actions; this does not prove a specific glutathione mechanism or support a human dosing recommendation.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
An antioxidant intervention preserved a glutamate transporter in this experimental model.
primary_references
[hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908
tissue_or_cell_type
Medial thalamus
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1283–1295
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male Sprague-Dawley rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day, with or without N-acetylcysteine 163 mg/kg/day intraperitoneally; day-14 symptomatic stage; pair-fed controls. · source_derived_draft · unverified_draft
### thiamine-def-nac-preserves-rat-eaat2 N-acetylcysteine co-treatment prevented the loss of EAAT2 protein in medial thalamus of the depleted rats. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An antioxidant intervention preserved a glutamate transporter in this experimental model. organism: Rattus norvegicus tissue_or_cell_type: Medial thalamus experimental_model: Male Sprague-Dawley rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day, with or without N-acetylcysteine 163 mg/kg/day intraperitoneally; day-14 symptomatic stage; pair-fed controls. limitations: N-acetylcysteine has multiple actions; this does not prove a specific glutathione mechanism or support a human dosing recommendation. evidence_location: Rat Model of TD; Results; Figures 6-7 evidence_span: NAC prevented downregulation of the transporter protein exposure: Pyrithiamine-assisted depletion with pharmacological N-acetylcysteine co-treatment [hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908
Complete structured claim and evidence
Medium from depleted astrocytes reduced glutamate uptake in naive recipient astrocytes by over 70% after 24 hours.
Thiamine (vitamin B1) → Astrocyte glutamate uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Results snippet: Effects of TD conditioned media on glutamate transport; Figure 1A
evidence_span
reduced by over 70% after 24 h
experimental_model
Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.
exposure
Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes
limitations
Conditioned medium is a mixture; this comparison alone cannot identify a secreted mediator or exclude carried-over medium components.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
The culture environment from depleted cells transferred a defect in glutamate removal.
primary_references
[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017
tissue_or_cell_type
Cultured astrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1297–1309
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. · source_derived_draft · unverified_draft
### thiamine-def-conditioned-medium-uptake Medium from depleted astrocytes reduced glutamate uptake in naive recipient astrocytes by over 70% after 24 hours. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The culture environment from depleted cells transferred a defect in glutamate removal. organism: Rattus norvegicus tissue_or_cell_type: Cultured astrocytes experimental_model: Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. limitations: Conditioned medium is a mixture; this comparison alone cannot identify a secreted mediator or exclude carried-over medium components. evidence_location: Results snippet: Effects of TD conditioned media on glutamate transport; Figure 1A evidence_span: reduced by over 70% after 24 h exposure: Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes [jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017
Complete structured claim and evidence
A TNF-alpha-neutralizing antibody blocked the increase in NF-kappa-B activation during astrocyte thiamine-disruption experiments.
Rat tumor necrosis factor alpha / Tnf → NF-kappa-B signaling source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract; TNF-alpha neutralization experiment
evidence_span
blocked the increased NF-κB activation
experimental_model
Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.
exposure
Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes
limitations
An antibody perturbation supports TNF involvement but does not establish that TNF alone explains every conditioned-medium effect.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Blocking TNF signaling interrupted an inflammatory response in the cultured cells.
primary_references
[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017
tissue_or_cell_type
Cultured astrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1311–1323
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. · source_derived_draft · unverified_draft
### thiamine-def-tnf-neutralization-nfkb A TNF-alpha-neutralizing antibody blocked the increase in NF-kappa-B activation during astrocyte thiamine-disruption experiments. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking TNF signaling interrupted an inflammatory response in the cultured cells. organism: Rattus norvegicus tissue_or_cell_type: Cultured astrocytes experimental_model: Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. limitations: An antibody perturbation supports TNF involvement but does not establish that TNF alone explains every conditioned-medium effect. evidence_location: Abstract; TNF-alpha neutralization experiment evidence_span: blocked the increased NF-κB activation exposure: Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes [jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017
Complete structured claim and evidence
NF-kappa-B inhibition attenuated GLT-1b loss in astrocytes exposed to the thiamine-disruption protocol.
NF-kappa-B signaling → Rat GLT-1b transporter isoform source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract; NF-kappa-B inhibitor experiment
evidence_span
ameliorated the decrease in GLT-1b
experimental_model
Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.
exposure
Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes
limitations
Pharmacological inhibition is not isoform-specific genetic proof; the accessible record does not establish efficacy in intact human brain.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Suppressing the inflammatory pathway helped preserve this particular glutamate-transporter isoform.
primary_references
[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017
tissue_or_cell_type
Cultured astrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1325–1337
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. · source_derived_draft · unverified_draft
### thiamine-def-nfkb-inhibition-glt1b NF-kappa-B inhibition attenuated GLT-1b loss in astrocytes exposed to the thiamine-disruption protocol. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suppressing the inflammatory pathway helped preserve this particular glutamate-transporter isoform. organism: Rattus norvegicus tissue_or_cell_type: Cultured astrocytes experimental_model: Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors. limitations: Pharmacological inhibition is not isoform-specific genetic proof; the accessible record does not establish efficacy in intact human brain. evidence_location: Abstract; NF-kappa-B inhibitor experiment evidence_span: ameliorated the decrease in GLT-1b exposure: Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes [jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. (2014). https://www.sciencedirect.com/science/article/abs/pii/S0006291X14006482 DOI: 10.1016/j.bbrc.2014.04.017
Complete structured claim and evidence
Intracellular thiamine diphosphate declined after thiamine withdrawal with an estimated elimination half-life of four to five days.
Thiamine (vitamin B1) → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
elimination half-life of 4-5 days
experimental_model
Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments.
exposure
Thiamine omitted from rat cardiac-cell growth medium
limitations
A culture-specific turnover estimate, not a universal body-store half-life.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
The active cofactor pool gradually ran down after thiamine was removed.
primary_references
[zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0
tissue_or_cell_type
Cultured cardiac cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1339–1351
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. · source_derived_draft · unverified_draft
### thiamine-def-cardiac-thdp-decay Intracellular thiamine diphosphate declined after thiamine withdrawal with an estimated elimination half-life of four to five days. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active cofactor pool gradually ran down after thiamine was removed. organism: Rattus norvegicus tissue_or_cell_type: Cultured cardiac cells experimental_model: Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. limitations: A culture-specific turnover estimate, not a universal body-store half-life. evidence_location: Abstract evidence_span: elimination half-life of 4-5 days exposure: Thiamine omitted from rat cardiac-cell growth medium [zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0
Complete structured claim and evidence
ATP began falling after eight days without thiamine and reached about half of control by day ten.
Thiamine (vitamin B1) → Cellular ATP content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
ATP level decreased after 8 days
experimental_model
Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments.
exposure
Thiamine omitted from rat cardiac-cell growth medium
limitations
Total ATP content does not distinguish reduced synthesis from altered consumption or identify one limiting enzyme.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Energy content fell before the reported onset of extensive degeneration.
primary_references
[zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0
tissue_or_cell_type
Cultured cardiac cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1353–1365
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. · source_derived_draft · unverified_draft
### thiamine-def-cardiac-atp-depletion ATP began falling after eight days without thiamine and reached about half of control by day ten. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Energy content fell before the reported onset of extensive degeneration. organism: Rattus norvegicus tissue_or_cell_type: Cultured cardiac cells experimental_model: Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. limitations: Total ATP content does not distinguish reduced synthesis from altered consumption or identify one limiting enzyme. evidence_location: Abstract evidence_span: ATP level decreased after 8 days exposure: Thiamine omitted from rat cardiac-cell growth medium [zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0
Complete structured claim and evidence
Spontaneous contractions stopped after ten to eleven days of thiamine withdrawal, as degeneration began.
Thiamine (vitamin B1) → Cardiomyocyte spontaneous contraction source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
spontaneous contractions ceased
experimental_model
Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments.
exposure
Thiamine omitted from rat cardiac-cell growth medium
limitations
This endpoint is distinct from human ejection fraction or arrhythmia risk; ATP causality was not isolated by this time course.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Prolonged deprivation eventually stopped the cultured heart cells beating.
primary_references
[zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0
tissue_or_cell_type
Cultured cardiac cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1367–1379
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. · source_derived_draft · unverified_draft
### thiamine-def-cardiac-contraction-cessation Spontaneous contractions stopped after ten to eleven days of thiamine withdrawal, as degeneration began. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Prolonged deprivation eventually stopped the cultured heart cells beating. organism: Rattus norvegicus tissue_or_cell_type: Cultured cardiac cells experimental_model: Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. limitations: This endpoint is distinct from human ejection fraction or arrhythmia risk; ATP causality was not isolated by this time course. evidence_location: Abstract evidence_span: spontaneous contractions ceased exposure: Thiamine omitted from rat cardiac-cell growth medium [zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0
Complete structured claim and evidence
The functional erythrocyte test compared transketolase activity before and after adding exogenous thiamine diphosphate.
Thiamine diphosphate → Blood transketolase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
before and after activation with exogenous thiamin diphosphate
experimental_model
Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays.
exposure
Laboratory assessment of thiamine status using erythrocytes or whole blood
limitations
Assay response is influenced by the enzyme preparation and assay conditions; a small response is not a measurement of every tissue.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
This asks how much extra cofactor can activate the sampled enzyme, whereas HPLC counts the cofactor itself.
primary_references
[baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617
tissue_or_cell_type
Erythrocyte hemolysates
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1381–1393
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. · source_derived_draft · unverified_draft
### thiamine-def-exogenous-thdp-functional-assay The functional erythrocyte test compared transketolase activity before and after adding exogenous thiamine diphosphate. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This asks how much extra cofactor can activate the sampled enzyme, whereas HPLC counts the cofactor itself. organism: Homo sapiens tissue_or_cell_type: Erythrocyte hemolysates experimental_model: Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. limitations: Assay response is influenced by the enzyme preparation and assay conditions; a small response is not a measurement of every tissue. evidence_location: Abstract evidence_span: before and after activation with exogenous thiamin diphosphate exposure: Laboratory assessment of thiamine status using erythrocytes or whole blood [baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617
Complete structured claim and evidence
Direct erythrocyte ThDP was more stable during frozen storage than transketolase activity in the evaluated preparations.
Erythrocyte thiamine diphosphate concentration → Blood transketolase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_location
Abstract
evidence_span
ETDP is more stable than ETKA in frozen erythrocytes
experimental_model
Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays.
exposure
Laboratory assessment of thiamine status using erythrocytes or whole blood
limitations
Historical assay comparison, not a validated stability duration for every modern collection tube or analytical platform.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Storage can affect the chemical measurement and the functional enzyme test differently.
primary_references
[baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617
tissue_or_cell_type
Frozen erythrocyte specimens
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1395–1407
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. · source_derived_draft · unverified_draft
### thiamine-def-frozen-erythrocyte-stability Direct erythrocyte ThDP was more stable during frozen storage than transketolase activity in the evaluated preparations. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Storage can affect the chemical measurement and the functional enzyme test differently. organism: Homo sapiens tissue_or_cell_type: Frozen erythrocyte specimens experimental_model: Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. limitations: Historical assay comparison, not a validated stability duration for every modern collection tube or analytical platform. evidence_location: Abstract evidence_span: ETDP is more stable than ETKA in frozen erythrocytes exposure: Laboratory assessment of thiamine status using erythrocytes or whole blood [baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617
Complete structured claim and evidence
HPLC whole-blood and erythrocyte ThDP measurements correlated at r = 0.97 in the study.
Whole-blood thiamine diphosphate concentration → Erythrocyte thiamine diphosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_location
Abstract Results
evidence_span
correlated strongly with that in whole blood
experimental_model
Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test.
exposure
Laboratory assessment of thiamine status using erythrocytes or whole blood
limitations
Correlation is not identity or a tissue-deficiency threshold; reported reference intervals were normalized to hemoglobin and are method-specific.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Whole blood and separated red cells gave closely related ThDP results under this method.
primary_references
[talwar-2000-blood-thdp] Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay (2000). https://pubmed.ncbi.nlm.nih.gov/10794754/ DOI: 10.1093/clinchem/46.5.704
tissue_or_cell_type
Whole blood and packed erythrocytes
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1409–1421
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test. · source_derived_draft · unverified_draft
### thiamine-def-wholeblood-erythrocyte-thdp-correlation HPLC whole-blood and erythrocyte ThDP measurements correlated at r = 0.97 in the study. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Whole blood and separated red cells gave closely related ThDP results under this method. organism: Homo sapiens tissue_or_cell_type: Whole blood and packed erythrocytes experimental_model: Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test. limitations: Correlation is not identity or a tissue-deficiency threshold; reported reference intervals were normalized to hemoglobin and are method-specific. evidence_location: Abstract Results evidence_span: correlated strongly with that in whole blood exposure: Laboratory assessment of thiamine status using erythrocytes or whole blood [talwar-2000-blood-thdp] Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay (2000). https://pubmed.ncbi.nlm.nih.gov/10794754/ DOI: 10.1093/clinchem/46.5.704
Complete structured claim and evidence
Some at-risk patients had low erythrocyte ThDP with a normal activation test, and one had an abnormal activation test with normal ThDP.
Erythrocyte thiamine diphosphate concentration → Erythrocyte transketolase activation coefficient source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_location
Abstract Results; classification comparison
evidence_span
normal by the activation test but had low TDP
experimental_model
Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test.
exposure
Laboratory assessment of thiamine status using erythrocytes or whole blood
limitations
Neither assay was independently validated against brain ThDP; no pooled sensitivity or specificity is inferred. The abstract contains inconsistent category totals, so no concordance percentage is calculated.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The direct and functional tests sometimes classified the same patient differently.
primary_references
[talwar-2000-blood-thdp] Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay (2000). https://pubmed.ncbi.nlm.nih.gov/10794754/ DOI: 10.1093/clinchem/46.5.704
tissue_or_cell_type
Blood
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1423–1435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test. · source_derived_draft · unverified_draft
### thiamine-def-direct-functional-assay-discordance Some at-risk patients had low erythrocyte ThDP with a normal activation test, and one had an abnormal activation test with normal ThDP. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The direct and functional tests sometimes classified the same patient differently. organism: Homo sapiens tissue_or_cell_type: Blood experimental_model: Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test. limitations: Neither assay was independently validated against brain ThDP; no pooled sensitivity or specificity is inferred. The abstract contains inconsistent category totals, so no concordance percentage is calculated. evidence_location: Abstract Results; classification comparison evidence_span: normal by the activation test but had low TDP exposure: Laboratory assessment of thiamine status using erythrocytes or whole blood [talwar-2000-blood-thdp] Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay (2000). https://pubmed.ncbi.nlm.nih.gov/10794754/ DOI: 10.1093/clinchem/46.5.704
Complete structured claim and evidence
Plasma thiamine increased significantly in both fortified-fish-sauce groups and was more responsive than the other measured thiamine forms.
Thiamine (vitamin B1) → Plasma thiamine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_location
Results 3.3; Table 3; Discussion
evidence_span
plasma thiamine was the most responsive measure
experimental_model
196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays.
exposure
Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women
limitations
An intake-responsive marker does not establish brain adequacy, clinical benefit or interchangeability with erythrocyte ThDP.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The plasma measurement was sensitive to added dietary thiamine in this population.
primary_references
[mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676
tissue_or_cell_type
Plasma
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1437–1449
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. · source_derived_draft · unverified_draft
### thiamine-def-plasma-thiamine-intake-response Plasma thiamine increased significantly in both fortified-fish-sauce groups and was more responsive than the other measured thiamine forms. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The plasma measurement was sensitive to added dietary thiamine in this population. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. limitations: An intake-responsive marker does not establish brain adequacy, clinical benefit or interchangeability with erythrocyte ThDP. evidence_location: Results 3.3; Table 3; Discussion evidence_span: plasma thiamine was the most responsive measure exposure: Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women [mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676
Complete structured claim and evidence
Baseline plasma thiamine correlated with erythrocyte ThDP at Spearman r = 0.41 in the 196 women.
Plasma thiamine concentration → Erythrocyte thiamine diphosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_location
Results 3.2; Table 2
evidence_span
Spearman correlation coefficients
experimental_model
196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays.
exposure
Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women
limitations
Cross-sectional correlation in healthy women does not validate a plasma cutoff for Wernicke encephalopathy.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Plasma and red-cell markers were related, but they captured different biological variation.
primary_references
[mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676
tissue_or_cell_type
Plasma and erythrocytes
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1451–1463
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. · source_derived_draft · unverified_draft
### thiamine-def-plasma-erythrocyte-imperfect-correlation Baseline plasma thiamine correlated with erythrocyte ThDP at Spearman r = 0.41 in the 196 women. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Plasma and red-cell markers were related, but they captured different biological variation. organism: Homo sapiens tissue_or_cell_type: Plasma and erythrocytes experimental_model: 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. limitations: Cross-sectional correlation in healthy women does not validate a plasma cutoff for Wernicke encephalopathy. evidence_location: Results 3.2; Table 2 evidence_span: Spearman correlation coefficients exposure: Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women [mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676
Complete structured claim and evidence
Baseline plasma thiamine monophosphate correlated with erythrocyte ThDP at Spearman r = 0.57 in 188 women.
Plasma thiamine monophosphate concentration → Erythrocyte thiamine diphosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_location
Results 3.2; Table 2
evidence_span
n = 188
experimental_model
196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays.
exposure
Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women
limitations
This is a different analyte from free plasma thiamine; a moderate correlation does not make the assays interchangeable.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The phosphorylated plasma form was also related to red-cell cofactor concentration.
primary_references
[mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676
tissue_or_cell_type
Plasma and erythrocytes
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1465–1477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. · source_derived_draft · unverified_draft
### thiamine-def-plasma-tmp-erythrocyte-correlation Baseline plasma thiamine monophosphate correlated with erythrocyte ThDP at Spearman r = 0.57 in 188 women. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphorylated plasma form was also related to red-cell cofactor concentration. organism: Homo sapiens tissue_or_cell_type: Plasma and erythrocytes experimental_model: 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. limitations: This is a different analyte from free plasma thiamine; a moderate correlation does not make the assays interchangeable. evidence_location: Results 3.2; Table 2 evidence_span: n = 188 exposure: Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women [mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676
Complete structured claim and evidence
All three infants with ophthalmoplegia-related neurological manifestations had blood lactic acidosis; two also had high cerebrospinal-fluid lactate.
Thiamine (vitamin B1) → Blood lactate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Results: three neurologically affected infants
evidence_span
All 3 had blood lactic acidosis
experimental_model
Nine Israeli infants aged 2-12 months exposed to a defective soy-based formula in the 2003 outbreak; clinical examination, erythrocyte transketolase activation, lactate and selected neuroimaging.
exposure
Consumption of a formula with thiamine below the assay detection limit
limitations
The paper reports blood without specifying plasma in the accessible results. All nine infants had concurrent infections, so lactate is not a specific deficiency test.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Severe infant deficiency could present with lactate accumulation alongside neurological signs.
primary_references
[fattal-valevski-2005-formula-outbreak] Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. (2005). https://pubmed.ncbi.nlm.nih.gov/15687431/ DOI: 10.1542/peds.2004-1255
tissue_or_cell_type
Blood and cerebrospinal fluid
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1479–1491
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine Israeli infants aged 2-12 months exposed to a defective soy-based formula in the 2003 outbreak; clinical examination, erythrocyte transketolase activation, lactate and selected neuroimaging. · source_derived_draft · unverified_draft
### thiamine-def-infant-neurologic-lactate All three infants with ophthalmoplegia-related neurological manifestations had blood lactic acidosis; two also had high cerebrospinal-fluid lactate. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe infant deficiency could present with lactate accumulation alongside neurological signs. organism: Homo sapiens tissue_or_cell_type: Blood and cerebrospinal fluid experimental_model: Nine Israeli infants aged 2-12 months exposed to a defective soy-based formula in the 2003 outbreak; clinical examination, erythrocyte transketolase activation, lactate and selected neuroimaging. limitations: The paper reports blood without specifying plasma in the accessible results. All nine infants had concurrent infections, so lactate is not a specific deficiency test. evidence_location: Results: three neurologically affected infants evidence_span: All 3 had blood lactic acidosis exposure: Consumption of a formula with thiamine below the assay detection limit [fattal-valevski-2005-formula-outbreak] Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. (2005). https://pubmed.ncbi.nlm.nih.gov/15687431/ DOI: 10.1542/peds.2004-1255
Complete structured claim and evidence
The index infant had nystagmus, ophthalmoplegia, elevated lactate and abnormal transketolase activation despite normal brain MRI.
Thiamine (vitamin B1) → Wernicke encephalopathy neurological symptoms source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Results: Patient 1
evidence_span
Brain magnetic resonance imaging (MRI) revealed no abnormalities
experimental_model
Nine Israeli infants aged 2-12 months exposed to a defective soy-based formula in the 2003 outbreak; clinical examination, erythrocyte transketolase activation, lactate and selected neuroimaging.
exposure
Consumption of a formula with thiamine below the assay detection limit
limitations
Single-patient diagnostic boundary; does not estimate MRI sensitivity or make every neurological symptom a thiamine-deficiency manifestation.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Normal structural imaging did not exclude clinically important deficiency in this infant.
primary_references
[fattal-valevski-2005-formula-outbreak] Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. (2005). https://pubmed.ncbi.nlm.nih.gov/15687431/ DOI: 10.1542/peds.2004-1255
tissue_or_cell_type
Neurological examination and brain MRI
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1493–1505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine Israeli infants aged 2-12 months exposed to a defective soy-based formula in the 2003 outbreak; clinical examination, erythrocyte transketolase activation, lactate and selected neuroimaging. · source_derived_draft · unverified_draft
### thiamine-def-infant-normal-mri-boundary The index infant had nystagmus, ophthalmoplegia, elevated lactate and abnormal transketolase activation despite normal brain MRI. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Normal structural imaging did not exclude clinically important deficiency in this infant. organism: Homo sapiens tissue_or_cell_type: Neurological examination and brain MRI experimental_model: Nine Israeli infants aged 2-12 months exposed to a defective soy-based formula in the 2003 outbreak; clinical examination, erythrocyte transketolase activation, lactate and selected neuroimaging. limitations: Single-patient diagnostic boundary; does not estimate MRI sensitivity or make every neurological symptom a thiamine-deficiency manifestation. evidence_location: Results: Patient 1 evidence_span: Brain magnetic resonance imaging (MRI) revealed no abnormalities exposure: Consumption of a formula with thiamine below the assay detection limit [fattal-valevski-2005-formula-outbreak] Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. (2005). https://pubmed.ncbi.nlm.nih.gov/15687431/ DOI: 10.1542/peds.2004-1255
Complete structured claim and evidence
In the 11-child severe-case series, three of five children with cardiac involvement had cardiomyopathy and died during the acute phase.
Thiamine (vitamin B1) → Infant cardiomyopathy source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract Patients
evidence_span
had cardiomyopathy and died in the acute phase
experimental_model
Case series of 11 severely affected children from the Israeli thiamine-deficient formula outbreak, with longitudinal follow-up of eight initial survivors.
exposure
Consumption of a formula with thiamine below the assay detection limit
limitations
Selected severe cases cannot estimate risk among all formula-exposed infants or demonstrate a particular molecular cause of cardiomyopathy.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Severe infant thiamine deficiency could involve fatal heart disease.
primary_references
[mimouni-bloch-2014-infant-followup] Thiamine deficiency in infancy: long-term follow-up. (2014). https://pubmed.ncbi.nlm.nih.gov/25160536/ DOI: 10.1016/j.pediatrneurol.2014.05.010
tissue_or_cell_type
Heart and clinical course
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1507–1519
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case series of 11 severely affected children from the Israeli thiamine-deficient formula outbreak, with longitudinal follow-up of eight initial survivors. · source_derived_draft · unverified_draft
### thiamine-def-infant-acute-cardiomyopathy In the 11-child severe-case series, three of five children with cardiac involvement had cardiomyopathy and died during the acute phase. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe infant thiamine deficiency could involve fatal heart disease. organism: Homo sapiens tissue_or_cell_type: Heart and clinical course experimental_model: Case series of 11 severely affected children from the Israeli thiamine-deficient formula outbreak, with longitudinal follow-up of eight initial survivors. limitations: Selected severe cases cannot estimate risk among all formula-exposed infants or demonstrate a particular molecular cause of cardiomyopathy. evidence_location: Abstract Patients evidence_span: had cardiomyopathy and died in the acute phase exposure: Consumption of a formula with thiamine below the assay detection limit [mimouni-bloch-2014-infant-followup] Thiamine deficiency in infancy: long-term follow-up. (2014). https://pubmed.ncbi.nlm.nih.gov/25160536/ DOI: 10.1016/j.pediatrneurol.2014.05.010
Complete structured claim and evidence
During follow-up, seven children had cognitive and motor impairment, and six developed severe epilepsy after the initial deficiency episode.
Thiamine (vitamin B1) → Infant neurodevelopmental impairment source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract Results
evidence_span
six developed severe epilepsy
experimental_model
Case series of 11 severely affected children from the Israeli thiamine-deficient formula outbreak, with longitudinal follow-up of eight initial survivors.
exposure
Consumption of a formula with thiamine below the assay detection limit
limitations
Selected severe survivor cohort without an unexposed comparison; not evidence that mild or asymptomatic low intake has the same prognosis.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Correction of the nutritional exposure did not guarantee recovery from established neurological injury.
primary_references
[mimouni-bloch-2014-infant-followup] Thiamine deficiency in infancy: long-term follow-up. (2014). https://pubmed.ncbi.nlm.nih.gov/25160536/ DOI: 10.1016/j.pediatrneurol.2014.05.010
tissue_or_cell_type
Longitudinal neurodevelopmental assessment
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1521–1533
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case series of 11 severely affected children from the Israeli thiamine-deficient formula outbreak, with longitudinal follow-up of eight initial survivors. · source_derived_draft · unverified_draft
### thiamine-def-infant-persistent-neurodevelopmental-sequelae During follow-up, seven children had cognitive and motor impairment, and six developed severe epilepsy after the initial deficiency episode. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correction of the nutritional exposure did not guarantee recovery from established neurological injury. organism: Homo sapiens tissue_or_cell_type: Longitudinal neurodevelopmental assessment experimental_model: Case series of 11 severely affected children from the Israeli thiamine-deficient formula outbreak, with longitudinal follow-up of eight initial survivors. limitations: Selected severe survivor cohort without an unexposed comparison; not evidence that mild or asymptomatic low intake has the same prognosis. evidence_location: Abstract Results evidence_span: six developed severe epilepsy exposure: Consumption of a formula with thiamine below the assay detection limit [mimouni-bloch-2014-infant-followup] Thiamine deficiency in infancy: long-term follow-up. (2014). https://pubmed.ncbi.nlm.nih.gov/25160536/ DOI: 10.1016/j.pediatrneurol.2014.05.010
Complete structured claim and evidence
Most nonalcoholic thiamine-deficiency neuropathy cases showed motor-dominant, relatively acute progression, unlike the more slowly progressive sensory-dominant pure alcoholic-neuropathy group.
Thiamine (vitamin B1) → Motor-dominant peripheral neuropathy source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract: clinical comparison
evidence_span
motor-dominant and acutely progressive pattern
experimental_model
Clinical and sural-nerve pathology comparison of 64 alcoholic-neuropathy patients subdivided by coexisting thiamine deficiency and 32 nonalcoholic thiamine-deficiency neuropathy patients.
exposure
Nonalcoholic thiamine-deficiency neuropathy identified in a clinical cohort
limitations
Observational referral cohort; mixed alcohol-plus-deficiency cases had overlapping features, so phenotype alone cannot determine cause.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Thiamine-related nerve injury and alcohol-related nerve injury showed different typical clinical patterns.
primary_references
[koike-2003-neuropathy-subtypes] Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy (2003). https://pubmed.ncbi.nlm.nih.gov/12838517/ DOI: 10.1002/ana.10550
tissue_or_cell_type
Peripheral neurological examination
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1535–1547
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical and sural-nerve pathology comparison of 64 alcoholic-neuropathy patients subdivided by coexisting thiamine deficiency and 32 nonalcoholic thiamine-deficiency neuropathy patients. · source_derived_draft · unverified_draft
### thiamine-def-motor-neuropathy-pattern Most nonalcoholic thiamine-deficiency neuropathy cases showed motor-dominant, relatively acute progression, unlike the more slowly progressive sensory-dominant pure alcoholic-neuropathy group. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thiamine-related nerve injury and alcohol-related nerve injury showed different typical clinical patterns. organism: Homo sapiens tissue_or_cell_type: Peripheral neurological examination experimental_model: Clinical and sural-nerve pathology comparison of 64 alcoholic-neuropathy patients subdivided by coexisting thiamine deficiency and 32 nonalcoholic thiamine-deficiency neuropathy patients. limitations: Observational referral cohort; mixed alcohol-plus-deficiency cases had overlapping features, so phenotype alone cannot determine cause. evidence_location: Abstract: clinical comparison evidence_span: motor-dominant and acutely progressive pattern exposure: Nonalcoholic thiamine-deficiency neuropathy identified in a clinical cohort [koike-2003-neuropathy-subtypes] Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy (2003). https://pubmed.ncbi.nlm.nih.gov/12838517/ DOI: 10.1002/ana.10550
Complete structured claim and evidence
Large-fiber-predominant axonal loss characterized the thiamine-deficiency group, whereas small-fiber loss predominated in the pure alcoholic-neuropathy group.
Thiamine (vitamin B1) → Peripheral large-fiber axonal loss source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract: sural-nerve pathology comparison
evidence_span
Large-fiber-predominant axonal loss predominated in TDN
experimental_model
Clinical and sural-nerve pathology comparison of 64 alcoholic-neuropathy patients subdivided by coexisting thiamine deficiency and 32 nonalcoholic thiamine-deficiency neuropathy patients.
exposure
Nonalcoholic thiamine-deficiency neuropathy identified in a clinical cohort
limitations
Biopsy association does not identify a single biochemical injury step or imply that every thiamine-deficient patient loses only large fibers.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The nerve biopsies also distinguished the dominant injury patterns.
primary_references
[koike-2003-neuropathy-subtypes] Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy (2003). https://pubmed.ncbi.nlm.nih.gov/12838517/ DOI: 10.1002/ana.10550
tissue_or_cell_type
Sural nerve biopsy specimens
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1549–1561
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical and sural-nerve pathology comparison of 64 alcoholic-neuropathy patients subdivided by coexisting thiamine deficiency and 32 nonalcoholic thiamine-deficiency neuropathy patients. · source_derived_draft · unverified_draft
### thiamine-def-large-fiber-neuropathy-pathology Large-fiber-predominant axonal loss characterized the thiamine-deficiency group, whereas small-fiber loss predominated in the pure alcoholic-neuropathy group. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nerve biopsies also distinguished the dominant injury patterns. organism: Homo sapiens tissue_or_cell_type: Sural nerve biopsy specimens experimental_model: Clinical and sural-nerve pathology comparison of 64 alcoholic-neuropathy patients subdivided by coexisting thiamine deficiency and 32 nonalcoholic thiamine-deficiency neuropathy patients. limitations: Biopsy association does not identify a single biochemical injury step or imply that every thiamine-deficient patient loses only large fibers. evidence_location: Abstract: sural-nerve pathology comparison evidence_span: Large-fiber-predominant axonal loss predominated in TDN exposure: Nonalcoholic thiamine-deficiency neuropathy identified in a clinical cohort [koike-2003-neuropathy-subtypes] Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy (2003). https://pubmed.ncbi.nlm.nih.gov/12838517/ DOI: 10.1002/ana.10550
Complete structured claim and evidence
Both beriberi cases had elevated cardiac output before treatment; output fell toward normal after thiamine treatment.
Thiamine (vitamin B1) → Cardiac output source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Two-patient hemodynamic report; baseline outputs 17.3 and 7.4 L/min.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
Case evidence, not a diagnostic rule; severe beriberi can have other hemodynamic patterns.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 deficiency can involve excessive circulatory flow, not only a weak pumping fraction.
primary_references
[b1-byrne-quinn1969] Beriberi heart disease in London (1969). https://pubmed.ncbi.nlm.nih.gov/5822083/ DOI: 10.1136/bmj.4.5674.25
tissue_or_cell_type
Cardiovascular circulation
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1563–1573
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-patient hemodynamic report; baseline outputs 17.3 and 7.4 L/min. · source_derived_draft · unverified_draft
### b1-beriberi-cardiac-output Both beriberi cases had elevated cardiac output before treatment; output fell toward normal after thiamine treatment. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 deficiency can involve excessive circulatory flow, not only a weak pumping fraction. organism: Homo sapiens tissue_or_cell_type: Cardiovascular circulation experimental_model: Two-patient hemodynamic report; baseline outputs 17.3 and 7.4 L/min. limitations: Case evidence, not a diagnostic rule; severe beriberi can have other hemodynamic patterns. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-byrne-quinn1969] Beriberi heart disease in London (1969). https://pubmed.ncbi.nlm.nih.gov/5822083/ DOI: 10.1136/bmj.4.5674.25
Complete structured claim and evidence
In the second patient, systemic vascular resistance rose within one to two hours after intravenous thiamine as cardiac output fell.
Thiamine (vitamin B1) → Systemic vascular resistance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Serial measurements in one of the two cases.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
No specific endothelial receptor, nitric oxide pathway or direct ATP mediator was isolated.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The abnormal circulation involved the blood vessels as well as the heart.
primary_references
[b1-byrne-quinn1969] Beriberi heart disease in London (1969). https://pubmed.ncbi.nlm.nih.gov/5822083/ DOI: 10.1136/bmj.4.5674.25
tissue_or_cell_type
Systemic vasculature
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1575–1585
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Serial measurements in one of the two cases. · source_derived_draft · unverified_draft
### b1-beriberi-vascular-resistance In the second patient, systemic vascular resistance rose within one to two hours after intravenous thiamine as cardiac output fell. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The abnormal circulation involved the blood vessels as well as the heart. organism: Homo sapiens tissue_or_cell_type: Systemic vasculature experimental_model: Serial measurements in one of the two cases. limitations: No specific endothelial receptor, nitric oxide pathway or direct ATP mediator was isolated. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-byrne-quinn1969] Beriberi heart disease in London (1969). https://pubmed.ncbi.nlm.nih.gov/5822083/ DOI: 10.1136/bmj.4.5674.25
Complete structured claim and evidence
The thiamine-containing infusion increased erythrocyte ThDP in both thiamine-treated groups at two hours.
Parenteral B-vitamin and vitamin C preparation → Erythrocyte thiamine diphosphate concentration source_derived_draftungraded
Experimental context and source evidence
experimental_model
Three-arm randomized trial.
exposure
Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations.
limitations
Most patients already had normal/high erythrocyte ThDP; an increase does not establish brain repletion. Pabrinex included other vitamins.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The blood cofactor measurement rose after the thiamine-containing infusion.
primary_references
[b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
tissue_or_cell_type
Erythrocytes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1587–1597
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-arm randomized trial. · source_derived_draft · unverified_draft
### b1-aws-thiamine-raises-thdp The thiamine-containing infusion increased erythrocyte ThDP in both thiamine-treated groups at two hours. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood cofactor measurement rose after the thiamine-containing infusion. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Three-arm randomized trial. limitations: Most patients already had normal/high erythrocyte ThDP; an increase does not establish brain repletion. Pabrinex included other vitamins. exposure: Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations. [b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
Complete structured claim and evidence
The trial found no significant between-group effect on its primary endpoint of change in erythrocyte transketolase activity.
Magnesium sulfate → Blood transketolase activity source_derived_draftungraded
Experimental context and source evidence
experimental_model
115 analyzed; biochemical measurement two hours after treatment.
exposure
Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations.
limitations
Does not refute molecular Mg requirements or prove no effect in deficient tissues; almost all participants lacked low erythrocyte ThDP.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The enzyme endpoint did not improve significantly across treatment groups.
primary_references
[b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
tissue_or_cell_type
Erythrocytes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1599–1609
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 115 analyzed; biochemical measurement two hours after treatment. · source_derived_draft · unverified_draft
### b1-aws-mg-transketolase-null The trial found no significant between-group effect on its primary endpoint of change in erythrocyte transketolase activity. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme endpoint did not improve significantly across treatment groups. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: 115 analyzed; biochemical measurement two hours after treatment. limitations: Does not refute molecular Mg requirements or prove no effect in deficient tissues; almost all participants lacked low erythrocyte ThDP. exposure: Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations. [b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
Complete structured claim and evidence
Median lactate normalized across overall treatment groups, but not in the low-magnesium subgroup receiving the thiamine-containing preparation alone.
Magnesium sulfate → Plasma lactate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium status -> response during thiamine-containing treatment.
experimental_model
Low-Mg thiamine-only subgroup n=22; two-hour measurement.
exposure
Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations.
limitations
Subgroup finding; no direct PDH flux or universal magnesium gate demonstrated. Pabrinex is multivitamins.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Low magnesium identified a subgroup whose lactate did not normalize with the vitamin infusion alone.
primary_references
[b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
tissue_or_cell_type
Plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1611–1622
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Low-Mg thiamine-only subgroup n=22; two-hour measurement. · source_derived_draft · unverified_draft
### b1-aws-low-mg-lactate-response Median lactate normalized across overall treatment groups, but not in the low-magnesium subgroup receiving the thiamine-containing preparation alone. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low magnesium identified a subgroup whose lactate did not normalize with the vitamin infusion alone. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Low-Mg thiamine-only subgroup n=22; two-hour measurement. limitations: Subgroup finding; no direct PDH flux or universal magnesium gate demonstrated. Pabrinex is multivitamins. cross_nutrient: Magnesium status -> response during thiamine-containing treatment. exposure: Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations. [b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
Complete structured claim and evidence
Median time to initial GMAWS zero was 10 hours with thiamine-containing treatment, 5.5 with combined treatment and 6 with initial magnesium.
Magnesium sulfate → Alcohol withdrawal symptom score source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized treatment plus routine withdrawal care.
exposure
Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations.
limitations
The magnesium-only arm received thiamine after its two-hour sample; this is not magnesium monotherapy throughout follow-up or proof of total withdrawal cure.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Initial withdrawal scores reached zero sooner in the magnesium arms.
primary_references
[b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
tissue_or_cell_type
Clinical symptom score
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1624–1634
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized treatment plus routine withdrawal care. · source_derived_draft · unverified_draft
### b1-aws-resolution-time Median time to initial GMAWS zero was 10 hours with thiamine-containing treatment, 5.5 with combined treatment and 6 with initial magnesium. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Initial withdrawal scores reached zero sooner in the magnesium arms. organism: Homo sapiens tissue_or_cell_type: Clinical symptom score experimental_model: Randomized treatment plus routine withdrawal care. limitations: The magnesium-only arm received thiamine after its two-hour sample; this is not magnesium monotherapy throughout follow-up or proof of total withdrawal cure. exposure: Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations. [b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
Complete structured claim and evidence
Thiamine did not significantly lower the 24-hour lactate primary outcome in the overall septic-shock pilot cohort.
Thiamine (vitamin B1) → Plasma lactate concentration source_derived_draftungraded
Experimental context and source evidence
experimental_model
88 patients; placebo comparison.
exposure
Intravenous thiamine 200 mg twice daily versus placebo for up to seven days or hospital discharge; trial exposure only.
limitations
The study was small; overall null results do not rule out deficiency-specific effects.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
An essential metabolic cofactor did not improve this endpoint for the whole trial population.
primary_references
[b1-donnino2016] Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study (2016). https://pubmed.ncbi.nlm.nih.gov/26771781/ DOI: 10.1097/ccm.0000000000001572
tissue_or_cell_type
Plasma
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1636–1646
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 88 patients; placebo comparison. · source_derived_draft · unverified_draft
### b1-sepsis-overall-lactate-null Thiamine did not significantly lower the 24-hour lactate primary outcome in the overall septic-shock pilot cohort. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An essential metabolic cofactor did not improve this endpoint for the whole trial population. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: 88 patients; placebo comparison. limitations: The study was small; overall null results do not rule out deficiency-specific effects. exposure: Intravenous thiamine 200 mg twice daily versus placebo for up to seven days or hospital discharge; trial exposure only. [b1-donnino2016] Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study (2016). https://pubmed.ncbi.nlm.nih.gov/26771781/ DOI: 10.1097/ccm.0000000000001572
Complete structured claim and evidence
Among the 35% classified deficient at baseline, the prespecified subgroup had lower 24-hour lactate with thiamine than placebo.
Thiamine (vitamin B1) → Plasma lactate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Prespecified subgroup within pilot trial.
exposure
Intravenous thiamine 200 mg twice daily versus placebo for up to seven days or hospital discharge; trial exposure only.
limitations
Small subgroup; treatment did not improve overall-cohort outcomes and the exact mediator was not measured.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Baseline status may help explain why some patients responded differently.
primary_references
[b1-donnino2016] Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study (2016). https://pubmed.ncbi.nlm.nih.gov/26771781/ DOI: 10.1097/ccm.0000000000001572
tissue_or_cell_type
Plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1648–1658
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prespecified subgroup within pilot trial. · source_derived_draft · unverified_draft
### b1-sepsis-deficient-subgroup Among the 35% classified deficient at baseline, the prespecified subgroup had lower 24-hour lactate with thiamine than placebo. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Baseline status may help explain why some patients responded differently. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Prespecified subgroup within pilot trial. limitations: Small subgroup; treatment did not improve overall-cohort outcomes and the exact mediator was not measured. exposure: Intravenous thiamine 200 mg twice daily versus placebo for up to seven days or hospital discharge; trial exposure only. [b1-donnino2016] Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study (2016). https://pubmed.ncbi.nlm.nih.gov/26771781/ DOI: 10.1097/ccm.0000000000001572
Complete structured claim and evidence
TRPSS did not find a statistically significant difference in its primary creatinine trajectory endpoint; the 72-hour estimate was -0.57 mg/dL, 95% CI -1.18 to 0.04.
Thiamine (vitamin B1) → Serum creatinine concentration source_derived_draftungraded
Experimental context and source evidence
experimental_model
88 treated patients with septic shock.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
ICU-free days favored thiamine as a secondary outcome; kidney replacement, severe AKI and mortality differences were not significant.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The renal-protection trial left an uncertain estimate rather than proving benefit.
primary_references
[b1-trpss2023] Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial (2023). https://pubmed.ncbi.nlm.nih.gov/37364280/ DOI: 10.1164/rccm.202301-0034oc
tissue_or_cell_type
Serum/clinical kidney endpoints
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1660–1670
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 88 treated patients with septic shock. · source_derived_draft · unverified_draft
### b1-trpss-creatinine-null TRPSS did not find a statistically significant difference in its primary creatinine trajectory endpoint; the 72-hour estimate was -0.57 mg/dL, 95% CI -1.18 to 0.04. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The renal-protection trial left an uncertain estimate rather than proving benefit. organism: Homo sapiens tissue_or_cell_type: Serum/clinical kidney endpoints experimental_model: 88 treated patients with septic shock. limitations: ICU-free days favored thiamine as a secondary outcome; kidney replacement, severe AKI and mortality differences were not significant. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-trpss2023] Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial (2023). https://pubmed.ncbi.nlm.nih.gov/37364280/ DOI: 10.1164/rccm.202301-0034oc
Complete structured claim and evidence
The nine-patient crossover trial reported an absolute LVEF treatment effect of 3.9 percentage points after 28 days.
Thiamine (vitamin B1) → Left ventricular ejection fraction source_derived_draftungraded
Experimental context and source evidence
experimental_model
Nine diuretic-treated patients; randomized crossover.
exposure
300 mg/day thiamine versus placebo for 28 days, six-week washout then crossover; trial exposure only.
limitations
Small pilot with short periods; not proof that all heart failure is B1 deficiency.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A very small heart-failure trial reported improved pumping fraction.
primary_references
[b1-schoenenberger2012] Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study (2012). https://pubmed.ncbi.nlm.nih.gov/22057652/ DOI: 10.1007/s00392-011-0376-2
tissue_or_cell_type
Heart imaging
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1672–1682
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine diuretic-treated patients; randomized crossover. · source_derived_draft · unverified_draft
### b1-hf-pilot-lvef-positive The nine-patient crossover trial reported an absolute LVEF treatment effect of 3.9 percentage points after 28 days. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A very small heart-failure trial reported improved pumping fraction. organism: Homo sapiens tissue_or_cell_type: Heart imaging experimental_model: Nine diuretic-treated patients; randomized crossover. limitations: Small pilot with short periods; not proof that all heart failure is B1 deficiency. exposure: 300 mg/day thiamine versus placebo for 28 days, six-week washout then crossover; trial exposure only. [b1-schoenenberger2012] Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study (2012). https://pubmed.ncbi.nlm.nih.gov/22057652/ DOI: 10.1007/s00392-011-0376-2
Complete structured claim and evidence
Six months of thiamine did not improve LVEF, exercise capacity or quality of life in 69 ambulatory patients. Baseline-adjusted LVEF was higher with placebo (38%) than thiamine (35%), P=0.047.
Thiamine (vitamin B1) → Left ventricular ejection fraction source_derived_draftungraded
Experimental context and source evidence
experimental_model
Placebo-controlled multicenter trial.
exposure
200 mg oral thiamine mononitrate daily versus placebo for six months; trial exposure only.
limitations
Dose, duration, participants and crossover versus parallel design differ from the earlier pilot; not a test of untreated beriberi or proof of universal cardiac harm.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The larger trial did not reproduce improved pumping; its adjusted LVEF comparison favored placebo.
primary_references
[b1-keith2019] Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31504093/ DOI: 10.1093/ajcn/nqz192
tissue_or_cell_type
Heart imaging and function
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1684–1694
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled multicenter trial. · source_derived_draft · unverified_draft
### b1-hf-larger-lvef-null Six months of thiamine did not improve LVEF, exercise capacity or quality of life in 69 ambulatory patients. Baseline-adjusted LVEF was higher with placebo (38%) than thiamine (35%), P=0.047. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The larger trial did not reproduce improved pumping; its adjusted LVEF comparison favored placebo. organism: Homo sapiens tissue_or_cell_type: Heart imaging and function experimental_model: Placebo-controlled multicenter trial. limitations: Dose, duration, participants and crossover versus parallel design differ from the earlier pilot; not a test of untreated beriberi or proof of universal cardiac harm. exposure: 200 mg oral thiamine mononitrate daily versus placebo for six months; trial exposure only. [b1-keith2019] Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31504093/ DOI: 10.1093/ajcn/nqz192
Complete structured claim and evidence
Erythrocyte thiamine pyrophosphate and urinary thiamine increased in the 2019 chronic-HF trial despite no functional benefit.
Thiamine (vitamin B1) → Erythrocyte thiamine diphosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Same 69-person trial; six-month biomarker measurement.
exposure
200 mg oral thiamine mononitrate daily versus placebo for six months; trial exposure only.
limitations
Biochemical uptake does not establish the rate-limiting cause of cardiac dysfunction.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A higher vitamin measurement did not guarantee better heart function.
primary_references
[b1-keith2019] Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31504093/ DOI: 10.1093/ajcn/nqz192
tissue_or_cell_type
Erythrocytes and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1696–1706
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same 69-person trial; six-month biomarker measurement. · source_derived_draft · unverified_draft
### b1-hf-biomarker-response Erythrocyte thiamine pyrophosphate and urinary thiamine increased in the 2019 chronic-HF trial despite no functional benefit. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher vitamin measurement did not guarantee better heart function. organism: Homo sapiens tissue_or_cell_type: Erythrocytes and urine experimental_model: Same 69-person trial; six-month biomarker measurement. limitations: Biochemical uptake does not establish the rate-limiting cause of cardiac dysfunction. exposure: 200 mg oral thiamine mononitrate daily versus placebo for six months; trial exposure only. [b1-keith2019] Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31504093/ DOI: 10.1093/ajcn/nqz192
Complete structured claim and evidence
The acute-HF trial found no consistent benefit across dyspnea measurements or secondary outcomes in predominantly nondeficient participants.
Thiamine (vitamin B1) → Dyspnea during acute heart failure source_derived_draftungraded
Experimental context and source evidence
experimental_model
118 evaluable participants of 130 randomized; two-day intervention.
exposure
100 mg thiamine versus placebo on each of the first two evenings; outcomes eight hours after infusion; trial exposure only.
limitations
One sitting-on-oxygen dyspnea comparison was significant; other dyspnea measures and secondary outcomes were not. Only one participant was deficient.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Routine supplementation did not produce a consistent symptom benefit in this population.
primary_references
[b1-smithline2019] Supplemental thiamine for the treatment of acute heart failure syndrome: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31060559/ DOI: 10.1186/s12906-019-2506-8
tissue_or_cell_type
Clinical symptoms
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1708–1718
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 118 evaluable participants of 130 randomized; two-day intervention. · source_derived_draft · unverified_draft
### b1-acute-hf-limited-response The acute-HF trial found no consistent benefit across dyspnea measurements or secondary outcomes in predominantly nondeficient participants. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Routine supplementation did not produce a consistent symptom benefit in this population. organism: Homo sapiens tissue_or_cell_type: Clinical symptoms experimental_model: 118 evaluable participants of 130 randomized; two-day intervention. limitations: One sitting-on-oxygen dyspnea comparison was significant; other dyspnea measures and secondary outcomes were not. Only one participant was deficient. exposure: 100 mg thiamine versus placebo on each of the first two evenings; outcomes eight hours after infusion; trial exposure only. [b1-smithline2019] Supplemental thiamine for the treatment of acute heart failure syndrome: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31060559/ DOI: 10.1186/s12906-019-2506-8
Complete structured claim and evidence
Furosemide and saline interventions increased urinary thiamine loss in six volunteers; excretion tracked urine flow without an additional intervention-type effect.
Urine flow rate → Urinary thiamine excretion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Diuresis links vitamin loss with renal electrolyte management.
experimental_model
Timed crossover physiologic measurements.
exposure
Single intravenous furosemide doses 1, 3 and 10 mg, and a separate 750 mL saline infusion; acute physiologic study exposures.
limitations
Acute small study; cannot predict chronic deficiency for every diuretic user or infer a universal flow threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Producing more urine can increase B1 loss even without a unique drug-specific mechanism.
primary_references
[b1-rieck1999] Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers (1999). https://pubmed.ncbi.nlm.nih.gov/10482308/ DOI: 10.1016/s0022-2143(99)90203-2
tissue_or_cell_type
Urine
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1720–1731
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Timed crossover physiologic measurements. · source_derived_draft · unverified_draft
### b1-diuresis-urinary-loss Furosemide and saline interventions increased urinary thiamine loss in six volunteers; excretion tracked urine flow without an additional intervention-type effect. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Producing more urine can increase B1 loss even without a unique drug-specific mechanism. organism: Homo sapiens tissue_or_cell_type: Urine experimental_model: Timed crossover physiologic measurements. limitations: Acute small study; cannot predict chronic deficiency for every diuretic user or infer a universal flow threshold. cross_nutrient: Diuresis links vitamin loss with renal electrolyte management. exposure: Single intravenous furosemide doses 1, 3 and 10 mg, and a separate 750 mL saline infusion; acute physiologic study exposures. [b1-rieck1999] Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers (1999). https://pubmed.ncbi.nlm.nih.gov/10482308/ DOI: 10.1016/s0022-2143(99)90203-2
Complete structured claim and evidence
Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support.
Thiamine (vitamin B1) → Electrolyte and fluid disorder during refeeding source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B1 repletion and K/P/Mg management address different requirements.
experimental_model
Prospective cohort and individual case histories.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Providing vitamins did not by itself prevent every electrolyte and fluid complication.
primary_references
[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
tissue_or_cell_type
Whole-body clinical nutrition
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1733–1744
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cohort and individual case histories. · source_derived_draft · unverified_draft
### b1-refeeding-vitamins-not-complete-rescue Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing vitamins did not by itself prevent every electrolyte and fluid complication. organism: Homo sapiens tissue_or_cell_type: Whole-body clinical nutrition experimental_model: Prospective cohort and individual case histories. limitations: No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency. cross_nutrient: B1 repletion and K/P/Mg management address different requirements. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
Complete structured claim and evidence
Low baseline serum magnesium was associated with subsequent refeeding syndrome in the cohort.
Serum magnesium concentration → Electrolyte and fluid disorder during refeeding source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Three syndrome events among 243 adults.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
Too few events for robust multivariable regression; association does not identify a universal causal bottleneck.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A mineral shortage was a risk signal alongside poor prior intake.
primary_references
[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
tissue_or_cell_type
Serum and clinical course
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1746–1756
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three syndrome events among 243 adults. · source_derived_draft · unverified_draft
### b1-refeeding-low-mg-association Low baseline serum magnesium was associated with subsequent refeeding syndrome in the cohort. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mineral shortage was a risk signal alongside poor prior intake. organism: Homo sapiens tissue_or_cell_type: Serum and clinical course experimental_model: Three syndrome events among 243 adults. limitations: Too few events for robust multivariable regression; association does not identify a universal causal bottleneck. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
Complete structured claim and evidence
Two leukemia cases with acute thiamine deficiency showed proximal tubular dysfunction and electrolyte abnormalities resembling refeeding syndrome.
Thiamine (vitamin B1) → Renal tubular electrolyte loss source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B1 shortage -> renal electrolyte handling in case evidence.
experimental_model
Two pediatric cases.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells.
primary_references
[b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019
tissue_or_cell_type
Kidney and blood
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1758–1769
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two pediatric cases. · source_derived_draft · unverified_draft
### b1-deficiency-renal-electrolyte-loss Two leukemia cases with acute thiamine deficiency showed proximal tubular dysfunction and electrolyte abnormalities resembling refeeding syndrome. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells. organism: Homo sapiens tissue_or_cell_type: Kidney and blood experimental_model: Two pediatric cases. limitations: The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here. cross_nutrient: B1 shortage -> renal electrolyte handling in case evidence. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019
Complete structured claim and evidence
Thiamine administration was followed by rapid resolution of tubular dysfunction, acidosis and electrolyte imbalance in the two cases.
Thiamine (vitamin B1) → Proximal renal tubular function source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Clinical treatment response.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
Temporal rescue supports the attribution but does not quantify how often it occurs or prove a specific transport-protein mechanism.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Replacing B1 was followed by recovery of the kidney-handling abnormality.
primary_references
[b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019
tissue_or_cell_type
Kidney and blood
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1771–1781
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical treatment response. · source_derived_draft · unverified_draft
### b1-repletion-tubular-recovery Thiamine administration was followed by rapid resolution of tubular dysfunction, acidosis and electrolyte imbalance in the two cases. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing B1 was followed by recovery of the kidney-handling abnormality. organism: Homo sapiens tissue_or_cell_type: Kidney and blood experimental_model: Clinical treatment response. limitations: Temporal rescue supports the attribution but does not quantify how often it occurs or prove a specific transport-protein mechanism. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019
Complete structured claim and evidence
Six patients developed severe lactic acidosis within four weeks of vitamin-unsupplemented parenteral nutrition; lactate and pyruvate were elevated.
Thiamine (vitamin B1) → Lactic acidosis in thiamine deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Six postoperative cases with severely limited oral intake.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
Clinical observations; no isolated test of PDH activity or tissue-specific thiamine threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Calories alone did not supply the cofactors needed to use them normally.
primary_references
[b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x
tissue_or_cell_type
Blood/systemic metabolism
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1783–1793
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six postoperative cases with severely limited oral intake. · source_derived_draft · unverified_draft
### b1-tpn-lactate-pyruvate Six patients developed severe lactic acidosis within four weeks of vitamin-unsupplemented parenteral nutrition; lactate and pyruvate were elevated. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calories alone did not supply the cofactors needed to use them normally. organism: Homo sapiens tissue_or_cell_type: Blood/systemic metabolism experimental_model: Six postoperative cases with severely limited oral intake. limitations: Clinical observations; no isolated test of PDH activity or tissue-specific thiamine threshold. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x
Complete structured claim and evidence
Thiamine replenishment resolved lactic acidosis and improved clinical status in three patients in the reported series.
Thiamine (vitamin B1) → Lactic acidosis in thiamine deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Case-series treatment response after conventional measures had failed.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
Not every patient responded or survived; no universal rescue claim.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A treatment response supported a role for the missing vitamin.
primary_references
[b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x
tissue_or_cell_type
Blood/clinical course
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1795–1805
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case-series treatment response after conventional measures had failed. · source_derived_draft · unverified_draft
### b1-tpn-thiamine-response Thiamine replenishment resolved lactic acidosis and improved clinical status in three patients in the reported series. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A treatment response supported a role for the missing vitamin. organism: Homo sapiens tissue_or_cell_type: Blood/clinical course experimental_model: Case-series treatment response after conventional measures had failed. limitations: Not every patient responded or survived; no universal rescue claim. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x
Complete structured claim and evidence
All three supplementation groups had higher milk total thiamine than placebo, without significant differences between active groups.
Thiamine (vitamin B1) → Human milk total thiamine concentration source_derived_draftungraded
Experimental context and source evidence
experimental_model
335 mother-infant dyads; 22-week intervention.
exposure
Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only.
limitations
Milk concentration alone is not an infant clinical outcome; model-derived optimal-dose estimate had wide uncertainty.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Maternal B1 intake changed the infant supply route, with a flattening response across the tested active doses.
primary_references
[b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052
tissue_or_cell_type
Human milk
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1807–1817
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 335 mother-infant dyads; 22-week intervention. · source_derived_draft · unverified_draft
### b1-maternal-intake-milk All three supplementation groups had higher milk total thiamine than placebo, without significant differences between active groups. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Maternal B1 intake changed the infant supply route, with a flattening response across the tested active doses. organism: Homo sapiens tissue_or_cell_type: Human milk experimental_model: 335 mother-infant dyads; 22-week intervention. limitations: Milk concentration alone is not an infant clinical outcome; model-derived optimal-dose estimate had wide uncertainty. exposure: Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only. [b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052
Complete structured claim and evidence
Infant whole-blood ThDP was higher in all maternal supplementation groups than placebo at 24 weeks.
Thiamine (vitamin B1) → Whole-blood thiamine diphosphate concentration source_derived_draftungraded
Experimental context and source evidence
experimental_model
Same trial; infants mostly breastfed.
exposure
Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only.
limitations
No direct measurement of each tissue cofactor pool or mortality benefit.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Improving maternal intake changed an infant blood marker.
primary_references
[b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052
tissue_or_cell_type
Infant blood
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1819–1829
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same trial; infants mostly breastfed. · source_derived_draft · unverified_draft
### b1-maternal-intake-infant-thdp Infant whole-blood ThDP was higher in all maternal supplementation groups than placebo at 24 weeks. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improving maternal intake changed an infant blood marker. organism: Homo sapiens tissue_or_cell_type: Infant blood experimental_model: Same trial; infants mostly breastfed. limitations: No direct measurement of each tissue cofactor pool or mortality benefit. exposure: Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only. [b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052
Complete structured claim and evidence
Infant ETK activation coefficient differed significantly only between the highest maternal-dose group and placebo, whereas infant ThDP differed for all active groups.
Thiamine (vitamin B1) → Erythrocyte transketolase activation coefficient source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Same infant biomarker comparison.
exposure
Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only.
limitations
Assay response is not a contradiction: endpoints differ. The study did not establish a universal clinical threshold.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The concentration marker and functional assay did not identify identical dose responses.
primary_references
[b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052
tissue_or_cell_type
Infant blood
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1831–1841
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same infant biomarker comparison. · source_derived_draft · unverified_draft
### b1-milk-trial-marker-difference Infant ETK activation coefficient differed significantly only between the highest maternal-dose group and placebo, whereas infant ThDP differed for all active groups. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The concentration marker and functional assay did not identify identical dose responses. organism: Homo sapiens tissue_or_cell_type: Infant blood experimental_model: Same infant biomarker comparison. limitations: Assay response is not a contradiction: endpoints differ. The study did not establish a universal clinical threshold. exposure: Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only. [b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052
Complete structured claim and evidence
In the 40-person pilot, urinary albumin excretion was lower after three months of thiamine than placebo; glycemic control, lipids and blood pressure did not change significantly.
Thiamine (vitamin B1) → Urinary albumin excretion source_derived_draftungraded
Experimental context and source evidence
experimental_model
Type 2 diabetes with microalbuminuria.
exposure
Three 100 mg thiamine capsules daily versus placebo for three months, then two-month washout; study exposure only.
limitations
Small short trial; no long-term kidney-failure outcome and no isolated proof of transketolase mediation.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A small trial suggested a renal biomarker benefit without showing its molecular cause.
primary_references
[b1-rabbani2009] High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study (2009). https://pubmed.ncbi.nlm.nih.gov/19057893/ DOI: 10.1007/s00125-008-1224-4
tissue_or_cell_type
Urine
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1843–1853
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Type 2 diabetes with microalbuminuria. · source_derived_draft · unverified_draft
### b1-diabetes-thiamine-albuminuria In the 40-person pilot, urinary albumin excretion was lower after three months of thiamine than placebo; glycemic control, lipids and blood pressure did not change significantly. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small trial suggested a renal biomarker benefit without showing its molecular cause. organism: Homo sapiens tissue_or_cell_type: Urine experimental_model: Type 2 diabetes with microalbuminuria. limitations: Small short trial; no long-term kidney-failure outcome and no isolated proof of transketolase mediation. exposure: Three 100 mg thiamine capsules daily versus placebo for three months, then two-month washout; study exposure only. [b1-rabbani2009] High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study (2009). https://pubmed.ncbi.nlm.nih.gov/19057893/ DOI: 10.1007/s00125-008-1224-4
Complete structured claim and evidence
Twelve weeks of benfotiamine did not significantly reduce urinary albumin or KIM-1 excretion despite improved thiamine status.
Benfotiamine → Urinary albumin excretion source_derived_draftungraded
Experimental context and source evidence
experimental_model
82 participants already receiving ACE inhibitor or ARB therapy.
exposure
Benfotiamine 900 mg/day versus placebo for 12 weeks on ACE inhibitor/ARB therapy; study exposure only.
limitations
Different compound, population and treatment context from the native-thiamine pilot; not a direct replication or proven explanation for the difference.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Higher vitamin status did not translate into the expected kidney-marker improvement.
primary_references
[b1-alkhalaf2010] A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy (2010). https://pubmed.ncbi.nlm.nih.gov/20413516/ DOI: 10.2337/dc09-2241
tissue_or_cell_type
Urine
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1855–1865
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 82 participants already receiving ACE inhibitor or ARB therapy. · source_derived_draft · unverified_draft
### b1-benfotiamine-kidney-null Twelve weeks of benfotiamine did not significantly reduce urinary albumin or KIM-1 excretion despite improved thiamine status. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher vitamin status did not translate into the expected kidney-marker improvement. organism: Homo sapiens tissue_or_cell_type: Urine experimental_model: 82 participants already receiving ACE inhibitor or ARB therapy. limitations: Different compound, population and treatment context from the native-thiamine pilot; not a direct replication or proven explanation for the difference. exposure: Benfotiamine 900 mg/day versus placebo for 12 weeks on ACE inhibitor/ARB therapy; study exposure only. [b1-alkhalaf2010] A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy (2010). https://pubmed.ncbi.nlm.nih.gov/20413516/ DOI: 10.2337/dc09-2241
Complete structured claim and evidence
The same trial found no significant reduction in plasma/urinary AGE markers or measured endothelial and inflammatory biomarkers.
Benfotiamine → Circulating and urinary glycation markers source_derived_draftungraded
Experimental context and source evidence
experimental_model
Same 82-person trial, biomarker report.
exposure
Same 900 mg/day, 12-week benfotiamine trial as b1-alkhalaf2010; not an independent sample.
limitations
Not an independent cohort; systemic biomarkers do not directly measure retinal pathway flux.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The proposed vascular pathways did not show a clear biomarker response in these participants.
primary_references
[b1-alkhalaf2012] Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy (2012). https://pubmed.ncbi.nlm.nih.gov/22792314/ DOI: 10.1371/journal.pone.0040427
tissue_or_cell_type
Plasma/urine
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1867–1877
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same 82-person trial, biomarker report. · source_derived_draft · unverified_draft
### b1-benfotiamine-human-age-null The same trial found no significant reduction in plasma/urinary AGE markers or measured endothelial and inflammatory biomarkers. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The proposed vascular pathways did not show a clear biomarker response in these participants. organism: Homo sapiens tissue_or_cell_type: Plasma/urine experimental_model: Same 82-person trial, biomarker report. limitations: Not an independent cohort; systemic biomarkers do not directly measure retinal pathway flux. exposure: Same 900 mg/day, 12-week benfotiamine trial as b1-alkhalaf2010; not an independent sample. [b1-alkhalaf2012] Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy (2012). https://pubmed.ncbi.nlm.nih.gov/22792314/ DOI: 10.1371/journal.pone.0040427
Complete structured claim and evidence
Benfotiamine increased retinal transketolase activity in diabetic rats.
Benfotiamine → Retinal transketolase activity source_derived_draftungraded
Experimental context and source evidence
experimental_model
High-glucose bovine endothelial cells and diabetic rat retinal experiments.
exposure
Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine.
limitations
Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Bos taurus; Rattus norvegicus
plain_language
A B1 derivative increased a carbon-transfer enzyme activity in the diabetic retina.
primary_references
[b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
tissue_or_cell_type
Endothelial cultures and retina
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1879–1889
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-glucose bovine endothelial cells and diabetic rat retinal experiments. · source_derived_draft · unverified_draft
### b1-benfotiamine-tkt Benfotiamine increased retinal transketolase activity in diabetic rats. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B1 derivative increased a carbon-transfer enzyme activity in the diabetic retina. organism: Bos taurus; Rattus norvegicus tissue_or_cell_type: Endothelial cultures and retina experimental_model: High-glucose bovine endothelial cells and diabetic rat retinal experiments. limitations: Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase. exposure: Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine. [b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
Complete structured claim and evidence
Benfotiamine inhibited hyperglycemia-associated hexosamine-pathway activation in the tested models.
Benfotiamine → Hexosamine pathway activity source_derived_draftungraded
Experimental context and source evidence
experimental_model
High-glucose bovine endothelial cells and diabetic rat retinal experiments.
exposure
Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine.
limitations
Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Bos taurus; Rattus norvegicus
plain_language
The intervention reduced one pathway fed by excess sugar intermediates.
primary_references
[b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
tissue_or_cell_type
Endothelial cultures and retina
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1891–1901
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-glucose bovine endothelial cells and diabetic rat retinal experiments. · source_derived_draft · unverified_draft
### b1-benfotiamine-hexosamine Benfotiamine inhibited hyperglycemia-associated hexosamine-pathway activation in the tested models. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intervention reduced one pathway fed by excess sugar intermediates. organism: Bos taurus; Rattus norvegicus tissue_or_cell_type: Endothelial cultures and retina experimental_model: High-glucose bovine endothelial cells and diabetic rat retinal experiments. limitations: Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase. exposure: Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine. [b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
Complete structured claim and evidence
Benfotiamine inhibited AGE-pathway activation in the experimental hyperglycemia models.
Benfotiamine → Advanced glycation end-product formation source_derived_draftungraded
Experimental context and source evidence
experimental_model
High-glucose bovine endothelial cells and diabetic rat retinal experiments.
exposure
Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine.
limitations
Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Bos taurus; Rattus norvegicus
plain_language
Less activation of a glycation pathway accompanied the intervention.
primary_references
[b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
tissue_or_cell_type
Endothelial cultures and retina
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1903–1913
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-glucose bovine endothelial cells and diabetic rat retinal experiments. · source_derived_draft · unverified_draft
### b1-benfotiamine-age Benfotiamine inhibited AGE-pathway activation in the experimental hyperglycemia models. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less activation of a glycation pathway accompanied the intervention. organism: Bos taurus; Rattus norvegicus tissue_or_cell_type: Endothelial cultures and retina experimental_model: High-glucose bovine endothelial cells and diabetic rat retinal experiments. limitations: Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase. exposure: Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine. [b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
Complete structured claim and evidence
Benfotiamine inhibited hyperglycemia-associated DAG-PKC pathway activation in the tested models.
Benfotiamine → Protein kinase C family source_derived_draftungraded
Experimental context and source evidence
experimental_model
High-glucose bovine endothelial cells and diabetic rat retinal experiments.
exposure
Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine.
limitations
Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Bos taurus; Rattus norvegicus
plain_language
Sugar processing was linked to a lipid-signaling pathway response.
primary_references
[b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
tissue_or_cell_type
Endothelial cultures and retina
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1915–1925
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-glucose bovine endothelial cells and diabetic rat retinal experiments. · source_derived_draft · unverified_draft
### b1-benfotiamine-pkc Benfotiamine inhibited hyperglycemia-associated DAG-PKC pathway activation in the tested models. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sugar processing was linked to a lipid-signaling pathway response. organism: Bos taurus; Rattus norvegicus tissue_or_cell_type: Endothelial cultures and retina experimental_model: High-glucose bovine endothelial cells and diabetic rat retinal experiments. limitations: Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase. exposure: Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine. [b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
Complete structured claim and evidence
Benfotiamine inhibited hyperglycemia-associated NF-kappaB activation in the tested models.
Benfotiamine → NF-kappaB family source_derived_draftungraded
Experimental context and source evidence
experimental_model
High-glucose bovine endothelial cells and diabetic rat retinal experiments.
exposure
Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine.
limitations
Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Bos taurus; Rattus norvegicus
plain_language
An inflammatory signaling readout also declined in these experiments.
primary_references
[b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
tissue_or_cell_type
Endothelial cultures and retina
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1927–1937
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-glucose bovine endothelial cells and diabetic rat retinal experiments. · source_derived_draft · unverified_draft
### b1-benfotiamine-nfkb Benfotiamine inhibited hyperglycemia-associated NF-kappaB activation in the tested models. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inflammatory signaling readout also declined in these experiments. organism: Bos taurus; Rattus norvegicus tissue_or_cell_type: Endothelial cultures and retina experimental_model: High-glucose bovine endothelial cells and diabetic rat retinal experiments. limitations: Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase. exposure: Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine. [b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
Complete structured claim and evidence
Benfotiamine prevented experimental diabetic retinopathy in the rat model reported by Hammes and colleagues.
Benfotiamine → Diabetic retinal microvascular damage source_derived_draftungraded
Experimental context and source evidence
experimental_model
High-glucose bovine endothelial cells and diabetic rat retinal experiments.
exposure
Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine.
limitations
Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Bos taurus; Rattus norvegicus
plain_language
The retinal disease endpoint improved in this animal experiment.
primary_references
[b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
tissue_or_cell_type
Endothelial cultures and retina
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1939–1949
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-glucose bovine endothelial cells and diabetic rat retinal experiments. · source_derived_draft · unverified_draft
### b1-benfotiamine-rat-retinopathy Benfotiamine prevented experimental diabetic retinopathy in the rat model reported by Hammes and colleagues. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The retinal disease endpoint improved in this animal experiment. organism: Bos taurus; Rattus norvegicus tissue_or_cell_type: Endothelial cultures and retina experimental_model: High-glucose bovine endothelial cells and diabetic rat retinal experiments. limitations: Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase. exposure: Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine. [b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834
Complete structured claim and evidence

Availability and dependencies

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

Inherited SLC19A2 transport impairment

Condition: machinery_impairment · Recessive frameshifting SLC19A2 variants.

Normal role: SLC19A2 imports free thiamine.

Recorded consequence: TRMA phenotype.

Scope: Human kindreds.

Experimental intestinal transporter knockdown

Condition: machinery_impairment · Transporter-specific siRNA in Caco-2 cells.

Normal role: SLC19A2 and SLC19A3 support thiamine entry.

Recorded consequence: Reduced carrier-mediated thiamine uptake.

Scope: Human intestinal epithelial cell model.

Mouse intestinal Slc19a3 loss

Condition: machinery_impairment · Gene deletion.

Normal role: Slc19a3 contributes to intestinal uptake.

Recorded consequence: Reduced thiamine uptake.

Scope: Mouse intestine.

Mouse compensation after Slc19a2 loss

Condition: machinery_impairment · Slc19a2 deletion.

Normal role: Two transporters contribute to uptake.

Recorded consequence: Slc19a3 expression rises with preserved intestinal uptake.

Scope: Mouse intestine.

Inherited SLC19A3 impairment

Condition: machinery_impairment · Pathogenic SLC19A3 variants.

Normal role: SLC19A3 supports thiamine entry.

Recorded consequence: Reduced transport and basal ganglia disease.

Scope: Families and variant-expression experiments.

Renal thiamine clearance was 24-fold higher in type 1 and 16-fold higher in type 2 diabetes; plasma thiamine was 76% and 75% lower, respectively.

Condition: biomarker_context · Diabetes status

Normal role: Read the matched control and canonical normal-mechanism records; this scenario does not infer the reverse relationship.

Recorded consequence: Renal thiamine clearance was 24-fold higher in type 1 and 16-fold higher in type 2 diabetes; plasma thiamine was 76% and 75% lower, respectively.

Scope: 26 type-1 and 48 type-2 patients versus 20 healthy controls

Biotin depletion changes thiamine-transporter RNA

Condition: nutrient_deficiency · Experimental marginal biotin deficiency.

Normal role: SLC19A3 imports thiamine.

Recorded consequence: Lower leukocyte SLC19A3 transcript abundance.

Scope: Seven adults over 28 days.

Wild-type mice fed thiamine-deficient diet for 10 days had higher plasma glucose, hepatic glucose and hepatic glycogen.

Condition: nutrient_deficiency · 0 mg/kg added thiamine diet

Normal role: Read the matched control and canonical normal-mechanism records; this scenario does not infer the reverse relationship.

Recorded consequence: Wild-type mice fed thiamine-deficient diet for 10 days had higher plasma glucose, hepatic glucose and hepatic glycogen.

Scope: Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment

Engineered TPK1 catalytic impairment

Condition: machinery_impairment · Asp71Asn substitution.

Normal role: TPK1 activates thiamine.

Recorded consequence: Reduced catalytic turnover.

Scope: Recombinant human enzyme.

Inherited thiamine activation defect

Condition: machinery_impairment · Biallelic TPK1 variants.

Normal role: TPK1 produces ThDP from thiamine and ATP.

Recorded consequence: Low ThDP and impaired cofactor-dependent activity.

Scope: Patient tissues and ex vivo assays.

Mitochondrial cofactor delivery defect

Condition: machinery_impairment · Inherited carrier variant or mouse knockout.

Normal role: SLC25A19 imports phosphorylated B1 into mitochondria.

Recorded consequence: Mitochondrial ThDP depletion despite cytosolic availability.

Scope: Fractionated cultured cells.

When drinking and thiamine deficiency arrive together

Condition: nutrient_deficiency · Chronic alcohol consumption alongside dietary thiamine deficiency.

Normal role: Thiamine diphosphate is the coenzyme for transketolase and the two mitochondrial dehydrogenase complexes.

Recorded consequence: Brain damage exceeds what either exposure produces alone, and the corpus callosum shows ultrastructural disruption.

Scope: Human and rodent studies of alcoholic brain damage

SLC25A19 G125S transport defect

Condition: machinery_impairment · G125S variant expression.

Normal role: SLC25A19 supplies mitochondrial ThDP.

Recorded consequence: Reduced mitochondrial uptake despite correct targeting.

Scope: HepG2 expression experiments.

Inherited mitochondrial thiamine dysfunction

Condition: machinery_impairment · Recessive SLC25A19 missense variant.

Normal role: SLC25A19 supports mitochondrial cofactor availability.

Recorded consequence: Episodic encephalopathy and progressive neuropathy.

Scope: Four related patients.

Loss of colonic phosphorylated-B1 uptake

Condition: machinery_impairment · Slc44a4 knockout, with DSS challenge for inflammation endpoint.

Normal role: Slc44a4 supports colonic ThDP uptake.

Recorded consequence: Reduced uptake and greater DSS susceptibility.

Scope: Mouse colon.

When a drug competes for the vitamin B1 carriers

Condition: nutrient_deficiency · Metformin, which is a substrate and inhibitor of both carriers.

Normal role: Thiamine enters cells through OCT1 in the liver and THTR-2 (SLC19A3) in the small intestine.

Recorded consequence: Thiamine uptake is competitively inhibited and intestinal thiamine accumulation falls in mice.

Scope: Transporter assays and mouse experiments

A lipoyl-synthesis defect limits a B1-dependent complex

Condition: machinery_impairment · Homozygous LIAS Arg249His.

Normal role: PDH uses both ThDP and a lipoylated E2 arm.

Recorded consequence: Reduced protein lipoylation and PDH activity.

Scope: Patient muscle and cultured fibroblasts.

When a drug competes for the vitamin B1 carriers

Condition: biomarker_context · Metformin, which is a substrate and inhibitor of both carriers.

Normal role: Thiamine enters cells through OCT1 in the liver and THTR-2 (SLC19A3) in the small intestine.

Recorded consequence: Thiamine uptake is competitively inhibited and intestinal thiamine accumulation falls in mice.

Scope: Transporter assays and mouse experiments

Branched-chain metabolites rise during rat thiamine deprivation

Condition: nutrient_deficiency · Four weeks of thiamine-deficient feeding; liver thiamine 2.4% of control.

Normal role: B1-dependent BCKDH helps dispose of amino-acid-derived ketoacids.

Recorded consequence: Plasma amino-acid and ketoacid pools increased.

Scope: Rat dietary experiment.

A DHTKD1 lesion blocks amino-acid ketoacid turnover

Condition: machinery_impairment · Biallelic DHTKD1 variants in the studied individuals.

Normal role: ThDP-dependent DHTKD1 enables 2-oxoadipate disposal.

Recorded consequence: 2-Oxoadipate accumulation in patient cells.

Scope: Human fibroblasts and lysine tracer assays.

DHTKD1 assembly failure despite preserved protein production

Condition: machinery_impairment · Recombinant DHTKD1 Arg715Cys.

Normal role: DHTKD1 must interact with DLST for complex function.

Recorded consequence: Weaker DLST association.

Scope: Purified human proteins.

Lyase disruption reroutes sphingoid-base-derived carbon

Condition: machinery_impairment · Hacl2 or combined Hacl1/Hacl2 knockout in CHO-K1 cells.

Normal role: HACL enzymes cleave 2-hydroxy acyl-CoA during lipid alpha oxidation.

Recorded consequence: Reduced selected lipid degradation readouts.

Scope: Chinese hamster cell model.

Regional cerebral energy deficits

Condition: nutrient_deficiency · Pyrithiamine-induced severe thiamine deficiency in rats