Thiamine (vitamin B1)

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations.

limitations

Assay chemistry; no clinical response measured.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor.

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

tissue_or_cell_type

Purified recombinant enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 481–491

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. · source_derived_draft · unverified_draft

### mg-tpk1-thiamine-to-thdp Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. limitations: Assay chemistry; no clinical response measured. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [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

availability_state

nutrient_deficiency Imported condition classification; unverified.

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mg/kg control diet 0 mg/kg added thiamine diet · Thiamine (vitamin B1) Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "0 mg/kg added thiamine diet", "comparator": "5 mg/kg control diet", "endpoint": "Plasma glucose", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "thiamine", "state": "0 mg/kg added thiamine diet"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

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

limitations

A separate dietary arm of the OCT1 paper; not a berberine exposure experiment or direct proof of human diabetes causation.

primary_references

OCT1 cardiometabolic study 2018; DOI:10.1371/journal.pbio.2002907; PMID:29659562; https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002907

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Diabetes cascade: targeted primary-source supplement · lines 36–36

See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment · source_derived_draft · unverified_draft

Wild-type mice fed thiamine-deficient diet for 10 days had higher plasma glucose, hepatic glucose and hepatic glycogen. Model: Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment. Limits: A separate dietary arm of the OCT1 paper; not a berberine exposure experiment or direct proof of human diabetes causation. Primary reference: OCT1 cardiometabolic study 2018; DOI:10.1371/journal.pbio.2002907; PMID:29659562; https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002907

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake

exposure

Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice

limitations

Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human transporter

plain_language

Short vitamin B1 switches on the same energy sensor the drug does.

primary_references

[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

tissue_or_cell_type

Liver and intestine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1269–1280

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake · source_derived_draft · unverified_draft

### metformin-oct1-loss-ampk-thiamine Loss of Oct1 raised the AMP to ATP ratio and activated AMPK, and thiamine deficiency itself enhanced phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Short vitamin B1 switches on the same energy sensor the drug does. organism: Mouse and human transporter tissue_or_cell_type: Liver and intestine experimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake limitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype. exposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice evidence_span: {"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"} [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

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

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

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

plain_language

An additional carrier connects thiamine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 72–78

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-thiamine An additional carrier connects thiamine to the transport network. Human SLC22A15 expression enabled uptake of thiamine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_span

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experimental_model

Human versus mouse transporter kinetics in transfected HEK293 cells

exposure

Thiamine and metformin transport; transporter chimeras

limitations

Human OCT1 affinity for thiamine was substantially lower than mouse Oct1. This is a shared-transporter connection, not proof berberine causes B1 deficiency.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human OCT1 and mouse Oct1

plain_language

Vitamin B1 shares this transporter, but the mouse and human versions behave differently.

primary_references

[berberine-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

tissue_or_cell_type

Cellular thiamine uptake

transport_effect

raises A species-affinity comparison, but the measurement is thiamine carried into the expressing cell, which stands for the hepatocyte.

transport_pool

the hepatocyte interior A species-affinity comparison, but the measurement is thiamine carried into the expressing cell, which stands for the hepatocyte.

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 298–309

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human versus mouse transporter kinetics in transfected HEK293 cells · source_derived_draft · unverified_draft

### berberine-human-thiamine-transport Human OCT1 transported thiamine with approximately 9.5-fold lower affinity than mouse Oct1. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B1 shares this transporter, but the mouse and human versions behave differently. organism: Human OCT1 and mouse Oct1 tissue_or_cell_type: Cellular thiamine uptake experimental_model: Human versus mouse transporter kinetics in transfected HEK293 cells limitations: Human OCT1 affinity for thiamine was substantially lower than mouse Oct1. This is a shared-transporter connection, not proof berberine causes B1 deficiency. exposure: Thiamine and metformin transport; transporter chimeras evidence_span: {"source_cache": "artifacts/berberine-research/33037045.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd", "start_char": 0, "end_char": 2298, "text_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd"} [berberine-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

evidence_span

{"source_cache": "artifacts/metformin-research/16807400.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "681a4ea4ae958690a5a707397ee3a2b254ebeaab832292f14beea5716e58a9b2", "start_char": 0, "end_char": 1742, "text_sha256": "681a4ea4ae958690a5a707397ee3a2b254ebeaab832292f14beea5716e58a9b2"}

experimental_model

Cloning, expression and kinetic characterisation of hMATE2-K from human kidney

exposure

Proton-gradient-dependent antiport; ammonium-chloride-induced intracellular acidification

limitations

Kidney-specific expression and substrate list from a transfected system; thiamine appears in the same substrate list, which is an observation about the transporter, not a drug-nutrient competition measurement.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human transporter

plain_language

The same exit pump also handles vitamin B1, so the drug and the vitamin share a route.

primary_references

[metformin-p16807400] Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. (2006). https://pubmed.ncbi.nlm.nih.gov/16807400/ DOI: 10.1681/asn.2006030205

tissue_or_cell_type

Renal proximal-tubule brush-border membrane

transport_effect

lowers Intracellular acidification stimulated the transport, which is the extrusion direction.

transport_pool

the renal tubular cell interior Intracellular acidification stimulated the transport, which is the extrusion direction.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 255–266

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning, expression and kinetic characterisation of hMATE2-K from human kidney · source_derived_draft · unverified_draft

### metformin-mate2k-thiamine-substrate Intracellular acidification stimulated hMATE2-K-dependent transport of organic cations including metformin and thiamine. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The same exit pump also handles vitamin B1, so the drug and the vitamin share a route. organism: Human transporter tissue_or_cell_type: Renal proximal-tubule brush-border membrane experimental_model: Cloning, expression and kinetic characterisation of hMATE2-K from human kidney limitations: Kidney-specific expression and substrate list from a transfected system; thiamine appears in the same substrate list, which is an observation about the transporter, not a drug-nutrient competition measurement. exposure: Proton-gradient-dependent antiport; ammonium-chloride-induced intracellular acidification evidence_span: {"source_cache": "artifacts/metformin-research/16807400.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "681a4ea4ae958690a5a707397ee3a2b254ebeaab832292f14beea5716e58a9b2", "start_char": 0, "end_char": 1742, "text_sha256": "681a4ea4ae958690a5a707397ee3a2b254ebeaab832292f14beea5716e58a9b2"} [metformin-p16807400] Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. (2006). https://pubmed.ncbi.nlm.nih.gov/16807400/ DOI: 10.1681/asn.2006030205

evidence_span

{"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"}

experimental_model

Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake

exposure

Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice

limitations

Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human transporter

plain_language

The transporter that carries the drug into the liver normally carries vitamin B1.

primary_references

[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

tissue_or_cell_type

Liver and intestine

transport_effect

raises Identified by isotopic uptake as a principal endogenous substrate.

transport_pool

the expressing cell Identified by isotopic uptake as a principal endogenous substrate.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1230–1241

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake · source_derived_draft · unverified_draft

### metformin-oct1-thiamine-substrate Metabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The transporter that carries the drug into the liver normally carries vitamin B1. organism: Mouse and human transporter tissue_or_cell_type: Liver and intestine experimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake limitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype. exposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice evidence_span: {"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"} [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium.

limitations

Crystal packing may affect oligomer state; nucleotide analog density was not confidently assigned.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

Magnesium participates in the enzyme pocket that handles vitamin B1 phosphorylation.

primary_references

[liu-2011-tpk-structure] A new crystal form of mouse thiamin pyrophosphokinase (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3088427/

tissue_or_cell_type

Recombinant protein crystals

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 505–515

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium. · source_derived_draft · unverified_draft

### mg-mouse-tpk-metal-site Mouse TPK structures place Mg2+ adjacent to thiamine/ThDP and coordinated by active-site aspartate residues. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium participates in the enzyme pocket that handles vitamin B1 phosphorylation. organism: Mus musculus tissue_or_cell_type: Recombinant protein crystals experimental_model: Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium. limitations: Crystal packing may affect oligomer state; nucleotide analog density was not confidently assigned. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [liu-2011-tpk-structure] A new crystal form of mouse thiamin pyrophosphokinase (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3088427/

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Purified recombinant mouse TPK1; forward and reverse reaction kinetics.

limitations

ATP concentration shifted the optimum; in vitro values are not intake targets.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

More magnesium did not continuously increase B1 activation in this assay.

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

Purified recombinant enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 517–527

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 reaction kinetics. · source_derived_draft · unverified_draft

### mg-mouse-tpk-nonmonotonic Recombinant mouse TPK1 showed an Mg optimum followed by inhibition as Mg was increased at fixed ATP. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: More magnesium did not continuously increase B1 activation in this assay. organism: Mus musculus tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reaction kinetics. limitations: ATP concentration shifted the optimum; in vitro values are not intake targets. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [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

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Purified recombinant mouse TPK1; forward and reverse reaction kinetics.

limitations

Product inhibition is a separate limit from Mg shortage.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

B1 activation has product feedback even when ATP and magnesium are supplied.

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

Purified recombinant enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 529–539

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 reaction kinetics. · source_derived_draft · unverified_draft

### mg-thdp-feedback-on-tpk Accumulated ThDP inhibited the forward reaction of purified mouse TPK1. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 activation has product feedback even when ATP and magnesium are supplied. organism: Mus musculus tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reaction kinetics. limitations: Product inhibition is a separate limit from Mg shortage. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Single 34-year-old man with alcohol withdrawal and Wernicke encephalopathy during intravenous thiamine treatment.

limitations

Single case during alcohol withdrawal; no controlled comparison or tissue-cofactor measurement.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

A patient improved with combined treatment after symptoms progressed during thiamine alone.

primary_references

[coughlan-2016-thiamine] Thiamine refractory Wernickes encephalopathy reversed with magnesium therapy (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5093844/ DOI: 10.1136/bcr-2016-218046

tissue_or_cell_type

Clinical neurological examination

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 759–769

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single 34-year-old man with alcohol withdrawal and Wernicke encephalopathy during intravenous thiamine treatment. · source_derived_draft · unverified_draft

### mg-thiamine-2016-neurologic-response In the 2016 case, neurological symptoms resolved after intravenous Mg was added to ongoing thiamine for documented hypomagnesemia. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A patient improved with combined treatment after symptoms progressed during thiamine alone. organism: Homo sapiens tissue_or_cell_type: Clinical neurological examination experimental_model: Single 34-year-old man with alcohol withdrawal and Wernicke encephalopathy during intravenous thiamine treatment. limitations: Single case during alcohol withdrawal; no controlled comparison or tissue-cofactor measurement. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [coughlan-2016-thiamine] Thiamine refractory Wernickes encephalopathy reversed with magnesium therapy (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5093844/ DOI: 10.1136/bcr-2016-218046

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment.

limitations

Three patients; blood transketolase is not direct brain flux.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Low serum magnesium accompanied a delayed blood-enzyme response to B1.

primary_references

[traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959

tissue_or_cell_type

Blood; acute Wernicke-Korsakoff patients

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 735–745

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. · source_derived_draft · unverified_draft

### mg-thiamine-delayed-blood-tkt In the 1974 report, blood transketolase recovered more slowly after thiamine in the hypomagnesemic patient than in two normomagnesemic patients. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low serum magnesium accompanied a delayed blood-enzyme response to B1. organism: Homo sapiens tissue_or_cell_type: Blood; acute Wernicke-Korsakoff patients experimental_model: Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. limitations: Three patients; blood transketolase is not direct brain flux. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment.

limitations

Uncontrolled within-patient sequence; no isolated enzyme mechanism established.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Eye-movement symptoms improved during magnesium correction after a delayed B1 response.

primary_references

[traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959

tissue_or_cell_type

Clinical neurological examination

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 747–757

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. · source_derived_draft · unverified_draft

### mg-thiamine-ocular-recovery Correcting hypomagnesemia in the 1974 patient coincided with clearing of ophthalmoplegia. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Eye-movement symptoms improved during magnesium correction after a delayed B1 response. organism: Homo sapiens tissue_or_cell_type: Clinical neurological examination experimental_model: Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. limitations: Uncontrolled within-patient sequence; no isolated enzyme mechanism established. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959

cross_nutrient

Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.

experimental_model

Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations.

limitations

Total concentrations and speciation must be distinguished; no human Mg cutoff follows.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The balance between ATP-bound and available magnesium affects activation of B1.

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

tissue_or_cell_type

Purified recombinant enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 493–503

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. · source_derived_draft · unverified_draft

### mg-tpk1-free-mg-restores-activity Mg2+ in excess over ATP restored human TPK1 activity at low MgATP concentrations compared with a 1:1 total Mg:ATP ratio. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The balance between ATP-bound and available magnesium affects activation of B1. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. limitations: Total concentrations and speciation must be distinguished; no human Mg cutoff follows. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [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

availability_state

biomarker_context Imported condition classification; unverified.

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

Healthy control group Diabetes status · Human diabetes status in the specified observational comparison Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "Diabetes status", "comparator": "Healthy control group", "endpoint": "Renal thiamine clearance", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "human-diabetes-study-state", "state": "Diabetes status"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

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

limitations

Cross-sectional association; not proof that dietary deficiency caused diabetes. Erythrocyte transporter changes complicate status assessment.

primary_references

Thornalley et al. 2007; PMID:17676306; PMCID:PMC1998885; https://pubmed.ncbi.nlm.nih.gov/17676306/

trigger_kind

biomarker_context Imported condition classification; unverified.

Diabetes cascade: targeted primary-source supplement · lines 27–27

See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · 26 type-1 and 48 type-2 patients versus 20 healthy controls · source_derived_draft · unverified_draft

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. Model: 26 type-1 and 48 type-2 patients versus 20 healthy controls. Limits: Cross-sectional association; not proof that dietary deficiency caused diabetes. Erythrocyte transporter changes complicate status assessment. Primary reference: Thornalley et al. 2007; PMID:17676306; PMCID:PMC1998885; https://pubmed.ncbi.nlm.nih.gov/17676306/

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Transporter abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human primary proximal-tubule epithelial cells; 5-day culture

limitations

Cell culture; does not by itself establish patient-level thiamine loss.

primary_references

Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

Diabetes cascade: targeted primary-source supplement · lines 18–18

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

SLC19A2 mRNA fell 76% and THTR-1 protein 77% under high glucose. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Cell culture; does not by itself establish patient-level thiamine loss. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Transporter abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human primary proximal-tubule epithelial cells; 5-day culture

limitations

Cell culture; does not by itself establish patient-level thiamine loss.

primary_references

Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

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

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

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

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Directional thiamine transport", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human primary proximal-tubule epithelial cells; 5-day culture

limitations

Transport assay; transporter-expression changes accompany the effect without proving exclusive mediation.

primary_references

Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets

exposure

Rats fed zinc-deficient diets; dietary content and duration not available in the abstract.

limitations

Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported.

nutrient_topic

Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc

organism

Rattus norvegicus

plain_language

Dietary zinc deficiency also reduced this measured enzyme activity in rat serum.

primary_references

[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

tissue_or_cell_type

Rat serum assayed ex vivo

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 846–857

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft

### zinc-enz-bvitamin-rat-hydrolysis Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary zinc deficiency also reduced this measured enzyme activity in rat serum. organism: Rattus norvegicus tissue_or_cell_type: Rat serum assayed ex vivo experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported. exposure: Rats fed zinc-deficient diets; dietary content and duration not available in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/berberine-research/29659562.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558", "start_char": 0, "end_char": 1652, "text_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558"}

experimental_model

Mouse gene deletion and dietary depletion, with human genetic associations

exposure

Oct1 deletion or a thiamine-deficient diet

limitations

Mouse Oct1 deletion is not pharmacological berberine inhibition; human genetic associations do not establish berberine-induced thiamine depletion.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Mice for causal thiamine and PDH experiments

plain_language

A transporter can affect how the liver uses a vitamin-dependent fuel pathway.

primary_references

[berberine-p29659562] Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content. (2018). https://pubmed.ncbi.nlm.nih.gov/29659562/ DOI: 10.1371/journal.pbio.2002907

tissue_or_cell_type

Hepatic thiamine-dependent metabolism

trigger_kind

machinery_impairment Imported condition classification; unverified.

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 311–322

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse gene deletion and dietary depletion, with human genetic associations · source_derived_draft · unverified_draft

### berberine-oct1-pdh Oct1 deletion reduced hepatic thiamine-dependent enzyme activity, including pyruvate dehydrogenase, in mice. Condition category: machinery_impairment nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can affect how the liver uses a vitamin-dependent fuel pathway. organism: Mice for causal thiamine and PDH experiments tissue_or_cell_type: Hepatic thiamine-dependent metabolism experimental_model: Mouse gene deletion and dietary depletion, with human genetic associations limitations: Mouse Oct1 deletion is not pharmacological berberine inhibition; human genetic associations do not establish berberine-induced thiamine depletion. exposure: Oct1 deletion or a thiamine-deficient diet evidence_span: {"source_cache": "artifacts/berberine-research/29659562.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558", "start_char": 0, "end_char": 1652, "text_sha256": "10efb675e4e0cf5cea9c8607b6b2a5e3ad77c383f8b0a55efff5ed6d163be558"} [berberine-p29659562] Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content. (2018). https://pubmed.ncbi.nlm.nih.gov/29659562/ DOI: 10.1371/journal.pbio.2002907

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/metformin-research/26528626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9", "start_char": 0, "end_char": 1436, "text_sha256": "67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9"}

experimental_model

Transporter uptake assays in cells expressing human THTR-1 and THTR-2

exposure

Metformin against thiamine uptake by SLC19A2 and SLC19A3

limitations

In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human transporters, with mouse orthologue comparison

plain_language

Because they share the carrier, the drug gets in the vitamin’s way.

primary_references

[metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501

tissue_or_cell_type

Small-intestinal absorption

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"}

experimental_model

Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake

exposure

Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice

limitations

Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse

plain_language

In a living animal, a dose of the drug lowered how much vitamin B1 the gut held.

primary_references

[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

tissue_or_cell_type

Liver and intestine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1256–1267

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake · source_derived_draft · unverified_draft

### metformin-metformin-intestinal-thiamine Acute administration of metformin to wild-type mice reduced intestinal accumulation of thiamine. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: In a living animal, a dose of the drug lowered how much vitamin B1 the gut held. organism: Mouse tissue_or_cell_type: Liver and intestine experimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake limitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype. exposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice evidence_span: {"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"} [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"}

experimental_model

Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake

exposure

Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice

limitations

Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human transporter

plain_language

The drug and the vitamin compete for the same door.

primary_references

[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

tissue_or_cell_type

Liver and intestine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1243–1254

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake · source_derived_draft · unverified_draft

### metformin-metformin-thiamine-competition Metformin and the biguanide analogue phenformin competitively inhibited OCT1-mediated thiamine uptake. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The drug and the vitamin compete for the same door. organism: Mouse and human transporter tissue_or_cell_type: Liver and intestine experimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake limitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype. exposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice evidence_span: {"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"} [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

evidence_span

{"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"}

experimental_model

Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling

exposure

Metformin and thiamine uptake kinetics; transmembrane-helix substitutions

limitations

A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human and mouse orthologues side by side

plain_language

The same species gap applies to the vitamin the transporter carries.

primary_references

[metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

tissue_or_cell_type

Hepatic uptake

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 333–344

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling · source_derived_draft · unverified_draft

### metformin-oct1-species-thiamine The affinity for thiamine was 9.5-fold lower in human than in mouse OCT1. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The same species gap applies to the vitamin the transporter carries. organism: Human and mouse orthologues side by side tissue_or_cell_type: Hepatic uptake experimental_model: Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling limitations: A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement. exposure: Metformin and thiamine uptake kinetics; transmembrane-helix substitutions evidence_span: {"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"} [metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/metformin-research/31764942.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b", "start_char": 0, "end_char": 1829, "text_sha256": "21758b02cd824f37a6e1e076657c0cf72d08cc6babcb66773613f129dc13f15b"}

experimental_model

High-throughput screen of 1360 compounds, in-silico modelling and electronic health record analysis

exposure

Inhibition kinetics with IC50 values and predicted intestinal concentrations

limitations

A screen plus a records analysis, not a trial. The trial termination cited as motivation involved a different, more potent inhibitor.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human transporter and human health records

plain_language

In real records, people on these drugs had lower vitamin B1, most of all those already at risk.

primary_references

[metformin-p31764942] Drug-nutrient interactions: discovering prescription drug inhibitors of the thiamine transporter ThTR-2 (SLC19A3). (2020). https://pubmed.ncbi.nlm.nih.gov/31764942/ DOI: 10.1093/ajcn/nqz255

tissue_or_cell_type

Intestinal thiamine absorption

trigger_kind

biomarker_context Imported condition classification; unverified.

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

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

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

cross_nutrient

B1-folate: shared carrier for folate and TMP; free thiamine is a different substrate.

experimental_model

Mouse L1210/R16 leukemia transport experiments

exposure

Short radiolabeled TMP uptake assays

limitations

Extracellular TMP hydrolysis and transformed cells constrain extrapolation.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Mus musculus

plain_language

A folate carrier also transported a phosphorylated B1 form.

primary_references

[zhao2002] Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells (2002). https://pubmed.ncbi.nlm.nih.gov/11997266/ DOI: 10.1152/ajpcell.00547.2001

tissue_or_cell_type

L1210/R16 leukemia cells

transport_effect

raises Overexpression increased thiamine-monophosphate influx about fivefold.

transport_pool

the expressing cell Overexpression increased thiamine-monophosphate influx about fivefold.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 180–191

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse L1210/R16 leukemia transport experiments · source_derived_draft · unverified_draft

### folate-mouse-rfc-tmp-entry RFC overexpression increased thiamine-monophosphate influx approximately fivefold in mouse R16 leukemia cells relative to the parent line. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A folate carrier also transported a phosphorylated B1 form. organism: Mus musculus tissue_or_cell_type: L1210/R16 leukemia cells experimental_model: Mouse L1210/R16 leukemia transport experiments limitations: Extracellular TMP hydrolysis and transformed cells constrain extrapolation. exposure: Short radiolabeled TMP uptake assays cross_nutrient: B1-folate: shared carrier for folate and TMP; free thiamine is a different substrate. [zhao2002] Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells (2002). https://pubmed.ncbi.nlm.nih.gov/11997266/ DOI: 10.1152/ajpcell.00547.2001

cross_nutrient

B1-folate: phosphorylated thiamine and folates share RFC recognition; exclusive physiological counter-substrate status remains unproven.

experimental_model

Human SLC19A1 structures and HEK293F uptake assays

exposure

Binding assays and extracellular competition

limitations

Supports shared recognition; does not prove dietary B1 deficiency blocks folate delivery.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Homo sapiens

plain_language

A vitamin B1 cofactor can occupy the folate carrier.

primary_references

[dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w

tissue_or_cell_type

Purified transporter and HEK293F cells

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 167–178

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC19A1 structures and HEK293F uptake assays · source_derived_draft · unverified_draft

### folate-rfc-thdp-shared-pocket Human SLC19A1 bound thiamine diphosphate in the same pocket as 5-MTHF; thiamine diphosphate inhibited methotrexate uptake with IC50 about 19 micromolar. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin B1 cofactor can occupy the folate carrier. organism: Homo sapiens tissue_or_cell_type: Purified transporter and HEK293F cells experimental_model: Human SLC19A1 structures and HEK293F uptake assays limitations: Supports shared recognition; does not prove dietary B1 deficiency blocks folate delivery. exposure: Binding assays and extracellular competition cross_nutrient: B1-folate: phosphorylated thiamine and folates share RFC recognition; exclusive physiological counter-substrate status remains unproven. [dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/alcohol-research/7596324.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30469341e3044e901ef2ebfa2e84bfb83b48044a455f1f0e415662eb2a9c6368", "start_char": 0, "end_char": 1186, "text_sha256": "30469341e3044e901ef2ebfa2e84bfb83b48044a455f1f0e415662eb2a9c6368"}

experimental_model

Review of alcoholic brain damage separating ethanol, thiamine deficiency and liver disease

exposure

Chronic alcohol exposure with and without thiamine deficiency

limitations

A review, labelled as such. Its value here is that it insists the three causes be separated rather than merged into one syndrome.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Human and animal

plain_language

The drinking and the missing vitamin do more damage together than either does alone.

primary_references

[alcohol-p7596324] Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. (1995). https://pubmed.ncbi.nlm.nih.gov/7596324/ DOI: 10.1007/bf01991777

tissue_or_cell_type

Brain

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 722–733

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of alcoholic brain damage separating ethanol, thiamine deficiency and liver disease · source_derived_draft · unverified_draft

### alcohol-thiamine-synergy The pathophysiology of alcoholic brain damage involves synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. Condition category: nutrient_deficiency nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: The drinking and the missing vitamin do more damage together than either does alone. organism: Human and animal tissue_or_cell_type: Brain experimental_model: Review of alcoholic brain damage separating ethanol, thiamine deficiency and liver disease limitations: A review, labelled as such. Its value here is that it insists the three causes be separated rather than merged into one syndrome. exposure: Chronic alcohol exposure with and without thiamine deficiency evidence_span: {"source_cache": "artifacts/alcohol-research/7596324.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30469341e3044e901ef2ebfa2e84bfb83b48044a455f1f0e415662eb2a9c6368", "start_char": 0, "end_char": 1186, "text_sha256": "30469341e3044e901ef2ebfa2e84bfb83b48044a455f1f0e415662eb2a9c6368"} [alcohol-p7596324] Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. (1995). https://pubmed.ncbi.nlm.nih.gov/7596324/ DOI: 10.1007/bf01991777