Nutrient chapter

Ethanol

Ethanol. Species, exposure and limitations are retained in each linked claim.

58 recorded mechanisms · 7 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Each subunit of the dimeric enzyme is organised into two unequal parts separated by a wide deep active-site cleft, with the catalytic zinc atoms bound at the bottom of the clefts about 20 angstrom from the molecular surface, and the adenosine moiety of the coenzyme bound within the smaller region.
Zinc → Horse liver alcohol dehydrogenase, the crystallographic model enzyme source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
X-ray crystallography of horse liver alcohol dehydrogenase at 2.9 angstrom
exposure
Inhibitor-bound and coenzyme-bound states
limitations
The founding structure of the enzyme family, in horse liver enzyme. It establishes where the zinc and the coenzyme sit; it is not a human kinetic measurement.
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
Horse enzyme
plain_language
The zinc that does the chemistry sits at the bottom of a deep slot, far from the surface.
primary_references
[alcohol-p4365379] Structure of liver alcohol dehydrogenase at 2.9-angstrom resolution. (1973). https://pubmed.ncbi.nlm.nih.gov/4365379/ DOI: 10.1073/pnas.70.8.2439
tissue_or_cell_type
Purified dimeric enzyme
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 59–70
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of horse liver alcohol dehydrogenase at 2.9 angstrom · source_derived_draft · unverified_draft
### alcohol-adh-catalytic-zinc-position Each subunit of the dimeric enzyme is organised into two unequal parts separated by a wide deep active-site cleft, with the catalytic zinc atoms bound at the bottom of the clefts about 20 angstrom from the molecular surface, and the adenosine moiety of the coenzyme bound within the smaller region. Condition category: normal 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 zinc that does the chemistry sits at the bottom of a deep slot, far from the surface. organism: Horse enzyme tissue_or_cell_type: Purified dimeric enzyme experimental_model: X-ray crystallography of horse liver alcohol dehydrogenase at 2.9 angstrom limitations: The founding structure of the enzyme family, in horse liver enzyme. It establishes where the zinc and the coenzyme sit; it is not a human kinetic measurement. exposure: Inhibitor-bound and coenzyme-bound states evidence_span: {"source_cache": "artifacts/alcohol-research/4365379.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "857dc9a65cac403f6591e0f33ea1bd3295f4a997274a26c362a3f392dbe9c987", "start_char": 0, "end_char": 912, "text_sha256": "857dc9a65cac403f6591e0f33ea1bd3295f4a997274a26c362a3f392dbe9c987"} [alcohol-p4365379] Structure of liver alcohol dehydrogenase at 2.9-angstrom resolution. (1973). https://pubmed.ncbi.nlm.nih.gov/4365379/ DOI: 10.1073/pnas.70.8.2439
Complete structured claim and evidence
In the closed subunits the catalytic zinc holds the substrate oxygen in classical tetrahedral coordination with Cys-43, Cys-153 and His-66, while in the open subunits the zinc takes an inverted coordination that adds the carboxylate of Glu-67, which may be an intermediate in displacing the zinc-bound water with the alcohol substrate.
Zinc → Saccharomyces cerevisiae alcohol dehydrogenase I / ADH1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/25157460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20", "start_char": 0, "end_char": 1560, "text_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20"}
experimental_model
X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis
exposure
Coenzyme-bound closed and open subunit conformations
limitations
A yeast enzyme, used because its asymmetric tetramer captures two catalytic states. The zinc coordination chemistry is conserved, but kinetic numbers are yeast numbers.
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
Yeast enzyme
plain_language
Three amino acids hold the zinc, and a fourth swings in to hand over the alcohol.
primary_references
[alcohol-p25157460] Yeast alcohol dehydrogenase structure and catalysis. (2014). https://pubmed.ncbi.nlm.nih.gov/25157460/ DOI: 10.1021/bi5006442
tissue_or_cell_type
Purified homotetramer
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 72–83
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis · source_derived_draft · unverified_draft
### alcohol-zinc-coordination-chemistry In the closed subunits the catalytic zinc holds the substrate oxygen in classical tetrahedral coordination with Cys-43, Cys-153 and His-66, while in the open subunits the zinc takes an inverted coordination that adds the carboxylate of Glu-67, which may be an intermediate in displacing the zinc-bound water with the alcohol substrate. Condition category: normal 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: Three amino acids hold the zinc, and a fourth swings in to hand over the alcohol. organism: Yeast enzyme tissue_or_cell_type: Purified homotetramer experimental_model: X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis limitations: A yeast enzyme, used because its asymmetric tetramer captures two catalytic states. The zinc coordination chemistry is conserved, but kinetic numbers are yeast numbers. exposure: Coenzyme-bound closed and open subunit conformations evidence_span: {"source_cache": "artifacts/alcohol-research/25157460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20", "start_char": 0, "end_char": 1560, "text_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20"} [alcohol-p25157460] Yeast alcohol dehydrogenase structure and catalysis. (2014). https://pubmed.ncbi.nlm.nih.gov/25157460/ DOI: 10.1021/bi5006442
Complete structured claim and evidence
Substituting Glu-67 with glutamine decreased catalytic efficiency a hundred-fold.
The Glu-67 carboxylate of yeast alcohol dehydrogenase → Whole-body ethanol clearance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/25157460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20", "start_char": 0, "end_char": 1560, "text_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20"}
experimental_model
X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis
exposure
Coenzyme-bound closed and open subunit conformations
limitations
A yeast enzyme, used because its asymmetric tetramer captures two catalytic states. The zinc coordination chemistry is conserved, but kinetic numbers are yeast numbers.
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
Yeast enzyme
plain_language
Change that one residue and the enzyme works a hundred times worse.
primary_references
[alcohol-p25157460] Yeast alcohol dehydrogenase structure and catalysis. (2014). https://pubmed.ncbi.nlm.nih.gov/25157460/ DOI: 10.1021/bi5006442
tissue_or_cell_type
Purified homotetramer
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 85–96
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis · source_derived_draft · unverified_draft
### alcohol-glu67-catalytic-efficiency Substituting Glu-67 with glutamine decreased catalytic efficiency a hundred-fold. Condition category: normal 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: Change that one residue and the enzyme works a hundred times worse. organism: Yeast enzyme tissue_or_cell_type: Purified homotetramer experimental_model: X-ray crystallography of yeast ADH1 at 2.4 angstrom with site-directed mutagenesis limitations: A yeast enzyme, used because its asymmetric tetramer captures two catalytic states. The zinc coordination chemistry is conserved, but kinetic numbers are yeast numbers. exposure: Coenzyme-bound closed and open subunit conformations evidence_span: {"source_cache": "artifacts/alcohol-research/25157460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20", "start_char": 0, "end_char": 1560, "text_sha256": "c91a7069c53b4af61096bdc09ce952b0277d63d547a94e5d3870d2980aa31e20"} [alcohol-p25157460] Yeast alcohol dehydrogenase structure and catalysis. (2014). https://pubmed.ncbi.nlm.nih.gov/25157460/ DOI: 10.1021/bi5006442
Complete structured claim and evidence
Ethanol administration caused an immediate decrease in the NAD+/NADH ratio of both cytoplasm and mitochondria, which persisted over the 30 minutes studied.
Ethanol → Cytosolic free NAD+/NADH ratio source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/4342558.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d", "start_char": 0, "end_char": 959, "text_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d"}
experimental_model
Freeze-clamped liver metabolite measurement in starved rats after ethanol
exposure
Single ethanol dose, sampled over 30 minutes in fed and starved animals
limitations
The classic redox measurement. Metabolite ratios are calculated from near-equilibrium assumptions rather than measured directly, which the authors state.
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
Rat
plain_language
Burning alcohol floods the cell with the reduced form of the carrier that every other pathway needs oxidised.
primary_references
[alcohol-p4342558] The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. (1972). https://pubmed.ncbi.nlm.nih.gov/4342558/ DOI: 10.1042/bj1270387
tissue_or_cell_type
Liver
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 98–109
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Freeze-clamped liver metabolite measurement in starved rats after ethanol · source_derived_draft · unverified_draft
### alcohol-redox-shift Ethanol administration caused an immediate decrease in the NAD+/NADH ratio of both cytoplasm and mitochondria, which persisted over the 30 minutes studied. Condition category: normal 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: Burning alcohol floods the cell with the reduced form of the carrier that every other pathway needs oxidised. organism: Rat tissue_or_cell_type: Liver experimental_model: Freeze-clamped liver metabolite measurement in starved rats after ethanol limitations: The classic redox measurement. Metabolite ratios are calculated from near-equilibrium assumptions rather than measured directly, which the authors state. exposure: Single ethanol dose, sampled over 30 minutes in fed and starved animals evidence_span: {"source_cache": "artifacts/alcohol-research/4342558.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d", "start_char": 0, "end_char": 959, "text_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d"} [alcohol-p4342558] The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. (1972). https://pubmed.ncbi.nlm.nih.gov/4342558/ DOI: 10.1042/bj1270387
Complete structured claim and evidence
The free cytosolic NADP+/NADPH ratio fell immediately and returned nearly to control by 15 minutes, while the cytosolic ATP/ADP phosphate ratio was elevated at 15 minutes in starved rats.
Ethanol → Hepatic cytosolic ATP/ADP phosphate ratio source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/4342558.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d", "start_char": 0, "end_char": 959, "text_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d"}
experimental_model
Freeze-clamped liver metabolite measurement in starved rats after ethanol
exposure
Single ethanol dose, sampled over 30 minutes in fed and starved animals
limitations
The classic redox measurement. Metabolite ratios are calculated from near-equilibrium assumptions rather than measured directly, which the authors state.
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
Rat
plain_language
Two other energy ratios move as well, and they recover on different timescales.
primary_references
[alcohol-p4342558] The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. (1972). https://pubmed.ncbi.nlm.nih.gov/4342558/ DOI: 10.1042/bj1270387
tissue_or_cell_type
Liver
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 111–122
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Freeze-clamped liver metabolite measurement in starved rats after ethanol · source_derived_draft · unverified_draft
### alcohol-nadp-and-phosphorylation The free cytosolic NADP+/NADPH ratio fell immediately and returned nearly to control by 15 minutes, while the cytosolic ATP/ADP phosphate ratio was elevated at 15 minutes in starved rats. Condition category: normal 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: Two other energy ratios move as well, and they recover on different timescales. organism: Rat tissue_or_cell_type: Liver experimental_model: Freeze-clamped liver metabolite measurement in starved rats after ethanol limitations: The classic redox measurement. Metabolite ratios are calculated from near-equilibrium assumptions rather than measured directly, which the authors state. exposure: Single ethanol dose, sampled over 30 minutes in fed and starved animals evidence_span: {"source_cache": "artifacts/alcohol-research/4342558.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d", "start_char": 0, "end_char": 959, "text_sha256": "dce57aa8128b432a841f087e3c4e70963b8fe318e462df980e6cdd66ed4af79d"} [alcohol-p4342558] The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. (1972). https://pubmed.ncbi.nlm.nih.gov/4342558/ DOI: 10.1042/bj1270387
Complete structured claim and evidence
The ethanol-induced hepatic redox change was attenuated after chronic alcohol consumption in baboons, with metabolic consequences measured both in vivo and in vitro.
Habitual alcohol consumption → Attenuation of the ethanol-induced hepatic redox change after chronic intake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/6793493.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5105956fd640dc7b32bd1d5e54a0df98bc5eb8d332220e27578ce5e631536fbe", "start_char": 0, "end_char": 986, "text_sha256": "5105956fd640dc7b32bd1d5e54a0df98bc5eb8d332220e27578ce5e631536fbe"}
experimental_model
Baboons fed alcohol chronically, with in vivo and in vitro redox measurement
exposure
Chronic alcohol consumption compared with acute administration
limitations
A primate chronic-feeding model. It shows the redox change is not fixed, which bears on reading any single acute measurement as the steady state.
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
Baboon
plain_language
The redox hit shrinks with habitual drinking, so a first-drink measurement does not describe a heavy drinker.
primary_references
[alcohol-p6793493] Attenuation of the ethanol-induced hepatic redox change after chronic alcohol consumption in baboons: metabolic consequences in vivo and in vitro. (1981). https://pubmed.ncbi.nlm.nih.gov/6793493/ DOI: 10.1002/hep.1840010106
tissue_or_cell_type
Liver
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 124–135
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Baboons fed alcohol chronically, with in vivo and in vitro redox measurement · source_derived_draft · unverified_draft
### alcohol-redox-adaptation The ethanol-induced hepatic redox change was attenuated after chronic alcohol consumption in baboons, with metabolic consequences measured both in vivo and in vitro. Condition category: normal 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 redox hit shrinks with habitual drinking, so a first-drink measurement does not describe a heavy drinker. organism: Baboon tissue_or_cell_type: Liver experimental_model: Baboons fed alcohol chronically, with in vivo and in vitro redox measurement limitations: A primate chronic-feeding model. It shows the redox change is not fixed, which bears on reading any single acute measurement as the steady state. exposure: Chronic alcohol consumption compared with acute administration evidence_span: {"source_cache": "artifacts/alcohol-research/6793493.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5105956fd640dc7b32bd1d5e54a0df98bc5eb8d332220e27578ce5e631536fbe", "start_char": 0, "end_char": 986, "text_sha256": "5105956fd640dc7b32bd1d5e54a0df98bc5eb8d332220e27578ce5e631536fbe"} [alcohol-p6793493] Attenuation of the ethanol-induced hepatic redox change after chronic alcohol consumption in baboons: metabolic consequences in vivo and in vitro. (1981). https://pubmed.ncbi.nlm.nih.gov/6793493/ DOI: 10.1002/hep.1840010106
Complete structured claim and evidence
Ethanol induces CYP2E1 by protein stabilisation, slowing the ubiquitin-conjugation-dependent rapid degradation of the enzyme rather than raising its synthesis.
Ethanol → CYP2E1 protein stability against ubiquitin-dependent degradation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/8530344.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689", "start_char": 0, "end_char": 909, "text_sha256": "94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689"}
experimental_model
Ethanol treatment with ubiquitin conjugation and degradation assays
exposure
Ethanol exposure with measurement of CYP2E1 turnover
limitations
A protein-turnover mechanism rather than a transcriptional one. It explains why the second oxidation route appears quickly without new transcription.
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
Rat and cell systems
plain_language
Alcohol does not make more of this enzyme; it stops the cell destroying it.
primary_references
[alcohol-p8530344] Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1. (1995). https://pubmed.ncbi.nlm.nih.gov/8530344/ DOI: 10.1074/jbc.270.50.29632
tissue_or_cell_type
Hepatic microsomes
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 137–148
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ethanol treatment with ubiquitin conjugation and degradation assays · source_derived_draft · unverified_draft
### alcohol-cyp2e1-stabilisation Ethanol induces CYP2E1 by protein stabilisation, slowing the ubiquitin-conjugation-dependent rapid degradation of the enzyme rather than raising its synthesis. Condition category: normal 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: Alcohol does not make more of this enzyme; it stops the cell destroying it. organism: Rat and cell systems tissue_or_cell_type: Hepatic microsomes experimental_model: Ethanol treatment with ubiquitin conjugation and degradation assays limitations: A protein-turnover mechanism rather than a transcriptional one. It explains why the second oxidation route appears quickly without new transcription. exposure: Ethanol exposure with measurement of CYP2E1 turnover evidence_span: {"source_cache": "artifacts/alcohol-research/8530344.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689", "start_char": 0, "end_char": 909, "text_sha256": "94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689"} [alcohol-p8530344] Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1. (1995). https://pubmed.ncbi.nlm.nih.gov/8530344/ DOI: 10.1074/jbc.270.50.29632
Complete structured claim and evidence
The inactive ALDH2 subunit carries a substitution of lysine for glutamate at position 487, and correlating genotype with phenotype in 24 Japanese livers shows the allele encoding the abnormal subunit is dominant.
The inactive ALDH2*2 subunit carrying lysine for glutamate at position 487 → Human mitochondrial aldehyde dehydrogenase 2 / ALDH2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/2562960.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1", "start_char": 0, "end_char": 800, "text_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1"}
experimental_model
Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype
exposure
ALDH2 genotype compared with measured enzyme activity
limitations
Establishes dominance of the inactive allele, so heterozygotes are affected. The sample is 24 livers.
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
plain_language
One bad copy is enough, because the faulty subunit poisons the four-part enzyme.
primary_references
[alcohol-p2562960] Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. (1989). https://pubmed.ncbi.nlm.nih.gov/2562960/ DOI: 10.1172/jci113875
tissue_or_cell_type
Liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 150–161
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype · source_derived_draft · unverified_draft
### alcohol-aldh2-allele-dominant The inactive ALDH2 subunit carries a substitution of lysine for glutamate at position 487, and correlating genotype with phenotype in 24 Japanese livers shows the allele encoding the abnormal subunit is dominant. Condition category: machinery_impairment 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: One bad copy is enough, because the faulty subunit poisons the four-part enzyme. organism: Human tissue_or_cell_type: Liver experimental_model: Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype limitations: Establishes dominance of the inactive allele, so heterozygotes are affected. The sample is 24 livers. exposure: ALDH2 genotype compared with measured enzyme activity evidence_span: {"source_cache": "artifacts/alcohol-research/2562960.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1", "start_char": 0, "end_char": 800, "text_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1"} [alcohol-p2562960] Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. (1989). https://pubmed.ncbi.nlm.nih.gov/2562960/ DOI: 10.1172/jci113875
Complete structured claim and evidence
The alcohol flush reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption.
Acetaldehyde → The alcohol flush reaction source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/2562960.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1", "start_char": 0, "end_char": 800, "text_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1"}
experimental_model
Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype
exposure
ALDH2 genotype compared with measured enzyme activity
limitations
Establishes dominance of the inactive allele, so heterozygotes are affected. The sample is 24 livers.
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
plain_language
The flush is the body reacting to the first breakdown product, not to alcohol itself.
primary_references
[alcohol-p2562960] Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. (1989). https://pubmed.ncbi.nlm.nih.gov/2562960/ DOI: 10.1172/jci113875
tissue_or_cell_type
Liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 163–174
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype · source_derived_draft · unverified_draft
### alcohol-flush-from-acetaldehyde The alcohol flush reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption. Condition category: machinery_impairment 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 flush is the body reacting to the first breakdown product, not to alcohol itself. organism: Human tissue_or_cell_type: Liver experimental_model: Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype limitations: Establishes dominance of the inactive allele, so heterozygotes are affected. The sample is 24 livers. exposure: ALDH2 genotype compared with measured enzyme activity evidence_span: {"source_cache": "artifacts/alcohol-research/2562960.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1", "start_char": 0, "end_char": 800, "text_sha256": "0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1"} [alcohol-p2562960] Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. (1989). https://pubmed.ncbi.nlm.nih.gov/2562960/ DOI: 10.1172/jci113875
Complete structured claim and evidence
ALDH2*2 but not ADH1B*2 is the causative variant allele for Asian alcohol flushing after a low-dose challenge, on correlated pharmacokinetic and pharmacodynamic findings.
The inactive ALDH2*2 subunit carrying lysine for glutamate at position 487 → The alcohol flush reaction source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/25365528.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "74fa331e891fe46dedf3789025686318b37eae41389f093bda084e4a6d482218", "start_char": 0, "end_char": 1803, "text_sha256": "74fa331e891fe46dedf3789025686318b37eae41389f093bda084e4a6d482218"}
experimental_model
Low-dose alcohol challenge in genotyped subjects with paired pharmacokinetics and pharmacodynamics
exposure
Low-dose alcohol challenge across ADH1B and ALDH2 genotypes
limitations
Separates the two candidate variants by measuring both blood levels and symptoms. A low-dose challenge may not represent ordinary drinking.
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
plain_language
Of the two variants people blame for flushing, only one actually causes it.
primary_references
[alcohol-p25365528] ALDH2*2 but not ADH1B*2 is a causative variant gene allele for Asian alcohol flushing after a low-dose challenge: correlation of the pharmacokinetic and pharmacodynamic findings. (2014). https://pubmed.ncbi.nlm.nih.gov/25365528/ DOI: 10.1097/fpc.0000000000000096
tissue_or_cell_type
Whole body
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 176–187
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Low-dose alcohol challenge in genotyped subjects with paired pharmacokinetics and pharmacodynamics · source_derived_draft · unverified_draft
### alcohol-aldh2-not-adh1b-flush ALDH2*2 but not ADH1B*2 is the causative variant allele for Asian alcohol flushing after a low-dose challenge, on correlated pharmacokinetic and pharmacodynamic findings. Condition category: machinery_impairment 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: Of the two variants people blame for flushing, only one actually causes it. organism: Human tissue_or_cell_type: Whole body experimental_model: Low-dose alcohol challenge in genotyped subjects with paired pharmacokinetics and pharmacodynamics limitations: Separates the two candidate variants by measuring both blood levels and symptoms. A low-dose challenge may not represent ordinary drinking. exposure: Low-dose alcohol challenge across ADH1B and ALDH2 genotypes evidence_span: {"source_cache": "artifacts/alcohol-research/25365528.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "74fa331e891fe46dedf3789025686318b37eae41389f093bda084e4a6d482218", "start_char": 0, "end_char": 1803, "text_sha256": "74fa331e891fe46dedf3789025686318b37eae41389f093bda084e4a6d482218"} [alcohol-p25365528] ALDH2*2 but not ADH1B*2 is a causative variant gene allele for Asian alcohol flushing after a low-dose challenge: correlation of the pharmacokinetic and pharmacodynamic findings. (2014). https://pubmed.ncbi.nlm.nih.gov/25365528/ DOI: 10.1097/fpc.0000000000000096
Complete structured claim and evidence
An animal model developed to test the mechanism of protection against alcoholism by an alcohol dehydrogenase polymorphism supports faster ethanol oxidation producing higher acetaldehyde as the protective step.
The ADH1B rs1229984 A-allele (ADH1B*2, Arg48His) → Blood acetaldehyde concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/19710201.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "22b9547745b08adaa8a9a722228e9c5987ac67442b20f2737d8c54f6988ec7c5", "start_char": 0, "end_char": 1426, "text_sha256": "22b9547745b08adaa8a9a722228e9c5987ac67442b20f2737d8c54f6988ec7c5"}
experimental_model
An animal model built to reproduce the human alcohol dehydrogenase polymorphism
exposure
Higher-activity alcohol dehydrogenase against voluntary intake
limitations
A constructed animal model of a human protective genotype. It supports the acetaldehyde-burst explanation; it is not a human trial.
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
Rat model of the human variant
plain_language
A faster first enzyme makes the unpleasant metabolite arrive sooner.
primary_references
[alcohol-p19710201] Mechanism of protection against alcoholism by an alcohol dehydrogenase polymorphism: development of an animal model. (2010). https://pubmed.ncbi.nlm.nih.gov/19710201/ DOI: 10.1096/fj.09-132563
tissue_or_cell_type
Liver and behaviour
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 189–200
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · An animal model built to reproduce the human alcohol dehydrogenase polymorphism · source_derived_draft · unverified_draft
### alcohol-adh1b-fast-oxidation An animal model developed to test the mechanism of protection against alcoholism by an alcohol dehydrogenase polymorphism supports faster ethanol oxidation producing higher acetaldehyde as the protective step. Condition category: machinery_impairment 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: A faster first enzyme makes the unpleasant metabolite arrive sooner. organism: Rat model of the human variant tissue_or_cell_type: Liver and behaviour experimental_model: An animal model built to reproduce the human alcohol dehydrogenase polymorphism limitations: A constructed animal model of a human protective genotype. It supports the acetaldehyde-burst explanation; it is not a human trial. exposure: Higher-activity alcohol dehydrogenase against voluntary intake evidence_span: {"source_cache": "artifacts/alcohol-research/19710201.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "22b9547745b08adaa8a9a722228e9c5987ac67442b20f2737d8c54f6988ec7c5", "start_char": 0, "end_char": 1426, "text_sha256": "22b9547745b08adaa8a9a722228e9c5987ac67442b20f2737d8c54f6988ec7c5"} [alcohol-p19710201] Mechanism of protection against alcoholism by an alcohol dehydrogenase polymorphism: development of an animal model. (2010). https://pubmed.ncbi.nlm.nih.gov/19710201/ DOI: 10.1096/fj.09-132563
Complete structured claim and evidence
Decreased gastric alcohol dehydrogenase activity and decreased first-pass metabolism accounted for higher blood alcohol levels in women given the same oral dose.
Gastric mucosal alcohol dehydrogenase activity → Blood ethanol concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/2248624.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8679c8360907919917314956d4febe0010e0e35619c2032360341f4964a3e16", "start_char": 0, "end_char": 1624, "text_sha256": "e8679c8360907919917314956d4febe0010e0e35619c2032360341f4964a3e16"}
experimental_model
Blood alcohol and gastric biopsy alcohol dehydrogenase activity in men and women
exposure
Oral versus intravenous ethanol, with gastric biopsy enzyme assay
limitations
The oral versus intravenous comparison is what isolates first-pass metabolism. Sample sizes are small and the effect size has been debated since.
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
plain_language
Some alcohol is destroyed in the stomach wall before it reaches the blood, and that barrier is smaller in women.
primary_references
[alcohol-p2248624] High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. (1990). https://pubmed.ncbi.nlm.nih.gov/2248624/ DOI: 10.1056/nejm199001113220205
tissue_or_cell_type
Gastric mucosa
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 202–213
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Blood alcohol and gastric biopsy alcohol dehydrogenase activity in men and women · source_derived_draft · unverified_draft
### alcohol-gastric-first-pass Decreased gastric alcohol dehydrogenase activity and decreased first-pass metabolism accounted for higher blood alcohol levels in women given the same oral dose. Condition category: normal 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: Some alcohol is destroyed in the stomach wall before it reaches the blood, and that barrier is smaller in women. organism: Human tissue_or_cell_type: Gastric mucosa experimental_model: Blood alcohol and gastric biopsy alcohol dehydrogenase activity in men and women limitations: The oral versus intravenous comparison is what isolates first-pass metabolism. Sample sizes are small and the effect size has been debated since. exposure: Oral versus intravenous ethanol, with gastric biopsy enzyme assay evidence_span: {"source_cache": "artifacts/alcohol-research/2248624.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8679c8360907919917314956d4febe0010e0e35619c2032360341f4964a3e16", "start_char": 0, "end_char": 1624, "text_sha256": "e8679c8360907919917314956d4febe0010e0e35619c2032360341f4964a3e16"} [alcohol-p2248624] High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. (1990). https://pubmed.ncbi.nlm.nih.gov/2248624/ DOI: 10.1056/nejm199001113220205
Complete structured claim and evidence
Human gastric alcohol dehydrogenase activity varied with age, sex and alcoholism in biopsy material.
Gastric mucosal alcohol dehydrogenase activity → Gastric first-pass metabolism of ethanol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/8244116.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "69408eea35e836f0be82630ffd1e713af36a3224f9fc2a87f9f14411d32ab4de", "start_char": 0, "end_char": 1985, "text_sha256": "69408eea35e836f0be82630ffd1e713af36a3224f9fc2a87f9f14411d32ab4de"}
experimental_model
Gastric biopsy alcohol dehydrogenase activity across age, sex and alcoholism
exposure
Measured enzyme activity in biopsy material
limitations
A larger observational series of the same enzyme. It reports how the activity varies, not what that variation causes.
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
plain_language
The size of the stomach barrier is not the same in everyone.
primary_references
[alcohol-p8244116] Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism. (1993). https://pubmed.ncbi.nlm.nih.gov/8244116/ DOI: 10.1136/gut.34.10.1433
tissue_or_cell_type
Gastric mucosa
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 215–226
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gastric biopsy alcohol dehydrogenase activity across age, sex and alcoholism · source_derived_draft · unverified_draft
### alcohol-gastric-adh-varies Human gastric alcohol dehydrogenase activity varied with age, sex and alcoholism in biopsy material. Condition category: normal 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 size of the stomach barrier is not the same in everyone. organism: Human tissue_or_cell_type: Gastric mucosa experimental_model: Gastric biopsy alcohol dehydrogenase activity across age, sex and alcoholism limitations: A larger observational series of the same enzyme. It reports how the activity varies, not what that variation causes. exposure: Measured enzyme activity in biopsy material evidence_span: {"source_cache": "artifacts/alcohol-research/8244116.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "69408eea35e836f0be82630ffd1e713af36a3224f9fc2a87f9f14411d32ab4de", "start_char": 0, "end_char": 1985, "text_sha256": "69408eea35e836f0be82630ffd1e713af36a3224f9fc2a87f9f14411d32ab4de"} [alcohol-p8244116] Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism. (1993). https://pubmed.ncbi.nlm.nih.gov/8244116/ DOI: 10.1136/gut.34.10.1433
Complete structured claim and evidence
Following an intoxicating dose of ethanol, Adh1-null mice and to a lesser extent Adh4-null mice, but not Adh3-null mice, showed significant reductions in blood ethanol clearance, and ethanol-induced sleep was significantly longer only in Adh1-null mice.
Experimental Adh1-null mouse genotype → Whole-body ethanol clearance source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"}
experimental_model
Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges
exposure
Intoxicating ethanol dose, formaldehyde LD50, and retinol administration
limitations
A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one.
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
Mouse
plain_language
Remove the main enzyme and the animal stays drunk longer.
primary_references
[alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
tissue_or_cell_type
Liver and embryo
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 228–239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges · source_derived_draft · unverified_draft
### alcohol-adh1-clearance Following an intoxicating dose of ethanol, Adh1-null mice and to a lesser extent Adh4-null mice, but not Adh3-null mice, showed significant reductions in blood ethanol clearance, and ethanol-induced sleep was significantly longer only in Adh1-null mice. Condition category: machinery_impairment 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: Remove the main enzyme and the animal stays drunk longer. organism: Mouse tissue_or_cell_type: Liver and embryo experimental_model: Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges limitations: A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one. exposure: Intoxicating ethanol dose, formaldehyde LD50, and retinol administration evidence_span: {"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"} [alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
Complete structured claim and evidence
Retinoic acid production following retinol administration was reduced 8.5-fold in Adh4-null mice and 4.8-fold in Adh1-null mice, showing overlapping roles for Adh1 and Adh4 in both ethanol and retinol metabolism.
Experimental Adh4-null mouse genotype → Production of retinoic acid from retinol source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"}
experimental_model
Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges
exposure
Intoxicating ethanol dose, formaldehyde LD50, and retinol administration
limitations
A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one.
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
Mouse
plain_language
The same enzymes that clear alcohol also turn vitamin A into its signalling form.
primary_references
[alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
tissue_or_cell_type
Liver and embryo
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 241–252
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges · source_derived_draft · unverified_draft
### alcohol-adh-retinoic-acid Retinoic acid production following retinol administration was reduced 8.5-fold in Adh4-null mice and 4.8-fold in Adh1-null mice, showing overlapping roles for Adh1 and Adh4 in both ethanol and retinol metabolism. Condition category: machinery_impairment 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 same enzymes that clear alcohol also turn vitamin A into its signalling form. organism: Mouse tissue_or_cell_type: Liver and embryo experimental_model: Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges limitations: A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one. exposure: Intoxicating ethanol dose, formaldehyde LD50, and retinol administration evidence_span: {"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"} [alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
Complete structured claim and evidence
Only Adh3-null mice had a significantly reduced formaldehyde LD50, and Adh3 played no role with ethanol or retinol.
Experimental Adh3-null mouse genotype → Formaldehyde source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"}
experimental_model
Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges
exposure
Intoxicating ethanol dose, formaldehyde LD50, and retinol administration
limitations
A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one.
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
Mouse
plain_language
The third enzyme has a different job entirely.
primary_references
[alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
tissue_or_cell_type
Liver and embryo
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 254–265
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges · source_derived_draft · unverified_draft
### alcohol-adh3-formaldehyde Only Adh3-null mice had a significantly reduced formaldehyde LD50, and Adh3 played no role with ethanol or retinol. Condition category: machinery_impairment 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 third enzyme has a different job entirely. organism: Mouse tissue_or_cell_type: Liver and embryo experimental_model: Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges limitations: A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one. exposure: Intoxicating ethanol dose, formaldehyde LD50, and retinol administration evidence_span: {"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"} [alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
Complete structured claim and evidence
The incidence of embryonic resorption following ethanol administration was increased threefold in Adh1-null mice and 1.5-fold in Adh4-null mice, but was unchanged in Adh3-null mice.
Experimental Adh1-null mouse genotype → Embryonic resorption after ethanol administration in mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"}
experimental_model
Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges
exposure
Intoxicating ethanol dose, formaldehyde LD50, and retinol administration
limitations
A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one.
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
Mouse
plain_language
Slower clearance in the mother meant more lost pregnancies after the same dose.
primary_references
[alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
tissue_or_cell_type
Liver and embryo
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 267–278
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges · source_derived_draft · unverified_draft
### alcohol-adh1-embryo The incidence of embryonic resorption following ethanol administration was increased threefold in Adh1-null mice and 1.5-fold in Adh4-null mice, but was unchanged in Adh3-null mice. Condition category: machinery_impairment 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: Slower clearance in the mother meant more lost pregnancies after the same dose. organism: Mouse tissue_or_cell_type: Liver and embryo experimental_model: Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges limitations: A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one. exposure: Intoxicating ethanol dose, formaldehyde LD50, and retinol administration evidence_span: {"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"} [alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796
Complete structured claim and evidence
Ethanol inhibited NMDA-activated ion current in hippocampal neurons at concentrations reached during intoxication.
Ethanol → NMDA receptor-mediated current source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/2467382.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c968c9a63cb2826e3986e1fd13f83fdf231adc1d46e0bc9aa73882cce6f0dca1", "start_char": 0, "end_char": 844, "text_sha256": "c968c9a63cb2826e3986e1fd13f83fdf231adc1d46e0bc9aa73882cce6f0dca1"}
experimental_model
Whole-cell recording from dissociated hippocampal neurons
exposure
Ethanol at intoxicating concentrations applied to NMDA-activated current
limitations
The founding electrophysiology result for this target. Concentrations are in the intoxicating range, which is what makes it relevant to drinking.
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
Rat
plain_language
Alcohol shuts down the brain’s main excitatory receptor at the doses people actually drink.
primary_references
[alcohol-p2467382] Ethanol inhibits NMDA-activated ion current in hippocampal neurons. (1989). https://pubmed.ncbi.nlm.nih.gov/2467382/ DOI: 10.1126/science.2467382
tissue_or_cell_type
Hippocampal neurons
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 280–291
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell recording from dissociated hippocampal neurons · source_derived_draft · unverified_draft
### alcohol-nmda-inhibition Ethanol inhibited NMDA-activated ion current in hippocampal neurons at concentrations reached during intoxication. Condition category: normal 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: Alcohol shuts down the brain’s main excitatory receptor at the doses people actually drink. organism: Rat tissue_or_cell_type: Hippocampal neurons experimental_model: Whole-cell recording from dissociated hippocampal neurons limitations: The founding electrophysiology result for this target. Concentrations are in the intoxicating range, which is what makes it relevant to drinking. exposure: Ethanol at intoxicating concentrations applied to NMDA-activated current evidence_span: {"source_cache": "artifacts/alcohol-research/2467382.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c968c9a63cb2826e3986e1fd13f83fdf231adc1d46e0bc9aa73882cce6f0dca1", "start_char": 0, "end_char": 844, "text_sha256": "c968c9a63cb2826e3986e1fd13f83fdf231adc1d46e0bc9aa73882cce6f0dca1"} [alcohol-p2467382] Ethanol inhibits NMDA-activated ion current in hippocampal neurons. (1989). https://pubmed.ncbi.nlm.nih.gov/2467382/ DOI: 10.1126/science.2467382
Complete structured claim and evidence
NMDA receptor-mediated synaptic excitation was selectively inhibited by ethanol in hippocampal slices from adult rats.
Ethanol → NMDA receptor-mediated synaptic excitation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/2158533.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62f29619272239be27b46fe08d9e439abb782cfe87fdb17351d50bfc0e22aa92", "start_char": 0, "end_char": 1708, "text_sha256": "62f29619272239be27b46fe08d9e439abb782cfe87fdb17351d50bfc0e22aa92"}
experimental_model
Extracellular recording in adult rat hippocampal slice
exposure
Ethanol applied to synaptic responses
limitations
Shows the inhibition is selective for the NMDA component rather than general synaptic depression.
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
Rat
plain_language
It is that one receptor being blocked, not the whole synapse being quietened.
primary_references
[alcohol-p2158533] NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat. (1990). https://pubmed.ncbi.nlm.nih.gov/2158533/ DOI: 10.1523/jneurosci.10-04-01372.1990
tissue_or_cell_type
Hippocampus
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 293–304
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Extracellular recording in adult rat hippocampal slice · source_derived_draft · unverified_draft
### alcohol-nmda-selective NMDA receptor-mediated synaptic excitation was selectively inhibited by ethanol in hippocampal slices from adult rats. Condition category: normal 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: It is that one receptor being blocked, not the whole synapse being quietened. organism: Rat tissue_or_cell_type: Hippocampus experimental_model: Extracellular recording in adult rat hippocampal slice limitations: Shows the inhibition is selective for the NMDA component rather than general synaptic depression. exposure: Ethanol applied to synaptic responses evidence_span: {"source_cache": "artifacts/alcohol-research/2158533.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62f29619272239be27b46fe08d9e439abb782cfe87fdb17351d50bfc0e22aa92", "start_char": 0, "end_char": 1708, "text_sha256": "62f29619272239be27b46fe08d9e439abb782cfe87fdb17351d50bfc0e22aa92"} [alcohol-p2158533] NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat. (1990). https://pubmed.ncbi.nlm.nih.gov/2158533/ DOI: 10.1523/jneurosci.10-04-01372.1990
Complete structured claim and evidence
Fyn kinase is a determinant of ethanol sensitivity through its relation to NMDA receptor function, with tyrosine phosphorylation of the receptor linked to acute tolerance.
Tyrosine-protein kinase Fyn → NMDA receptor-mediated current source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/9381182.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008253b9262aee0b3acd845dfea4f9c087c00e0078bd1ba9b4eaa265192ec782", "start_char": 0, "end_char": 742, "text_sha256": "008253b9262aee0b3acd845dfea4f9c087c00e0078bd1ba9b4eaa265192ec782"}
experimental_model
Fyn-null mice with NMDA receptor phosphorylation measurement
exposure
Ethanol sensitivity and tyrosine phosphorylation in Fyn-deficient mice
limitations
Links acute tolerance to a specific kinase. The behavioural readout is hypnotic sensitivity, not drinking.
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
Mouse
plain_language
A kinase decides how quickly the receptor adapts, and so how quickly tolerance appears.
primary_references
[alcohol-p9381182] Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function. (1997). https://pubmed.ncbi.nlm.nih.gov/9381182/ DOI: 10.1126/science.278.5338.698
tissue_or_cell_type
Hippocampus
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 306–317
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fyn-null mice with NMDA receptor phosphorylation measurement · source_derived_draft · unverified_draft
### alcohol-fyn-tolerance Fyn kinase is a determinant of ethanol sensitivity through its relation to NMDA receptor function, with tyrosine phosphorylation of the receptor linked to acute tolerance. Condition category: machinery_impairment 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: A kinase decides how quickly the receptor adapts, and so how quickly tolerance appears. organism: Mouse tissue_or_cell_type: Hippocampus experimental_model: Fyn-null mice with NMDA receptor phosphorylation measurement limitations: Links acute tolerance to a specific kinase. The behavioural readout is hypnotic sensitivity, not drinking. exposure: Ethanol sensitivity and tyrosine phosphorylation in Fyn-deficient mice evidence_span: {"source_cache": "artifacts/alcohol-research/9381182.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008253b9262aee0b3acd845dfea4f9c087c00e0078bd1ba9b4eaa265192ec782", "start_char": 0, "end_char": 742, "text_sha256": "008253b9262aee0b3acd845dfea4f9c087c00e0078bd1ba9b4eaa265192ec782"} [alcohol-p9381182] Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function. (1997). https://pubmed.ncbi.nlm.nih.gov/9381182/ DOI: 10.1126/science.278.5338.698
Complete structured claim and evidence
A naturally occurring GABA-A receptor subunit partnership was identified with high sensitivity to ethanol.
Ethanol → Tonic GABA-A receptor current source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/17159992.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fbee66c99566521e71ae6b95b34c77426888dd791b27b2e3dad3a215a12441f7", "start_char": 0, "end_char": 1048, "text_sha256": "fbee66c99566521e71ae6b95b34c77426888dd791b27b2e3dad3a215a12441f7"}
experimental_model
Recombinant GABA-A receptor subunit combinations tested for ethanol sensitivity
exposure
Ethanol at low millimolar concentrations on defined subunit partnerships
limitations
Identifies a subunit combination sensitive at drinking-relevant concentrations, which had been the main objection to GABA-A as a direct target.
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
Recombinant human and rodent subunits
plain_language
A specific combination of receptor parts responds to alcohol at the concentrations drinking produces.
primary_references
[alcohol-p17159992] A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol. (2007). https://pubmed.ncbi.nlm.nih.gov/17159992/ DOI: 10.1038/nn1813
tissue_or_cell_type
Extrasynaptic GABA-A receptors
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 319–330
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant GABA-A receptor subunit combinations tested for ethanol sensitivity · source_derived_draft · unverified_draft
### alcohol-gaba-subunit-sensitivity A naturally occurring GABA-A receptor subunit partnership was identified with high sensitivity to ethanol. Condition category: normal 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: A specific combination of receptor parts responds to alcohol at the concentrations drinking produces. organism: Recombinant human and rodent subunits tissue_or_cell_type: Extrasynaptic GABA-A receptors experimental_model: Recombinant GABA-A receptor subunit combinations tested for ethanol sensitivity limitations: Identifies a subunit combination sensitive at drinking-relevant concentrations, which had been the main objection to GABA-A as a direct target. exposure: Ethanol at low millimolar concentrations on defined subunit partnerships evidence_span: {"source_cache": "artifacts/alcohol-research/17159992.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fbee66c99566521e71ae6b95b34c77426888dd791b27b2e3dad3a215a12441f7", "start_char": 0, "end_char": 1048, "text_sha256": "fbee66c99566521e71ae6b95b34c77426888dd791b27b2e3dad3a215a12441f7"} [alcohol-p17159992] A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol. (2007). https://pubmed.ncbi.nlm.nih.gov/17159992/ DOI: 10.1038/nn1813
Complete structured claim and evidence
GABA-A receptor delta subunit knockout mice have multiple defects in behavioural responses to ethanol.
Experimental GABA-A delta subunit knockout mouse genotype → Tonic GABA-A receptor current source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/11781502.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9aa25b5b0c1c81f09205b27cbe518898225af41cd3d7e9a948db66619311ca0b", "start_char": 0, "end_char": 1079, "text_sha256": "9aa25b5b0c1c81f09205b27cbe518898225af41cd3d7e9a948db66619311ca0b"}
experimental_model
GABA-A delta subunit knockout mice across behavioural ethanol assays
exposure
Ethanol behavioural responses in delta-subunit-null mice
limitations
A genetic test of the extrasynaptic receptor. Multiple behavioural defects are reported, so the subunit is not specific to one ethanol effect.
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
Mouse
plain_language
Delete the subunit and the animal responds to alcohol differently across several tests.
primary_references
[alcohol-p11781502] GABA(A)-receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol. (2001). https://pubmed.ncbi.nlm.nih.gov/11781502/ DOI: 10.1097/00000374-200112000-00003
tissue_or_cell_type
Brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 332–343
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · GABA-A delta subunit knockout mice across behavioural ethanol assays · source_derived_draft · unverified_draft
### alcohol-gabrd-null-behaviour GABA-A receptor delta subunit knockout mice have multiple defects in behavioural responses to ethanol. Condition category: machinery_impairment 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: Delete the subunit and the animal responds to alcohol differently across several tests. organism: Mouse tissue_or_cell_type: Brain experimental_model: GABA-A delta subunit knockout mice across behavioural ethanol assays limitations: A genetic test of the extrasynaptic receptor. Multiple behavioural defects are reported, so the subunit is not specific to one ethanol effect. exposure: Ethanol behavioural responses in delta-subunit-null mice evidence_span: {"source_cache": "artifacts/alcohol-research/11781502.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9aa25b5b0c1c81f09205b27cbe518898225af41cd3d7e9a948db66619311ca0b", "start_char": 0, "end_char": 1079, "text_sha256": "9aa25b5b0c1c81f09205b27cbe518898225af41cd3d7e9a948db66619311ca0b"} [alcohol-p11781502] GABA(A)-receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol. (2001). https://pubmed.ncbi.nlm.nih.gov/11781502/ DOI: 10.1097/00000374-200112000-00003
Complete structured claim and evidence
Enhancement of glycine receptor function by ethanol was inversely correlated with the molecular volume at position alpha267, implying a size-limited site rather than a general membrane effect.
Ethanol → Glycine receptor chloride current source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/9452448.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1dd90423748e82a02cec583a8bbfcfd2ee9dcf8da9c126ddf5c5198011820ec", "start_char": 0, "end_char": 1618, "text_sha256": "e1dd90423748e82a02cec583a8bbfcfd2ee9dcf8da9c126ddf5c5198011820ec"}
experimental_model
Site-directed mutagenesis of glycine receptor position alpha267 with alcohols of differing size
exposure
A series of alcohols against residue volume at alpha267
limitations
A volume-series experiment that argues for a discrete binding pocket rather than a membrane-disordering effect. It is recombinant receptor electrophysiology.
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
Recombinant receptor
plain_language
Make the pocket smaller and alcohol works less, which is what a real binding site looks like.
primary_references
[alcohol-p9452448] Enhancement of glycine receptor function by ethanol is inversely correlated with molecular volume at position alpha267. (1998). https://pubmed.ncbi.nlm.nih.gov/9452448/ DOI: 10.1074/jbc.273.6.3314
tissue_or_cell_type
Glycine receptor
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 345–356
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis of glycine receptor position alpha267 with alcohols of differing size · source_derived_draft · unverified_draft
### alcohol-glycine-receptor-pocket Enhancement of glycine receptor function by ethanol was inversely correlated with the molecular volume at position alpha267, implying a size-limited site rather than a general membrane effect. Condition category: normal 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: Make the pocket smaller and alcohol works less, which is what a real binding site looks like. organism: Recombinant receptor tissue_or_cell_type: Glycine receptor experimental_model: Site-directed mutagenesis of glycine receptor position alpha267 with alcohols of differing size limitations: A volume-series experiment that argues for a discrete binding pocket rather than a membrane-disordering effect. It is recombinant receptor electrophysiology. exposure: A series of alcohols against residue volume at alpha267 evidence_span: {"source_cache": "artifacts/alcohol-research/9452448.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1dd90423748e82a02cec583a8bbfcfd2ee9dcf8da9c126ddf5c5198011820ec", "start_char": 0, "end_char": 1618, "text_sha256": "e1dd90423748e82a02cec583a8bbfcfd2ee9dcf8da9c126ddf5c5198011820ec"} [alcohol-p9452448] Enhancement of glycine receptor function by ethanol is inversely correlated with molecular volume at position alpha267. (1998). https://pubmed.ncbi.nlm.nih.gov/9452448/ DOI: 10.1074/jbc.273.6.3314
Complete structured claim and evidence
An alcohol-sensing site was identified in the calcium- and voltage-gated large conductance potassium channel.
Ethanol → Large-conductance calcium- and voltage-gated potassium (BK) channel source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/24927535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef6f89212505affcd872cd85809dfd8f4036b04e6d3a86b2b24a3b5bdc33f706", "start_char": 0, "end_char": 1201, "text_sha256": "ef6f89212505affcd872cd85809dfd8f4036b04e6d3a86b2b24a3b5bdc33f706"}
experimental_model
Structure-function mapping of the BK channel cytosolic gating ring
exposure
Alcohol applied to defined channel constructs
limitations
Identifies a discrete alcohol-sensing site. A site in a recombinant channel is not proof that occupancy explains an intact behaviour.
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
Recombinant channel
plain_language
Alcohol has a physical docking place on this potassium channel.
primary_references
[alcohol-p24927535] An alcohol-sensing site in the calcium- and voltage-gated, large conductance potassium (BK) channel. (2014). https://pubmed.ncbi.nlm.nih.gov/24927535/ DOI: 10.1073/pnas.1317363111
tissue_or_cell_type
BK channel
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 358–369
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Structure-function mapping of the BK channel cytosolic gating ring · source_derived_draft · unverified_draft
### alcohol-bk-alcohol-site An alcohol-sensing site was identified in the calcium- and voltage-gated large conductance potassium channel. Condition category: normal 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: Alcohol has a physical docking place on this potassium channel. organism: Recombinant channel tissue_or_cell_type: BK channel experimental_model: Structure-function mapping of the BK channel cytosolic gating ring limitations: Identifies a discrete alcohol-sensing site. A site in a recombinant channel is not proof that occupancy explains an intact behaviour. exposure: Alcohol applied to defined channel constructs evidence_span: {"source_cache": "artifacts/alcohol-research/24927535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef6f89212505affcd872cd85809dfd8f4036b04e6d3a86b2b24a3b5bdc33f706", "start_char": 0, "end_char": 1201, "text_sha256": "ef6f89212505affcd872cd85809dfd8f4036b04e6d3a86b2b24a3b5bdc33f706"} [alcohol-p24927535] An alcohol-sensing site in the calcium- and voltage-gated, large conductance potassium (BK) channel. (2014). https://pubmed.ncbi.nlm.nih.gov/24927535/ DOI: 10.1073/pnas.1317363111
Complete structured claim and evidence
A BK channel auxiliary protein was identified that controls molecular and behavioural tolerance to alcohol.
BK channel auxiliary beta-4 subunit → Molecular and behavioural tolerance to alcohol at the BK channel source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/18981408.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e67be69c00867e16027760fe3f5f6818d63da287c671683b2f83e57b6fae434d", "start_char": 0, "end_char": 1596, "text_sha256": "e67be69c00867e16027760fe3f5f6818d63da287c671683b2f83e57b6fae434d"}
experimental_model
Identification of a BK auxiliary subunit controlling tolerance, with behavioural testing
exposure
Repeated alcohol exposure with and without the auxiliary subunit
limitations
Connects a molecular tolerance mechanism to behaviour. The auxiliary subunit work spans model systems, so the mapping to human tolerance is indirect.
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
Invertebrate and mammalian systems
plain_language
A helper subunit decides whether repeated drinking makes the channel stop responding.
primary_references
[alcohol-p18981408] Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol. (2008). https://pubmed.ncbi.nlm.nih.gov/18981408/ DOI: 10.1073/pnas.0801068105
tissue_or_cell_type
BK channel complexes
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 371–382
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Identification of a BK auxiliary subunit controlling tolerance, with behavioural testing · source_derived_draft · unverified_draft
### alcohol-bk-beta4-tolerance A BK channel auxiliary protein was identified that controls molecular and behavioural tolerance to alcohol. Condition category: normal 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: A helper subunit decides whether repeated drinking makes the channel stop responding. organism: Invertebrate and mammalian systems tissue_or_cell_type: BK channel complexes experimental_model: Identification of a BK auxiliary subunit controlling tolerance, with behavioural testing limitations: Connects a molecular tolerance mechanism to behaviour. The auxiliary subunit work spans model systems, so the mapping to human tolerance is indirect. exposure: Repeated alcohol exposure with and without the auxiliary subunit evidence_span: {"source_cache": "artifacts/alcohol-research/18981408.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e67be69c00867e16027760fe3f5f6818d63da287c671683b2f83e57b6fae434d", "start_char": 0, "end_char": 1596, "text_sha256": "e67be69c00867e16027760fe3f5f6818d63da287c671683b2f83e57b6fae434d"} [alcohol-p18981408] Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol. (2008). https://pubmed.ncbi.nlm.nih.gov/18981408/ DOI: 10.1073/pnas.0801068105
Complete structured claim and evidence
G-protein-gated inwardly rectifying potassium channels are targets of alcohol action, activated at intoxicating concentrations.
Ethanol → GIRK channel potassium current source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Heterologous expression of GIRK channels with alcohol application
exposure
Intoxicating alcohol concentrations
limitations
Establishes the channel family as a direct target. Recombinant expression, not native neurons.
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
Recombinant channels
plain_language
Alcohol opens a potassium channel that quietens neurons.
primary_references
[alcohol-p10570485] G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. (1999). https://pubmed.ncbi.nlm.nih.gov/10570485/ DOI: 10.1038/16012
tissue_or_cell_type
Neuronal potassium channels
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 384–395
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous expression of GIRK channels with alcohol application · source_derived_draft · unverified_draft
### alcohol-girk-target G-protein-gated inwardly rectifying potassium channels are targets of alcohol action, activated at intoxicating concentrations. Condition category: normal 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: Alcohol opens a potassium channel that quietens neurons. organism: Recombinant channels tissue_or_cell_type: Neuronal potassium channels experimental_model: Heterologous expression of GIRK channels with alcohol application limitations: Establishes the channel family as a direct target. Recombinant expression, not native neurons. exposure: Intoxicating alcohol concentrations evidence_span: {"source_cache": "artifacts/alcohol-research/10570485.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "42da0b6588f0ec74c04be8d7a13a0aec3d34ed9e01b92af9cfad92eb3e79714b", "start_char": 0, "end_char": 827, "text_sha256": "42da0b6588f0ec74c04be8d7a13a0aec3d34ed9e01b92af9cfad92eb3e79714b"} [alcohol-p10570485] G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. (1999). https://pubmed.ncbi.nlm.nih.gov/10570485/ DOI: 10.1038/16012
Complete structured claim and evidence
A discrete alcohol pocket in the channel cytoplasmic domain was shown to be involved in GIRK channel activation.
Ethanol → The hydrophobic alcohol pocket of the GIRK channel cytoplasmic domain source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Mutagenesis and structural mapping of the GIRK cytoplasmic domain
exposure
Alcohol binding to a defined hydrophobic pocket
limitations
Locates the site to a discrete pocket, which supports direct binding over a bulk membrane effect.
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
Recombinant channels
plain_language
The same picture again: a specific pocket, not a general softening of the membrane.
primary_references
[alcohol-p19561601] A discrete alcohol pocket involved in GIRK channel activation. (2009). https://pubmed.ncbi.nlm.nih.gov/19561601/ DOI: 10.1038/nn.2358
tissue_or_cell_type
GIRK cytoplasmic domain
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 397–408
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis and structural mapping of the GIRK cytoplasmic domain · source_derived_draft · unverified_draft
### alcohol-girk-pocket A discrete alcohol pocket in the channel cytoplasmic domain was shown to be involved in GIRK channel activation. Condition category: normal 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 same picture again: a specific pocket, not a general softening of the membrane. organism: Recombinant channels tissue_or_cell_type: GIRK cytoplasmic domain experimental_model: Mutagenesis and structural mapping of the GIRK cytoplasmic domain limitations: Locates the site to a discrete pocket, which supports direct binding over a bulk membrane effect. exposure: Alcohol binding to a defined hydrophobic pocket evidence_span: {"source_cache": "artifacts/alcohol-research/19561601.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6aa4c10bd615439d1b5e008da1031a4ed244aeef6a0be4764930a7f183778428", "start_char": 0, "end_char": 1103, "text_sha256": "6aa4c10bd615439d1b5e008da1031a4ed244aeef6a0be4764930a7f183778428"} [alcohol-p19561601] A discrete alcohol pocket involved in GIRK channel activation. (2009). https://pubmed.ncbi.nlm.nih.gov/19561601/ DOI: 10.1038/nn.2358
Complete structured claim and evidence
Ethanol increased extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter.
Ethanol → Cellular adenosine uptake by the nucleoside transporter source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/2298733.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3933013c774b52112ebb838291e240d625dbf664faa2e94db35204bc38fb73d9", "start_char": 0, "end_char": 1419, "text_sha256": "3933013c774b52112ebb838291e240d625dbf664faa2e94db35204bc38fb73d9"}
experimental_model
Nucleoside transport and adenosine measurement in cultured cells during ethanol exposure
exposure
Ethanol exposure with adenosine uptake measurement
limitations
A transport mechanism for an indirect target: the effect is on adenosine handling, not on a receptor. Cultured cells.
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
Cultured cells
plain_language
Alcohol raises a natural sedative by blocking its reuptake.
primary_references
[alcohol-p2298733] Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter. (1990). https://pubmed.ncbi.nlm.nih.gov/2298733/ DOI: 10.1016/s0021-9258(19)39923-5
tissue_or_cell_type
Nucleoside transporter
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 410–421
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nucleoside transport and adenosine measurement in cultured cells during ethanol exposure · source_derived_draft · unverified_draft
### alcohol-ent1-inhibition Ethanol increased extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter. Condition category: normal 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: Alcohol raises a natural sedative by blocking its reuptake. organism: Cultured cells tissue_or_cell_type: Nucleoside transporter experimental_model: Nucleoside transport and adenosine measurement in cultured cells during ethanol exposure limitations: A transport mechanism for an indirect target: the effect is on adenosine handling, not on a receptor. Cultured cells. exposure: Ethanol exposure with adenosine uptake measurement evidence_span: {"source_cache": "artifacts/alcohol-research/2298733.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3933013c774b52112ebb838291e240d625dbf664faa2e94db35204bc38fb73d9", "start_char": 0, "end_char": 1419, "text_sha256": "3933013c774b52112ebb838291e240d625dbf664faa2e94db35204bc38fb73d9"} [alcohol-p2298733] Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter. (1990). https://pubmed.ncbi.nlm.nih.gov/2298733/ DOI: 10.1016/s0021-9258(19)39923-5
Complete structured claim and evidence
Ethanol preferentially stimulated dopamine release in the nucleus accumbens of freely moving rats.
Ethanol → Dopamine release in the nucleus accumbens source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/3761194.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98cf7c1ea1f6fbf3da6b89ab6beaed01a679ea1c8d4823f00952692a0c9203ca", "start_char": 0, "end_char": 1539, "text_sha256": "98cf7c1ea1f6fbf3da6b89ab6beaed01a679ea1c8d4823f00952692a0c9203ca"}
experimental_model
In vivo microdialysis in freely moving rats
exposure
Ethanol administration with regional dopamine measurement
limitations
A reward-pathway measurement in freely moving animals. Dopamine release is a correlate of reinforcement, not a measure of liking or dependence.
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
Rat
plain_language
Alcohol raises dopamine in the brain region that marks things as worth repeating.
primary_references
[alcohol-p3761194] Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. (1986). https://pubmed.ncbi.nlm.nih.gov/3761194/ DOI: 10.1016/s0022-3565(25)23929-5
tissue_or_cell_type
Nucleus accumbens
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 423–434
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo microdialysis in freely moving rats · source_derived_draft · unverified_draft
### alcohol-accumbens-dopamine Ethanol preferentially stimulated dopamine release in the nucleus accumbens of freely moving rats. Condition category: normal 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: Alcohol raises dopamine in the brain region that marks things as worth repeating. organism: Rat tissue_or_cell_type: Nucleus accumbens experimental_model: In vivo microdialysis in freely moving rats limitations: A reward-pathway measurement in freely moving animals. Dopamine release is a correlate of reinforcement, not a measure of liking or dependence. exposure: Ethanol administration with regional dopamine measurement evidence_span: {"source_cache": "artifacts/alcohol-research/3761194.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98cf7c1ea1f6fbf3da6b89ab6beaed01a679ea1c8d4823f00952692a0c9203ca", "start_char": 0, "end_char": 1539, "text_sha256": "98cf7c1ea1f6fbf3da6b89ab6beaed01a679ea1c8d4823f00952692a0c9203ca"} [alcohol-p3761194] Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. (1986). https://pubmed.ncbi.nlm.nih.gov/3761194/ DOI: 10.1016/s0022-3565(25)23929-5
Complete structured claim and evidence
Ethanol regulated hepatic lipin-1 through AMP-activated protein kinase and sterol regulatory element-binding protein 1 signalling in mice.
Ethanol → Hepatic de novo lipogenesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/21953514.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "acfcd2656e45aab9abcf367ed27e447001ddaa55ac143e9cc2f24b0958ea15a7", "start_char": 0, "end_char": 1626, "text_sha256": "acfcd2656e45aab9abcf367ed27e447001ddaa55ac143e9cc2f24b0958ea15a7"}
experimental_model
Ethanol-fed mice with hepatic AMPK and SREBP-1 measurement
exposure
Chronic ethanol feeding
limitations
A signalling route to steatosis measured in mice. It sits alongside, not instead of, the redox explanation for fatty liver.
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
Mouse
plain_language
Alcohol rewires the liver’s fat-building programme through the energy sensor.
primary_references
[alcohol-p21953514] Regulation of hepatic lipin-1 by ethanol: role of AMP-activated protein kinase/sterol regulatory element-binding protein 1 signaling in mice. (2012). https://pubmed.ncbi.nlm.nih.gov/21953514/ DOI: 10.1002/hep.24708
tissue_or_cell_type
Liver
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 436–447
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ethanol-fed mice with hepatic AMPK and SREBP-1 measurement · source_derived_draft · unverified_draft
### alcohol-lipin1-srebp Ethanol regulated hepatic lipin-1 through AMP-activated protein kinase and sterol regulatory element-binding protein 1 signalling in mice. Condition category: normal 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: Alcohol rewires the liver’s fat-building programme through the energy sensor. organism: Mouse tissue_or_cell_type: Liver experimental_model: Ethanol-fed mice with hepatic AMPK and SREBP-1 measurement limitations: A signalling route to steatosis measured in mice. It sits alongside, not instead of, the redox explanation for fatty liver. exposure: Chronic ethanol feeding evidence_span: {"source_cache": "artifacts/alcohol-research/21953514.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "acfcd2656e45aab9abcf367ed27e447001ddaa55ac143e9cc2f24b0958ea15a7", "start_char": 0, "end_char": 1626, "text_sha256": "acfcd2656e45aab9abcf367ed27e447001ddaa55ac143e9cc2f24b0958ea15a7"} [alcohol-p21953514] Regulation of hepatic lipin-1 by ethanol: role of AMP-activated protein kinase/sterol regulatory element-binding protein 1 signaling in mice. (2012). https://pubmed.ncbi.nlm.nih.gov/21953514/ DOI: 10.1002/hep.24708
Complete structured claim and evidence
Adenosine signalling contributed to ethanol-induced fatty liver in mice, with the effect traced through adenosine receptors and the equilibrative nucleoside transporter.
Extracellular adenosine concentration → Hepatic steatosis / fatty liver source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/19221436.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21c9018b01ea529427ab3e8f55fd2f561e0a9ba03c22788fb1875609bf9d4312", "start_char": 0, "end_char": 1663, "text_sha256": "21c9018b01ea529427ab3e8f55fd2f561e0a9ba03c22788fb1875609bf9d4312"}
experimental_model
Ethanol-fed mice with adenosine receptor and transporter deletion
exposure
Chronic ethanol feeding in Ent1-null and adenosine receptor-null mice
limitations
Connects the adenosine target to an organ outcome using genetic deletion, which is stronger than correlation.
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
Mouse
plain_language
The same adenosine rise that sedates the brain also drives fat into the liver.
primary_references
[alcohol-p19221436] Adenosine signaling contributes to ethanol-induced fatty liver in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19221436/ DOI: 10.1172/jci37409
tissue_or_cell_type
Liver
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 449–460
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ethanol-fed mice with adenosine receptor and transporter deletion · source_derived_draft · unverified_draft
### alcohol-adenosine-fatty-liver Adenosine signalling contributed to ethanol-induced fatty liver in mice, with the effect traced through adenosine receptors and the equilibrative nucleoside transporter. Condition category: normal 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 same adenosine rise that sedates the brain also drives fat into the liver. organism: Mouse tissue_or_cell_type: Liver experimental_model: Ethanol-fed mice with adenosine receptor and transporter deletion limitations: Connects the adenosine target to an organ outcome using genetic deletion, which is stronger than correlation. exposure: Chronic ethanol feeding in Ent1-null and adenosine receptor-null mice evidence_span: {"source_cache": "artifacts/alcohol-research/19221436.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21c9018b01ea529427ab3e8f55fd2f561e0a9ba03c22788fb1875609bf9d4312", "start_char": 0, "end_char": 1663, "text_sha256": "21c9018b01ea529427ab3e8f55fd2f561e0a9ba03c22788fb1875609bf9d4312"} [alcohol-p19221436] Adenosine signaling contributes to ethanol-induced fatty liver in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19221436/ DOI: 10.1172/jci37409
Complete structured claim and evidence
Patients with chronic alcohol abuse showed increased intestinal permeability to macromolecules and endotoxaemia, varying across stages of alcohol-induced liver disease.
Habitual alcohol consumption → Intestinal permeability to macromolecules source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/10845660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d", "start_char": 0, "end_char": 1618, "text_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d"}
experimental_model
Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease
exposure
Chronic alcohol abuse, staged by liver disease severity
limitations
Human observational staging. It shows permeability tracks disease stage; it cannot establish which came first.
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
plain_language
The gut wall leaks and bacterial fragments reach the blood.
primary_references
[alcohol-p10845660] Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. (2000). https://pubmed.ncbi.nlm.nih.gov/10845660/ DOI: 10.1016/s0168-8278(00)80242-1
tissue_or_cell_type
Intestine and blood
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 462–473
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease · source_derived_draft · unverified_draft
### alcohol-permeability-endotoxin Patients with chronic alcohol abuse showed increased intestinal permeability to macromolecules and endotoxaemia, varying across stages of alcohol-induced liver disease. Condition category: normal 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 gut wall leaks and bacterial fragments reach the blood. organism: Human tissue_or_cell_type: Intestine and blood experimental_model: Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease limitations: Human observational staging. It shows permeability tracks disease stage; it cannot establish which came first. exposure: Chronic alcohol abuse, staged by liver disease severity evidence_span: {"source_cache": "artifacts/alcohol-research/10845660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d", "start_char": 0, "end_char": 1618, "text_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d"} [alcohol-p10845660] Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. (2000). https://pubmed.ncbi.nlm.nih.gov/10845660/ DOI: 10.1016/s0168-8278(00)80242-1
Complete structured claim and evidence
Endotoxaemia accompanied the permeability defect and differed across stages of alcohol-induced liver disease.
Circulating endotoxin concentration → Alcoholic liver injury source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/10845660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d", "start_char": 0, "end_char": 1618, "text_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d"}
experimental_model
Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease
exposure
Chronic alcohol abuse, staged by liver disease severity
limitations
Human observational staging. It shows permeability tracks disease stage; it cannot establish which came first.
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
plain_language
The leak and the liver damage travel together.
primary_references
[alcohol-p10845660] Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. (2000). https://pubmed.ncbi.nlm.nih.gov/10845660/ DOI: 10.1016/s0168-8278(00)80242-1
tissue_or_cell_type
Intestine and blood
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 475–486
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease · source_derived_draft · unverified_draft
### alcohol-endotoxin-liver Endotoxaemia accompanied the permeability defect and differed across stages of alcohol-induced liver disease. Condition category: normal 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 leak and the liver damage travel together. organism: Human tissue_or_cell_type: Intestine and blood experimental_model: Intestinal permeability and endotoxin measurement across stages of alcohol-induced liver disease limitations: Human observational staging. It shows permeability tracks disease stage; it cannot establish which came first. exposure: Chronic alcohol abuse, staged by liver disease severity evidence_span: {"source_cache": "artifacts/alcohol-research/10845660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d", "start_char": 0, "end_char": 1618, "text_sha256": "0342f8e351dde29e075eaf2d1920f26d1e8ef9d9a704947dc6c08f6f5fde846d"} [alcohol-p10845660] Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. (2000). https://pubmed.ncbi.nlm.nih.gov/10845660/ DOI: 10.1016/s0168-8278(00)80242-1
Complete structured claim and evidence
Intestinal permeability and gut bacterial dysbiosis were associated with behavioural markers of alcohol-dependence severity.
Intestinal permeability to macromolecules → Alcohol craving and dependence severity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/25288760.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b62793e216036689dd924357291c4512c5e9bcf7e7b41429e6bb72b2022f6a6c", "start_char": 0, "end_char": 1345, "text_sha256": "b62793e216036689dd924357291c4512c5e9bcf7e7b41429e6bb72b2022f6a6c"}
experimental_model
Alcohol-dependent patients with permeability, microbiome and behavioural measures
exposure
Alcohol dependence with detoxification
limitations
Links the gut measurements to craving. It is an association in a dependent population, and the direction of causation is not established.
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
plain_language
How leaky the gut is tracks with how severe the dependence is.
primary_references
[alcohol-p25288760] Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. (2014). https://pubmed.ncbi.nlm.nih.gov/25288760/ DOI: 10.1073/pnas.1415174111
tissue_or_cell_type
Intestine and behaviour
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 488–499
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Alcohol-dependent patients with permeability, microbiome and behavioural measures · source_derived_draft · unverified_draft
### alcohol-permeability-craving Intestinal permeability and gut bacterial dysbiosis were associated with behavioural markers of alcohol-dependence severity. Condition category: normal 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: How leaky the gut is tracks with how severe the dependence is. organism: Human tissue_or_cell_type: Intestine and behaviour experimental_model: Alcohol-dependent patients with permeability, microbiome and behavioural measures limitations: Links the gut measurements to craving. It is an association in a dependent population, and the direction of causation is not established. exposure: Alcohol dependence with detoxification evidence_span: {"source_cache": "artifacts/alcohol-research/25288760.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b62793e216036689dd924357291c4512c5e9bcf7e7b41429e6bb72b2022f6a6c", "start_char": 0, "end_char": 1345, "text_sha256": "b62793e216036689dd924357291c4512c5e9bcf7e7b41429e6bb72b2022f6a6c"} [alcohol-p25288760] Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. (2014). https://pubmed.ncbi.nlm.nih.gov/25288760/ DOI: 10.1073/pnas.1415174111
Complete structured claim and evidence
Fructose promoted leaky gut, endotoxaemia and liver fibrosis through ethanol-inducible cytochrome P450-2E1-mediated oxidative and nitrative stress.
Human cytochrome P450 2E1 → Intestinal permeability to macromolecules source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/30959577.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d", "start_char": 0, "end_char": 1961, "text_sha256": "1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d"}
experimental_model
Fructose feeding in mice with CYP2E1 deletion and gut barrier measurement
exposure
Fructose feeding with and without CYP2E1
limitations
Recorded because it isolates the enzyme: the leak and fibrosis required CYP2E1, which ethanol induces. The driver here is fructose, not ethanol.
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
Mouse
plain_language
The enzyme alcohol stabilises is itself enough to open the gut barrier.
primary_references
[alcohol-p30959577] Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress. (2021). https://pubmed.ncbi.nlm.nih.gov/30959577/ DOI: 10.1002/hep.30652
tissue_or_cell_type
Intestine and liver
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 501–512
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fructose feeding in mice with CYP2E1 deletion and gut barrier measurement · source_derived_draft · unverified_draft
### alcohol-cyp2e1-leaky-gut Fructose promoted leaky gut, endotoxaemia and liver fibrosis through ethanol-inducible cytochrome P450-2E1-mediated oxidative and nitrative stress. Condition category: normal 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 enzyme alcohol stabilises is itself enough to open the gut barrier. organism: Mouse tissue_or_cell_type: Intestine and liver experimental_model: Fructose feeding in mice with CYP2E1 deletion and gut barrier measurement limitations: Recorded because it isolates the enzyme: the leak and fibrosis required CYP2E1, which ethanol induces. The driver here is fructose, not ethanol. exposure: Fructose feeding with and without CYP2E1 evidence_span: {"source_cache": "artifacts/alcohol-research/30959577.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d", "start_char": 0, "end_char": 1961, "text_sha256": "1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d"} [alcohol-p30959577] Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress. (2021). https://pubmed.ncbi.nlm.nih.gov/30959577/ DOI: 10.1002/hep.30652
Complete structured claim and evidence
A defect of the mitochondrial respiratory chain was identified as a mechanism of reactive oxygen species overproduction in a rat model of alcoholic liver disease, with a role for zinc deficiency.
Habitual alcohol consumption → Hepatic reactive oxygen species production source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/26585415.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6743a8cefec8f9b3504ea8cc068c50c2b8fca42934fef4309d7e9819ff10d28c", "start_char": 0, "end_char": 1907, "text_sha256": "6743a8cefec8f9b3504ea8cc068c50c2b8fca42934fef4309d7e9819ff10d28c"}
experimental_model
Rat model of alcoholic liver disease with mitochondrial respiratory chain assays
exposure
Chronic alcohol feeding with zinc status measured
limitations
Assigns the reactive oxygen species source to a respiratory chain defect and ties it to zinc. A rat model of the disease.
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
Rat
plain_language
The damaged energy chain leaks reactive oxygen, and short zinc makes it worse.
primary_references
[alcohol-p26585415] Defect of mitochondrial respiratory chain is a mechanism of ROS overproduction in a rat model of alcoholic liver disease: role of zinc deficiency. (2016). https://pubmed.ncbi.nlm.nih.gov/26585415/ DOI: 10.1152/ajpgi.00270.2015
tissue_or_cell_type
Liver mitochondria
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 514–525
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat model of alcoholic liver disease with mitochondrial respiratory chain assays · source_derived_draft · unverified_draft
### alcohol-mitochondrial-ros A defect of the mitochondrial respiratory chain was identified as a mechanism of reactive oxygen species overproduction in a rat model of alcoholic liver disease, with a role for zinc deficiency. Condition category: normal 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 damaged energy chain leaks reactive oxygen, and short zinc makes it worse. organism: Rat tissue_or_cell_type: Liver mitochondria experimental_model: Rat model of alcoholic liver disease with mitochondrial respiratory chain assays limitations: Assigns the reactive oxygen species source to a respiratory chain defect and ties it to zinc. A rat model of the disease. exposure: Chronic alcohol feeding with zinc status measured evidence_span: {"source_cache": "artifacts/alcohol-research/26585415.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6743a8cefec8f9b3504ea8cc068c50c2b8fca42934fef4309d7e9819ff10d28c", "start_char": 0, "end_char": 1907, "text_sha256": "6743a8cefec8f9b3504ea8cc068c50c2b8fca42934fef4309d7e9819ff10d28c"} [alcohol-p26585415] Defect of mitochondrial respiratory chain is a mechanism of ROS overproduction in a rat model of alcoholic liver disease: role of zinc deficiency. (2016). https://pubmed.ncbi.nlm.nih.gov/26585415/ DOI: 10.1152/ajpgi.00270.2015
Complete structured claim and evidence
Levels of the acetaldehyde-derived DNA adduct N2-ethyl-deoxyguanosine were increased in oral mucosa DNA from rhesus monkeys exposed to alcohol.
Acetaldehyde → N2-ethyl-2′-deoxyguanosine, the acetaldehyde-derived DNA adduct source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/27056945.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c01bbdf333ac3266271f33f59dc90b58fb733575ade7193b1e9c1664983ac4f5", "start_char": 0, "end_char": 2034, "text_sha256": "c01bbdf333ac3266271f33f59dc90b58fb733575ade7193b1e9c1664983ac4f5"}
experimental_model
Rhesus monkeys exposed to alcohol with oral mucosa DNA adduct measurement
exposure
Alcohol exposure with mass-spectrometric adduct quantification
limitations
A primate measurement of the specific adduct. It establishes exposure of the tissue DNA, not that a tumour follows.
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
Rhesus monkey
plain_language
The first breakdown product sticks to DNA in the tissue that alcohol touches first.
primary_references
[alcohol-p27056945] Increased levels of the acetaldehyde-derived DNA adduct N 2-ethyldeoxyguanosine in oral mucosa DNA from Rhesus monkeys exposed to alcohol. (2016). https://pubmed.ncbi.nlm.nih.gov/27056945/ DOI: 10.1093/mutage/gew016
tissue_or_cell_type
Oral mucosa
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 527–538
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rhesus monkeys exposed to alcohol with oral mucosa DNA adduct measurement · source_derived_draft · unverified_draft
### alcohol-dna-adducts Levels of the acetaldehyde-derived DNA adduct N2-ethyl-deoxyguanosine were increased in oral mucosa DNA from rhesus monkeys exposed to alcohol. Condition category: normal 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 first breakdown product sticks to DNA in the tissue that alcohol touches first. organism: Rhesus monkey tissue_or_cell_type: Oral mucosa experimental_model: Rhesus monkeys exposed to alcohol with oral mucosa DNA adduct measurement limitations: A primate measurement of the specific adduct. It establishes exposure of the tissue DNA, not that a tumour follows. exposure: Alcohol exposure with mass-spectrometric adduct quantification evidence_span: {"source_cache": "artifacts/alcohol-research/27056945.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c01bbdf333ac3266271f33f59dc90b58fb733575ade7193b1e9c1664983ac4f5", "start_char": 0, "end_char": 2034, "text_sha256": "c01bbdf333ac3266271f33f59dc90b58fb733575ade7193b1e9c1664983ac4f5"} [alcohol-p27056945] Increased levels of the acetaldehyde-derived DNA adduct N 2-ethyldeoxyguanosine in oral mucosa DNA from Rhesus monkeys exposed to alcohol. (2016). https://pubmed.ncbi.nlm.nih.gov/27056945/ DOI: 10.1093/mutage/gew016
Complete structured claim and evidence
Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhanced oesophageal cancer risk.
The inactive ALDH2*2 subunit carrying lysine for glutamate at position 487 → Oesophageal squamous cell cancer risk source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/19698717.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4262a0549d8e78b4e7719f62bfa61849f3cf6eb3403bf45fe28d32b7d7662c58", "start_char": 0, "end_char": 1706, "text_sha256": "4262a0549d8e78b4e7719f62bfa61849f3cf6eb3403bf45fe28d32b7d7662c58"}
experimental_model
Case-control study of oesophageal cancer with ADH1B and ALDH2 genotypes and smoking
exposure
Alcohol consumption and smoking across functional genotypes
limitations
A gene-environment interaction study. Synergy is reported on a statistical interaction scale, and the design is case-control.
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
plain_language
The variant that makes drinking unpleasant also makes each drink more carcinogenic.
primary_references
[alcohol-p19698717] Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. (2009). https://pubmed.ncbi.nlm.nih.gov/19698717/ DOI: 10.1053/j.gastro.2009.07.070
tissue_or_cell_type
Oesophagus
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 540–551
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case-control study of oesophageal cancer with ADH1B and ALDH2 genotypes and smoking · source_derived_draft · unverified_draft
### alcohol-genotype-cancer-synergy Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhanced oesophageal cancer risk. Condition category: machinery_impairment 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 variant that makes drinking unpleasant also makes each drink more carcinogenic. organism: Human tissue_or_cell_type: Oesophagus experimental_model: Case-control study of oesophageal cancer with ADH1B and ALDH2 genotypes and smoking limitations: A gene-environment interaction study. Synergy is reported on a statistical interaction scale, and the design is case-control. exposure: Alcohol consumption and smoking across functional genotypes evidence_span: {"source_cache": "artifacts/alcohol-research/19698717.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4262a0549d8e78b4e7719f62bfa61849f3cf6eb3403bf45fe28d32b7d7662c58", "start_char": 0, "end_char": 1706, "text_sha256": "4262a0549d8e78b4e7719f62bfa61849f3cf6eb3403bf45fe28d32b7d7662c58"} [alcohol-p19698717] Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. (2009). https://pubmed.ncbi.nlm.nih.gov/19698717/ DOI: 10.1053/j.gastro.2009.07.070
Complete structured claim and evidence
ALDH2 deficiency promoted alcohol-associated liver cancer by activating oncogenic pathways via oxidised-DNA-enriched extracellular vesicles.
The inactive ALDH2*2 subunit carrying lysine for glutamate at position 487 → Alcohol-associated liver cancer source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/31279903.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a0e9d2f127fd9454b41431aa6ed4bdcfd30723cc3acee2a1678015ac5299887", "start_char": 0, "end_char": 2706, "text_sha256": "3a0e9d2f127fd9454b41431aa6ed4bdcfd30723cc3acee2a1678015ac5299887"}
experimental_model
ALDH2-deficient mice and human samples with extracellular vesicle analysis
exposure
Alcohol exposure on an ALDH2-deficient background
limitations
Proposes a specific transmissible mechanism. The oncogenic pathway activation is measured in a model, not in treated patients.
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
Mouse and human samples
plain_language
Damaged DNA is packaged into vesicles that carry the cancer signal to other cells.
primary_references
[alcohol-p31279903] ALDH2 deficiency promotes alcohol-associated liver cancer by activating oncogenic pathways via oxidized DNA-enriched extracellular vesicles. (2019). https://pubmed.ncbi.nlm.nih.gov/31279903/ DOI: 10.1016/j.jhep.2019.06.018
tissue_or_cell_type
Liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 553–564
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ALDH2-deficient mice and human samples with extracellular vesicle analysis · source_derived_draft · unverified_draft
### alcohol-aldh2-liver-cancer ALDH2 deficiency promoted alcohol-associated liver cancer by activating oncogenic pathways via oxidised-DNA-enriched extracellular vesicles. Condition category: machinery_impairment 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: Damaged DNA is packaged into vesicles that carry the cancer signal to other cells. organism: Mouse and human samples tissue_or_cell_type: Liver experimental_model: ALDH2-deficient mice and human samples with extracellular vesicle analysis limitations: Proposes a specific transmissible mechanism. The oncogenic pathway activation is measured in a model, not in treated patients. exposure: Alcohol exposure on an ALDH2-deficient background evidence_span: {"source_cache": "artifacts/alcohol-research/31279903.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a0e9d2f127fd9454b41431aa6ed4bdcfd30723cc3acee2a1678015ac5299887", "start_char": 0, "end_char": 2706, "text_sha256": "3a0e9d2f127fd9454b41431aa6ed4bdcfd30723cc3acee2a1678015ac5299887"} [alcohol-p31279903] ALDH2 deficiency promotes alcohol-associated liver cancer by activating oncogenic pathways via oxidized DNA-enriched extracellular vesicles. (2019). https://pubmed.ncbi.nlm.nih.gov/31279903/ DOI: 10.1016/j.jhep.2019.06.018
Complete structured claim and evidence
Carriers of the ADH1B rs1229984 A-allele consumed 17.2% fewer units per week, had lower systolic blood pressure, interleukin-6, waist circumference and body mass index, and had lower odds of coronary heart disease (odds ratio 0.90), with the protective association the same across all categories of alcohol consumption.
The ADH1B rs1229984 A-allele (ADH1B*2, Arg48His) → Coronary heart disease source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/25011450.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8f5f9f8c57fc5e32e827d8db1f212ebb427553d9b9f59db611a622bd99c4a10", "start_char": 0, "end_char": 1978, "text_sha256": "d8f5f9f8c57fc5e32e827d8db1f212ebb427553d9b9f59db611a622bd99c4a10"}
experimental_model
Mendelian randomisation meta-analysis of 56 studies and 261,991 individuals
exposure
The ADH1B rs1229984 variant as an instrument for alcohol exposure
limitations
Genetic instrument design, which avoids the confounding and reverse causation of consumption questionnaires. It cannot speak to drinking patterns the variant does not affect.
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
plain_language
The gene variant that makes people drink less also gives them less heart disease, including among light drinkers.
primary_references
[alcohol-p25011450] Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. (2014). https://pubmed.ncbi.nlm.nih.gov/25011450/ DOI: 10.1136/bmj.g4164
tissue_or_cell_type
Cardiovascular system
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 566–577
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mendelian randomisation meta-analysis of 56 studies and 261,991 individuals · source_derived_draft · unverified_draft
### alcohol-mendelian-cardiovascular Carriers of the ADH1B rs1229984 A-allele consumed 17.2% fewer units per week, had lower systolic blood pressure, interleukin-6, waist circumference and body mass index, and had lower odds of coronary heart disease (odds ratio 0.90), with the protective association the same across all categories of alcohol consumption. Condition category: normal 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 gene variant that makes people drink less also gives them less heart disease, including among light drinkers. organism: Human tissue_or_cell_type: Cardiovascular system experimental_model: Mendelian randomisation meta-analysis of 56 studies and 261,991 individuals limitations: Genetic instrument design, which avoids the confounding and reverse causation of consumption questionnaires. It cannot speak to drinking patterns the variant does not affect. exposure: The ADH1B rs1229984 variant as an instrument for alcohol exposure evidence_span: {"source_cache": "artifacts/alcohol-research/25011450.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8f5f9f8c57fc5e32e827d8db1f212ebb427553d9b9f59db611a622bd99c4a10", "start_char": 0, "end_char": 1978, "text_sha256": "d8f5f9f8c57fc5e32e827d8db1f212ebb427553d9b9f59db611a622bd99c4a10"} [alcohol-p25011450] Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. (2014). https://pubmed.ncbi.nlm.nih.gov/25011450/ DOI: 10.1136/bmj.g4164
Complete structured claim and evidence
Without adjustment the meta-analysis replicated the classic J-shaped curve with reduced mortality for low-volume drinkers (relative risk 0.86), but after adjustment for abstainer biases and study quality no significant reduction remained (relative risk 0.97), while former drinkers had elevated risk (1.22).
Misclassification of former and occasional drinkers as abstainers → All-cause mortality source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/26997174.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db6a3810963367be7e87327becdf62060843fbd53c764a0d5c8f3d6c3084e9ec", "start_char": 0, "end_char": 2096, "text_sha256": "db6a3810963367be7e87327becdf62060843fbd53c764a0d5c8f3d6c3084e9ec"}
experimental_model
Systematic review and meta-regression of 87 studies, 3,998,626 people and 367,103 deaths
exposure
Alcohol consumption categories against all-cause mortality, adjusted for study quality
limitations
A bias-adjustment analysis. It does not report new participants; it reanalyses the existing cohorts after correcting how abstainers were defined.
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
plain_language
The apparent benefit of light drinking disappears once sick ex-drinkers are taken out of the comparison group.
primary_references
[alcohol-p26997174] Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality. (2016). https://pubmed.ncbi.nlm.nih.gov/26997174/ DOI: 10.15288/jsad.2016.77.185
tissue_or_cell_type
Whole body
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 579–590
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Systematic review and meta-regression of 87 studies, 3,998,626 people and 367,103 deaths · source_derived_draft · unverified_draft
### alcohol-jcurve-artefact Without adjustment the meta-analysis replicated the classic J-shaped curve with reduced mortality for low-volume drinkers (relative risk 0.86), but after adjustment for abstainer biases and study quality no significant reduction remained (relative risk 0.97), while former drinkers had elevated risk (1.22). Condition category: normal 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 apparent benefit of light drinking disappears once sick ex-drinkers are taken out of the comparison group. organism: Human tissue_or_cell_type: Whole body experimental_model: Systematic review and meta-regression of 87 studies, 3,998,626 people and 367,103 deaths limitations: A bias-adjustment analysis. It does not report new participants; it reanalyses the existing cohorts after correcting how abstainers were defined. exposure: Alcohol consumption categories against all-cause mortality, adjusted for study quality evidence_span: {"source_cache": "artifacts/alcohol-research/26997174.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db6a3810963367be7e87327becdf62060843fbd53c764a0d5c8f3d6c3084e9ec", "start_char": 0, "end_char": 2096, "text_sha256": "db6a3810963367be7e87327becdf62060843fbd53c764a0d5c8f3d6c3084e9ec"} [alcohol-p26997174] Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality. (2016). https://pubmed.ncbi.nlm.nih.gov/26997174/ DOI: 10.15288/jsad.2016.77.185
Complete structured claim and evidence
In unadjusted models, protective effects were identified for alcohol consumption against all-cause mortality in pooled English cohorts of adults aged 50 and over, which the authors examine to test the suitability of age-specific limits.
Habitual alcohol consumption → All-cause mortality source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/25670624.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2915b9b52e02cedee89d34376f15e2efc97c6a66e83377240892b305c0c5c1b8", "start_char": 0, "end_char": 3171, "text_sha256": "2915b9b52e02cedee89d34376f15e2efc97c6a66e83377240892b305c0c5c1b8"}
experimental_model
Pooled analysis of up to 10 population cohorts from the Health Survey for England
exposure
Self-reported weekly and heaviest-day consumption in adults aged 50 and over
limitations
A large observational cohort with the abstainer comparison the reanalysis above criticises. Protective effects were identified in unadjusted models.
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
plain_language
In the raw numbers, older people who drank moderately died less often.
primary_references
[alcohol-p25670624] All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts. (2015). https://pubmed.ncbi.nlm.nih.gov/25670624/ DOI: 10.1136/bmj.h384
tissue_or_cell_type
Whole body
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 592–603
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pooled analysis of up to 10 population cohorts from the Health Survey for England · source_derived_draft · unverified_draft
### alcohol-jcurve-observed In unadjusted models, protective effects were identified for alcohol consumption against all-cause mortality in pooled English cohorts of adults aged 50 and over, which the authors examine to test the suitability of age-specific limits. Condition category: normal 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: In the raw numbers, older people who drank moderately died less often. organism: Human tissue_or_cell_type: Whole body experimental_model: Pooled analysis of up to 10 population cohorts from the Health Survey for England limitations: A large observational cohort with the abstainer comparison the reanalysis above criticises. Protective effects were identified in unadjusted models. exposure: Self-reported weekly and heaviest-day consumption in adults aged 50 and over evidence_span: {"source_cache": "artifacts/alcohol-research/25670624.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2915b9b52e02cedee89d34376f15e2efc97c6a66e83377240892b305c0c5c1b8", "start_char": 0, "end_char": 3171, "text_sha256": "2915b9b52e02cedee89d34376f15e2efc97c6a66e83377240892b305c0c5c1b8"} [alcohol-p25670624] All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts. (2015). https://pubmed.ncbi.nlm.nih.gov/25670624/ DOI: 10.1136/bmj.h384
Complete structured claim and evidence
Naltrexone with coping skills therapy reduced drinking in alcohol dependence in a controlled study.
Naltrexone → Proportion of heavy drinking days source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/1444726.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4cd480a90f2d2272c693445386c42ee68f90b9db24d5f91b6e499ffeb1d10ed", "start_char": 0, "end_char": 962, "text_sha256": "e4cd480a90f2d2272c693445386c42ee68f90b9db24d5f91b6e499ffeb1d10ed"}
experimental_model
Controlled trial of naltrexone with coping skills therapy in alcohol dependence
exposure
Naltrexone with psychosocial treatment versus control
limitations
An early randomised trial in a specialist setting. Effect sizes in later, larger trials have generally been smaller.
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
plain_language
Blocking the opioid receptor reduced how much people drank.
primary_references
[alcohol-p1444726] Naltrexone and coping skills therapy for alcohol dependence. A controlled study. (1992). https://pubmed.ncbi.nlm.nih.gov/1444726/ DOI: 10.1001/archpsyc.1992.01820110045007
tissue_or_cell_type
Whole body
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 605–616
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled trial of naltrexone with coping skills therapy in alcohol dependence · source_derived_draft · unverified_draft
### alcohol-naltrexone-drinking Naltrexone with coping skills therapy reduced drinking in alcohol dependence in a controlled study. Condition category: normal 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: Blocking the opioid receptor reduced how much people drank. organism: Human tissue_or_cell_type: Whole body experimental_model: Controlled trial of naltrexone with coping skills therapy in alcohol dependence limitations: An early randomised trial in a specialist setting. Effect sizes in later, larger trials have generally been smaller. exposure: Naltrexone with psychosocial treatment versus control evidence_span: {"source_cache": "artifacts/alcohol-research/1444726.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4cd480a90f2d2272c693445386c42ee68f90b9db24d5f91b6e499ffeb1d10ed", "start_char": 0, "end_char": 962, "text_sha256": "e4cd480a90f2d2272c693445386c42ee68f90b9db24d5f91b6e499ffeb1d10ed"} [alcohol-p1444726] Naltrexone and coping skills therapy for alcohol dependence. A controlled study. (1992). https://pubmed.ncbi.nlm.nih.gov/1444726/ DOI: 10.1001/archpsyc.1992.01820110045007
Complete structured claim and evidence
Long-acting injectable naltrexone reduced heavy drinking in a randomised controlled trial in alcohol dependence, with acceptable tolerability.
Naltrexone → Proportion of heavy drinking days source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/alcohol-research/15811981.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7a465c529de6ca90435bf684f771315d916f418979902fd0af0a7d712eaa3f", "start_char": 0, "end_char": 2211, "text_sha256": "bb7a465c529de6ca90435bf684f771315d916f418979902fd0af0a7d712eaa3f"}
experimental_model
Randomised controlled trial of long-acting injectable naltrexone
exposure
Monthly injectable naltrexone versus placebo
limitations
A large randomised trial of a depot formulation, which removes the adherence problem of daily dosing.
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
plain_language
A monthly injection of the same blocker worked too.
primary_references
[alcohol-p15811981] Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/15811981/ DOI: 10.1001/jama.293.13.1617
tissue_or_cell_type
Whole body
Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 618–629
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised controlled trial of long-acting injectable naltrexone · source_derived_draft · unverified_draft
### alcohol-naltrexone-depot Long-acting injectable naltrexone reduced heavy drinking in a randomised controlled trial in alcohol dependence, with acceptable tolerability. Condition category: normal 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: A monthly injection of the same blocker worked too. organism: Human tissue_or_cell_type: Whole body experimental_model: Randomised controlled trial of long-acting injectable naltrexone limitations: A large randomised trial of a depot formulation, which removes the adherence problem of daily dosing. exposure: Monthly injectable naltrexone versus placebo evidence_span: {"source_cache": "artifacts/alcohol-research/15811981.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7a465c529de6ca90435bf684f771315d916f418979902fd0af0a7d712eaa3f", "start_char": 0, "end_char": 2211, "text_sha256": "bb7a465c529de6ca90435bf684f771315d916f418979902fd0af0a7d712eaa3f"} [alcohol-p15811981] Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/15811981/ DOI: 10.1001/jama.293.13.1617
Complete structured claim and evidence
Thirty-five of 66 alcoholic subjects selected for normal liver function and haematology had plasma PLP below 5 ng/ml, the lowest value found in 94 controls.
Habitual alcohol consumption → Plasma pyridoxal 5-prime-phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/4359937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08", "start_char": 0, "end_char": 1650, "text_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08"}
experimental_model
Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays
exposure
Chronic alcohol abuse; acetaldehyde and ethanol applied to erythrocytes
limitations
Selecting subjects without abnormal liver function isolates the vitamin effect from liver disease. The phosphatase mechanism is shown in erythrocytes, not liver.
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
plain_language
More than half had less of the active vitamin than any healthy control, with healthy livers.
primary_references
[alcohol-p4359937] Vitamin B6 metabolism in chronic alcohol abuse. Pyridoxal phosphate levels in plasma and the effects of acetaldehyde on pyridoxal phosphate synthesis and degradation in human erythrocytes. (1974). https://pubmed.ncbi.nlm.nih.gov/4359937/ DOI: 10.1172/jci107607
tissue_or_cell_type
Plasma and erythrocytes
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 631–642
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays · source_derived_draft · unverified_draft
### alcohol-low-plp-prevalence Thirty-five of 66 alcoholic subjects selected for normal liver function and haematology had plasma PLP below 5 ng/ml, the lowest value found in 94 controls. 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: More than half had less of the active vitamin than any healthy control, with healthy livers. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays limitations: Selecting subjects without abnormal liver function isolates the vitamin effect from liver disease. The phosphatase mechanism is shown in erythrocytes, not liver. exposure: Chronic alcohol abuse; acetaldehyde and ethanol applied to erythrocytes evidence_span: {"source_cache": "artifacts/alcohol-research/4359937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08", "start_char": 0, "end_char": 1650, "text_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08"} [alcohol-p4359937] Vitamin B6 metabolism in chronic alcohol abuse. Pyridoxal phosphate levels in plasma and the effects of acetaldehyde on pyridoxal phosphate synthesis and degradation in human erythrocytes. (1974). https://pubmed.ncbi.nlm.nih.gov/4359937/ DOI: 10.1172/jci107607
Complete structured claim and evidence
Acetaldehyde, but not ethanol, impaired net formation of PLP from pyridoxal, pyridoxine and pyridoxine phosphate by erythrocytes, and the effect was abolished when the B6-phosphate phosphatase was inhibited by 80 mM phosphate, while pyridoxal kinase and pyridoxine phosphate oxidase activities were not decreased.
Acetaldehyde → Erythrocyte pyridoxal 5′-phosphate synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/4359937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08", "start_char": 0, "end_char": 1650, "text_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08"}
experimental_model
Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays
exposure
Chronic alcohol abuse; acetaldehyde and ethanol applied to erythrocytes
limitations
Selecting subjects without abnormal liver function isolates the vitamin effect from liver disease. The phosphatase mechanism is shown in erythrocytes, not liver.
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
plain_language
It is the breakdown product that destroys the vitamin, and it works by exposing it to a phosphatase rather than by blocking its synthesis.
primary_references
[alcohol-p4359937] Vitamin B6 metabolism in chronic alcohol abuse. Pyridoxal phosphate levels in plasma and the effects of acetaldehyde on pyridoxal phosphate synthesis and degradation in human erythrocytes. (1974). https://pubmed.ncbi.nlm.nih.gov/4359937/ DOI: 10.1172/jci107607
tissue_or_cell_type
Plasma and erythrocytes
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 644–655
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays · source_derived_draft · unverified_draft
### alcohol-acetaldehyde-not-ethanol Acetaldehyde, but not ethanol, impaired net formation of PLP from pyridoxal, pyridoxine and pyridoxine phosphate by erythrocytes, and the effect was abolished when the B6-phosphate phosphatase was inhibited by 80 mM phosphate, while pyridoxal kinase and pyridoxine phosphate oxidase activities were not decreased. 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: It is the breakdown product that destroys the vitamin, and it works by exposing it to a phosphatase rather than by blocking its synthesis. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Plasma PLP in 66 alcoholic subjects without liver abnormality, plus erythrocyte enzyme assays limitations: Selecting subjects without abnormal liver function isolates the vitamin effect from liver disease. The phosphatase mechanism is shown in erythrocytes, not liver. exposure: Chronic alcohol abuse; acetaldehyde and ethanol applied to erythrocytes evidence_span: {"source_cache": "artifacts/alcohol-research/4359937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08", "start_char": 0, "end_char": 1650, "text_sha256": "1df4485150b1be55f3e5214c424f960ff627cfc317e643c86a0f6747efed8b08"} [alcohol-p4359937] Vitamin B6 metabolism in chronic alcohol abuse. Pyridoxal phosphate levels in plasma and the effects of acetaldehyde on pyridoxal phosphate synthesis and degradation in human erythrocytes. (1974). https://pubmed.ncbi.nlm.nih.gov/4359937/ DOI: 10.1172/jci107607
Complete structured claim and evidence
Acetaldehyde was shown to mediate the deleterious effect of ethanol on pyridoxal 5-phosphate metabolism.
Acetaldehyde → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/27531.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98", "start_char": 0, "end_char": 2014, "text_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98"}
experimental_model
Erythrocyte and hepatic experiments isolating acetaldehyde from ethanol
exposure
Acetaldehyde exposure with PLP measurement
limitations
A confirmatory mechanism study attributing the effect specifically to acetaldehyde.
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 rat material
plain_language
The vitamin damage is done by the metabolite, which is why it tracks with how fast alcohol is oxidised.
primary_references
[alcohol-p27531] The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism. (1978). https://pubmed.ncbi.nlm.nih.gov/27531/ DOI: 10.1172/jci109128
tissue_or_cell_type
Erythrocytes and liver
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 657–668
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocyte and hepatic experiments isolating acetaldehyde from ethanol · source_derived_draft · unverified_draft
### alcohol-acetaldehyde-mediates-b6 Acetaldehyde was shown to mediate the deleterious effect of ethanol on pyridoxal 5-phosphate metabolism. 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 vitamin damage is done by the metabolite, which is why it tracks with how fast alcohol is oxidised. organism: Human and rat material tissue_or_cell_type: Erythrocytes and liver experimental_model: Erythrocyte and hepatic experiments isolating acetaldehyde from ethanol limitations: A confirmatory mechanism study attributing the effect specifically to acetaldehyde. exposure: Acetaldehyde exposure with PLP measurement evidence_span: {"source_cache": "artifacts/alcohol-research/27531.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98", "start_char": 0, "end_char": 2014, "text_sha256": "e30f315b327e70a22ed855a935921234fad553d9ed765578c0292446c7bace98"} [alcohol-p27531] The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism. (1978). https://pubmed.ncbi.nlm.nih.gov/27531/ DOI: 10.1172/jci109128
Complete structured claim and evidence
The effect of ethanol oxidation on hepatic pyridoxal 5-phosphate metabolism accompanied the plasma changes seen in chronic alcohol abuse.
Ethanol → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/1168205.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d", "start_char": 0, "end_char": 1391, "text_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d"}
experimental_model
Hepatic PLP metabolism during ethanol oxidation
exposure
Ethanol oxidation with hepatic PLP measurement
limitations
Extends the mechanism to liver. Part of the same series as the erythrocyte work, so the records share a laboratory lineage.
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 liver
plain_language
The same loss shows up in the organ that does the oxidising.
primary_references
[alcohol-p1168205] Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism. (1975). https://pubmed.ncbi.nlm.nih.gov/1168205/ DOI: 10.1172/jci108003
tissue_or_cell_type
Liver
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 670–681
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepatic PLP metabolism during ethanol oxidation · source_derived_draft · unverified_draft
### alcohol-ethanol-oxidation-hepatic-plp The effect of ethanol oxidation on hepatic pyridoxal 5-phosphate metabolism accompanied the plasma changes seen in chronic alcohol abuse. 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 same loss shows up in the organ that does the oxidising. organism: Human and animal liver tissue_or_cell_type: Liver experimental_model: Hepatic PLP metabolism during ethanol oxidation limitations: Extends the mechanism to liver. Part of the same series as the erythrocyte work, so the records share a laboratory lineage. exposure: Ethanol oxidation with hepatic PLP measurement evidence_span: {"source_cache": "artifacts/alcohol-research/1168205.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d", "start_char": 0, "end_char": 1391, "text_sha256": "b436a7e8353028a5eb7cf608b2a272b39968ee2af717dbae8fb03a39cb77180d"} [alcohol-p1168205] Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism. (1975). https://pubmed.ncbi.nlm.nih.gov/1168205/ DOI: 10.1172/jci108003
Complete structured claim and evidence
Ethanol reduces intestinal and renal uptake of folate by altering the binding and transport kinetics of folate transport systems and by reducing the expression of folate transporters, with ethanol ingestion described as the major contributor to folate deficiency.
Ethanol → Intestinal folate uptake across the brush border source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/19292860.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "596af06cee715270d990c6fd6f421a3cf4efe2448193da3e58a35d74c2949e30", "start_char": 0, "end_char": 2909, "text_sha256": "596af06cee715270d990c6fd6f421a3cf4efe2448193da3e58a35d74c2949e30"}
experimental_model
Review of folate transport systems in relation to alcoholism-induced malabsorption
exposure
Chronic ethanol ingestion against folate transport
limitations
A review, labelled as such, used for the enumeration of routes. The individual transport measurements are recorded from their own primary papers where available.
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
Alcohol attacks the vitamin at the doorway, in both gut and kidney.
primary_references
[alcohol-p19292860] New perspectives on folate transport in relation to alcoholism-induced folate malabsorption--association with epigenome stability and cancer development. (2009). https://pubmed.ncbi.nlm.nih.gov/19292860/ DOI: 10.1111/j.1742-4658.2009.06959.x
tissue_or_cell_type
Intestine, liver and kidney
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 683–694
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of folate transport systems in relation to alcoholism-induced malabsorption · source_derived_draft · unverified_draft
### alcohol-ethanol-folate-transport Ethanol reduces intestinal and renal uptake of folate by altering the binding and transport kinetics of folate transport systems and by reducing the expression of folate transporters, with ethanol ingestion described as the major contributor to folate deficiency. 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: Alcohol attacks the vitamin at the doorway, in both gut and kidney. organism: Human and animal tissue_or_cell_type: Intestine, liver and kidney experimental_model: Review of folate transport systems in relation to alcoholism-induced malabsorption limitations: A review, labelled as such, used for the enumeration of routes. The individual transport measurements are recorded from their own primary papers where available. exposure: Chronic ethanol ingestion against folate transport evidence_span: {"source_cache": "artifacts/alcohol-research/19292860.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "596af06cee715270d990c6fd6f421a3cf4efe2448193da3e58a35d74c2949e30", "start_char": 0, "end_char": 2909, "text_sha256": "596af06cee715270d990c6fd6f421a3cf4efe2448193da3e58a35d74c2949e30"} [alcohol-p19292860] New perspectives on folate transport in relation to alcoholism-induced folate malabsorption--association with epigenome stability and cancer development. (2009). https://pubmed.ncbi.nlm.nih.gov/19292860/ DOI: 10.1111/j.1742-4658.2009.06959.x
Complete structured claim and evidence
Down-regulation of the reduced folate carrier may result in folate malabsorption across the intestinal brush border membrane during experimental alcoholism.
Ethanol → Reduced folate carrier expression at the intestinal brush border source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/18005257.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1987e526f06b05a8f98b20048b73a9d01941fae9f69a718cc2fe134992b4a25b", "start_char": 0, "end_char": 2252, "text_sha256": "1987e526f06b05a8f98b20048b73a9d01941fae9f69a718cc2fe134992b4a25b"}
experimental_model
Experimental alcoholism model with intestinal brush border membrane transport measurement
exposure
Chronic ethanol feeding with reduced folate carrier measurement
limitations
Assigns the malabsorption to a named carrier. It is an animal model of chronic alcoholism.
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
Rat
plain_language
The specific carrier is made in smaller amounts.
primary_references
[alcohol-p18005257] Down-regulation of reduced folate carrier may result in folate malabsorption across intestinal brush border membrane during experimental alcoholism. (2007). https://pubmed.ncbi.nlm.nih.gov/18005257/ DOI: 10.1111/j.1742-4658.2007.06150.x
tissue_or_cell_type
Intestinal brush border
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 696–707
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Experimental alcoholism model with intestinal brush border membrane transport measurement · source_derived_draft · unverified_draft
### alcohol-rfc-downregulation Down-regulation of the reduced folate carrier may result in folate malabsorption across the intestinal brush border membrane during experimental alcoholism. 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 specific carrier is made in smaller amounts. organism: Rat tissue_or_cell_type: Intestinal brush border experimental_model: Experimental alcoholism model with intestinal brush border membrane transport measurement limitations: Assigns the malabsorption to a named carrier. It is an animal model of chronic alcoholism. exposure: Chronic ethanol feeding with reduced folate carrier measurement evidence_span: {"source_cache": "artifacts/alcohol-research/18005257.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1987e526f06b05a8f98b20048b73a9d01941fae9f69a718cc2fe134992b4a25b", "start_char": 0, "end_char": 2252, "text_sha256": "1987e526f06b05a8f98b20048b73a9d01941fae9f69a718cc2fe134992b4a25b"} [alcohol-p18005257] Down-regulation of reduced folate carrier may result in folate malabsorption across intestinal brush border membrane during experimental alcoholism. (2007). https://pubmed.ncbi.nlm.nih.gov/18005257/ DOI: 10.1111/j.1742-4658.2007.06150.x
Complete structured claim and evidence
In vivo intestinal perfusion studies in alcoholic pigs showed reduced folate absorption.
Habitual alcohol consumption → Intestinal folate uptake across the brush border source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/2596432.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f9e82990ef618c97924f29862366c0c718c3465edd42ceb1dc89e6bcda4e13", "start_char": 0, "end_char": 1018, "text_sha256": "44f9e82990ef618c97924f29862366c0c718c3465edd42ceb1dc89e6bcda4e13"}
experimental_model
In vivo intestinal perfusion in alcoholic pigs
exposure
Chronic alcohol feeding with in vivo perfusion
limitations
A whole-animal perfusion measurement rather than a membrane preparation, in a species with human-like intestinal physiology.
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
Pig
plain_language
Measured in a living gut, the absorption really is lower.
primary_references
[alcohol-p2596432] Folate absorption in alcoholic pigs: in vivo intestinal perfusion studies. (1989). https://pubmed.ncbi.nlm.nih.gov/2596432/ DOI: 10.1093/ajcn/50.6.1429
tissue_or_cell_type
Small intestine
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 709–720
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo intestinal perfusion in alcoholic pigs · source_derived_draft · unverified_draft
### alcohol-pig-folate-absorption In vivo intestinal perfusion studies in alcoholic pigs showed reduced folate absorption. 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: Measured in a living gut, the absorption really is lower. organism: Pig tissue_or_cell_type: Small intestine experimental_model: In vivo intestinal perfusion in alcoholic pigs limitations: A whole-animal perfusion measurement rather than a membrane preparation, in a species with human-like intestinal physiology. exposure: Chronic alcohol feeding with in vivo perfusion evidence_span: {"source_cache": "artifacts/alcohol-research/2596432.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f9e82990ef618c97924f29862366c0c718c3465edd42ceb1dc89e6bcda4e13", "start_char": 0, "end_char": 1018, "text_sha256": "44f9e82990ef618c97924f29862366c0c718c3465edd42ceb1dc89e6bcda4e13"} [alcohol-p2596432] Folate absorption in alcoholic pigs: in vivo intestinal perfusion studies. (1989). https://pubmed.ncbi.nlm.nih.gov/2596432/ DOI: 10.1093/ajcn/50.6.1429
Complete structured claim and evidence
The pathophysiology of alcoholic brain damage involves synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease.
Thiamine deficiency → Alcoholic brain damage source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Interaction of thiamine deficiency and voluntary alcohol consumption disrupted rat corpus callosum ultrastructure.
Thiamine deficiency → Corpus callosum ultrastructure source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/17299515.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e691ddc58fc07fe2716bf42e4cc6a65eed1b59ebc3696a28749459c7c27e4772", "start_char": 0, "end_char": 2513, "text_sha256": "e691ddc58fc07fe2716bf42e4cc6a65eed1b59ebc3696a28749459c7c27e4772"}
experimental_model
Rats given voluntary alcohol with and without induced thiamine deficiency, with electron microscopy
exposure
Voluntary alcohol consumption combined with thiamine deficiency
limitations
A controlled factorial animal experiment, which is what an observational human series cannot provide.
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
Rat
plain_language
In a controlled experiment the combination damaged the bridge between the brain hemispheres.
primary_references
[alcohol-p17299515] Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure. (2007). https://pubmed.ncbi.nlm.nih.gov/17299515/ DOI: 10.1038/sj.npp.1301332
tissue_or_cell_type
Corpus callosum
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 735–746
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats given voluntary alcohol with and without induced thiamine deficiency, with electron microscopy · source_derived_draft · unverified_draft
### alcohol-corpus-callosum Interaction of thiamine deficiency and voluntary alcohol consumption disrupted rat corpus callosum ultrastructure. 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: In a controlled experiment the combination damaged the bridge between the brain hemispheres. organism: Rat tissue_or_cell_type: Corpus callosum experimental_model: Rats given voluntary alcohol with and without induced thiamine deficiency, with electron microscopy limitations: A controlled factorial animal experiment, which is what an observational human series cannot provide. exposure: Voluntary alcohol consumption combined with thiamine deficiency evidence_span: {"source_cache": "artifacts/alcohol-research/17299515.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e691ddc58fc07fe2716bf42e4cc6a65eed1b59ebc3696a28749459c7c27e4772", "start_char": 0, "end_char": 2513, "text_sha256": "e691ddc58fc07fe2716bf42e4cc6a65eed1b59ebc3696a28749459c7c27e4772"} [alcohol-p17299515] Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure. (2007). https://pubmed.ncbi.nlm.nih.gov/17299515/ DOI: 10.1038/sj.npp.1301332
Complete structured claim and evidence
Thiamine deficiency impairs oxidative metabolic pathways and contributes to ethanol-induced neurotoxicity, with poor nutrition contributing to the alcoholic syndrome.
Thiamine deficiency → Transketolase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/28225048.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14985f03480c03e14fe75f00e454323cd6f5d414f3775e5ee0d4d4da7825e8c6", "start_char": 0, "end_char": 1824, "text_sha256": "14985f03480c03e14fe75f00e454323cd6f5d414f3775e5ee0d4d4da7825e8c6"}
experimental_model
Review of thiamine deficiency and oxidative metabolic pathways in ethanol neurotoxicity
exposure
Chronic alcohol use with poor nutrition
limitations
A review, labelled as such, linking the coenzyme role to the clinical syndrome. Marchiafava-Bignami disease is rare, so the clinical anchor is narrow.
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
plain_language
Without the coenzyme the pathways that burn sugar for the brain stall.
primary_references
[alcohol-p28225048] Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity: how poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease. (2017). https://pubmed.ncbi.nlm.nih.gov/28225048/ DOI: 10.1038/ejcn.2016.267
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 748–759
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of thiamine deficiency and oxidative metabolic pathways in ethanol neurotoxicity · source_derived_draft · unverified_draft
### alcohol-thiamine-oxidative-pathways Thiamine deficiency impairs oxidative metabolic pathways and contributes to ethanol-induced neurotoxicity, with poor nutrition contributing to the alcoholic syndrome. 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: Without the coenzyme the pathways that burn sugar for the brain stall. organism: Human tissue_or_cell_type: Brain experimental_model: Review of thiamine deficiency and oxidative metabolic pathways in ethanol neurotoxicity limitations: A review, labelled as such, linking the coenzyme role to the clinical syndrome. Marchiafava-Bignami disease is rare, so the clinical anchor is narrow. exposure: Chronic alcohol use with poor nutrition evidence_span: {"source_cache": "artifacts/alcohol-research/28225048.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14985f03480c03e14fe75f00e454323cd6f5d414f3775e5ee0d4d4da7825e8c6", "start_char": 0, "end_char": 1824, "text_sha256": "14985f03480c03e14fe75f00e454323cd6f5d414f3775e5ee0d4d4da7825e8c6"} [alcohol-p28225048] Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity: how poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease. (2017). https://pubmed.ncbi.nlm.nih.gov/28225048/ DOI: 10.1038/ejcn.2016.267
Complete structured claim and evidence
Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species, and significantly increased permeability of the ileum without affecting the duodenum or jejunum.
Ethanol → Ileal tissue zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/20167873.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e", "start_char": 0, "end_char": 1542, "text_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e"}
experimental_model
Pair-fed alcohol mice with regional permeability measurement and Caco-2 zinc deprivation
exposure
Four weeks of alcohol liquid diet; zinc deprivation in culture
limitations
The regional specificity and the separate zinc-deprivation arm are what make the nutrient claim interpretable. The exaggeration experiment is in cultured cells.
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
Mouse
plain_language
Alcohol drains zinc from one specific stretch of gut, and that is exactly where it leaks.
primary_references
[alcohol-p20167873] The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. (2010). https://pubmed.ncbi.nlm.nih.gov/20167873/ DOI: 10.1152/ajpgi.00350.2009
tissue_or_cell_type
Ileum and Caco-2 monolayers
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 761–772
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pair-fed alcohol mice with regional permeability measurement and Caco-2 zinc deprivation · source_derived_draft · unverified_draft
### alcohol-alcohol-ileal-zinc Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species, and significantly increased permeability of the ileum without affecting the duodenum or jejunum. 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: Alcohol drains zinc from one specific stretch of gut, and that is exactly where it leaks. organism: Mouse tissue_or_cell_type: Ileum and Caco-2 monolayers experimental_model: Pair-fed alcohol mice with regional permeability measurement and Caco-2 zinc deprivation limitations: The regional specificity and the separate zinc-deprivation arm are what make the nutrient claim interpretable. The exaggeration experiment is in cultured cells. exposure: Four weeks of alcohol liquid diet; zinc deprivation in culture evidence_span: {"source_cache": "artifacts/alcohol-research/20167873.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e", "start_char": 0, "end_char": 1542, "text_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e"} [alcohol-p20167873] The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. (2010). https://pubmed.ncbi.nlm.nih.gov/20167873/ DOI: 10.1152/ajpgi.00350.2009
Complete structured claim and evidence
Zinc deprivation caused epithelial barrier disruption in association with disassembly of tight junction proteins in Caco-2 monolayers, and minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier.
Zinc → Tight junction proteins at the ileal epithelium source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/20167873.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e", "start_char": 0, "end_char": 1542, "text_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e"}
experimental_model
Pair-fed alcohol mice with regional permeability measurement and Caco-2 zinc deprivation
exposure
Four weeks of alcohol liquid diet; zinc deprivation in culture
limitations
The regional specificity and the separate zinc-deprivation arm are what make the nutrient claim interpretable. The exaggeration experiment is in cultured cells.
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
Mouse and human cells
plain_language
Take zinc away and the seals between cells come apart, with or without alcohol.
primary_references
[alcohol-p20167873] The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. (2010). https://pubmed.ncbi.nlm.nih.gov/20167873/ DOI: 10.1152/ajpgi.00350.2009
tissue_or_cell_type
Ileum and Caco-2 monolayers
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 774–785
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pair-fed alcohol mice with regional permeability measurement and Caco-2 zinc deprivation · source_derived_draft · unverified_draft
### alcohol-zinc-tight-junctions Zinc deprivation caused epithelial barrier disruption in association with disassembly of tight junction proteins in Caco-2 monolayers, and minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier. 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: Take zinc away and the seals between cells come apart, with or without alcohol. organism: Mouse and human cells tissue_or_cell_type: Ileum and Caco-2 monolayers experimental_model: Pair-fed alcohol mice with regional permeability measurement and Caco-2 zinc deprivation limitations: The regional specificity and the separate zinc-deprivation arm are what make the nutrient claim interpretable. The exaggeration experiment is in cultured cells. exposure: Four weeks of alcohol liquid diet; zinc deprivation in culture evidence_span: {"source_cache": "artifacts/alcohol-research/20167873.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e", "start_char": 0, "end_char": 1542, "text_sha256": "12b4bf025e28831a9d613fd7d6b62275f573f8a8999efb73d763bb8e8059b15e"} [alcohol-p20167873] The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. (2010). https://pubmed.ncbi.nlm.nih.gov/20167873/ DOI: 10.1152/ajpgi.00350.2009
Complete structured claim and evidence
Zinc supplementation prevented alcoholic liver injury in mice through attenuation of oxidative stress.
Zinc → Alcoholic liver injury source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/15920153.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c25d41f17a1af981cc13b2e85ff6017ea8d48817b1fe8e4f22f8a3126e1af244", "start_char": 0, "end_char": 1654, "text_sha256": "c25d41f17a1af981cc13b2e85ff6017ea8d48817b1fe8e4f22f8a3126e1af244"}
experimental_model
Alcohol-fed mice given zinc supplementation with oxidative stress measurement
exposure
Chronic alcohol feeding with and without zinc supplementation
limitations
A repletion experiment, which is stronger than an association. It is a mouse prevention model, not a treatment trial.
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
Mouse
plain_language
Giving zinc back prevented the liver damage in this model.
primary_references
[alcohol-p15920153] Zinc supplementation prevents alcoholic liver injury in mice through attenuation of oxidative stress. (2005). https://pubmed.ncbi.nlm.nih.gov/15920153/ DOI: 10.1016/s0002-9440(10)62478-9
tissue_or_cell_type
Liver
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 787–798
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Alcohol-fed mice given zinc supplementation with oxidative stress measurement · source_derived_draft · unverified_draft
### alcohol-zinc-supplementation-liver Zinc supplementation prevented alcoholic liver injury in mice through attenuation of oxidative stress. 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: Giving zinc back prevented the liver damage in this model. organism: Mouse tissue_or_cell_type: Liver experimental_model: Alcohol-fed mice given zinc supplementation with oxidative stress measurement limitations: A repletion experiment, which is stronger than an association. It is a mouse prevention model, not a treatment trial. exposure: Chronic alcohol feeding with and without zinc supplementation evidence_span: {"source_cache": "artifacts/alcohol-research/15920153.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c25d41f17a1af981cc13b2e85ff6017ea8d48817b1fe8e4f22f8a3126e1af244", "start_char": 0, "end_char": 1654, "text_sha256": "c25d41f17a1af981cc13b2e85ff6017ea8d48817b1fe8e4f22f8a3126e1af244"} [alcohol-p15920153] Zinc supplementation prevents alcoholic liver injury in mice through attenuation of oxidative stress. (2005). https://pubmed.ncbi.nlm.nih.gov/15920153/ DOI: 10.1016/s0002-9440(10)62478-9
Complete structured claim and evidence
Hepatic zinc content differed across stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis.
Habitual alcohol consumption → Hepatic zinc content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/alcohol-research/3192174.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f6eab91e632a1ddf96193486fc1be8bffa4acb0b48d062fef2b65affe168ca3", "start_char": 0, "end_char": 1588, "text_sha256": "7f6eab91e632a1ddf96193486fc1be8bffa4acb0b48d062fef2b65affe168ca3"}
experimental_model
Hepatic zinc measurement across stages of alcoholic liver disease and chronic hepatitis
exposure
Staged alcoholic liver disease compared with chronic hepatitis
limitations
A human tissue measurement with a disease control group, which separates alcohol from liver disease in general.
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
plain_language
The liver itself holds less zinc as the disease advances.
primary_references
[alcohol-p3192174] Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. (1988). https://pubmed.ncbi.nlm.nih.gov/3192174/ DOI: 10.1002/hep.1840080622
tissue_or_cell_type
Liver
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 800–811
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepatic zinc measurement across stages of alcoholic liver disease and chronic hepatitis · source_derived_draft · unverified_draft
### alcohol-hepatic-zinc-depletion Hepatic zinc content differed across stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. 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 liver itself holds less zinc as the disease advances. organism: Human tissue_or_cell_type: Liver experimental_model: Hepatic zinc measurement across stages of alcoholic liver disease and chronic hepatitis limitations: A human tissue measurement with a disease control group, which separates alcohol from liver disease in general. exposure: Staged alcoholic liver disease compared with chronic hepatitis evidence_span: {"source_cache": "artifacts/alcohol-research/3192174.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f6eab91e632a1ddf96193486fc1be8bffa4acb0b48d062fef2b65affe168ca3", "start_char": 0, "end_char": 1588, "text_sha256": "7f6eab91e632a1ddf96193486fc1be8bffa4acb0b48d062fef2b65affe168ca3"} [alcohol-p3192174] Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. (1988). https://pubmed.ncbi.nlm.nih.gov/3192174/ DOI: 10.1002/hep.1840080622
Complete structured claim and evidence

Availability and dependencies

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

When acetaldehyde cannot be cleared

Condition: machinery_impairment · The ALDH2*2 allele substituting lysine for glutamate at position 487, which is dominant.

Normal role: Mitochondrial ALDH2 oxidises the acetaldehyde produced from ethanol to acetate.

Recorded consequence: Acetaldehyde accumulates after drinking, producing the flush reaction, and lifetime exposure raises cancer risk while reducing how much people drink.

Scope: Human genotype and liver enzyme activity

When the first enzyme runs fast

Condition: machinery_impairment · The ADH1B rs1229984 A-allele, which encodes a higher-activity enzyme.

Normal role: ADH1B oxidises ethanol to acetaldehyde, which ALDH2 then clears.

Recorded consequence: Acetaldehyde appears faster, drinking falls, and carriers show lower coronary heart disease in Mendelian randomisation.

Scope: Animal model of the human variant, with human genetic epidemiology

When the clearing enzymes are deleted

Condition: machinery_impairment · Targeted deletion of Adh1, Adh3 or Adh4 in mice.

Normal role: Adh1 and Adh4 clear ethanol and also oxidise retinol towards retinoic acid, while Adh3 handles formaldehyde.

Recorded consequence: Ethanol clearance falls and sleep lengthens in Adh1-null mice, embryonic resorption after ethanol rises threefold, and retinoic acid production from retinol falls several-fold.

Scope: Mouse gene knockouts

When the tolerance kinase is missing

Condition: machinery_impairment · Fyn gene deletion in mice.

Normal role: Fyn phosphorylates the NMDA receptor and contributes to acute tolerance to ethanol.

Recorded consequence: Ethanol sensitivity and the phosphorylation response change.

Scope: Mouse hippocampus

When alcohol becomes the acetyl donor for chromatin

Condition: biomarker_context · Breakdown of alcohol in the liver, which leads to a rapid increase in blood acetate and makes alcohol a major source of acetate in the body.

Normal role: Acetylation of histones in neurons relies on acetyl-CoA produced from acetate by chromatin-bound ACSS2.

Recorded consequence: Acetyl groups derived from alcohol are deposited directly onto brain histones in an ACSS2-dependent manner, labelled acetyl groups appear in gestating fetal brains after maternal exposure, and alcohol-related associative learning requires ACSS2.

Scope: Mouse in vivo stable-isotope labelling with behavioural testing

When the extrasynaptic GABA subunit is deleted

Condition: machinery_impairment · Delta subunit knockout in mice.

Normal role: The delta subunit forms extrasynaptic GABA-A receptors carrying a tonic inhibitory current sensitive to ethanol.

Recorded consequence: Behavioural responses to ethanol are altered across several assays.

Scope: Mouse behaviour

When acetaldehyde exposure is lifelong

Condition: machinery_impairment · Carrying the inactive ALDH2 allele while continuing to drink, especially alongside smoking.

Normal role: ALDH2 clears acetaldehyde from every drink.

Recorded consequence: Acetaldehyde exposure of the upper aerodigestive mucosa rises, and oesophageal and liver cancer risk rise with it.

Scope: Human case-control genetics and an ALDH2-deficient mouse model

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Do moderate drinkers really live longer?Pooled cohort analyses reproduce a J-shaped curve in which low-volume drinkers have lower all-cause mortality than abstainers. A meta-regression of 87 studies covering nearly four million people found that the curve disappears once former and occasional drinkers are no longer counted as abstainers and study quality is controlled, with the relative risk moving from 0.86 to a non-significant 0.97. A Mendelian randomisation study of 261,991 people, using a variant that lowers consumption, found lower coronary heart disease in carriers across every consumption category, which is the opposite of a protective effect of alcohol. The observational and genetic designs differ in what they can be confounded by, and the cohorts differ in how abstainers were defined. The disagreement is recorded, not resolved.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which enzyme carries what share of human ethanol clearance at ordinary drinking concentrations, given that the structural work is horse and yeast enzyme and the gene-deletion work is mouse.No record here measures the relative contribution of ADH1B, ADH1C, ADH4 and CYP2E1 in human liver across the concentration range.
Whether correcting zinc, thiamine, folate or vitamin B6 changes any clinical outcome in people who continue to drink.The repletion evidence here is a mouse liver-injury prevention model and a cell-culture barrier experiment; no record in this collection reports a randomised repletion trial with a clinical endpoint in drinkers.
Whether the vitamin A interaction runs through competition for alcohol dehydrogenase at concentrations reached by drinking.The retinol result is a mouse gene-deletion experiment showing the same enzymes handle both substrates; no record here measures competition between ethanol and retinol at physiological concentrations.
How much of the vitamin B6 loss in a drinker is acetaldehyde-driven displacement versus reduced intake and liver disease.The subjects in the plasma survey were selected for normal liver function, which separates liver disease, but intake was not measured.
Whether the discrete alcohol pockets identified in the glycine receptor, BK and GIRK channels are occupied at the concentrations that produce human intoxication, and in what proportion.Each site was mapped in a recombinant system at its own concentration range; no record here compares occupancy across targets at a common blood alcohol concentration.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Ethanol

The mechanisms

Each subunit of the dimeric enzyme is organised into two unequal parts separated by a wide deep active-site cleft, with the catalytic zinc atoms bound at the bottom of the clefts about 20 angstrom from the molecular surface, and the adenosine moiety of the coenzyme bound within the smaller region.

Substituting Glu-67 with glutamine decreased catalytic efficiency a hundred-fold.

Ethanol administration caused an immediate decrease in the NAD+/NADH ratio of both cytoplasm and mitochondria, which persisted over the 30 minutes studied.

The free cytosolic NADP+/NADPH ratio fell immediately and returned nearly to control by 15 minutes, while the cytosolic ATP/ADP phosphate ratio was elevated at 15 minutes in starved rats.

The ethanol-induced hepatic redox change was attenuated after chronic alcohol consumption in baboons, with metabolic consequences measured both in vivo and in vitro.

Ethanol induces CYP2E1 by protein stabilisation, slowing the ubiquitin-conjugation-dependent rapid degradation of the enzyme rather than raising its synthesis.

The inactive ALDH2 subunit carries a substitution of lysine for glutamate at position 487, and correlating genotype with phenotype in 24 Japanese livers shows the allele encoding the abnormal subunit is dominant.

The alcohol flush reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption.

ALDH2*2 but not ADH1B*2 is the causative variant allele for Asian alcohol flushing after a low-dose challenge, on correlated pharmacokinetic and pharmacodynamic findings.

An animal model developed to test the mechanism of protection against alcoholism by an alcohol dehydrogenase polymorphism supports faster ethanol oxidation producing higher acetaldehyde as the protective step.

Decreased gastric alcohol dehydrogenase activity and decreased first-pass metabolism accounted for higher blood alcohol levels in women given the same oral dose.

Human gastric alcohol dehydrogenase activity varied with age, sex and alcoholism in biopsy material.

Following an intoxicating dose of ethanol, Adh1-null mice and to a lesser extent Adh4-null mice, but not Adh3-null mice, showed significant reductions in blood ethanol clearance, and ethanol-induced sleep was significantly longer only in Adh1-null mice.

Retinoic acid production following retinol administration was reduced 8.5-fold in Adh4-null mice and 4.8-fold in Adh1-null mice, showing overlapping roles for Adh1 and Adh4 in both ethanol and retinol metabolism.

Only Adh3-null mice had a significantly reduced formaldehyde LD50, and Adh3 played no role with ethanol or retinol.

The incidence of embryonic resorption following ethanol administration was increased threefold in Adh1-null mice and 1.5-fold in Adh4-null mice, but was unchanged in Adh3-null mice.

Ethanol inhibited NMDA-activated ion current in hippocampal neurons at concentrations reached during intoxication.

NMDA receptor-mediated synaptic excitation was selectively inhibited by ethanol in hippocampal slices from adult rats.

Fyn kinase is a determinant of ethanol sensitivity through its relation to NMDA receptor function, with tyrosine phosphorylation of the receptor linked to acute tolerance.

A naturally occurring GABA-A receptor subunit partnership was identified with high sensitivity to ethanol.

GABA-A receptor delta subunit knockout mice have multiple defects in behavioural responses to ethanol.

Enhancement of glycine receptor function by ethanol was inversely correlated with the molecular volume at position alpha267, implying a size-limited site rather than a general membrane effect.

An alcohol-sensing site was identified in the calcium- and voltage-gated large conductance potassium channel.

A BK channel auxiliary protein was identified that controls molecular and behavioural tolerance to alcohol.

G-protein-gated inwardly rectifying potassium channels are targets of alcohol action, activated at intoxicating concentrations.

A discrete alcohol pocket in the channel cytoplasmic domain was shown to be involved in GIRK channel activation.

Ethanol increased extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter.

Ethanol preferentially stimulated dopamine release in the nucleus accumbens of freely moving rats.

Ethanol regulated hepatic lipin-1 through AMP-activated protein kinase and sterol regulatory element-binding protein 1 signalling in mice.

Adenosine signalling contributed to ethanol-induced fatty liver in mice, with the effect traced through adenosine receptors and the equilibrative nucleoside transporter.

Patients with chronic alcohol abuse showed increased intestinal permeability to macromolecules and endotoxaemia, varying across stages of alcohol-induced liver disease.

Endotoxaemia accompanied the permeability defect and differed across stages of alcohol-induced liver disease.

Intestinal permeability and gut bacterial dysbiosis were associated with behavioural markers of alcohol-dependence severity.

Fructose promoted leaky gut, endotoxaemia and liver fibrosis through ethanol-inducible cytochrome P450-2E1-mediated oxidative and nitrative stress.

A defect of the mitochondrial respiratory chain was identified as a mechanism of reactive oxygen species overproduction in a rat model of alcoholic liver disease, with a role for zinc deficiency.

Levels of the acetaldehyde-derived DNA adduct N2-ethyl-deoxyguanosine were increased in oral mucosa DNA from rhesus monkeys exposed to alcohol.

Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhanced oesophageal cancer risk.

ALDH2 deficiency promoted alcohol-associated liver cancer by activating oncogenic pathways via oxidised-DNA-enriched extracellular vesicles.

In unadjusted models, protective effects were identified for alcohol consumption against all-cause mortality in pooled English cohorts of adults aged 50 and over, which the authors examine to test the suitability of age-specific limits.

Naltrexone with coping skills therapy reduced drinking in alcohol dependence in a controlled study.

Long-acting injectable naltrexone reduced heavy drinking in a randomised controlled trial in alcohol dependence, with acceptable tolerability.

Thirty-five of 66 alcoholic subjects selected for normal liver function and haematology had plasma PLP below 5 ng/ml, the lowest value found in 94 controls.

Acetaldehyde was shown to mediate the deleterious effect of ethanol on pyridoxal 5-phosphate metabolism.

The effect of ethanol oxidation on hepatic pyridoxal 5-phosphate metabolism accompanied the plasma changes seen in chronic alcohol abuse.

Ethanol reduces intestinal and renal uptake of folate by altering the binding and transport kinetics of folate transport systems and by reducing the expression of folate transporters, with ethanol ingestion described as the major contributor to folate deficiency.

Down-regulation of the reduced folate carrier may result in folate malabsorption across the intestinal brush border membrane during experimental alcoholism.

In vivo intestinal perfusion studies in alcoholic pigs showed reduced folate absorption.

The pathophysiology of alcoholic brain damage involves synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease.

Interaction of thiamine deficiency and voluntary alcohol consumption disrupted rat corpus callosum ultrastructure.

Thiamine deficiency impairs oxidative metabolic pathways and contributes to ethanol-induced neurotoxicity, with poor nutrition contributing to the alcoholic syndrome.

Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species, and significantly increased permeability of the ileum without affecting the duodenum or jejunum.

Zinc deprivation caused epithelial barrier disruption in association with disassembly of tight junction proteins in Caco-2 monolayers, and minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier.

Zinc supplementation prevented alcoholic liver injury in mice through attenuation of oxidative stress.

Hepatic zinc content differed across stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis.

Availability and dependencies

The sources

Recorded disagreements

Open questions in this collection

ALDH22 but not ADH1B2 is the causative variant allele for Asian alcohol flushing after a low-dose challenge, on correlated pharmacokinetic and pharmacodynamic findings.