Nutrient chapter

Vitamin E

Vitamin E comprises related tocopherols and tocotrienols. Follow their transport, membrane protection, deficiency effects and nutrient interactions. Individual forms and experimental outcomes have separate records.

110 recorded mechanisms · 24 availability situations · 5 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.

Co-incubation with tocopherol significantly impaired cholecalciferol uptake in Caco-2 cells.
Alpha-tocopherol → Intestinal cholecalciferol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract.
experimental_model
Caco-2 apical uptake assay
exposure
Tocopherol and cholecalciferol co-incubation; dose/time unavailable in primary abstract.
limitations
The primary abstract says tocopherol; the authors' subsequent primary paper identifies it as alpha-tocopherol. No evidence here warrants separating normal oral supplements or diagnosing D malabsorption.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens
plain_language
Vitamin E competed with D3 uptake in an intestinal cell model.
primary_references
[reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553 [goncalves2015] Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption. (2015). https://pubmed.ncbi.nlm.nih.gov/25442537/ DOI: 10.1016/j.foodchem.2014.09.021
tissue_or_cell_type
Caco-2 intestinal epithelial model
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 211–225
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Caco-2 apical uptake assay · source_derived_draft · unverified_draft
### vd-act-tocopherol-uptake-competition Co-incubation with tocopherol significantly impaired cholecalciferol uptake in Caco-2 cells. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E competed with D3 uptake in an intestinal cell model. organism: Homo sapiens tissue_or_cell_type: Caco-2 intestinal epithelial model experimental_model: Caco-2 apical uptake assay limitations: The primary abstract says tocopherol; the authors' subsequent primary paper identifies it as alpha-tocopherol. No evidence here warrants separating normal oral supplements or diagnosing D malabsorption. exposure: Tocopherol and cholecalciferol co-incubation; dose/time unavailable in primary abstract. cross_nutrient: true evidence_location: Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract. nutrient: Vitamin D2 and D3 [reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553 [goncalves2015] Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption. (2015). https://pubmed.ncbi.nlm.nih.gov/25442537/ DOI: 10.1016/j.foodchem.2014.09.021
Complete structured claim and evidence
Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels.
Intestine-specific homeobox protein / ISX → Alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Retinoid/ISX control of a shared intestinal transporter affects vitamin E status.
evidence_location
Figure 7
experimental_model
Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets.
exposure
Females; ten weeks of AIN93G with 75 IU vitamin E/kg, with or without 50 mg zeaxanthin/kg.
limitations
Accumulation is not a clinical benefit; compound mutants had a larger effect than Isx single mutants.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Mus musculus
outcome
Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels.
plain_language
Disrupting vitamin A feedback also changed vitamin E accumulation.
primary_references
[va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
tissue_or_cell_type
Jejunum and liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 302–315
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. · source_derived_draft · unverified_draft
### va-isx-loss-tocopherol Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disrupting vitamin A feedback also changed vitamin E accumulation. organism: Mus musculus tissue_or_cell_type: Jejunum and liver experimental_model: Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. limitations: Accumulation is not a clinical benefit; compound mutants had a larger effect than Isx single mutants. exposure: Females; ten weeks of AIN93G with 75 IU vitamin E/kg, with or without 50 mg zeaxanthin/kg. outcome: Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels. evidence_location: Figure 7 cross_nutrient: Retinoid/ISX control of a shared intestinal transporter affects vitamin E status. [va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
Complete structured claim and evidence
Aqueous ascorbate reduced bilayer alpha-tocopheroxyl radical back to alpha-tocopherol in oxidizing soybean phosphatidylcholine liposomes; the reported apparent bimolecular rate constant was about 2 × 10^5 M^-1 s^-1 under those conditions.
L-Ascorbate → Alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract radical accessibility and kinetic result
experimental_model
Soybean L-alpha-phosphatidylcholine liposomes undergoing Fe(III)-triethylenetetramine-initiated peroxidation; EPR, optical and polarographic measurements
exposure
Aqueous ascorbic acid described as physiological concentration in abstract (exact dose unavailable); bilayer alpha-tocopheroxyl radical detected at 10^-8–10^-7 M.
limitations
Membrane composition, radical initiator and assay conditions determine kinetics; no human clinical benefit or universal membrane rate is established.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Glycine max lipid preparation; cell-free
plain_language
Vitamin C recycled the vitamin E radical back into vitamin E across this artificial membrane-water interface.
primary_references
[c-reg-scarpa] Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study. (1984). https://pubmed.ncbi.nlm.nih.gov/6089911/ DOI: 10.1016/0304-4165(84)90070-9
tissue_or_cell_type
Artificial liposomes
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1201–1213
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Soybean L-alpha-phosphatidylcholine liposomes undergoing Fe(III)-triethylenetetramine-initiated peroxidation; EPR, optical and polarographic measurements · source_derived_draft · unverified_draft
### c-reg-tocopherol-radical-recycling Aqueous ascorbate reduced bilayer alpha-tocopheroxyl radical back to alpha-tocopherol in oxidizing soybean phosphatidylcholine liposomes; the reported apparent bimolecular rate constant was about 2 × 10^5 M^-1 s^-1 under those conditions. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C recycled the vitamin E radical back into vitamin E across this artificial membrane-water interface. organism: Glycine max lipid preparation; cell-free tissue_or_cell_type: Artificial liposomes experimental_model: Soybean L-alpha-phosphatidylcholine liposomes undergoing Fe(III)-triethylenetetramine-initiated peroxidation; EPR, optical and polarographic measurements limitations: Membrane composition, radical initiator and assay conditions determine kinetics; no human clinical benefit or universal membrane rate is established. exposure: Aqueous ascorbic acid described as physiological concentration in abstract (exact dose unavailable); bilayer alpha-tocopheroxyl radical detected at 10^-8–10^-7 M. cross_nutrient: true evidence_location: Primary abstract radical accessibility and kinetic result [c-reg-scarpa] Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study. (1984). https://pubmed.ncbi.nlm.nih.gov/6089911/ DOI: 10.1016/0304-4165(84)90070-9
Complete structured claim and evidence
The inhibitory effect of alpha-tocopherol on liposome lipid peroxidation persisted while aqueous ascorbic acid remained available, consistent with continued tocopherol-radical recycling.
L-Ascorbate → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract final result
experimental_model
Soybean L-alpha-phosphatidylcholine liposomes undergoing Fe(III)-triethylenetetramine-initiated peroxidation; EPR, optical and polarographic measurements
exposure
Aqueous ascorbic acid described as physiological concentration in abstract (exact dose unavailable); bilayer alpha-tocopheroxyl radical detected at 10^-8–10^-7 M.
limitations
This persistence endpoint is separate from the radical-reduction reaction and does not establish a supplementation effect in people.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Glycine max lipid preparation; cell-free
plain_language
Vitamin C prolonged vitamin E’s protection against oxidation in the liposome experiment.
primary_references
[c-reg-scarpa] Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study. (1984). https://pubmed.ncbi.nlm.nih.gov/6089911/ DOI: 10.1016/0304-4165(84)90070-9
tissue_or_cell_type
Artificial liposomes
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1215–1227
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Soybean L-alpha-phosphatidylcholine liposomes undergoing Fe(III)-triethylenetetramine-initiated peroxidation; EPR, optical and polarographic measurements · source_derived_draft · unverified_draft
### c-reg-tocopherol-antiperoxidation-persistence The inhibitory effect of alpha-tocopherol on liposome lipid peroxidation persisted while aqueous ascorbic acid remained available, consistent with continued tocopherol-radical recycling. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C prolonged vitamin E’s protection against oxidation in the liposome experiment. organism: Glycine max lipid preparation; cell-free tissue_or_cell_type: Artificial liposomes experimental_model: Soybean L-alpha-phosphatidylcholine liposomes undergoing Fe(III)-triethylenetetramine-initiated peroxidation; EPR, optical and polarographic measurements limitations: This persistence endpoint is separate from the radical-reduction reaction and does not establish a supplementation effect in people. exposure: Aqueous ascorbic acid described as physiological concentration in abstract (exact dose unavailable); bilayer alpha-tocopheroxyl radical detected at 10^-8–10^-7 M. cross_nutrient: true evidence_location: Primary abstract final result [c-reg-scarpa] Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study. (1984). https://pubmed.ncbi.nlm.nih.gov/6089911/ DOI: 10.1016/0304-4165(84)90070-9
Complete structured claim and evidence
Another defense changes how vulnerable cells are to GPX4 loss.
FSP1 reduces CoQ and supplies a lipid-radical defense operating in parallel with GPX4.
FSP1 → Reduced CoQ10 source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
Experimental cultured cells
experimental_model
Cell genetics and biochemical experiments
limitations
Capacity and dependence vary by cell; not a universal dietary threshold.
organism
Human cell models
Selenium: literature corrections and mechanism additions · lines 1492–1502
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Cell genetics and biochemical experiments · secondary_verified · secondary_verified
## fsp1-parallel Another defense changes how vulnerable cells are to GPX4 loss. FSP1 reduces CoQ and supplies a lipid-radical defense operating in parallel with GPX4. Organism: Human cell models Cell type: Experimental cultured cells Experimental model: Cell genetics and biochemical experiments Limitations: Capacity and dependence vary by cell; not a universal dietary threshold. Primary reference: [The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis](https://www.nature.com/articles/s41586-019-1705-2)
Complete structured claim and evidence
Replacing selenium with sulfur retains some function but weakens peroxide resistance.
GPX4 Sec-to-Cys substitution retains context-dependent residual function but increases peroxide-induced inactivation and ferroptosis susceptibility.
GPX4 Sec-to-Cys variant → Ferroptosis source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
Knock-in tissues and derived/engineered cells
experimental_model
Gpx4 Sec-to-Cys knock-in mice, tissue assays and cell peroxide challenges
limitations
Tissue PCOOH activity was undetectable in reported brain/kidney assays; mutation is not nutritional deficiency.
organism
Mus musculus
Selenium: literature corrections and mechanism additions · lines 1263–1273
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Gpx4 Sec-to-Cys knock-in mice, tissue assays and cell peroxide challenges · secondary_verified · secondary_verified
## gpx4-cys-vulnerability Replacing selenium with sulfur retains some function but weakens peroxide resistance. GPX4 Sec-to-Cys substitution retains context-dependent residual function but increases peroxide-induced inactivation and ferroptosis susceptibility. Organism: Mus musculus Cell type: Knock-in tissues and derived/engineered cells Experimental model: Gpx4 Sec-to-Cys knock-in mice, tissue assays and cell peroxide challenges Limitations: Tissue PCOOH activity was undetectable in reported brain/kidney assays; mutation is not nutritional deficiency. Primary reference: [Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis](https://pubmed.ncbi.nlm.nih.gov/29290465/)
Complete structured claim and evidence
ACSL4 prepares the fatty acid for membrane incorporation.
ACSL4 activates arachidonic acid to arachidonoyl-CoA upstream of phospholipid incorporation.
ACSL4 → arachidonoyl-CoA source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
Experimental cell models
experimental_model
Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics
limitations
Not proof of ACSL4 dependence in every ferroptosis model.
organism
Mus musculus
Selenium: literature corrections and mechanism additions · lines 1215–1225
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics · secondary_verified · secondary_verified
## acsl4-activation ACSL4 prepares the fatty acid for membrane incorporation. ACSL4 activates arachidonic acid to arachidonoyl-CoA upstream of phospholipid incorporation. Organism: Mus musculus Cell type: Experimental cell models Experimental model: Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics Limitations: Not proof of ACSL4 dependence in every ferroptosis model. Primary reference: [Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis](https://pubmed.ncbi.nlm.nih.gov/27842066/)
Complete structured claim and evidence
Membrane incorporation follows fatty-acid activation.
LPCAT3-mediated acyl incorporation contributes to arachidonoyl PE formation after fatty-acid activation.
LPCAT3 → PE-AA source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
Lung epithelial cells
experimental_model
Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics
limitations
Substrate preference and ferroptosis dependence vary by cell.
organism
Mus musculus
Selenium: literature corrections and mechanism additions · lines 1227–1237
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics · secondary_verified · secondary_verified
## lpcat3-incorporation Membrane incorporation follows fatty-acid activation. LPCAT3-mediated acyl incorporation contributes to arachidonoyl PE formation after fatty-acid activation. Organism: Mus musculus Cell type: Lung epithelial cells Experimental model: Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics Limitations: Substrate preference and ferroptosis dependence vary by cell. Primary reference: [Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis](https://pubmed.ncbi.nlm.nih.gov/27842066/)
Complete structured claim and evidence
Beta-carotene increased lung-cancer incidence in the male-smoker trial; alpha-tocopherol did not show a significant interaction with this effect.
All-trans-beta-carotene → Lung cancer incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Carotene/vitamin E/tobacco context.
experimental_model
29,133 male smokers; factorial randomized trial.
exposure
20 mg/day beta-carotene, 5-8 years; study exposure only.
limitations
Supplement exposure is not equivalent to eating carotenoid-rich foods; the molecular cause was not isolated.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
The proposed antioxidant benefit did not predict the actual outcome.
primary_references
[va-atbc1994] The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers (1994). https://pubmed.ncbi.nlm.nih.gov/8127329/ DOI: 10.1056/nejm199404143301501
tissue_or_cell_type
Clinical lung-cancer incidence
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1718–1729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 29,133 male smokers; factorial randomized trial. · source_derived_draft · unverified_draft
### va-atbc-carotene-lung-cancer Beta-carotene increased lung-cancer incidence in the male-smoker trial; alpha-tocopherol did not show a significant interaction with this effect. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The proposed antioxidant benefit did not predict the actual outcome. organism: Homo sapiens tissue_or_cell_type: Clinical lung-cancer incidence experimental_model: 29,133 male smokers; factorial randomized trial. limitations: Supplement exposure is not equivalent to eating carotenoid-rich foods; the molecular cause was not isolated. cross_nutrient: Carotene/vitamin E/tobacco context. exposure: 20 mg/day beta-carotene, 5-8 years; study exposure only. [va-atbc1994] The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers (1994). https://pubmed.ncbi.nlm.nih.gov/8127329/ DOI: 10.1056/nejm199404143301501
Complete structured claim and evidence
In a rat alpha-TTP membrane-transfer competition assay, SRR-alpha-tocopherol had relative affinity 10.5% of RRR-alpha-tocopherol (100%).
Rat alpha-tocopherol transfer protein → SRR-alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified rat liver protein and membrane-transfer competition
exposure
37 °C, 30 min; Table 1 competition-derived affinity.
limitations
Relative transfer competition, not a direct Kd or human clinical efficacy ratio.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Rat alpha-TTP distinguished this form from RRR-alpha-tocopherol.
primary_references
[hosomi1997] Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. (1997). https://pubmed.ncbi.nlm.nih.gov/9199513/ DOI: 10.1016/s0014-5793(97)00499-7
tissue_or_cell_type
Liver protein/liposomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 142–153
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver protein and membrane-transfer competition · source_derived_draft · unverified_draft
### ve-transport-rat-ttp-affinity-srr-alpha-tocopherol In a rat alpha-TTP membrane-transfer competition assay, SRR-alpha-tocopherol had relative affinity 10.5% of RRR-alpha-tocopherol (100%). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Rat alpha-TTP distinguished this form from RRR-alpha-tocopherol. organism: Rattus norvegicus tissue_or_cell_type: Liver protein/liposomes experimental_model: Purified rat liver protein and membrane-transfer competition limitations: Relative transfer competition, not a direct Kd or human clinical efficacy ratio. exposure: 37 °C, 30 min; Table 1 competition-derived affinity. cross_nutrient: false [hosomi1997] Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. (1997). https://pubmed.ncbi.nlm.nih.gov/9199513/ DOI: 10.1016/s0014-5793(97)00499-7
Complete structured claim and evidence
In a rat alpha-TTP membrane-transfer competition assay, gamma-tocopherol had relative affinity 8.9% of RRR-alpha-tocopherol (100%).
Rat alpha-tocopherol transfer protein → Gamma-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified rat liver protein and membrane-transfer competition
exposure
37 °C, 30 min; Table 1 competition-derived affinity.
limitations
Relative transfer competition, not a direct Kd or human clinical efficacy ratio.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Rat alpha-TTP distinguished this form from RRR-alpha-tocopherol.
primary_references
[hosomi1997] Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. (1997). https://pubmed.ncbi.nlm.nih.gov/9199513/ DOI: 10.1016/s0014-5793(97)00499-7
tissue_or_cell_type
Liver protein/liposomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 155–166
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver protein and membrane-transfer competition · source_derived_draft · unverified_draft
### ve-transport-rat-ttp-affinity-gamma-tocopherol In a rat alpha-TTP membrane-transfer competition assay, gamma-tocopherol had relative affinity 8.9% of RRR-alpha-tocopherol (100%). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Rat alpha-TTP distinguished this form from RRR-alpha-tocopherol. organism: Rattus norvegicus tissue_or_cell_type: Liver protein/liposomes experimental_model: Purified rat liver protein and membrane-transfer competition limitations: Relative transfer competition, not a direct Kd or human clinical efficacy ratio. exposure: 37 °C, 30 min; Table 1 competition-derived affinity. cross_nutrient: false [hosomi1997] Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. (1997). https://pubmed.ncbi.nlm.nih.gov/9199513/ DOI: 10.1016/s0014-5793(97)00499-7
Complete structured claim and evidence
In a rat alpha-TTP membrane-transfer competition assay, alpha-tocotrienol had relative affinity 12.4% of RRR-alpha-tocopherol (100%).
Rat alpha-tocopherol transfer protein → Alpha-tocotrienol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified rat liver protein and membrane-transfer competition
exposure
37 °C, 30 min; Table 1 competition-derived affinity.
limitations
Relative transfer competition, not a direct Kd or human clinical efficacy ratio.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Rat alpha-TTP distinguished this form from RRR-alpha-tocopherol.
primary_references
[hosomi1997] Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. (1997). https://pubmed.ncbi.nlm.nih.gov/9199513/ DOI: 10.1016/s0014-5793(97)00499-7
tissue_or_cell_type
Liver protein/liposomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 168–179
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver protein and membrane-transfer competition · source_derived_draft · unverified_draft
### ve-transport-rat-ttp-affinity-alpha-tocotrienol In a rat alpha-TTP membrane-transfer competition assay, alpha-tocotrienol had relative affinity 12.4% of RRR-alpha-tocopherol (100%). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Rat alpha-TTP distinguished this form from RRR-alpha-tocopherol. organism: Rattus norvegicus tissue_or_cell_type: Liver protein/liposomes experimental_model: Purified rat liver protein and membrane-transfer competition limitations: Relative transfer competition, not a direct Kd or human clinical efficacy ratio. exposure: 37 °C, 30 min; Table 1 competition-derived affinity. cross_nutrient: false [hosomi1997] Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. (1997). https://pubmed.ncbi.nlm.nih.gov/9199513/ DOI: 10.1016/s0014-5793(97)00499-7
Complete structured claim and evidence
Blocking SR-BI with an extracellular antibody or BLT1 reduced RRR-alpha-tocopherol uptake by human Caco-2 TC7 cells.
Scavenger receptor class B type 1 / SCARB1 → Intestinal alpha-tocopherol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Differentiated Caco-2 TC7 monolayers
exposure
60-min pretreatment: antibody 3.75 µg/mL or BLT1 10 µM; 40 µM micellar RRR-alpha-tocopherol for 60 min.
limitations
Inhibitor/antibody evidence; contribution under these conditions is not the sole absorption route.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
SR-BI helped these intestinal cells take up vitamin E.
primary_references
[reboul2006] Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. (2006). https://pubmed.ncbi.nlm.nih.gov/16380385/ DOI: 10.1074/jbc.m509042200
tissue_or_cell_type
Intestinal epithelial cell model
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 181–192
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated Caco-2 TC7 monolayers · source_derived_draft · unverified_draft
### ve-transport-scarb1-uptake Blocking SR-BI with an extracellular antibody or BLT1 reduced RRR-alpha-tocopherol uptake by human Caco-2 TC7 cells. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: SR-BI helped these intestinal cells take up vitamin E. organism: Homo sapiens tissue_or_cell_type: Intestinal epithelial cell model experimental_model: Differentiated Caco-2 TC7 monolayers limitations: Inhibitor/antibody evidence; contribution under these conditions is not the sole absorption route. exposure: 60-min pretreatment: antibody 3.75 µg/mL or BLT1 10 µM; 40 µM micellar RRR-alpha-tocopherol for 60 min. cross_nutrient: false [reboul2006] Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. (2006). https://pubmed.ncbi.nlm.nih.gov/16380385/ DOI: 10.1074/jbc.m509042200
Complete structured claim and evidence
SR-BI antibody or BLT1 reduced RRR-alpha-tocopherol efflux from loaded Caco-2 TC7 cells into apical vitamin-free mixed micelles.
Scavenger receptor class B type 1 / SCARB1 → Intestinal alpha-tocopherol apical efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Preloaded Caco-2 TC7 monolayers
exposure
Tocopherol-preloaded cells; apical acceptor micelles; time-course Figure 4.
limitations
Apical return is distinct from basolateral secretion; acceptor availability affects the result.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The same receptor also helped vitamin E leave toward the gut-facing side.
primary_references
[reboul2006] Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. (2006). https://pubmed.ncbi.nlm.nih.gov/16380385/ DOI: 10.1074/jbc.m509042200
tissue_or_cell_type
Intestinal epithelial cell model
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 194–205
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Preloaded Caco-2 TC7 monolayers · source_derived_draft · unverified_draft
### ve-transport-scarb1-apical-efflux SR-BI antibody or BLT1 reduced RRR-alpha-tocopherol efflux from loaded Caco-2 TC7 cells into apical vitamin-free mixed micelles. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same receptor also helped vitamin E leave toward the gut-facing side. organism: Homo sapiens tissue_or_cell_type: Intestinal epithelial cell model experimental_model: Preloaded Caco-2 TC7 monolayers limitations: Apical return is distinct from basolateral secretion; acceptor availability affects the result. exposure: Tocopherol-preloaded cells; apical acceptor micelles; time-course Figure 4. cross_nutrient: false [reboul2006] Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. (2006). https://pubmed.ncbi.nlm.nih.gov/16380385/ DOI: 10.1074/jbc.m509042200
Complete structured claim and evidence
Human NPC1L1 overexpression increased alpha-tocopherol uptake, which was inhibited by ezetimibe.
Human Niemann-Pick C1-like protein 1 / NPC1L1 → Intestinal alpha-tocopherol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human NPC1L1 overexpression uptake assay
exposure
NPC1L1 expression with alpha-tocopherol and ezetimibe; dose/time not reported in abstract.
limitations
Cell experiment does not establish a clinical vitamin E deficiency from ezetimibe.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in cultured cells
plain_language
The cholesterol transporter NPC1L1 can also take up vitamin E.
primary_references
[narushima2008] Niemann-pick C1-like 1 mediates alpha-tocopherol transport. (2008). https://pubmed.ncbi.nlm.nih.gov/18403720/ DOI: 10.1124/mol.107.043034
tissue_or_cell_type
Cellular uptake model
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 207–218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NPC1L1 overexpression uptake assay · source_derived_draft · unverified_draft
### ve-transport-npc1l1-uptake Human NPC1L1 overexpression increased alpha-tocopherol uptake, which was inhibited by ezetimibe. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cholesterol transporter NPC1L1 can also take up vitamin E. organism: Human protein in cultured cells tissue_or_cell_type: Cellular uptake model experimental_model: Human NPC1L1 overexpression uptake assay limitations: Cell experiment does not establish a clinical vitamin E deficiency from ezetimibe. exposure: NPC1L1 expression with alpha-tocopherol and ezetimibe; dose/time not reported in abstract. cross_nutrient: false [narushima2008] Niemann-pick C1-like 1 mediates alpha-tocopherol transport. (2008). https://pubmed.ncbi.nlm.nih.gov/18403720/ DOI: 10.1124/mol.107.043034
Complete structured claim and evidence
Cholesterol inhibited human NPC1L1-mediated alpha-tocopherol uptake in mutual substrate-interaction experiments.
Cholesterol → Intestinal alpha-tocopherol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human NPC1L1 overexpression co-substrate assay
exposure
Cholesterol and alpha-tocopherol co-incubation; concentrations unavailable in abstract.
limitations
No dietary cholesterol threshold or universal supplement-spacing rule follows.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in cultured cells
plain_language
Cholesterol changed vitamin E uptake through their shared transporter.
primary_references
[narushima2008] Niemann-pick C1-like 1 mediates alpha-tocopherol transport. (2008). https://pubmed.ncbi.nlm.nih.gov/18403720/ DOI: 10.1124/mol.107.043034
tissue_or_cell_type
Cellular uptake model
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 220–231
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NPC1L1 overexpression co-substrate assay · source_derived_draft · unverified_draft
### ve-transport-npc1l1-cholesterol-competition Cholesterol inhibited human NPC1L1-mediated alpha-tocopherol uptake in mutual substrate-interaction experiments. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cholesterol changed vitamin E uptake through their shared transporter. organism: Human protein in cultured cells tissue_or_cell_type: Cellular uptake model experimental_model: Human NPC1L1 overexpression co-substrate assay limitations: No dietary cholesterol threshold or universal supplement-spacing rule follows. exposure: Cholesterol and alpha-tocopherol co-incubation; concentrations unavailable in abstract. cross_nutrient: true [narushima2008] Niemann-pick C1-like 1 mediates alpha-tocopherol transport. (2008). https://pubmed.ncbi.nlm.nih.gov/18403720/ DOI: 10.1124/mol.107.043034
Complete structured claim and evidence
Rat NPC1L1 overexpression mediated alpha-tocopherol uptake but did not mediate retinol uptake in the tested Caco-2 system.
Rat Niemann-Pick C1-like 1 protein → Intestinal retinol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Rat NPC1L1-overexpressing human Caco-2 cells
exposure
Retinol compared with alpha-tocopherol uptake; dose/time not reported in abstract.
limitations
Substrate-specific negative result; does not prove vitamins A and E cannot interact through other routes.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus protein; Homo sapiens cells
plain_language
This vitamin E uptake route did not carry retinol in the same assay.
primary_references
[narushima2008] Niemann-pick C1-like 1 mediates alpha-tocopherol transport. (2008). https://pubmed.ncbi.nlm.nih.gov/18403720/ DOI: 10.1124/mol.107.043034
tissue_or_cell_type
Intestinal epithelial cell model
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 233–244
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat NPC1L1-overexpressing human Caco-2 cells · source_derived_draft · unverified_draft
### ve-transport-rat-npc1l1-retinol-negative Rat NPC1L1 overexpression mediated alpha-tocopherol uptake but did not mediate retinol uptake in the tested Caco-2 system. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: This vitamin E uptake route did not carry retinol in the same assay. organism: Rattus norvegicus protein; Homo sapiens cells tissue_or_cell_type: Intestinal epithelial cell model experimental_model: Rat NPC1L1-overexpressing human Caco-2 cells limitations: Substrate-specific negative result; does not prove vitamins A and E cannot interact through other routes. exposure: Retinol compared with alpha-tocopherol uptake; dose/time not reported in abstract. cross_nutrient: true [narushima2008] Niemann-pick C1-like 1 mediates alpha-tocopherol transport. (2008). https://pubmed.ncbi.nlm.nih.gov/18403720/ DOI: 10.1124/mol.107.043034
Complete structured claim and evidence
Primary enterocytes from Mttp-deficient mice secreted less alpha-tocopherol with chylomicrons.
Mouse Mttp loss → Chylomicron-associated alpha-tocopherol secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Primary Mttp-deficient mouse enterocytes
exposure
Mttp deficiency; radiolabeled alpha-tocopherol; exact genotype induction and incubation details unavailable in abstract.
limitations
Genetic machinery impairment, not low dietary vitamin E; HDL secretion is a distinct route.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
A chylomicron assembly defect reduced one major vitamin E export route.
primary_references
[anwar2007] Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption. (2007). https://pubmed.ncbi.nlm.nih.gov/17582142/ DOI: 10.1194/jlr.m700207-jlr200
tissue_or_cell_type
Small-intestinal enterocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 246–257
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary Mttp-deficient mouse enterocytes · source_derived_draft · unverified_draft
### ve-transport-mttp-chylomicron-loss Primary enterocytes from Mttp-deficient mice secreted less alpha-tocopherol with chylomicrons. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A chylomicron assembly defect reduced one major vitamin E export route. organism: Mus musculus tissue_or_cell_type: Small-intestinal enterocytes experimental_model: Primary Mttp-deficient mouse enterocytes limitations: Genetic machinery impairment, not low dietary vitamin E; HDL secretion is a distinct route. exposure: Mttp deficiency; radiolabeled alpha-tocopherol; exact genotype induction and incubation details unavailable in abstract. cross_nutrient: false [anwar2007] Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption. (2007). https://pubmed.ncbi.nlm.nih.gov/17582142/ DOI: 10.1194/jlr.m700207-jlr200
Complete structured claim and evidence
Primary rodent enterocytes secreted alpha-tocopherol with HDL even without exogenous lipid; this secretion was not reduced by MTP inhibition.
Alpha-tocopherol → HDL-associated alpha-tocopherol secretion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Primary rat/mouse enterocyte lipoprotein fractionation
exposure
Radiolabeled alpha-tocopherol; exogenous lipid omission and MTP inhibition comparisons.
limitations
Demonstrates a route, not adequate whole-body compensation for impaired chylomicron assembly.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus and Mus musculus
plain_language
A separate HDL-associated export route remained available in the experiment.
primary_references
[anwar2007] Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption. (2007). https://pubmed.ncbi.nlm.nih.gov/17582142/ DOI: 10.1194/jlr.m700207-jlr200
tissue_or_cell_type
Small-intestinal enterocytes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 259–270
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary rat/mouse enterocyte lipoprotein fractionation · source_derived_draft · unverified_draft
### ve-transport-hdl-route-mtp-independent Primary rodent enterocytes secreted alpha-tocopherol with HDL even without exogenous lipid; this secretion was not reduced by MTP inhibition. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate HDL-associated export route remained available in the experiment. organism: Rattus norvegicus and Mus musculus tissue_or_cell_type: Small-intestinal enterocytes experimental_model: Primary rat/mouse enterocyte lipoprotein fractionation limitations: Demonstrates a route, not adequate whole-body compensation for impaired chylomicron assembly. exposure: Radiolabeled alpha-tocopherol; exogenous lipid omission and MTP inhibition comparisons. cross_nutrient: false [anwar2007] Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption. (2007). https://pubmed.ncbi.nlm.nih.gov/17582142/ DOI: 10.1194/jlr.m700207-jlr200
Complete structured claim and evidence
Expression of human ABCA1 in BHK cells increased alpha-tocopherol efflux to apoA-I.
Human ATP-binding cassette transporter A1 → ApoA-I-directed alpha-tocopherol efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human ABCA1 gain of function in BHK cells
exposure
Radiolabeled alpha-tocopherol; 2-hour efflux to 5 µg/mL apoA-I with 1 mg/mL BSA.
limitations
Engineered cell assay; does not identify ABCA1 as the only vitamin E exporter.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in hamster cells
plain_language
ABCA1 helped transfer cellular vitamin E to an extracellular lipoprotein protein.
primary_references
[oram2001] ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol. (2001). https://pubmed.ncbi.nlm.nih.gov/11546785/ DOI: 10.1074/jbc.m106984200
tissue_or_cell_type
BHK kidney-derived cell line
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 272–283
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ABCA1 gain of function in BHK cells · source_derived_draft · unverified_draft
### ve-transport-abca1-apoa1-efflux Expression of human ABCA1 in BHK cells increased alpha-tocopherol efflux to apoA-I. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: ABCA1 helped transfer cellular vitamin E to an extracellular lipoprotein protein. organism: Human protein in hamster cells tissue_or_cell_type: BHK kidney-derived cell line experimental_model: Human ABCA1 gain of function in BHK cells limitations: Engineered cell assay; does not identify ABCA1 as the only vitamin E exporter. exposure: Radiolabeled alpha-tocopherol; 2-hour efflux to 5 µg/mL apoA-I with 1 mg/mL BSA. cross_nutrient: false [oram2001] ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol. (2001). https://pubmed.ncbi.nlm.nih.gov/11546785/ DOI: 10.1074/jbc.m106984200
Complete structured claim and evidence
ApoA-I failed to remove alpha-tocopherol from Tangier disease fibroblasts with nonfunctional ABCA1.
Nonfunctional ABCA1 in Tangier disease fibroblasts → ApoA-I-directed alpha-tocopherol efflux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Normal versus Tangier disease fibroblasts
exposure
Radiolabeled alpha-tocopherol; cholesterol/8-bromo-cAMP pretreatment; 6-hour apoA-I efflux assay.
limitations
Patient-cell machinery defect; not dietary deprivation or a claim that all HDL-mediated efflux is absent.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
An inherited transporter defect blocked this vitamin E export route in patient cells.
primary_references
[oram2001] ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol. (2001). https://pubmed.ncbi.nlm.nih.gov/11546785/ DOI: 10.1074/jbc.m106984200
tissue_or_cell_type
Cultured fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 285–296
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Normal versus Tangier disease fibroblasts · source_derived_draft · unverified_draft
### ve-transport-abca1-tangier-efflux-loss ApoA-I failed to remove alpha-tocopherol from Tangier disease fibroblasts with nonfunctional ABCA1. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited transporter defect blocked this vitamin E export route in patient cells. organism: Homo sapiens tissue_or_cell_type: Cultured fibroblasts experimental_model: Normal versus Tangier disease fibroblasts limitations: Patient-cell machinery defect; not dietary deprivation or a claim that all HDL-mediated efflux is absent. exposure: Radiolabeled alpha-tocopherol; cholesterol/8-bromo-cAMP pretreatment; 6-hour apoA-I efflux assay. cross_nutrient: false [oram2001] ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol. (2001). https://pubmed.ncbi.nlm.nih.gov/11546785/ DOI: 10.1074/jbc.m106984200
Complete structured claim and evidence
After equal oral labeled RRR- and SRR-alpha-tocopheryl acetate, the human chylomicron fraction contained similar concentrations of the two tocopherol stereoisomers.
RRR-alpha-tocopherol → Chylomicron alpha-tocopherol stereoisomer delivery source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human stable-isotope oral study with lipoprotein fractionation
exposure
Four subjects received equal paired doses of labeled RRR and SRR acetate ester with breakfast: 40, 50, 75 or 75 mg of each ester; samples through 76 hours.
limitations
Small tracer study; fraction enrichment alone does not prove the molecular sorting step or clinical benefit.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Early chylomicron delivery did not strongly distinguish the two tested stereoisomers.
primary_references
[traber1990] RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. (1990). https://pubmed.ncbi.nlm.nih.gov/2351872/ DOI: 10.1016/s0022-2275(20)42836-6
tissue_or_cell_type
Plasma chylomicron or VLDL fractions
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 298–309
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human stable-isotope oral study with lipoprotein fractionation · source_derived_draft · unverified_draft
### ve-transport-chylomicron-stereoisomers After equal oral labeled RRR- and SRR-alpha-tocopheryl acetate, the human chylomicron fraction contained similar concentrations of the two tocopherol stereoisomers. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Early chylomicron delivery did not strongly distinguish the two tested stereoisomers. organism: Homo sapiens tissue_or_cell_type: Plasma chylomicron or VLDL fractions experimental_model: Human stable-isotope oral study with lipoprotein fractionation limitations: Small tracer study; fraction enrichment alone does not prove the molecular sorting step or clinical benefit. exposure: Four subjects received equal paired doses of labeled RRR and SRR acetate ester with breakfast: 40, 50, 75 or 75 mg of each ester; samples through 76 hours. cross_nutrient: false [traber1990] RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. (1990). https://pubmed.ncbi.nlm.nih.gov/2351872/ DOI: 10.1016/s0022-2275(20)42836-6
Complete structured claim and evidence
After equal oral labeled RRR- and SRR-alpha-tocopheryl acetate, human VLDL became enriched in RRR-alpha-tocopherol relative to SRR-alpha-tocopherol by 11 hours.
RRR-alpha-tocopherol → VLDL alpha-tocopherol stereoisomer enrichment source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human stable-isotope oral study with lipoprotein fractionation
exposure
Four subjects received equal paired doses of labeled RRR and SRR acetate ester with breakfast: 40, 50, 75 or 75 mg of each ester; samples through 76 hours.
limitations
Small tracer study; fraction enrichment alone does not prove the molecular sorting step or clinical benefit.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
A later lipoprotein fraction favored the RRR form.
primary_references
[traber1990] RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. (1990). https://pubmed.ncbi.nlm.nih.gov/2351872/ DOI: 10.1016/s0022-2275(20)42836-6
tissue_or_cell_type
Plasma chylomicron or VLDL fractions
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 311–322
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human stable-isotope oral study with lipoprotein fractionation · source_derived_draft · unverified_draft
### ve-transport-vldl-stereoisomers After equal oral labeled RRR- and SRR-alpha-tocopheryl acetate, human VLDL became enriched in RRR-alpha-tocopherol relative to SRR-alpha-tocopherol by 11 hours. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later lipoprotein fraction favored the RRR form. organism: Homo sapiens tissue_or_cell_type: Plasma chylomicron or VLDL fractions experimental_model: Human stable-isotope oral study with lipoprotein fractionation limitations: Small tracer study; fraction enrichment alone does not prove the molecular sorting step or clinical benefit. exposure: Four subjects received equal paired doses of labeled RRR and SRR acetate ester with breakfast: 40, 50, 75 or 75 mg of each ester; samples through 76 hours. cross_nutrient: false [traber1990] RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. (1990). https://pubmed.ncbi.nlm.nih.gov/2351872/ DOI: 10.1016/s0022-2275(20)42836-6
Complete structured claim and evidence
The deposited mouse alpha-TTP complex contains alpha-tocopherol and PI(4,5)P2, with phosphoinositide binding at the protein surface linked to opening of its ligand pocket.
Mouse alpha-tocopherol transfer protein → Phosphatidylinositol 4,5-bisphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
X-ray complex PDB 3W68
exposure
Crystallized protein with alpha-tocopherol and PI(4,5)P2.
limitations
Structure is mouse protein; no dietary phosphorus requirement or human affinity value is inferred.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus protein
plain_language
A membrane phosphoinositide interacts with the vitamin E transfer protein.
primary_references
[kono2013] Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency. (2013). https://pubmed.ncbi.nlm.nih.gov/23599266/ DOI: 10.1126/science.1233508
tissue_or_cell_type
Purified protein-lipid complex
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 324–335
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray complex PDB 3W68 · source_derived_draft · unverified_draft
### ve-transport-mouse-ttp-pip2-binding The deposited mouse alpha-TTP complex contains alpha-tocopherol and PI(4,5)P2, with phosphoinositide binding at the protein surface linked to opening of its ligand pocket. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane phosphoinositide interacts with the vitamin E transfer protein. organism: Mus musculus protein tissue_or_cell_type: Purified protein-lipid complex experimental_model: X-ray complex PDB 3W68 limitations: Structure is mouse protein; no dietary phosphorus requirement or human affinity value is inferred. exposure: Crystallized protein with alpha-tocopherol and PI(4,5)P2. cross_nutrient: false [kono2013] Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency. (2013). https://pubmed.ncbi.nlm.nih.gov/23599266/ DOI: 10.1126/science.1233508
Complete structured claim and evidence
Adding alpha-tocopherol to vitamin E-depleted rat hepatoma cells expressing human TTP changed its punctate perinuclear distribution to a diffuse cellular pattern.
RRR-alpha-tocopherol → Alpha-TTP intracellular redistribution source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human TTP expressed in depleted McARH7777 cells; Figure 2A
exposure
More than 10 passages in alpha-tocopherol-free defined serum; 35 µM serum-complexed d-alpha-tocopherol for 24 hours.
limitations
Depletion/repletion model with overexpressed human protein; localization is not a clinical deficiency threshold.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus cells; Homo sapiens protein
plain_language
Vitamin E supply changed where its transfer protein accumulated in these cells.
primary_references
[chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
tissue_or_cell_type
Hepatoma cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 337–348
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TTP expressed in depleted McARH7777 cells; Figure 2A · source_derived_draft · unverified_draft
### ve-transport-depletion-repletion-ttp-localization Adding alpha-tocopherol to vitamin E-depleted rat hepatoma cells expressing human TTP changed its punctate perinuclear distribution to a diffuse cellular pattern. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E supply changed where its transfer protein accumulated in these cells. organism: Rattus norvegicus cells; Homo sapiens protein tissue_or_cell_type: Hepatoma cells experimental_model: Human TTP expressed in depleted McARH7777 cells; Figure 2A limitations: Depletion/repletion model with overexpressed human protein; localization is not a clinical deficiency threshold. exposure: More than 10 passages in alpha-tocopherol-free defined serum; 35 µM serum-complexed d-alpha-tocopherol for 24 hours. cross_nutrient: false [chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
Complete structured claim and evidence
Human TTP(R221W) remained punctate after alpha-tocopherol treatment in rat McARH7777 cells, unlike wild-type TTP.
Human alpha-TTP R221W → Alpha-TTP intracellular redistribution source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human wild-type versus R221W TTP expression; Figure 2B
exposure
35 µM serum-complexed alpha-tocopherol for 24 hours after medium depletion.
limitations
Mutation contrast is machinery impairment; this does not establish that supplementation cannot help AVED clinically.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human proteins in Rattus norvegicus cells
plain_language
An AVED-associated variant failed to change location when vitamin E was supplied.
primary_references
[chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
tissue_or_cell_type
Hepatoma cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 350–361
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human wild-type versus R221W TTP expression; Figure 2B · source_derived_draft · unverified_draft
### ve-transport-r221w-localization Human TTP(R221W) remained punctate after alpha-tocopherol treatment in rat McARH7777 cells, unlike wild-type TTP. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: An AVED-associated variant failed to change location when vitamin E was supplied. organism: Human proteins in Rattus norvegicus cells tissue_or_cell_type: Hepatoma cells experimental_model: Human wild-type versus R221W TTP expression; Figure 2B limitations: Mutation contrast is machinery impairment; this does not establish that supplementation cannot help AVED clinically. exposure: 35 µM serum-complexed alpha-tocopherol for 24 hours after medium depletion. cross_nutrient: false [chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
Complete structured claim and evidence
Engineered depletion of plasma-membrane PI(4,5)P2 impaired TTP-dependent NBD-alpha-tocopherol secretion in McARH7777 cells.
Plasma membrane PI(4,5)P2 depletion → TTP-dependent NBD-alpha-tocopherol secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human TTP-expressing cells with membrane-targeted inositol phosphatase; Figure 5
exposure
IPP-CAAX expression; pulse loading with 10 µM serum-complexed NBD-alpha-tocopherol.
limitations
Phosphoinositide machinery perturbation and fluorescent analog; not dietary phosphorus or vitamin E deprivation as the causal contrast.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus cells; Homo sapiens TTP
plain_language
A membrane lipid signal was needed for efficient reporter export.
primary_references
[chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
tissue_or_cell_type
Hepatoma cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 363–374
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TTP-expressing cells with membrane-targeted inositol phosphatase; Figure 5 · source_derived_draft · unverified_draft
### ve-transport-pip2-depletion-ttp-export Engineered depletion of plasma-membrane PI(4,5)P2 impaired TTP-dependent NBD-alpha-tocopherol secretion in McARH7777 cells. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane lipid signal was needed for efficient reporter export. organism: Rattus norvegicus cells; Homo sapiens TTP tissue_or_cell_type: Hepatoma cells experimental_model: Human TTP-expressing cells with membrane-targeted inositol phosphatase; Figure 5 limitations: Phosphoinositide machinery perturbation and fluorescent analog; not dietary phosphorus or vitamin E deprivation as the causal contrast. exposure: IPP-CAAX expression; pulse loading with 10 µM serum-complexed NBD-alpha-tocopherol. cross_nutrient: false [chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
Complete structured claim and evidence
Co-immunoprecipitation/Western blot experiments identified an association of sheep alpha-TTP with Rab8a in a liver/primary-hepatocyte study.
Sheep alpha-tocopherol transfer protein → Sheep RAB8A protein source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Co-IP/Western blot validation in sheep liver/hepatocyte study
exposure
Endogenous interaction profiling and validation; exact pull-down exposures not assigned from accessible sections.
limitations
Association is not proof of direct binary binding or a defined stable complex; no human nutritional outcome is inferred.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Ovis aries
plain_language
The sheep study linked this trafficking protein with alpha-TTP.
primary_references
[jian2025] Rab8a and Vps35 influence intracellular transport of vitamin E via α-Tocopherol transport protein in hepatocytes. (2025). https://pubmed.ncbi.nlm.nih.gov/40258550/ DOI: 10.1016/j.ijbiomac.2025.143021
tissue_or_cell_type
Liver and newborn male Australian White sheep primary hepatocytes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 376–387
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Co-IP/Western blot validation in sheep liver/hepatocyte study · source_derived_draft · unverified_draft
### ve-transport-sheep-ttp-rab8a Co-immunoprecipitation/Western blot experiments identified an association of sheep alpha-TTP with Rab8a in a liver/primary-hepatocyte study. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sheep study linked this trafficking protein with alpha-TTP. organism: Ovis aries tissue_or_cell_type: Liver and newborn male Australian White sheep primary hepatocytes experimental_model: Co-IP/Western blot validation in sheep liver/hepatocyte study limitations: Association is not proof of direct binary binding or a defined stable complex; no human nutritional outcome is inferred. exposure: Endogenous interaction profiling and validation; exact pull-down exposures not assigned from accessible sections. cross_nutrient: false [jian2025] Rab8a and Vps35 influence intracellular transport of vitamin E via α-Tocopherol transport protein in hepatocytes. (2025). https://pubmed.ncbi.nlm.nih.gov/40258550/ DOI: 10.1016/j.ijbiomac.2025.143021
Complete structured claim and evidence
Co-immunoprecipitation/Western blot experiments identified an association of sheep alpha-TTP with Vps35 in a liver/primary-hepatocyte study.
Sheep alpha-tocopherol transfer protein → Sheep VPS35 protein source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Co-IP/Western blot validation in sheep liver/hepatocyte study
exposure
Endogenous interaction profiling and validation; exact pull-down exposures not assigned from accessible sections.
limitations
Association is not proof of direct binary binding or a defined stable complex; no human nutritional outcome is inferred.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Ovis aries
plain_language
The sheep study linked this trafficking protein with alpha-TTP.
primary_references
[jian2025] Rab8a and Vps35 influence intracellular transport of vitamin E via α-Tocopherol transport protein in hepatocytes. (2025). https://pubmed.ncbi.nlm.nih.gov/40258550/ DOI: 10.1016/j.ijbiomac.2025.143021
tissue_or_cell_type
Liver and newborn male Australian White sheep primary hepatocytes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 389–400
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Co-IP/Western blot validation in sheep liver/hepatocyte study · source_derived_draft · unverified_draft
### ve-transport-sheep-ttp-vps35 Co-immunoprecipitation/Western blot experiments identified an association of sheep alpha-TTP with Vps35 in a liver/primary-hepatocyte study. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sheep study linked this trafficking protein with alpha-TTP. organism: Ovis aries tissue_or_cell_type: Liver and newborn male Australian White sheep primary hepatocytes experimental_model: Co-IP/Western blot validation in sheep liver/hepatocyte study limitations: Association is not proof of direct binary binding or a defined stable complex; no human nutritional outcome is inferred. exposure: Endogenous interaction profiling and validation; exact pull-down exposures not assigned from accessible sections. cross_nutrient: false [jian2025] Rab8a and Vps35 influence intracellular transport of vitamin E via α-Tocopherol transport protein in hepatocytes. (2025). https://pubmed.ncbi.nlm.nih.gov/40258550/ DOI: 10.1016/j.ijbiomac.2025.143021
Complete structured claim and evidence
Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of alpha-tocopherol to its 13′-hydroxy product.
Human cytochrome P450 4F2 → 13′-Hydroxy-alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Recombinant human P450 enzyme comparison
exposure
alpha-Tocopherol substrate with NADPH; quantitative incubation details not assigned here.
limitations
Initial oxidation only; other enzymes perform subsequent side-chain shortening.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in recombinant microsomes
plain_language
CYP4F2 begins breakdown of this tocopherol form.
primary_references
[sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 402–413
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human P450 enzyme comparison · source_derived_draft · unverified_draft
### ve-transport-cyp4f2-alpha-hydroxylation Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of alpha-tocopherol to its 13′-hydroxy product. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP4F2 begins breakdown of this tocopherol form. organism: Human protein in recombinant microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant human P450 enzyme comparison limitations: Initial oxidation only; other enzymes perform subsequent side-chain shortening. exposure: alpha-Tocopherol substrate with NADPH; quantitative incubation details not assigned here. cross_nutrient: false [sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
Complete structured claim and evidence
Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of gamma-tocopherol to its 13′-hydroxy product.
Human cytochrome P450 4F2 → 13′-Hydroxy-gamma-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Recombinant human P450 enzyme comparison
exposure
gamma-Tocopherol substrate with NADPH; quantitative incubation details not assigned here.
limitations
Initial oxidation only; other enzymes perform subsequent side-chain shortening.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in recombinant microsomes
plain_language
CYP4F2 begins breakdown of this tocopherol form.
primary_references
[sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 415–426
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human P450 enzyme comparison · source_derived_draft · unverified_draft
### ve-transport-cyp4f2-gamma-hydroxylation Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of gamma-tocopherol to its 13′-hydroxy product. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP4F2 begins breakdown of this tocopherol form. organism: Human protein in recombinant microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant human P450 enzyme comparison limitations: Initial oxidation only; other enzymes perform subsequent side-chain shortening. exposure: gamma-Tocopherol substrate with NADPH; quantitative incubation details not assigned here. cross_nutrient: false [sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
Complete structured claim and evidence
HepG2 cultures exposed to gamma-tocopherol produced side-chain oxidation/shortening intermediates culminating in gamma-CEHC, identified by GC-MS.
Gamma-tocopherol → Gamma-carboxyethyl hydroxychromanol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
HepG2 metabolite profiling
exposure
50 µM gamma-tocopherol; primary Figure 1.
limitations
Pathway-level conversion; not a one-step CYP4F2 reaction or a human excretion-rate estimate.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Several metabolic steps convert gamma-tocopherol into a shorter-chain product.
primary_references
[sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
tissue_or_cell_type
Hepatoma cells
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 428–439
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HepG2 metabolite profiling · source_derived_draft · unverified_draft
### ve-transport-gamma-multistep-cehc HepG2 cultures exposed to gamma-tocopherol produced side-chain oxidation/shortening intermediates culminating in gamma-CEHC, identified by GC-MS. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several metabolic steps convert gamma-tocopherol into a shorter-chain product. organism: Homo sapiens tissue_or_cell_type: Hepatoma cells experimental_model: HepG2 metabolite profiling limitations: Pathway-level conversion; not a one-step CYP4F2 reaction or a human excretion-rate estimate. exposure: 50 µM gamma-tocopherol; primary Figure 1. cross_nutrient: false [sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
Complete structured claim and evidence
Rat liver microsomes formed initial alpha- and gamma-tocopherol side-chain oxidation products with NADPH but not without it.
NADPH → Microsomal tocopherol omega-hydroxylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Cofactor omission/addition; Figure 6
exposure
0.5 mM NADPH; reaction followed for 80 minutes.
limitations
Direct NADPH dependence; no dietary niacin or riboflavin shortage, universal supplement combination or magnesium requirement was tested.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
The initial microsomal oxidation required a reducing cofactor.
primary_references
[sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
tissue_or_cell_type
Liver microsomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 441–452
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor omission/addition; Figure 6 · source_derived_draft · unverified_draft
### ve-transport-nadph-microsomal-oxidation Rat liver microsomes formed initial alpha- and gamma-tocopherol side-chain oxidation products with NADPH but not without it. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The initial microsomal oxidation required a reducing cofactor. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomes experimental_model: Cofactor omission/addition; Figure 6 limitations: Direct NADPH dependence; no dietary niacin or riboflavin shortage, universal supplement combination or magnesium requirement was tested. exposure: 0.5 mM NADPH; reaction followed for 80 minutes. cross_nutrient: true [sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
Complete structured claim and evidence
Human CYP4F2-expressing microsomes hydroxylated phylloquinone, demonstrating substrate overlap with tocopherol catabolism.
Human cytochrome P450 4F2 → Omega-hydroxyphylloquinone source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant CYP4F2 kinetic assay
exposure
25 pmol CYP4F2; labeled phylloquinone 1–100 µM; 1 mM NADPH; 30 min at 37 °C.
limitations
Shared substrate use alone does not imply vitamin E accelerates vitamin K depletion.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in insect microsomes
plain_language
Vitamins E and K1 share an initial catabolic enzyme.
primary_references
[farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 454–465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP4F2 kinetic assay · source_derived_draft · unverified_draft
### ve-transport-cyp4f2-k1-hydroxylation Human CYP4F2-expressing microsomes hydroxylated phylloquinone, demonstrating substrate overlap with tocopherol catabolism. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamins E and K1 share an initial catabolic enzyme. organism: Human protein in insect microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant CYP4F2 kinetic assay limitations: Shared substrate use alone does not imply vitamin E accelerates vitamin K depletion. exposure: 25 pmol CYP4F2; labeled phylloquinone 1–100 µM; 1 mM NADPH; 30 min at 37 °C. cross_nutrient: true [farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
Complete structured claim and evidence
Alpha-tocopherol did not increase phylloquinone omega-hydroxylation in CYP4F2 microsomes; the study reported a slight decrease in apparent phylloquinone Vmax.
RRR-alpha-tocopherol → CYP4F2-mediated phylloquinone omega-hydroxylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human CYP4F2 co-substrate kinetics
exposure
Labeled phylloquinone 0–50 µM with RRR-alpha-tocopherol 0–50 µM or SRR-alpha-tocopherol 0–100 µM; 30 min, 37 °C, 1 mM NADPH.
limitations
Does not exclude other mechanisms of vitamin E–K interaction in animals or humans.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in insect microsomes
plain_language
This assay did not support faster vitamin K1 breakdown caused by alpha-tocopherol.
primary_references
[farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 467–478
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP4F2 co-substrate kinetics · source_derived_draft · unverified_draft
### ve-transport-alpha-does-not-activate-k1-catabolism Alpha-tocopherol did not increase phylloquinone omega-hydroxylation in CYP4F2 microsomes; the study reported a slight decrease in apparent phylloquinone Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: This assay did not support faster vitamin K1 breakdown caused by alpha-tocopherol. organism: Human protein in insect microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant human CYP4F2 co-substrate kinetics limitations: Does not exclude other mechanisms of vitamin E–K interaction in animals or humans. exposure: Labeled phylloquinone 0–50 µM with RRR-alpha-tocopherol 0–50 µM or SRR-alpha-tocopherol 0–100 µM; 30 min, 37 °C, 1 mM NADPH. cross_nutrient: true [farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
Complete structured claim and evidence
In azo-initiated methyl linoleate oxidation in solution, alpha-tocopherol interrupted the radical chain; the reported inhibition rate constant was 5.1 × 10^5 M^-1 s^-1 at 37 °C, with kinetics consistent with trapping two peroxyl radicals per molecule under those conditions.
Alpha-tocopherol → Lipid peroxyl radicals source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract
experimental_model
Solution autoxidation kinetics
exposure
Azo initiators; 37 °C.
limitations
Solution-specific kinetics and inferred stoichiometry, not a universal membrane rate.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free
plain_language
Vitamin E intercepted radicals that would otherwise continue oxidizing this fatty-acid ester.
primary_references
[ver-niki1984] Inhibition of oxidation of methyl linoleate in solution by vitamin E and vitamin C. (1984). https://pubmed.ncbi.nlm.nih.gov/6706998/ DOI: 10.1016/s0021-9258(17)43026-2
tissue_or_cell_type
Organic solution
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 480–492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Solution autoxidation kinetics · source_derived_draft · unverified_draft
### ver-peroxyl-trapping In azo-initiated methyl linoleate oxidation in solution, alpha-tocopherol interrupted the radical chain; the reported inhibition rate constant was 5.1 × 10^5 M^-1 s^-1 at 37 °C, with kinetics consistent with trapping two peroxyl radicals per molecule under those conditions. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E intercepted radicals that would otherwise continue oxidizing this fatty-acid ester. organism: Cell-free tissue_or_cell_type: Organic solution experimental_model: Solution autoxidation kinetics limitations: Solution-specific kinetics and inferred stoichiometry, not a universal membrane rate. exposure: Azo initiators; 37 °C. cross_nutrient: false evidence_location: Primary abstract [ver-niki1984] Inhibition of oxidation of methyl linoleate in solution by vitamin E and vitamin C. (1984). https://pubmed.ncbi.nlm.nih.gov/6706998/ DOI: 10.1016/s0021-9258(17)43026-2
Complete structured claim and evidence
Electron paramagnetic resonance detected alpha-tocopheroxyl radical at approximately 10^-8–10^-7 M during Fe(III)-complex-initiated oxidation of soybean phosphatidylcholine liposomes containing alpha-tocopherol.
Alpha-tocopherol → Alpha-tocopheroxyl radical source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract
experimental_model
EPR with optical and oxygen-consumption measurements
exposure
Fe(III)-triethylenetetramine initiator.
limitations
Artificial membrane system; does not quantify in vivo radical abundance.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free soybean lipid preparation
plain_language
The experiment directly observed the vitamin E radical intermediate inside an artificial membrane.
primary_references
[ver-scarpa1984-reuse] Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study. (1984). https://pubmed.ncbi.nlm.nih.gov/6089911/ DOI: 10.1016/0304-4165(84)90070-9
tissue_or_cell_type
Phosphatidylcholine liposomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 494–506
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · EPR with optical and oxygen-consumption measurements · source_derived_draft · unverified_draft
### ver-tocopheroxyl-detection Electron paramagnetic resonance detected alpha-tocopheroxyl radical at approximately 10^-8–10^-7 M during Fe(III)-complex-initiated oxidation of soybean phosphatidylcholine liposomes containing alpha-tocopherol. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The experiment directly observed the vitamin E radical intermediate inside an artificial membrane. organism: Cell-free soybean lipid preparation tissue_or_cell_type: Phosphatidylcholine liposomes experimental_model: EPR with optical and oxygen-consumption measurements limitations: Artificial membrane system; does not quantify in vivo radical abundance. exposure: Fe(III)-triethylenetetramine initiator. cross_nutrient: false evidence_location: Primary abstract [ver-scarpa1984-reuse] Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study. (1984). https://pubmed.ncbi.nlm.nih.gov/6089911/ DOI: 10.1016/0304-4165(84)90070-9
Complete structured claim and evidence
Ubiquinol-10 reduced alpha-tocopheroxyl to alpha-tocopherol in stopped-flow solution experiments, with second-order rate constants of 3.74 × 10^5 M^-1 s^-1 in benzene and 2.15 × 10^5 M^-1 s^-1 in ethanol at 25 °C.
Reduced CoQ10 → Alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Stopped-flow spectrophotometry
exposure
25 °C; reduced CoQ10.
limitations
No direct tissue flux or oral CoQ10 effect was measured.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free
plain_language
Reduced CoQ10 recycled the vitamin E radical in these chemical assays.
primary_references
[ver-mukai1990] Stopped-flow kinetic study of the regeneration reaction of tocopheroxyl radical by reduced ubiquinone-10 in solution. (1990). https://pubmed.ncbi.nlm.nih.gov/2383582/ DOI: 10.1016/0304-4165(90)90176-w
tissue_or_cell_type
Benzene or ethanol solution
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 508–520
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stopped-flow spectrophotometry · source_derived_draft · unverified_draft
### ver-ubiquinol-regeneration Ubiquinol-10 reduced alpha-tocopheroxyl to alpha-tocopherol in stopped-flow solution experiments, with second-order rate constants of 3.74 × 10^5 M^-1 s^-1 in benzene and 2.15 × 10^5 M^-1 s^-1 in ethanol at 25 °C. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced CoQ10 recycled the vitamin E radical in these chemical assays. organism: Cell-free tissue_or_cell_type: Benzene or ethanol solution experimental_model: Stopped-flow spectrophotometry limitations: No direct tissue flux or oral CoQ10 effect was measured. exposure: 25 °C; reduced CoQ10. cross_nutrient: true evidence_location: Primary abstract [ver-mukai1990] Stopped-flow kinetic study of the regeneration reaction of tocopheroxyl radical by reduced ubiquinone-10 in solution. (1990). https://pubmed.ncbi.nlm.nih.gov/2383582/ DOI: 10.1016/0304-4165(90)90176-w
Complete structured claim and evidence
The same solution study detected no reaction of oxidized ubiquinone-10 with tocopheroxyl radicals, distinguishing it from the active reduced ubiquinol-10 form.
Ubiquinone-10 → Alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Stopped-flow comparison of CoQ10 redox states
exposure
Oxidized ubiquinone-10 comparator.
limitations
A non-detected reaction under these assay conditions is not an assertion that cellular CoQ cannot first be reduced.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free
plain_language
CoQ10 needed to be in its reduced state for the measured recycling reaction.
primary_references
[ver-mukai1990] Stopped-flow kinetic study of the regeneration reaction of tocopheroxyl radical by reduced ubiquinone-10 in solution. (1990). https://pubmed.ncbi.nlm.nih.gov/2383582/ DOI: 10.1016/0304-4165(90)90176-w
tissue_or_cell_type
Chemical solution
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 522–534
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stopped-flow comparison of CoQ10 redox states · source_derived_draft · unverified_draft
### ver-oxidized-coq-no-regeneration The same solution study detected no reaction of oxidized ubiquinone-10 with tocopheroxyl radicals, distinguishing it from the active reduced ubiquinol-10 form. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: CoQ10 needed to be in its reduced state for the measured recycling reaction. organism: Cell-free tissue_or_cell_type: Chemical solution experimental_model: Stopped-flow comparison of CoQ10 redox states limitations: A non-detected reaction under these assay conditions is not an assertion that cellular CoQ cannot first be reduced. exposure: Oxidized ubiquinone-10 comparator. cross_nutrient: true evidence_location: Primary abstract [ver-mukai1990] Stopped-flow kinetic study of the regeneration reaction of tocopheroxyl radical by reduced ubiquinone-10 in solution. (1990). https://pubmed.ncbi.nlm.nih.gov/2383582/ DOI: 10.1016/0304-4165(90)90176-w
Complete structured claim and evidence
Vitamin K1 hydroquinone reacted with alpha-tocopheroxyl in stopped-flow assays; it regenerated vitamin E more rapidly than ubiquinol-10 across the tested ethanol, benzene and isopropanol/water solvent systems.
Phylloquinol / vitamin K1 hydroquinone → Alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Biological hydroquinone comparison
exposure
Reduced K1; isopropanol/water 5:1 v/v and separate organic solvents.
limitations
Does not establish dietary K/E synergy, clinical benefit or competition in coagulation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free
plain_language
The reduced form of vitamin K1 recycled vitamin E in solution.
primary_references
[ver-mukai1992] Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones (reduced forms of ubiquinone, vitamin K, and tocopherolquinone) in solution. (1992). https://pubmed.ncbi.nlm.nih.gov/1429580/ DOI: 10.1016/s0021-9258(18)41666-3
tissue_or_cell_type
Chemical solutions
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 536–548
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biological hydroquinone comparison · source_derived_draft · unverified_draft
### ver-phylloquinol-regeneration Vitamin K1 hydroquinone reacted with alpha-tocopheroxyl in stopped-flow assays; it regenerated vitamin E more rapidly than ubiquinol-10 across the tested ethanol, benzene and isopropanol/water solvent systems. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reduced form of vitamin K1 recycled vitamin E in solution. organism: Cell-free tissue_or_cell_type: Chemical solutions experimental_model: Biological hydroquinone comparison limitations: Does not establish dietary K/E synergy, clinical benefit or competition in coagulation. exposure: Reduced K1; isopropanol/water 5:1 v/v and separate organic solvents. cross_nutrient: true evidence_location: Primary abstract [ver-mukai1992] Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones (reduced forms of ubiquinone, vitamin K, and tocopherolquinone) in solution. (1992). https://pubmed.ncbi.nlm.nih.gov/1429580/ DOI: 10.1016/s0021-9258(18)41666-3
Complete structured claim and evidence
Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage.
GPX4 → Phospholipid hydroperoxides source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Rose-bengal photoperoxidation followed by enzyme treatment
exposure
GSH/PHGPX after photooxidation.
limitations
Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human-derived cell-free membranes
plain_language
GPX4 removed peroxide groups from membrane phospholipids using glutathione.
primary_references
[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
tissue_or_cell_type
Erythrocyte ghosts
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 550–562
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rose-bengal photoperoxidation followed by enzyme treatment · source_derived_draft · unverified_draft
### ver-gpx4-pl-hydroperoxide-reduction Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: GPX4 removed peroxide groups from membrane phospholipids using glutathione. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Rose-bengal photoperoxidation followed by enzyme treatment limitations: Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping. exposure: GSH/PHGPX after photooxidation. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
Complete structured claim and evidence
GSH/PHGPX reduced membrane cholesterol hydroperoxides, predominantly the photo-generated 5-alpha product, to diol-like products; cholesterol hydroperoxide decay was about one-sixth the phospholipid hydroperoxide decay rate in the ghost-membrane assay.
GPX4 → Cholesterol hydroperoxides source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Radiolabeled sterol analysis in erythrocyte ghosts
exposure
Photooxidation followed by GSH/PHGPX.
limitations
Product co-migration and assay-specific relative kinetics; no universal cellular rate.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human-derived cell-free membranes
plain_language
The enzyme also removed peroxide groups from oxidized cholesterol, more slowly than from phospholipids in this preparation.
primary_references
[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
tissue_or_cell_type
Erythrocyte ghosts
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 564–576
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled sterol analysis in erythrocyte ghosts · source_derived_draft · unverified_draft
### ver-gpx4-cholesterol-hydroperoxide GSH/PHGPX reduced membrane cholesterol hydroperoxides, predominantly the photo-generated 5-alpha product, to diol-like products; cholesterol hydroperoxide decay was about one-sixth the phospholipid hydroperoxide decay rate in the ghost-membrane assay. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme also removed peroxide groups from oxidized cholesterol, more slowly than from phospholipids in this preparation. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Radiolabeled sterol analysis in erythrocyte ghosts limitations: Product co-migration and assay-specific relative kinetics; no universal cellular rate. exposure: Photooxidation followed by GSH/PHGPX. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
Complete structured claim and evidence
GSH/PHGPX pretreatment completely suppressed the subsequent radical-peroxidation burst when photooxidized erythrocyte ghosts were challenged with ascorbate/iron or xanthine/xanthine-oxidase/iron.
GPX4 → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Sequential peroxide reduction and iron challenge
exposure
Photoperoxidation → GSH/PHGPX → iron-dependent challenge.
limitations
Ascorbate participates in this deliberately pro-oxidizing assay; this is not evidence that normal vitamin C intake damages membranes.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human-derived cell-free membranes
plain_language
Removing membrane hydroperoxides prevented an iron-driven burst of further oxidation.
primary_references
[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
tissue_or_cell_type
Erythrocyte ghosts
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 578–590
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequential peroxide reduction and iron challenge · source_derived_draft · unverified_draft
### ver-peroxide-removal-iron-burst GSH/PHGPX pretreatment completely suppressed the subsequent radical-peroxidation burst when photooxidized erythrocyte ghosts were challenged with ascorbate/iron or xanthine/xanthine-oxidase/iron. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing membrane hydroperoxides prevented an iron-driven burst of further oxidation. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Sequential peroxide reduction and iron challenge limitations: Ascorbate participates in this deliberately pro-oxidizing assay; this is not evidence that normal vitamin C intake damages membranes. exposure: Photoperoxidation → GSH/PHGPX → iron-dependent challenge. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
Complete structured claim and evidence
At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present.
Alpha-tocopherol → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Microsomes and Triton-dispersed lipid micelles
exposure
Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract.
limitations
Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations.
primary_references
[ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
tissue_or_cell_type
Liver microsomal lipids
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 592–604
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomes and Triton-dispersed lipid micelles · source_derived_draft · unverified_draft
### ver-gpx4-gsh-tocopherol-cooperation At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal lipids experimental_model: Microsomes and Triton-dispersed lipid micelles limitations: Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection. exposure: Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract. cross_nutrient: true evidence_location: Primary abstract [ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
Complete structured claim and evidence
Maternal dietary supplementation with 500 IU/kg DL-alpha-tocopheryl acetate through gestation and nursing allowed Alb-Cre;Gpx4fl/fl pups to survive to weaning, whereas liver-specific Gpx4-null pups on standard chow died within 48 hours after birth.
All-rac-alpha-tocopheryl acetate → Hepatocyte-directed GPX4 loss source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Results/Table 2; standard-chow comparison Table 1
experimental_model
Alb-Cre conditional Gpx4 deletion and maternal diet
exposure
500 IU/kg DL-alpha-tocopheryl acetate during gestation/lactation; weaning at 3 weeks.
limitations
Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Extra dietary vitamin E rescued early survival in mice lacking liver GPX4.
primary_references
[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
tissue_or_cell_type
Hepatocytes and whole-animal survival
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 606–618
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Alb-Cre conditional Gpx4 deletion and maternal diet · source_derived_draft · unverified_draft
### ver-liver-gpx4-e-rescue Maternal dietary supplementation with 500 IU/kg DL-alpha-tocopheryl acetate through gestation and nursing allowed Alb-Cre;Gpx4fl/fl pups to survive to weaning, whereas liver-specific Gpx4-null pups on standard chow died within 48 hours after birth. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra dietary vitamin E rescued early survival in mice lacking liver GPX4. organism: Mus musculus tissue_or_cell_type: Hepatocytes and whole-animal survival experimental_model: Alb-Cre conditional Gpx4 deletion and maternal diet limitations: Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability. exposure: 500 IU/kg DL-alpha-tocopheryl acetate during gestation/lactation; weaning at 3 weeks. cross_nutrient: true evidence_location: Results/Table 2; standard-chow comparison Table 1 [ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
Complete structured claim and evidence
After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal.
Hepatocyte-directed GPX4 loss → Hepatocyte necrosis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Figures 4–5
experimental_model
Diet withdrawal after developmental rescue
exposure
E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks.
limitations
Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
The rescued mice remained dependent on continued vitamin E supply.
primary_references
[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
tissue_or_cell_type
Liver
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 620–632
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diet withdrawal after developmental rescue · source_derived_draft · unverified_draft
### ver-liver-gpx4-e-withdrawal After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rescued mice remained dependent on continued vitamin E supply. organism: Mus musculus tissue_or_cell_type: Liver experimental_model: Diet withdrawal after developmental rescue limitations: Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability. exposure: E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks. cross_nutrient: true evidence_location: Figures 4–5 [ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
Complete structured claim and evidence
Endothelium-specific Gpx4 deletion produced no obvious impairment of vascular homeostasis in mice maintained on a normal diet in the reported study.
Endothelium-directed GPX4 loss → Vascular homeostasis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Endothelial Gpx4 conditional deletion
exposure
Normal diet; no quantitative vitamin E content assigned from abstract.
limitations
Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Loss of endothelial GPX4 alone did not produce an obvious vascular phenotype under the normal-diet conditions tested.
primary_references
[ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
tissue_or_cell_type
Vascular endothelium
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 634–646
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Endothelial Gpx4 conditional deletion · source_derived_draft · unverified_draft
### ver-endo-gpx4-normal-diet Endothelium-specific Gpx4 deletion produced no obvious impairment of vascular homeostasis in mice maintained on a normal diet in the reported study. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of endothelial GPX4 alone did not produce an obvious vascular phenotype under the normal-diet conditions tested. organism: Mus musculus tissue_or_cell_type: Vascular endothelium experimental_model: Endothelial Gpx4 conditional deletion limitations: Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence. exposure: Normal diet; no quantitative vitamin E content assigned from abstract. cross_nutrient: true evidence_location: Primary abstract [ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
Complete structured claim and evidence
Six weeks of vitamin E-depleted diet before inducible endothelial Gpx4 deletion led to endothelial detachment and cell death in multiple mouse organs, accompanied by thrombosis and approximately 80% knockout mortality.
Endothelium-directed GPX4 loss → Endothelial cell death source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Combined dietary depletion and 4-hydroxytamoxifen-induced deletion
exposure
Six-week vitamin E depletion preceding Gpx4 deletion.
limitations
Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted.
primary_references
[ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
tissue_or_cell_type
Multiorgan vascular endothelium
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 648–660
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combined dietary depletion and 4-hydroxytamoxifen-induced deletion · source_derived_draft · unverified_draft
### ver-endo-combined-e-gpx4-loss Six weeks of vitamin E-depleted diet before inducible endothelial Gpx4 deletion led to endothelial detachment and cell death in multiple mouse organs, accompanied by thrombosis and approximately 80% knockout mortality. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted. organism: Mus musculus tissue_or_cell_type: Multiorgan vascular endothelium experimental_model: Combined dietary depletion and 4-hydroxytamoxifen-induced deletion limitations: Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence. exposure: Six-week vitamin E depletion preceding Gpx4 deletion. cross_nutrient: true evidence_location: Primary abstract [ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
Complete structured claim and evidence
Loading C2C12 cells with 200 µM alpha-tocopherol for 18 hours reduced FM1-43 entry after laser injury in calcium-containing buffer, consistent with faster membrane resealing.
All-rac-alpha-tocopherol → Plasma membrane repair source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Figure 1a–b
experimental_model
Laser wounding and time-resolved dye exclusion
exposure
200 µM racemic alpha-tocopherol (96% pure) for 18 h, washed; 1.2 mM extracellular calcium.
limitations
Pharmacologic cell loading; not a dietary intake equivalent.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Vitamin E loading helped cultured muscle-line cells close laser-induced membrane wounds.
primary_references
[ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594
tissue_or_cell_type
C2C12 myoblasts
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 662–674
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Laser wounding and time-resolved dye exclusion · source_derived_draft · unverified_draft
### ver-c2c12-membrane-repair Loading C2C12 cells with 200 µM alpha-tocopherol for 18 hours reduced FM1-43 entry after laser injury in calcium-containing buffer, consistent with faster membrane resealing. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E loading helped cultured muscle-line cells close laser-induced membrane wounds. organism: Mus musculus tissue_or_cell_type: C2C12 myoblasts experimental_model: Laser wounding and time-resolved dye exclusion limitations: Pharmacologic cell loading; not a dietary intake equivalent. exposure: 200 µM racemic alpha-tocopherol (96% pure) for 18 h, washed; 1.2 mM extracellular calcium. cross_nutrient: true evidence_location: Figure 1a–b [ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594
Complete structured claim and evidence
Alpha-tocopherol-loaded HeLa cells still failed to restrict dye entry after laser injury when extracellular calcium was omitted, despite improved repair in calcium-containing buffer.
Calcium ion → Plasma membrane repair source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Figure 1c
experimental_model
Laser wounding with extracellular calcium control
exposure
200 µM racemic alpha-tocopherol (96% pure) for 24 h; with versus without added extracellular calcium.
limitations
Acute assay calcium removal is not dietary calcium deficiency; does not identify the calcium sensor.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Vitamin E loading did not eliminate the need for extracellular calcium during membrane repair.
primary_references
[ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594
tissue_or_cell_type
HeLa cells
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 676–688
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Laser wounding with extracellular calcium control · source_derived_draft · unverified_draft
### ver-repair-extracellular-calcium Alpha-tocopherol-loaded HeLa cells still failed to restrict dye entry after laser injury when extracellular calcium was omitted, despite improved repair in calcium-containing buffer. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E loading did not eliminate the need for extracellular calcium during membrane repair. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: Laser wounding with extracellular calcium control limitations: Acute assay calcium removal is not dietary calcium deficiency; does not identify the calcium sensor. exposure: 200 µM racemic alpha-tocopherol (96% pure) for 24 h; with versus without added extracellular calcium. cross_nutrient: true evidence_location: Figure 1c [ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594
Complete structured claim and evidence
Pretreatment of BS-C-1 cells with 200 µM alpha-tocopherol for 24 hours prevented the membrane-repair defect caused by 1 mM hydrogen peroxide during laser injury.
All-rac-alpha-tocopherol → Plasma membrane repair source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Figure 4a–b
experimental_model
Oxidant challenge during laser-wound assay
exposure
200 µM racemic alpha-tocopherol (96% pure), 24 h; 1 mM H2O2 during injury.
limitations
Oxidant and loading concentrations are experimental; no specific fusion protein target was identified.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
African green monkey-derived cell line
plain_language
Vitamin E loading protected the repair response against this oxidant challenge.
primary_references
[ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594
tissue_or_cell_type
BS-C-1 kidney epithelial cells
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 690–702
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oxidant challenge during laser-wound assay · source_derived_draft · unverified_draft
### ver-oxidant-challenged-repair Pretreatment of BS-C-1 cells with 200 µM alpha-tocopherol for 24 hours prevented the membrane-repair defect caused by 1 mM hydrogen peroxide during laser injury. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E loading protected the repair response against this oxidant challenge. organism: African green monkey-derived cell line tissue_or_cell_type: BS-C-1 kidney epithelial cells experimental_model: Oxidant challenge during laser-wound assay limitations: Oxidant and loading concentrations are experimental; no specific fusion protein target was identified. exposure: 200 µM racemic alpha-tocopherol (96% pure), 24 h; 1 mM H2O2 during injury. cross_nutrient: false evidence_location: Figure 4a–b [ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594
Complete structured claim and evidence
Following 11 months on vitamin E-stripped chow, rat flexor digitorum brevis fibers displayed continued dye influx after controlled laser injury; normal chow and alpha-tocopherol-add-back controls resealed more effectively.
Alpha-tocopherol → Plasma membrane repair source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Methods; Figure 3
experimental_model
Dietary depletion with chow and add-back controls; laser assay
exposure
Male Sprague-Dawley rats started diets at 4 weeks; assay at 11-month diet interval.
limitations
Long-term rat dietary deprivation and controlled wound assays; not evidence that ordinary supplementation improves muscle performance in replete people.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Long-term vitamin E deprivation impaired muscle-fiber wound repair in rats.
primary_references
[ver-labazi2015] The antioxidant requirement for plasma membrane repair in skeletal muscle. (2015). https://pubmed.ncbi.nlm.nih.gov/25843658/ DOI: 10.1016/j.freeradbiomed.2015.03.016
tissue_or_cell_type
Flexor digitorum brevis muscle
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 704–716
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary depletion with chow and add-back controls; laser assay · source_derived_draft · unverified_draft
### ver-diet-e-muscle-repair-failure Following 11 months on vitamin E-stripped chow, rat flexor digitorum brevis fibers displayed continued dye influx after controlled laser injury; normal chow and alpha-tocopherol-add-back controls resealed more effectively. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Long-term vitamin E deprivation impaired muscle-fiber wound repair in rats. organism: Rattus norvegicus tissue_or_cell_type: Flexor digitorum brevis muscle experimental_model: Dietary depletion with chow and add-back controls; laser assay limitations: Long-term rat dietary deprivation and controlled wound assays; not evidence that ordinary supplementation improves muscle performance in replete people. exposure: Male Sprague-Dawley rats started diets at 4 weeks; assay at 11-month diet interval. cross_nutrient: false evidence_location: Methods; Figure 3 [ver-labazi2015] The antioxidant requirement for plasma membrane repair in skeletal muscle. (2015). https://pubmed.ncbi.nlm.nih.gov/25843658/ DOI: 10.1016/j.freeradbiomed.2015.03.016
Complete structured claim and evidence
In mouse embryonic fibroblasts subjected to 48-hour inducible Gpx4 deletion, 200 µM alpha-tocopherol supplementation for the preceding 24 hours prevented the pronounced laser-wound repair defect.
Alpha-tocopherol → Plasma membrane repair source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Figure 4d; Methods
experimental_model
Tamoxifen-inducible Gpx4 deletion with re-expression controls
exposure
1 µM tamoxifen for 48 h; 200 µM alpha-tocopherol for 24 h before repair assay.
limitations
Genetic GPX4 loss, not nutritional selenium deficiency; repair mechanism downstream of oxidation was not resolved.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Vitamin E loading rescued membrane resealing after GPX4 deletion in these fibroblasts.
primary_references
[ver-labazi2015] The antioxidant requirement for plasma membrane repair in skeletal muscle. (2015). https://pubmed.ncbi.nlm.nih.gov/25843658/ DOI: 10.1016/j.freeradbiomed.2015.03.016
tissue_or_cell_type
Embryonic fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 718–730
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tamoxifen-inducible Gpx4 deletion with re-expression controls · source_derived_draft · unverified_draft
### ver-gpx4-fibroblast-repair-rescue In mouse embryonic fibroblasts subjected to 48-hour inducible Gpx4 deletion, 200 µM alpha-tocopherol supplementation for the preceding 24 hours prevented the pronounced laser-wound repair defect. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E loading rescued membrane resealing after GPX4 deletion in these fibroblasts. organism: Mus musculus tissue_or_cell_type: Embryonic fibroblasts experimental_model: Tamoxifen-inducible Gpx4 deletion with re-expression controls limitations: Genetic GPX4 loss, not nutritional selenium deficiency; repair mechanism downstream of oxidation was not resolved. exposure: 1 µM tamoxifen for 48 h; 200 µM alpha-tocopherol for 24 h before repair assay. cross_nutrient: true evidence_location: Figure 4d; Methods [ver-labazi2015] The antioxidant requirement for plasma membrane repair in skeletal muscle. (2015). https://pubmed.ncbi.nlm.nih.gov/25843658/ DOI: 10.1016/j.freeradbiomed.2015.03.016
Complete structured claim and evidence
After nine months on a diet without added vitamin E, zebrafish brain PC(16:0/22:6) was about one-third lower than in fish receiving 500 mg RRR-alpha-tocopheryl acetate/kg diet (4.3 versus 6.5 mg/g).
Alpha-tocopherol → PC(16:0/22:6) source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Defined-diet comparison and brain lipidomics
exposure
9 months; no added E versus 500 mg RRR-alpha-tocopheryl acetate/kg.
limitations
Adult zebrafish dietary comparison; lipid abundance and oxidation product measurements do not by themselves prove causal remodeling flux or human neuroprotection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Danio rerio
plain_language
Vitamin E depletion was associated with loss of a DHA-containing membrane lipid.
primary_references
[ver-choi2015] Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. (2015). https://pubmed.ncbi.nlm.nih.gov/25855633/ DOI: 10.1194/jlr.m058941
tissue_or_cell_type
Adult brain
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 732–744
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Defined-diet comparison and brain lipidomics · source_derived_draft · unverified_draft
### ver-dha-pc-depletion After nine months on a diet without added vitamin E, zebrafish brain PC(16:0/22:6) was about one-third lower than in fish receiving 500 mg RRR-alpha-tocopheryl acetate/kg diet (4.3 versus 6.5 mg/g). Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E depletion was associated with loss of a DHA-containing membrane lipid. organism: Danio rerio tissue_or_cell_type: Adult brain experimental_model: Defined-diet comparison and brain lipidomics limitations: Adult zebrafish dietary comparison; lipid abundance and oxidation product measurements do not by themselves prove causal remodeling flux or human neuroprotection. exposure: 9 months; no added E versus 500 mg RRR-alpha-tocopheryl acetate/kg. cross_nutrient: true evidence_location: Primary abstract [ver-choi2015] Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. (2015). https://pubmed.ncbi.nlm.nih.gov/25855633/ DOI: 10.1194/jlr.m058941
Complete structured claim and evidence
Vitamin E-depleted zebrafish brains contained more hydroxy-DHA-PC 38:6 than supplemented-diet controls, consistent with increased oxidation of DHA-containing phosphatidylcholine.
Alpha-tocopherol → Hydroxy-DHA-PC 38:6 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Defined-diet comparison and brain lipidomics
exposure
9 months; no added E versus 500 mg RRR-alpha-tocopheryl acetate/kg.
limitations
Adult zebrafish dietary comparison; lipid abundance and oxidation product measurements do not by themselves prove causal remodeling flux or human neuroprotection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Danio rerio
plain_language
An oxidized DHA-containing lipid accumulated in the vitamin E-depleted brains.
primary_references
[ver-choi2015] Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. (2015). https://pubmed.ncbi.nlm.nih.gov/25855633/ DOI: 10.1194/jlr.m058941
tissue_or_cell_type
Adult brain
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 746–758
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Defined-diet comparison and brain lipidomics · source_derived_draft · unverified_draft
### ver-dha-pc-oxidation Vitamin E-depleted zebrafish brains contained more hydroxy-DHA-PC 38:6 than supplemented-diet controls, consistent with increased oxidation of DHA-containing phosphatidylcholine. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: An oxidized DHA-containing lipid accumulated in the vitamin E-depleted brains. organism: Danio rerio tissue_or_cell_type: Adult brain experimental_model: Defined-diet comparison and brain lipidomics limitations: Adult zebrafish dietary comparison; lipid abundance and oxidation product measurements do not by themselves prove causal remodeling flux or human neuroprotection. exposure: 9 months; no added E versus 500 mg RRR-alpha-tocopheryl acetate/kg. cross_nutrient: true evidence_location: Primary abstract [ver-choi2015] Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. (2015). https://pubmed.ncbi.nlm.nih.gov/25855633/ DOI: 10.1194/jlr.m058941
Complete structured claim and evidence
Embryos from vitamin E-depleted zebrafish parents incorporated more water-18O label into LPC 22:6 and three DHA-containing phosphatidylcholines during 48–72 hours post-fertilization than vitamin E-sufficient controls, supporting increased acyl turnover.
Alpha-tocopherol → DHA phospholipid remodeling source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Figure 7; isotope-labeling Methods
experimental_model
Parental diet manipulation and stable-isotope lipidomics
exposure
Parents fed no added E or 500 mg RRR-alpha-tocopheryl acetate/kg for ≥80 days; embryos incubated in 40% H2(18)O from 48 to 72 hpf.
limitations
Embryos rely on maternally deposited nutrients; whole-embryo tracing does not directly measure brain delivery or prove a particular repair enzyme.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Danio rerio
plain_language
Labeled-water tracing showed faster turnover of selected DHA lipids during vitamin E depletion.
primary_references
[ver-mcdougall2016] Lipidomics and H2(18)O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos. (2016). https://pubmed.ncbi.nlm.nih.gov/26774753/ DOI: 10.1016/j.redox.2016.01.004
tissue_or_cell_type
Whole embryos
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 760–772
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Parental diet manipulation and stable-isotope lipidomics · source_derived_draft · unverified_draft
### ver-dha-remodeling-flux Embryos from vitamin E-depleted zebrafish parents incorporated more water-18O label into LPC 22:6 and three DHA-containing phosphatidylcholines during 48–72 hours post-fertilization than vitamin E-sufficient controls, supporting increased acyl turnover. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Labeled-water tracing showed faster turnover of selected DHA lipids during vitamin E depletion. organism: Danio rerio tissue_or_cell_type: Whole embryos experimental_model: Parental diet manipulation and stable-isotope lipidomics limitations: Embryos rely on maternally deposited nutrients; whole-embryo tracing does not directly measure brain delivery or prove a particular repair enzyme. exposure: Parents fed no added E or 500 mg RRR-alpha-tocopheryl acetate/kg for ≥80 days; embryos incubated in 40% H2(18)O from 48 to 72 hpf. cross_nutrient: true evidence_location: Figure 7; isotope-labeling Methods [ver-mcdougall2016] Lipidomics and H2(18)O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos. (2016). https://pubmed.ncbi.nlm.nih.gov/26774753/ DOI: 10.1016/j.redox.2016.01.004
Complete structured claim and evidence
In Pfa1 mouse fibroblasts with inducible Gpx4 deletion, alpha-tocotrienol preserved viability at an EC50 of 0.12 µM compared with 2.0 µM for alpha-tocopherol over 72 hours.
Alpha-tocotrienol → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Figure 3
experimental_model
Inducible Gpx4 deletion and resazurin viability assay
exposure
1 µM 4-hydroxytamoxifen for 72 h; tocotrienol 0–10 µM and tocopherol 0–100 µM.
limitations
Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Alpha-tocotrienol was more potent than alpha-tocopherol in this GPX4-deletion cell-rescue assay.
primary_references
[ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1
tissue_or_cell_type
Pfa1 embryonic fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 774–786
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Gpx4 deletion and resazurin viability assay · source_derived_draft · unverified_draft
### ver-alpha-t3-gpx4-rescue-potency In Pfa1 mouse fibroblasts with inducible Gpx4 deletion, alpha-tocotrienol preserved viability at an EC50 of 0.12 µM compared with 2.0 µM for alpha-tocopherol over 72 hours. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Alpha-tocotrienol was more potent than alpha-tocopherol in this GPX4-deletion cell-rescue assay. organism: Mus musculus tissue_or_cell_type: Pfa1 embryonic fibroblasts experimental_model: Inducible Gpx4 deletion and resazurin viability assay limitations: Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols. exposure: 1 µM 4-hydroxytamoxifen for 72 h; tocotrienol 0–10 µM and tocopherol 0–100 µM. cross_nutrient: true evidence_location: Figure 3 [ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1
Complete structured claim and evidence
Alpha-tocotrienol suppressed AAPH-initiated liposomal oxidation more strongly than alpha-tocopherol in the study’s FENIX assay, which tracked competitive oxidation of a fluorescent reporter.
Alpha-tocotrienol → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Figure 4A; FENIX Methods
experimental_model
Cell-free fluorescence-enabled inhibited autoxidation
exposure
Vitamin E forms tested at 1, 10 and 100 µM; 1 mM lipid, 1 mM AAPH, 37 °C.
limitations
Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols. Fluorescent reporter kinetics are not a universal radical-trapping rate constant.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free
plain_language
The two alpha forms differed in protection of artificial lipid membranes.
primary_references
[ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1
tissue_or_cell_type
Phosphatidylcholine liposomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 788–800
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free fluorescence-enabled inhibited autoxidation · source_derived_draft · unverified_draft
### ver-alpha-t3-liposomal-oxidation Alpha-tocotrienol suppressed AAPH-initiated liposomal oxidation more strongly than alpha-tocopherol in the study’s FENIX assay, which tracked competitive oxidation of a fluorescent reporter. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two alpha forms differed in protection of artificial lipid membranes. organism: Cell-free tissue_or_cell_type: Phosphatidylcholine liposomes experimental_model: Cell-free fluorescence-enabled inhibited autoxidation limitations: Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols. Fluorescent reporter kinetics are not a universal radical-trapping rate constant. exposure: Vitamin E forms tested at 1, 10 and 100 µM; 1 mM lipid, 1 mM AAPH, 37 °C. cross_nutrient: false evidence_location: Figure 4A; FENIX Methods [ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1
Complete structured claim and evidence
In HT-1080 cells challenged with the GPX4 inhibitor RSL3, alpha-tocotrienol suppressed the oxidized C11-BODIPY signal at lower tested concentrations than alpha-tocopherol.
Alpha-tocotrienol → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Figure 4B
experimental_model
RSL3 challenge and flow-cytometric C11-BODIPY assay
exposure
E forms at 1 and 30 µM for 1 h before 0.5 µM RSL3 for 2 h.
limitations
Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols. Probe oxidation is not a chemically resolved inventory of endogenous phospholipid products.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Alpha-tocotrienol more effectively limited the lipid-oxidation reporter in this cancer-cell assay.
primary_references
[ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1
tissue_or_cell_type
HT-1080 fibrosarcoma cells
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 802–814
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RSL3 challenge and flow-cytometric C11-BODIPY assay · source_derived_draft · unverified_draft
### ver-alpha-t3-cellular-oxidation In HT-1080 cells challenged with the GPX4 inhibitor RSL3, alpha-tocotrienol suppressed the oxidized C11-BODIPY signal at lower tested concentrations than alpha-tocopherol. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Alpha-tocotrienol more effectively limited the lipid-oxidation reporter in this cancer-cell assay. organism: Homo sapiens tissue_or_cell_type: HT-1080 fibrosarcoma cells experimental_model: RSL3 challenge and flow-cytometric C11-BODIPY assay limitations: Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols. Probe oxidation is not a chemically resolved inventory of endogenous phospholipid products. exposure: E forms at 1 and 30 µM for 1 h before 0.5 µM RSL3 for 2 h. cross_nutrient: true evidence_location: Figure 4B [ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1
Complete structured claim and evidence
SIN-1 exposure converted gamma-tocopherol to 5-nitro-gamma-tocopherol in soybean phosphatidylcholine liposomes and isolated human LDL. Product yields were approximately 50% and 75%, respectively; alpha-tocopherol did not prevent gamma nitration.
Gamma-tocopherol → 5-Nitro-gamma-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
HPLC analysis of tocopherols and nitration products
exposure
Liposomes: 20 mM phosphatidylcholine, 20 µM tocopherol and 1 mM SIN-1 at 37°C. LDL: 0.2 mM SIN-1; Figure 3 initial gamma-tocopherol 0.98 µM.
limitations
This identifies a stable nitration product, not every reactive intermediate or clinical anti-inflammatory efficacy. Liposome-versus-LDL antioxidant rankings differed.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free and Homo sapiens-derived LDL
plain_language
Gamma-tocopherol captured nitrating chemistry as a measurable nitrogen-containing product in artificial membranes and isolated blood lipoproteins.
primary_references
[christen1997] gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. (1997). https://pubmed.ncbi.nlm.nih.gov/9096373/ DOI: 10.1073/pnas.94.7.3217
tissue_or_cell_type
Soybean phosphatidylcholine liposomes; isolated plasma LDL
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 816–827
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HPLC analysis of tocopherols and nitration products · source_derived_draft · unverified_draft
### e-sig-gamma-nitro-product SIN-1 exposure converted gamma-tocopherol to 5-nitro-gamma-tocopherol in soybean phosphatidylcholine liposomes and isolated human LDL. Product yields were approximately 50% and 75%, respectively; alpha-tocopherol did not prevent gamma nitration. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gamma-tocopherol captured nitrating chemistry as a measurable nitrogen-containing product in artificial membranes and isolated blood lipoproteins. organism: Cell-free and Homo sapiens-derived LDL tissue_or_cell_type: Soybean phosphatidylcholine liposomes; isolated plasma LDL experimental_model: HPLC analysis of tocopherols and nitration products limitations: This identifies a stable nitration product, not every reactive intermediate or clinical anti-inflammatory efficacy. Liposome-versus-LDL antioxidant rankings differed. exposure: Liposomes: 20 mM phosphatidylcholine, 20 µM tocopherol and 1 mM SIN-1 at 37°C. LDL: 0.2 mM SIN-1; Figure 3 initial gamma-tocopherol 0.98 µM. cross_nutrient: false [christen1997] gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. (1997). https://pubmed.ncbi.nlm.nih.gov/9096373/ DOI: 10.1073/pnas.94.7.3217
Complete structured claim and evidence
Gamma-tocopherol reduced LPS-stimulated PGE2 in mouse RAW264.7 macrophages with an apparent IC50 of 7.5 µM. COX-2 protein expression was not reduced in the tested 10 and 40 µM groups.
Gamma-tocopherol → Prostaglandin E2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Stimulated RAW264.7 culture; PGE2 assay and immunoblot
exposure
8–14 h tocopherol pretreatment in 0.5% FBS-DMEM, then 0.1 µg/mL LPS for 14 h.
limitations
A cellular product endpoint does not establish direct parent-vitamin binding to COX-2, exclude metabolism, or predict human supplement benefit.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Gamma-tocopherol lowered this inflammatory lipid signal in cultured mouse immune cells without reducing the measured amount of COX-2 protein.
primary_references
[jiang2000] gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. (2000). https://pubmed.ncbi.nlm.nih.gov/11005841/ DOI: 10.1073/pnas.200357097
tissue_or_cell_type
Macrophage cell line
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 829–840
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stimulated RAW264.7 culture; PGE2 assay and immunoblot · source_derived_draft · unverified_draft
### e-sig-gamma-macrophage-pge2 Gamma-tocopherol reduced LPS-stimulated PGE2 in mouse RAW264.7 macrophages with an apparent IC50 of 7.5 µM. COX-2 protein expression was not reduced in the tested 10 and 40 µM groups. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gamma-tocopherol lowered this inflammatory lipid signal in cultured mouse immune cells without reducing the measured amount of COX-2 protein. organism: Mus musculus tissue_or_cell_type: Macrophage cell line experimental_model: Stimulated RAW264.7 culture; PGE2 assay and immunoblot limitations: A cellular product endpoint does not establish direct parent-vitamin binding to COX-2, exclude metabolism, or predict human supplement benefit. exposure: 8–14 h tocopherol pretreatment in 0.5% FBS-DMEM, then 0.1 µg/mL LPS for 14 h. cross_nutrient: false [jiang2000] gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. (2000). https://pubmed.ncbi.nlm.nih.gov/11005841/ DOI: 10.1073/pnas.200357097
Complete structured claim and evidence
Gamma-CEHC suppressed cytokine-stimulated PGE2 in A549 cells, with an apparent IC50 near 30 µM. It also inhibited PGE2 after only 1 h exposure of COX-2-preinduced cells before arachidonic acid addition.
Gamma-carboxyethyl hydroxychromanol → Prostaglandin E2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
A549 culture and preinduced cellular COX assay
exposure
IL-1β 10 ng/mL for 24 h; postinduction gamma-CEHC 1 h, then 5 or 15 µM arachidonic acid for 10 min at 37°C.
limitations
Cancer-derived culture, not treatment evidence. Intact-cell IC50 and purified COX inhibition are distinct measurements; increasing substrate weakened inhibition.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
A breakdown product of gamma-tocopherol reduced prostaglandin production in a human lung cell model, including after brief exposure.
primary_references
[jiang2000] gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. (2000). https://pubmed.ncbi.nlm.nih.gov/11005841/ DOI: 10.1073/pnas.200357097
tissue_or_cell_type
Lung epithelial carcinoma cell line
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 842–853
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · A549 culture and preinduced cellular COX assay · source_derived_draft · unverified_draft
### e-sig-cehc-a549-pge2 Gamma-CEHC suppressed cytokine-stimulated PGE2 in A549 cells, with an apparent IC50 near 30 µM. It also inhibited PGE2 after only 1 h exposure of COX-2-preinduced cells before arachidonic acid addition. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A breakdown product of gamma-tocopherol reduced prostaglandin production in a human lung cell model, including after brief exposure. organism: Homo sapiens tissue_or_cell_type: Lung epithelial carcinoma cell line experimental_model: A549 culture and preinduced cellular COX assay limitations: Cancer-derived culture, not treatment evidence. Intact-cell IC50 and purified COX inhibition are distinct measurements; increasing substrate weakened inhibition. exposure: IL-1β 10 ng/mL for 24 h; postinduction gamma-CEHC 1 h, then 5 or 15 µM arachidonic acid for 10 min at 37°C. cross_nutrient: false [jiang2000] gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. (2000). https://pubmed.ncbi.nlm.nih.gov/11005841/ DOI: 10.1073/pnas.200357097
Complete structured claim and evidence
Delta-tocopherol-13′-carboxychromanol competitively inhibited purified ovine COX-1 cyclooxygenase activity with a reported Ki of 3.9 µM, measured by initial oxygen consumption while varying arachidonic acid.
Delta-tocopherol-13′-carboxychromanol → Ovine cyclooxygenase-1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified-enzyme oxygen-electrode kinetics
exposure
13′-COOH 0, 7.5, 15 or 25 µM; arachidonic acid 6–200 µM in Tris pH 8 with 1 µM hematin, phenol and EDTA.
limitations
Purified enzyme kinetics do not establish human anti-inflammatory benefit. Cyclooxygenase and peroxidase activities must not be conflated.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Ovis aries
plain_language
The long-chain delta-tocopherol metabolite interfered with this purified enzyme’s use of arachidonic acid.
primary_references
[jiang2008] Long-chain carboxychromanols, metabolites of vitamin E, are potent inhibitors of cyclooxygenases. (2008). https://pubmed.ncbi.nlm.nih.gov/19074288/ DOI: 10.1073/pnas.0810962106
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 855–866
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme oxygen-electrode kinetics · source_derived_draft · unverified_draft
### e-sig-delta-acid-cox1 Delta-tocopherol-13′-carboxychromanol competitively inhibited purified ovine COX-1 cyclooxygenase activity with a reported Ki of 3.9 µM, measured by initial oxygen consumption while varying arachidonic acid. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The long-chain delta-tocopherol metabolite interfered with this purified enzyme’s use of arachidonic acid. organism: Ovis aries tissue_or_cell_type: Cell-free enzyme experimental_model: Purified-enzyme oxygen-electrode kinetics limitations: Purified enzyme kinetics do not establish human anti-inflammatory benefit. Cyclooxygenase and peroxidase activities must not be conflated. exposure: 13′-COOH 0, 7.5, 15 or 25 µM; arachidonic acid 6–200 µM in Tris pH 8 with 1 µM hematin, phenol and EDTA. cross_nutrient: false [jiang2008] Long-chain carboxychromanols, metabolites of vitamin E, are potent inhibitors of cyclooxygenases. (2008). https://pubmed.ncbi.nlm.nih.gov/19074288/ DOI: 10.1073/pnas.0810962106
Complete structured claim and evidence
Delta-tocopherol-13′-carboxychromanol competitively inhibited purified human COX-2 cyclooxygenase activity with a reported Ki of 10.7 µM, measured by initial oxygen consumption while varying arachidonic acid.
Delta-tocopherol-13′-carboxychromanol → Cyclooxygenase-2 (PTGS2) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified-enzyme oxygen-electrode kinetics
exposure
13′-COOH 0, 7.5, 15 or 25 µM; arachidonic acid 6–200 µM in Tris pH 8 with 1 µM hematin, phenol and EDTA.
limitations
Purified enzyme kinetics do not establish human anti-inflammatory benefit. Cyclooxygenase and peroxidase activities must not be conflated.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The long-chain delta-tocopherol metabolite interfered with this purified enzyme’s use of arachidonic acid.
primary_references
[jiang2008] Long-chain carboxychromanols, metabolites of vitamin E, are potent inhibitors of cyclooxygenases. (2008). https://pubmed.ncbi.nlm.nih.gov/19074288/ DOI: 10.1073/pnas.0810962106
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 868–879
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme oxygen-electrode kinetics · source_derived_draft · unverified_draft
### e-sig-delta-acid-cox2 Delta-tocopherol-13′-carboxychromanol competitively inhibited purified human COX-2 cyclooxygenase activity with a reported Ki of 10.7 µM, measured by initial oxygen consumption while varying arachidonic acid. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The long-chain delta-tocopherol metabolite interfered with this purified enzyme’s use of arachidonic acid. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Purified-enzyme oxygen-electrode kinetics limitations: Purified enzyme kinetics do not establish human anti-inflammatory benefit. Cyclooxygenase and peroxidase activities must not be conflated. exposure: 13′-COOH 0, 7.5, 15 or 25 µM; arachidonic acid 6–200 µM in Tris pH 8 with 1 µM hematin, phenol and EDTA. cross_nutrient: false [jiang2008] Long-chain carboxychromanols, metabolites of vitamin E, are potent inhibitors of cyclooxygenases. (2008). https://pubmed.ncbi.nlm.nih.gov/19074288/ DOI: 10.1073/pnas.0810962106
Complete structured claim and evidence
Delta-tocopherol at 50 µM inhibited LTB4 production stimulated by S1P or LPA in differentiated HL-60 cells, but did not inhibit the response to fMLP under the tested conditions.
Delta-tocopherol → Leukotriene B4 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
DMSO-differentiated human HL-60 neutrophil-like cells
exposure
10 min pretreatment; S1P 50 µM, LPA 100 µM or fMLP 1 µM for 10 min.
limitations
Stimulus specificity precludes a universal anti-inflammatory claim. High-dose lipid stimuli and transformed cells limit extrapolation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Delta-tocopherol reduced leukotriene output only for some ways of activating these cells.
primary_references
[jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
tissue_or_cell_type
Neutrophil-like leukemia-derived cell culture
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 881–892
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DMSO-differentiated human HL-60 neutrophil-like cells · source_derived_draft · unverified_draft
### e-sig-delta-ltb4-stimulus Delta-tocopherol at 50 µM inhibited LTB4 production stimulated by S1P or LPA in differentiated HL-60 cells, but did not inhibit the response to fMLP under the tested conditions. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delta-tocopherol reduced leukotriene output only for some ways of activating these cells. organism: Homo sapiens tissue_or_cell_type: Neutrophil-like leukemia-derived cell culture experimental_model: DMSO-differentiated human HL-60 neutrophil-like cells limitations: Stimulus specificity precludes a universal anti-inflammatory claim. High-dose lipid stimuli and transformed cells limit extrapolation. exposure: 10 min pretreatment; S1P 50 µM, LPA 100 µM or fMLP 1 µM for 10 min. cross_nutrient: false [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
Complete structured claim and evidence
Delta-tocopherol at 50 µM diminished A23187-triggered extracellular calcium entry in differentiated HL-60 cells, monitored with fluo-4 after calcium was added to calcium-free buffer.
Delta-tocopherol → Stimulus-induced calcium influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
DMSO-differentiated human HL-60 neutrophil-like cells; fluo-4 fluorescence
exposure
2 µM fluo-4 AM loading; 50 µM delta-tocopherol for 10 min; A23187 0.5 µM before extracellular calcium addition.
limitations
Methods and figure caption disagree on added calcium units (mM versus µM). No specific calcium channel was identified; membrane stabilization remains a proposed explanation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Delta-tocopherol reduced calcium entry caused by an experimental ion carrier in this cell model.
primary_references
[jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
tissue_or_cell_type
Neutrophil-like leukemia-derived cell culture
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 894–905
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DMSO-differentiated human HL-60 neutrophil-like cells; fluo-4 fluorescence · source_derived_draft · unverified_draft
### e-sig-delta-calcium-influx Delta-tocopherol at 50 µM diminished A23187-triggered extracellular calcium entry in differentiated HL-60 cells, monitored with fluo-4 after calcium was added to calcium-free buffer. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delta-tocopherol reduced calcium entry caused by an experimental ion carrier in this cell model. organism: Homo sapiens tissue_or_cell_type: Neutrophil-like leukemia-derived cell culture experimental_model: DMSO-differentiated human HL-60 neutrophil-like cells; fluo-4 fluorescence limitations: Methods and figure caption disagree on added calcium units (mM versus µM). No specific calcium channel was identified; membrane stabilization remains a proposed explanation. exposure: 2 µM fluo-4 AM loading; 50 µM delta-tocopherol for 10 min; A23187 0.5 µM before extracellular calcium addition. cross_nutrient: true [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
Complete structured claim and evidence
Delta-tocopherol pretreatment largely prevented A23187-induced redistribution of 5-LOX from cytosolic to nuclear fractions in differentiated HL-60 cells.
Delta-tocopherol → 5-Lipoxygenase nuclear translocation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
DMSO-differentiated human HL-60 neutrophil-like cells; fractionation and immunoblot
exposure
50 µM delta-tocopherol for 10 min followed by 2.5 µM A23187 for 15 min.
limitations
Fractionation is a localization assay, not proof of direct enzyme inhibition; purified 5-LOX was unaffected by tocopherols at 50 µM in this paper.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Delta-tocopherol kept much of the enzyme from moving to the cell location associated with leukotriene production.
primary_references
[jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
tissue_or_cell_type
Neutrophil-like leukemia-derived cell culture
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 907–918
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DMSO-differentiated human HL-60 neutrophil-like cells; fractionation and immunoblot · source_derived_draft · unverified_draft
### e-sig-delta-lox-translocation Delta-tocopherol pretreatment largely prevented A23187-induced redistribution of 5-LOX from cytosolic to nuclear fractions in differentiated HL-60 cells. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delta-tocopherol kept much of the enzyme from moving to the cell location associated with leukotriene production. organism: Homo sapiens tissue_or_cell_type: Neutrophil-like leukemia-derived cell culture experimental_model: DMSO-differentiated human HL-60 neutrophil-like cells; fractionation and immunoblot limitations: Fractionation is a localization assay, not proof of direct enzyme inhibition; purified 5-LOX was unaffected by tocopherols at 50 µM in this paper. exposure: 50 µM delta-tocopherol for 10 min followed by 2.5 µM A23187 for 15 min. cross_nutrient: false [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
Complete structured claim and evidence
Delta-tocopherol-13′-carboxychromanol inhibited human recombinant 5-LOX with IC50 0.5–1 µM in a hydroperoxide-sensitive FOX assay; parent alpha-, gamma- and delta-tocopherols did not inhibit at 50 µM.
Delta-tocopherol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human recombinant 5-LOX and FOX endpoint
exposure
4 min preincubation; arachidonic acid 75 µM; FOX absorbance at 560 and 575 nm.
limitations
FOX reports oxidation products, not binding-site structure. Potency depends on assay conditions; later papers use other assays.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The long-chain metabolite inhibited the isolated leukotriene-producing enzyme much more strongly than the parent tocopherols in this assay.
primary_references
[jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 920–931
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX and FOX endpoint · source_derived_draft · unverified_draft
### e-sig-delta-acid-lox Delta-tocopherol-13′-carboxychromanol inhibited human recombinant 5-LOX with IC50 0.5–1 µM in a hydroperoxide-sensitive FOX assay; parent alpha-, gamma- and delta-tocopherols did not inhibit at 50 µM. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The long-chain metabolite inhibited the isolated leukotriene-producing enzyme much more strongly than the parent tocopherols in this assay. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX and FOX endpoint limitations: FOX reports oxidation products, not binding-site structure. Potency depends on assay conditions; later papers use other assays. exposure: 4 min preincubation; arachidonic acid 75 µM; FOX absorbance at 560 and 575 nm. cross_nutrient: false [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
Complete structured claim and evidence
RRR-alpha-tocopherol at 0.1–10 µM inhibited cofactor-dependent recombinant human PKC alpha activity in phosphatidylserine-containing assays.
RRR-alpha-tocopherol → Protein kinase C alpha (PRKCA) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant HIS-tagged human PKC alpha biochemical assay
exposure
15 ng PKC alpha; 2 mM CaCl2; phosphatidylserine 15–60 µg/mL; 5 min pretreatment, 30 min kinase assay.
limitations
Effect depends on reconstituted lipid composition and activation mode; it is not a clinical dosing claim.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Natural alpha-tocopherol reduced PKC alpha activity in a purified system containing its lipid and calcium cofactors.
primary_references
[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 933–944
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant HIS-tagged human PKC alpha biochemical assay · source_derived_draft · unverified_draft
### e-sig-alpha-pkc-cofactor RRR-alpha-tocopherol at 0.1–10 µM inhibited cofactor-dependent recombinant human PKC alpha activity in phosphatidylserine-containing assays. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Natural alpha-tocopherol reduced PKC alpha activity in a purified system containing its lipid and calcium cofactors. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Recombinant HIS-tagged human PKC alpha biochemical assay limitations: Effect depends on reconstituted lipid composition and activation mode; it is not a clinical dosing claim. exposure: 15 ng PKC alpha; 2 mM CaCl2; phosphatidylserine 15–60 µg/mL; 5 min pretreatment, 30 min kinase assay. cross_nutrient: true [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
Complete structured claim and evidence
RRR-gamma-tocopherol at 1 µM increased recombinant human PKC alpha activity with 15–30 µg/mL phosphatidylserine and calcium; it did not increase the low activity in the absence of phosphatidylserine.
RRR-gamma-tocopherol → Protein kinase C alpha (PRKCA) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant HIS-tagged human PKC alpha biochemical assay
exposure
1 µM gamma-tocopherol; 2 mM CaCl2; 15–30 µg/mL phosphatidylserine; 5 min pretreatment, 30 min kinase assay.
limitations
Small biochemical activation is not equivalent to uniformly increased inflammation in people; oxidative activation shows a different response.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Natural gamma-tocopherol increased this kinase’s activity only when the required lipid cofactor was present.
primary_references
[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 946–957
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant HIS-tagged human PKC alpha biochemical assay · source_derived_draft · unverified_draft
### e-sig-gamma-pkc-cofactor RRR-gamma-tocopherol at 1 µM increased recombinant human PKC alpha activity with 15–30 µg/mL phosphatidylserine and calcium; it did not increase the low activity in the absence of phosphatidylserine. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Natural gamma-tocopherol increased this kinase’s activity only when the required lipid cofactor was present. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Recombinant HIS-tagged human PKC alpha biochemical assay limitations: Small biochemical activation is not equivalent to uniformly increased inflammation in people; oxidative activation shows a different response. exposure: 1 µM gamma-tocopherol; 2 mM CaCl2; 15–30 µg/mL phosphatidylserine; 5 min pretreatment, 30 min kinase assay. cross_nutrient: true [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
Complete structured claim and evidence
RRR-alpha-tocopherol at 0.01 µM inhibited peroxide/iron-induced activation of recombinant PKC alpha; gamma-tocopherol required 0.1 µM for significant inhibition in the same assay.
RRR-alpha-tocopherol → Protein kinase C alpha (PRKCA) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant HIS-tagged human PKC alpha biochemical assay with iron and peroxide
exposure
15 ng dialyzed PKC alpha; 45 µM FeCl2; 1 or 10 mM H2O2 activation for 2 min, stopped with 9 mM DTT; no PS or calcium cofactors.
limitations
Millimolar peroxide in a cell-free reaction is not normal intracellular exposure. This is distinct from cofactor-dependent gamma activation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Both natural tocopherols reduced oxidative activation of this kinase, with alpha active at a lower tested concentration.
primary_references
[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 959–970
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant HIS-tagged human PKC alpha biochemical assay with iron and peroxide · source_derived_draft · unverified_draft
### e-sig-alpha-pkc-oxidative RRR-alpha-tocopherol at 0.01 µM inhibited peroxide/iron-induced activation of recombinant PKC alpha; gamma-tocopherol required 0.1 µM for significant inhibition in the same assay. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both natural tocopherols reduced oxidative activation of this kinase, with alpha active at a lower tested concentration. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Recombinant HIS-tagged human PKC alpha biochemical assay with iron and peroxide limitations: Millimolar peroxide in a cell-free reaction is not normal intracellular exposure. This is distinct from cofactor-dependent gamma activation. exposure: 15 ng dialyzed PKC alpha; 45 µM FeCl2; 1 or 10 mM H2O2 activation for 2 min, stopped with 9 mM DTT; no PS or calcium cofactors. cross_nutrient: true [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
Complete structured claim and evidence
NBD-alpha-tocopherol bound recombinant human PKC alpha in solution: fluorescence increased at 1 µM probe, and 5 µM was used in competition assays with 0.1 µM enzyme.
NBD-alpha-tocopherol → Protein kinase C alpha (PRKCA) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Fluorescence ligand binding in solution
exposure
0.1 µM PKC alpha; 1–5 µM NBD-alpha-tocopherol; 30 min at room temperature; 1% ethanol buffer.
limitations
The fluorophore reports a hydrophobic environment. Competition controls support specific binding, but the labeled probe is distinct from native tocopherol.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
A fluorescently tagged vitamin E probe associated directly with purified PKC alpha.
primary_references
[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 972–983
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fluorescence ligand binding in solution · source_derived_draft · unverified_draft
### e-sig-nbd-pkc-binding NBD-alpha-tocopherol bound recombinant human PKC alpha in solution: fluorescence increased at 1 µM probe, and 5 µM was used in competition assays with 0.1 µM enzyme. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A fluorescently tagged vitamin E probe associated directly with purified PKC alpha. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Fluorescence ligand binding in solution limitations: The fluorophore reports a hydrophobic environment. Competition controls support specific binding, but the labeled probe is distinct from native tocopherol. exposure: 0.1 µM PKC alpha; 1–5 µM NBD-alpha-tocopherol; 30 min at room temperature; 1% ethanol buffer. cross_nutrient: false [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
Complete structured claim and evidence
Retinol competed with 5 µM NBD-alpha-tocopherol for binding to 0.1 µM recombinant PKC alpha, whereas phosphatidylserine and cholesterol did not compete in the same study.
All-trans-retinol → NBD-alpha-tocopherol binding to PKC alpha source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Fluorescence competition assay, Figure 6G
exposure
5 µM NBD-alpha-tocopherol; 0.1 µM PKC alpha; retinol concentration series; 30 min at room temperature, 1% ethanol.
limitations
Exact retinol axis values were not extracted; this is direct in-vitro competition, not demonstrated competition between dietary vitamins in human tissues.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Vitamin A alcohol competed with the labeled vitamin E probe for association with this purified kinase.
primary_references
[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 985–996
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fluorescence competition assay, Figure 6G · source_derived_draft · unverified_draft
### e-sig-retinol-pkc-competition Retinol competed with 5 µM NBD-alpha-tocopherol for binding to 0.1 µM recombinant PKC alpha, whereas phosphatidylserine and cholesterol did not compete in the same study. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A alcohol competed with the labeled vitamin E probe for association with this purified kinase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Fluorescence competition assay, Figure 6G limitations: Exact retinol axis values were not extracted; this is direct in-vitro competition, not demonstrated competition between dietary vitamins in human tissues. exposure: 5 µM NBD-alpha-tocopherol; 0.1 µM PKC alpha; retinol concentration series; 30 min at room temperature, 1% ethanol. cross_nutrient: true [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
Complete structured claim and evidence
Adding 1 mol% alpha-tocopherol enhanced isolated PKC alpha C2-domain association with phosphatidylserine-containing lipid surfaces by surface plasmon resonance. Tocopherol without phosphatidylserine did not support binding.
RRR-alpha-tocopherol → PKC alpha C2-domain association with phosphatidylserine membranes source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Surface plasmon resonance with recombinant C2 domain and lipid vesicles
exposure
Base lipid composition 70:20:10 mol%; alpha-tocopherol at 1 mol% replacing POPC; no-PS control had 10 mol% tocopherol.
limitations
A membrane association endpoint is distinct from kinase activation. No direct C2-domain binding to free tocopherol is claimed.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Recombinant construct; species not independently stated
plain_language
Alpha-tocopherol changed how the kinase’s membrane-binding domain associated with a membrane containing phosphatidylserine.
primary_references
[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
tissue_or_cell_type
Artificial POPC/POPE/POPS membrane
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 998–1009
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Surface plasmon resonance with recombinant C2 domain and lipid vesicles · source_derived_draft · unverified_draft
### e-sig-alpha-pkc-ps-association Adding 1 mol% alpha-tocopherol enhanced isolated PKC alpha C2-domain association with phosphatidylserine-containing lipid surfaces by surface plasmon resonance. Tocopherol without phosphatidylserine did not support binding. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Alpha-tocopherol changed how the kinase’s membrane-binding domain associated with a membrane containing phosphatidylserine. organism: Recombinant construct; species not independently stated tissue_or_cell_type: Artificial POPC/POPE/POPS membrane experimental_model: Surface plasmon resonance with recombinant C2 domain and lipid vesicles limitations: A membrane association endpoint is distinct from kinase activation. No direct C2-domain binding to free tocopherol is claimed. exposure: Base lipid composition 70:20:10 mol%; alpha-tocopherol at 1 mol% replacing POPC; no-PS control had 10 mol% tocopherol. cross_nutrient: false [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318
Complete structured claim and evidence
Alpha-tocopherol-13′-carboxychromanol inhibited 5-LO product formation in activated human polymorphonuclear leukocytes with an IC50 of approximately 0.08 µM, compared with 0.27 µM for isolated recombinant human 5-LO.
Alpha-tocopherol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Primary human PMNL and recombinant enzyme, Table 1
exposure
10 min compound pretreatment at 37°C; PMNL in PBS pH 7.4, 1 mg/mL glucose and 1 mM CaCl2, stimulated with 2.5 µM A23187 and/or 20 µM arachidonic acid for 10 min; IC50 80 nM.
limitations
Potency cannot be equated with oral vitamin E dosing. The activated leukocyte IC50 differs greatly from parent alpha-tocopherol and from other laboratories’ assay results.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The alpha-tocopherol metabolite reduced leukotriene-pathway enzyme output in isolated human immune cells.
primary_references
[pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
tissue_or_cell_type
Isolated blood polymorphonuclear leukocytes and cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1011–1022
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human PMNL and recombinant enzyme, Table 1 · source_derived_draft · unverified_draft
### e-sig-alpha-acid-leukocyte-lox Alpha-tocopherol-13′-carboxychromanol inhibited 5-LO product formation in activated human polymorphonuclear leukocytes with an IC50 of approximately 0.08 µM, compared with 0.27 µM for isolated recombinant human 5-LO. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The alpha-tocopherol metabolite reduced leukotriene-pathway enzyme output in isolated human immune cells. organism: Homo sapiens tissue_or_cell_type: Isolated blood polymorphonuclear leukocytes and cell-free enzyme experimental_model: Primary human PMNL and recombinant enzyme, Table 1 limitations: Potency cannot be equated with oral vitamin E dosing. The activated leukocyte IC50 differs greatly from parent alpha-tocopherol and from other laboratories’ assay results. exposure: 10 min compound pretreatment at 37°C; PMNL in PBS pH 7.4, 1 mg/mL glucose and 1 mM CaCl2, stimulated with 2.5 µM A23187 and/or 20 µM arachidonic acid for 10 min; IC50 80 nM. cross_nutrient: false [pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
Complete structured claim and evidence
Pein and colleagues interpreted delta-tocotrienol-13′-carboxychromanol inhibition of human 5-LO as reversible and allosteric: activity inhibition persisted when arachidonic acid was varied, and immobilized metabolite captured the enzyme despite excess arachidonic acid.
Delta-tocotrienol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified human 5-LO; substrate variation, dilution and immobilized-ligand pull-down
exposure
Purified 5-LO 0.5 µg in PBS pH 7.4, EDTA 1 mM and ATP 1 mM; 10 min compound preincubation at 4°C, then 5–80 µM arachidonic acid and 2 mM CaCl2 at 37°C. Reported IC50 35–40 nM; pull-down competitor arachidonic acid 100 µM.
limitations
Binding-site assignment combines biochemical evidence with docking and mutagenesis, not a solved inhibitor-bound structure. Park 2022 explicitly disputes the noncompetitive interpretation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
One study concluded that this tocotrienol metabolite inhibits 5-lipoxygenase at a site distinct from the usual fatty-acid binding site.
primary_references
[pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1024–1035
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human 5-LO; substrate variation, dilution and immobilized-ligand pull-down · source_derived_draft · unverified_draft
### e-sig-delta-te-acid-allosteric Pein and colleagues interpreted delta-tocotrienol-13′-carboxychromanol inhibition of human 5-LO as reversible and allosteric: activity inhibition persisted when arachidonic acid was varied, and immobilized metabolite captured the enzyme despite excess arachidonic acid. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: One study concluded that this tocotrienol metabolite inhibits 5-lipoxygenase at a site distinct from the usual fatty-acid binding site. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Purified human 5-LO; substrate variation, dilution and immobilized-ligand pull-down limitations: Binding-site assignment combines biochemical evidence with docking and mutagenesis, not a solved inhibitor-bound structure. Park 2022 explicitly disputes the noncompetitive interpretation. exposure: Purified 5-LO 0.5 µg in PBS pH 7.4, EDTA 1 mM and ATP 1 mM; 10 min compound preincubation at 4°C, then 5–80 µM arachidonic acid and 2 mM CaCl2 at 37°C. Reported IC50 35–40 nM; pull-down competitor arachidonic acid 100 µM. cross_nutrient: false [pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
Complete structured claim and evidence
Park and colleagues classified Delta-tocotrienol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 0.8 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax.
Delta-tocotrienol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human recombinant 5-LOX oxygen-electrode initial-rate kinetics
exposure
10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM.
limitations
Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.
primary_references
[park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1037–1048
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX oxygen-electrode initial-rate kinetics · source_derived_draft · unverified_draft
### e-sig-delta-te-acid-competitive Park and colleagues classified Delta-tocotrienol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 0.8 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX oxygen-electrode initial-rate kinetics limitations: Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts. exposure: 10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
Complete structured claim and evidence
Park and colleagues classified Delta-tocopherol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 1.6 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax.
Delta-tocopherol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human recombinant 5-LOX oxygen-electrode initial-rate kinetics
exposure
10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM.
limitations
Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.
primary_references
[park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1050–1061
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX oxygen-electrode initial-rate kinetics · source_derived_draft · unverified_draft
### e-sig-delta-acid-competitive Park and colleagues classified Delta-tocopherol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 1.6 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX oxygen-electrode initial-rate kinetics limitations: Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts. exposure: 10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
Complete structured claim and evidence
Park and colleagues classified Delta-tocotrienol as a competitive inhibitor of human recombinant 5-LOX, with Ki 2.2 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax.
Delta-tocotrienol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human recombinant 5-LOX oxygen-electrode initial-rate kinetics
exposure
10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM.
limitations
Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.
primary_references
[park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1063–1074
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX oxygen-electrode initial-rate kinetics · source_derived_draft · unverified_draft
### e-sig-delta-te-competitive Park and colleagues classified Delta-tocotrienol as a competitive inhibitor of human recombinant 5-LOX, with Ki 2.2 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX oxygen-electrode initial-rate kinetics limitations: Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts. exposure: 10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
Complete structured claim and evidence
Delta-tocopherol-13′-carboxychromanol reduced A23187-stimulated TXB2 output from washed rat platelets, with the metabolite experiments reporting IC50 values in the 1.5–2.5 µM range.
Delta-tocopherol-13′-carboxychromanol → Thromboxane B2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Washed rat platelet stimulation and TXB2 enzyme immunoassay
exposure
25 min compound preincubation at 37°C; 1–2 µM A23187 with 1–2 mM CaCl2 for 10 min.
limitations
TXB2 is a stable surrogate for TXA2 production; neither clinical bleeding nor platelet aggregation was measured in this endpoint. Isolated rat platelets do not establish human antithrombotic benefit.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
The metabolite reduced a measured marker of thromboxane production in isolated rat platelets.
primary_references
[park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
tissue_or_cell_type
Isolated blood platelets
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1076–1087
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Washed rat platelet stimulation and TXB2 enzyme immunoassay · source_derived_draft · unverified_draft
### e-sig-delta-acid-platelet-txb2 Delta-tocopherol-13′-carboxychromanol reduced A23187-stimulated TXB2 output from washed rat platelets, with the metabolite experiments reporting IC50 values in the 1.5–2.5 µM range. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metabolite reduced a measured marker of thromboxane production in isolated rat platelets. organism: Rattus norvegicus tissue_or_cell_type: Isolated blood platelets experimental_model: Washed rat platelet stimulation and TXB2 enzyme immunoassay limitations: TXB2 is a stable surrogate for TXA2 production; neither clinical bleeding nor platelet aggregation was measured in this endpoint. Isolated rat platelets do not establish human antithrombotic benefit. exposure: 25 min compound preincubation at 37°C; 1–2 µM A23187 with 1–2 mM CaCl2 for 10 min. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
Complete structured claim and evidence
Gamma-tocopherol inhibited human recombinant COX-1 in a prostaglandin-product assay, with the tested non-alpha vitamin E forms showing IC50 values of 1–2.5 µM. Parent vitamin E forms did not significantly inhibit COX-2 in the same system.
Gamma-tocopherol → Cyclooxygenase-1 (PTGS1) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Recombinant human COX enzyme assay; PGF2alpha readout after chemical reduction
exposure
10 min compound preincubation; arachidonic acid 5 µM for 2 min; stannous chloride converted PG intermediates to PGF2alpha for ELISA.
limitations
This assay differs from older ovine COX-1/oxygen-electrode work; species and substrate differences preclude labeling every potency discrepancy as a contradiction.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Gamma-tocopherol reduced activity of purified human COX-1 under these assay conditions.
primary_references
[park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
tissue_or_cell_type
Cell-free enzyme
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1089–1100
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human COX enzyme assay; PGF2alpha readout after chemical reduction · source_derived_draft · unverified_draft
### e-sig-gamma-human-cox1 Gamma-tocopherol inhibited human recombinant COX-1 in a prostaglandin-product assay, with the tested non-alpha vitamin E forms showing IC50 values of 1–2.5 µM. Parent vitamin E forms did not significantly inhibit COX-2 in the same system. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gamma-tocopherol reduced activity of purified human COX-1 under these assay conditions. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Recombinant human COX enzyme assay; PGF2alpha readout after chemical reduction limitations: This assay differs from older ovine COX-1/oxygen-electrode work; species and substrate differences preclude labeling every potency discrepancy as a contradiction. exposure: 10 min compound preincubation; arachidonic acid 5 µM for 2 min; stannous chloride converted PG intermediates to PGF2alpha for ELISA. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
Complete structured claim and evidence
In HepG2 cells, gamma-tocotrienol inhibited incorporation of [14C]acetate into cholesterol with approximately 50% inhibition at 2 µM and maximal approximately 80% inhibition within 6 h, while incorporation of [3H]mevalonate was not inhibited.
Gamma-tocotrienol → Cholesterol biosynthesis source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Radiolabeled precursor incorporation in HepG2 cells
exposure
Gamma-tocotrienol approximately 2 µM for half-maximal inhibition; response developed within 6 h.
limitations
Primary abstract only; media and viability protocol unavailable. Tracer localization supports action upstream of mevalonate use, not a human cholesterol-lowering recommendation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Gamma-tocotrienol reduced cholesterol production from an early precursor, while leaving production from the later precursor mevalonate intact in cultured liver cells.
primary_references
[parker1993] Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1993). https://pubmed.ncbi.nlm.nih.gov/8388388/ DOI: 10.1016/s0021-9258(18)82115-9
tissue_or_cell_type
Hepatoma cell culture
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1102–1113
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled precursor incorporation in HepG2 cells · source_derived_draft · unverified_draft
### e-sig-gamma-te-cholesterol In HepG2 cells, gamma-tocotrienol inhibited incorporation of [14C]acetate into cholesterol with approximately 50% inhibition at 2 µM and maximal approximately 80% inhibition within 6 h, while incorporation of [3H]mevalonate was not inhibited. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gamma-tocotrienol reduced cholesterol production from an early precursor, while leaving production from the later precursor mevalonate intact in cultured liver cells. organism: Homo sapiens tissue_or_cell_type: Hepatoma cell culture experimental_model: Radiolabeled precursor incorporation in HepG2 cells limitations: Primary abstract only; media and viability protocol unavailable. Tracer localization supports action upstream of mevalonate use, not a human cholesterol-lowering recommendation. exposure: Gamma-tocotrienol approximately 2 µM for half-maximal inhibition; response developed within 6 h. cross_nutrient: false [parker1993] Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1993). https://pubmed.ncbi.nlm.nih.gov/8388388/ DOI: 10.1016/s0021-9258(18)82115-9
Complete structured claim and evidence
At 10 µM gamma-tocotrienol, HepG2 HMG-CoA reductase degradation increased 2.4-fold and its half-life fell from 3.73 to 1.59 h, measured by [35S]methionine pulse-chase and immunoprecipitation.
Gamma-tocotrienol → HMG-CoA reductase protein degradation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Radiolabeled protein pulse-chase and HMGCR immunoprecipitation
exposure
10 µM gamma-tocotrienol; reported HMGCR half-life 3.73 h control versus 1.59 h treated.
limitations
Primary abstract only; these data do not by themselves identify Insig proteins or prove direct binding to the reductase. Human supplementation effects cannot be inferred.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Gamma-tocotrienol made the cholesterol-synthesis enzyme turn over faster in cultured human liver tumor cells.
primary_references
[parker1993] Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1993). https://pubmed.ncbi.nlm.nih.gov/8388388/ DOI: 10.1016/s0021-9258(18)82115-9
tissue_or_cell_type
Hepatoma cell culture
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1115–1126
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled protein pulse-chase and HMGCR immunoprecipitation · source_derived_draft · unverified_draft
### e-sig-gamma-te-hmgcr-turnover At 10 µM gamma-tocotrienol, HepG2 HMG-CoA reductase degradation increased 2.4-fold and its half-life fell from 3.73 to 1.59 h, measured by [35S]methionine pulse-chase and immunoprecipitation. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gamma-tocotrienol made the cholesterol-synthesis enzyme turn over faster in cultured human liver tumor cells. organism: Homo sapiens tissue_or_cell_type: Hepatoma cell culture experimental_model: Radiolabeled protein pulse-chase and HMGCR immunoprecipitation limitations: Primary abstract only; these data do not by themselves identify Insig proteins or prove direct binding to the reductase. Human supplementation effects cannot be inferred. exposure: 10 µM gamma-tocotrienol; reported HMGCR half-life 3.73 h control versus 1.59 h treated. cross_nutrient: false [parker1993] Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1993). https://pubmed.ncbi.nlm.nih.gov/8388388/ DOI: 10.1016/s0021-9258(18)82115-9
Complete structured claim and evidence
Delta-tocotrienol stimulated HMG-CoA reductase ubiquitination in isolated SV-589 fibroblast membrane fractions supplemented with ubiquitin-activating enzyme; gamma-tocotrienol showed the same activity. The reconstituted result supported action without further tocotrienol metabolism.
Delta-tocotrienol → HMG-CoA reductase ubiquitination source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Isolated membranes from sterol-depleted SV-589 human fibroblasts; FLAG-ubiquitin and purified E1 assay
exposure
Figure 5B: purified E1 5 µg/mL, FLAG-ubiquitin 0.1 mg/mL, ubiquitin-aldehyde 0.01 mg/mL and ATP-regenerating system; tocotrienol concentration not fully retrieved.
limitations
The assay does not prove direct molecular binding of tocotrienol to HMGCR or INSIG. No human cholesterol outcome follows from this reconstituted experiment.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
These tocotrienols promoted attachment of degradation tags to the cholesterol-synthesis enzyme in isolated cell membranes.
primary_references
[song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
tissue_or_cell_type
Fibroblast-derived membrane fractions
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1128–1139
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated membranes from sterol-depleted SV-589 human fibroblasts; FLAG-ubiquitin and purified E1 assay · source_derived_draft · unverified_draft
### e-sig-delta-te-hmgcr-ubiquitination Delta-tocotrienol stimulated HMG-CoA reductase ubiquitination in isolated SV-589 fibroblast membrane fractions supplemented with ubiquitin-activating enzyme; gamma-tocotrienol showed the same activity. The reconstituted result supported action without further tocotrienol metabolism. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: These tocotrienols promoted attachment of degradation tags to the cholesterol-synthesis enzyme in isolated cell membranes. organism: Homo sapiens tissue_or_cell_type: Fibroblast-derived membrane fractions experimental_model: Isolated membranes from sterol-depleted SV-589 human fibroblasts; FLAG-ubiquitin and purified E1 assay limitations: The assay does not prove direct molecular binding of tocotrienol to HMGCR or INSIG. No human cholesterol outcome follows from this reconstituted experiment. exposure: Figure 5B: purified E1 5 µg/mL, FLAG-ubiquitin 0.1 mg/mL, ubiquitin-aldehyde 0.01 mg/mL and ATP-regenerating system; tocotrienol concentration not fully retrieved. cross_nutrient: false [song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
Complete structured claim and evidence
Combined RNAi against INSIG1 and INSIG2 abolished gamma- and delta-tocotrienol-stimulated degradation of endogenous HMG-CoA reductase in sterol-depleted SV-589 fibroblasts supplied with 10 mM mevalonate.
Combined INSIG1 and INSIG2 depletion → HMG-CoA reductase protein degradation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Combined INSIG1/INSIG2 RNA interference in immortalized human SV-589 fibroblasts
exposure
Sterol depletion 16 h; gamma- or delta-tocotrienol plus 10 mM mevalonate for 5 h; tocotrienol concentration not retrieved from the accessible Figure 3 text.
limitations
Combined knockdown establishes a machinery requirement in this model, not the unique role of either INSIG isoform or nutritional deficiency. Does not quantify viability or predict supplement benefit.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Removing both INSIG regulators prevented these tocotrienols from accelerating loss of the reductase protein in this cell experiment.
primary_references
[song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
tissue_or_cell_type
Human fibroblast cell culture
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1141–1152
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combined INSIG1/INSIG2 RNA interference in immortalized human SV-589 fibroblasts · source_derived_draft · unverified_draft
### e-sig-insig-depletion-hmgcr-turnover Combined RNAi against INSIG1 and INSIG2 abolished gamma- and delta-tocotrienol-stimulated degradation of endogenous HMG-CoA reductase in sterol-depleted SV-589 fibroblasts supplied with 10 mM mevalonate. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing both INSIG regulators prevented these tocotrienols from accelerating loss of the reductase protein in this cell experiment. organism: Homo sapiens tissue_or_cell_type: Human fibroblast cell culture experimental_model: Combined INSIG1/INSIG2 RNA interference in immortalized human SV-589 fibroblasts limitations: Combined knockdown establishes a machinery requirement in this model, not the unique role of either INSIG isoform or nutritional deficiency. Does not quantify viability or predict supplement benefit. exposure: Sterol depletion 16 h; gamma- or delta-tocotrienol plus 10 mM mevalonate for 5 h; tocotrienol concentration not retrieved from the accessible Figure 3 text. cross_nutrient: false [song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
Complete structured claim and evidence
Serum vitamin E normalized during one year of supplementation in the 24-patient AVED cohort.
Vitamin E → Circulating alpha-tocopherol concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients
exposure
Vitamin E 800 mg/day for one year; formulation stereochemistry not specified in the retrieved abstract.
limitations
Small uncontrolled genetic-disease cohort; no inference of complete reversal, a general population dose or isolated dietary deficiency.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Extra vitamin E restored the blood measurement despite the inherited transport disorder.
primary_references
[e-clin-aved2001] Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11554913/ DOI: 10.1046/j.1468-1331.2001.00273.x
tissue_or_cell_type
Nervous system and serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1154–1165
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients · source_derived_draft · unverified_draft
### e-clin-aved-serum Serum vitamin E normalized during one year of supplementation in the 24-patient AVED cohort. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra vitamin E restored the blood measurement despite the inherited transport disorder. organism: Homo sapiens tissue_or_cell_type: Nervous system and serum experimental_model: Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients limitations: Small uncontrolled genetic-disease cohort; no inference of complete reversal, a general population dose or isolated dietary deficiency. exposure: Vitamin E 800 mg/day for one year; formulation stereochemistry not specified in the retrieved abstract. cross_nutrient: false [e-clin-aved2001] Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11554913/ DOI: 10.1046/j.1468-1331.2001.00273.x
Complete structured claim and evidence
Ataxia Rating Scale scores improved modestly but significantly after one year of vitamin E in the AVED cohort; results were better with shorter disease duration.
Vitamin E → Cerebellar ataxia severity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients
exposure
Vitamin E 800 mg/day for one year; formulation stereochemistry not specified in the retrieved abstract.
limitations
Small uncontrolled genetic-disease cohort; no inference of complete reversal, a general population dose or isolated dietary deficiency.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Treating the inherited vitamin E shortage modestly improved coordination in this study.
primary_references
[e-clin-aved2001] Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11554913/ DOI: 10.1046/j.1468-1331.2001.00273.x
tissue_or_cell_type
Nervous system and serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1167–1178
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients · source_derived_draft · unverified_draft
### e-clin-aved-ataxia Ataxia Rating Scale scores improved modestly but significantly after one year of vitamin E in the AVED cohort; results were better with shorter disease duration. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Treating the inherited vitamin E shortage modestly improved coordination in this study. organism: Homo sapiens tissue_or_cell_type: Nervous system and serum experimental_model: Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients limitations: Small uncontrolled genetic-disease cohort; no inference of complete reversal, a general population dose or isolated dietary deficiency. exposure: Vitamin E 800 mg/day for one year; formulation stereochemistry not specified in the retrieved abstract. cross_nutrient: false [e-clin-aved2001] Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11554913/ DOI: 10.1046/j.1468-1331.2001.00273.x
Complete structured claim and evidence
Absent reflexes and posterior-column disturbances persisted despite normalization of serum vitamin E during AVED supplementation.
Vitamin E → AVED reflex and posterior-column deficits source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients
exposure
Vitamin E 800 mg/day for one year; formulation stereochemistry not specified in the retrieved abstract.
limitations
Small uncontrolled genetic-disease cohort; no inference of complete reversal, a general population dose or isolated dietary deficiency.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Correcting the blood level did not reverse every established nerve deficit.
primary_references
[e-clin-aved2001] Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11554913/ DOI: 10.1046/j.1468-1331.2001.00273.x
tissue_or_cell_type
Nervous system and serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1180–1191
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients · source_derived_draft · unverified_draft
### e-clin-aved-residual-deficits Absent reflexes and posterior-column disturbances persisted despite normalization of serum vitamin E during AVED supplementation. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the blood level did not reverse every established nerve deficit. organism: Homo sapiens tissue_or_cell_type: Nervous system and serum experimental_model: Uncontrolled one-year supplementation study; 24 genetically investigated AVED patients limitations: Small uncontrolled genetic-disease cohort; no inference of complete reversal, a general population dose or isolated dietary deficiency. exposure: Vitamin E 800 mg/day for one year; formulation stereochemistry not specified in the retrieved abstract. cross_nutrient: false [e-clin-aved2001] Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. (2001). https://pubmed.ncbi.nlm.nih.gov/11554913/ DOI: 10.1046/j.1468-1331.2001.00273.x
Complete structured claim and evidence
In the historical premature-infant series, blood vitamin E below 0.6 mg/100 mL was associated with greater hydrogen-peroxide-induced erythrocyte hemolysis.
Circulating alpha-tocopherol concentration → Erythrocyte peroxide-induced hemolysis source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Historical clinical series of 50 premature infants aged 6–8 weeks
exposure
Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered.
limitations
Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract. The reported concentration is specific to this study, not a universal cellular adequacy threshold.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
In this infant study, a low vitamin E reading accompanied fragile red cells in a peroxide test.
primary_references
[e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360
tissue_or_cell_type
Blood and erythrocytes
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1193–1204
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical clinical series of 50 premature infants aged 6–8 weeks · source_derived_draft · unverified_draft
### e-clin-infant-peroxide-association In the historical premature-infant series, blood vitamin E below 0.6 mg/100 mL was associated with greater hydrogen-peroxide-induced erythrocyte hemolysis. Condition category: biomarker_context nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this infant study, a low vitamin E reading accompanied fragile red cells in a peroxide test. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Historical clinical series of 50 premature infants aged 6–8 weeks limitations: Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract. The reported concentration is specific to this study, not a universal cellular adequacy threshold. exposure: Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered. cross_nutrient: false [e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360
Complete structured claim and evidence
Peroxide hemolysis normalized within days of oral vitamin E administration and rising blood vitamin E in the premature-infant series.
Vitamin E → Erythrocyte peroxide-induced hemolysis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Historical clinical series of 50 premature infants aged 6–8 weeks
exposure
Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered.
limitations
Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Restoring vitamin E reduced red-cell fragility in the tested infants.
primary_references
[e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360
tissue_or_cell_type
Blood and erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1206–1217
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical clinical series of 50 premature infants aged 6–8 weeks · source_derived_draft · unverified_draft
### e-clin-infant-peroxide-repletion Peroxide hemolysis normalized within days of oral vitamin E administration and rising blood vitamin E in the premature-infant series. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring vitamin E reduced red-cell fragility in the tested infants. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Historical clinical series of 50 premature infants aged 6–8 weeks limitations: Historical feeding conditions and infant ages; an ex vivo hemolysis assay is not a universal explanation for anemia of prematurity. Formulation not specified in the abstract. exposure: Blood vitamin E and hydrogen-peroxide hemolysis were assessed; oral vitamin E 10 mg/day was administered. cross_nutrient: false [e-clin-lo1973] Vitamin E and haemolytic anaemia in premature infants. (1973). https://pubmed.ncbi.nlm.nih.gov/4739911/ DOI: 10.1136/adc.48.5.360
Complete structured claim and evidence
No infant developed clinical or hematological vitamin E-deficiency signs during the ten-week trial when feeds maintained the reported E:PUFA balance and no supplemental iron was given.
Vitamin E → Premature-infant anemia source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Ten-week double-blind feeding trial; 42 premature infants
exposure
Placebo, 5 or 15 mg/day extra vitamin E; all feeds had E:PUFA at least 0.6, and no supplemental iron was given.
limitations
These findings are bounded by the contemporary feeds and absence of supplemental iron; they do not refute hemolysis in actual vitamin E deficiency. The design does not isolate iron as a causal modifier or establish the reported ratio as a universal recommendation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Early anemia was not automatically a vitamin E-shortage syndrome under these feeding conditions.
primary_references
[e-clin-neonatal1987] The early anaemia of the premature infant: is there a place for vitamin E supplementation? (1986). https://pubmed.ncbi.nlm.nih.gov/3676185/ DOI: 10.1079/bjn19860090
tissue_or_cell_type
Blood and erythrocytes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1219–1230
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-week double-blind feeding trial; 42 premature infants · source_derived_draft · unverified_draft
### e-clin-adequate-infant-feeds No infant developed clinical or hematological vitamin E-deficiency signs during the ten-week trial when feeds maintained the reported E:PUFA balance and no supplemental iron was given. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Early anemia was not automatically a vitamin E-shortage syndrome under these feeding conditions. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Ten-week double-blind feeding trial; 42 premature infants limitations: These findings are bounded by the contemporary feeds and absence of supplemental iron; they do not refute hemolysis in actual vitamin E deficiency. The design does not isolate iron as a causal modifier or establish the reported ratio as a universal recommendation. exposure: Placebo, 5 or 15 mg/day extra vitamin E; all feeds had E:PUFA at least 0.6, and no supplemental iron was given. cross_nutrient: true [e-clin-neonatal1987] The early anaemia of the premature infant: is there a place for vitamin E supplementation? (1986). https://pubmed.ncbi.nlm.nih.gov/3676185/ DOI: 10.1079/bjn19860090
Complete structured claim and evidence
Among 59 specimens with alpha-tocopherol below 5 mg/L, 28 were reclassified within the study lipid-ratio reference interval after cholesterol and triglycerides were considered.
Cholesterol → Vitamin E status classification source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Original patient-specimen laboratory analysis within an article indexed as review
exposure
Lipid-adjusted assessment; reference specimens n=307; low-concentration subset n=59.
limitations
Laboratory reclassification, not a direct tissue-deficiency gold standard. The abstract has an apparent typo in a separate high-concentration denominator; that statistic is not used here.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
A low vitamin E concentration can look different once blood lipids are considered.
primary_references
[e-clin-winbauer1999] Evaluating serum alpha-tocopherol (vitamin E) in terms of a lipid ratio. (1999). https://pubmed.ncbi.nlm.nih.gov/10440582/
tissue_or_cell_type
Serum
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1232–1243
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Original patient-specimen laboratory analysis within an article indexed as review · source_derived_draft · unverified_draft
### e-clin-lipid-ratio-reclassification Among 59 specimens with alpha-tocopherol below 5 mg/L, 28 were reclassified within the study lipid-ratio reference interval after cholesterol and triglycerides were considered. Condition category: biomarker_context nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low vitamin E concentration can look different once blood lipids are considered. organism: Homo sapiens tissue_or_cell_type: Serum experimental_model: Original patient-specimen laboratory analysis within an article indexed as review limitations: Laboratory reclassification, not a direct tissue-deficiency gold standard. The abstract has an apparent typo in a separate high-concentration denominator; that statistic is not used here. exposure: Lipid-adjusted assessment; reference specimens n=307; low-concentration subset n=59. cross_nutrient: false [e-clin-winbauer1999] Evaluating serum alpha-tocopherol (vitamin E) in terms of a lipid ratio. (1999). https://pubmed.ncbi.nlm.nih.gov/10440582/
Complete structured claim and evidence
In the cirrhosis cohort, cholesterol normalization classified fewer patients as vitamin E deficient than absolute concentrations; the authors cautioned that the ratio could obscure reduced status in advanced liver disease.
Cholesterol → Vitamin E status classification source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Observational comparison of 85 cirrhosis and 50 noncirrhotic liver-disease patients
exposure
Absolute vitamin E compared with vitamin E/cholesterol ratio using study-specific healthy-control reference limits.
limitations
No direct tissue adequacy test. Cirrhosis changes lipid handling; neither an absolute concentration nor a normalized ratio alone establishes cellular function.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Lipid correction is useful context, but it can also conceal a problem when liver disease changes both measurements.
primary_references
[e-clin-cirrhosis1999] Vitamin E status in patients with liver cirrhosis: normal or deficient? (1999). https://pubmed.ncbi.nlm.nih.gov/9920150/ DOI: 10.1016/s0026-0495(99)90015-x
tissue_or_cell_type
Serum and liver-disease context
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1245–1256
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational comparison of 85 cirrhosis and 50 noncirrhotic liver-disease patients · source_derived_draft · unverified_draft
### e-clin-cirrhosis-ratio-boundary In the cirrhosis cohort, cholesterol normalization classified fewer patients as vitamin E deficient than absolute concentrations; the authors cautioned that the ratio could obscure reduced status in advanced liver disease. Condition category: biomarker_context nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lipid correction is useful context, but it can also conceal a problem when liver disease changes both measurements. organism: Homo sapiens tissue_or_cell_type: Serum and liver-disease context experimental_model: Observational comparison of 85 cirrhosis and 50 noncirrhotic liver-disease patients limitations: No direct tissue adequacy test. Cirrhosis changes lipid handling; neither an absolute concentration nor a normalized ratio alone establishes cellular function. exposure: Absolute vitamin E compared with vitamin E/cholesterol ratio using study-specific healthy-control reference limits. cross_nutrient: false [e-clin-cirrhosis1999] Vitamin E status in patients with liver cirrhosis: normal or deficient? (1999). https://pubmed.ncbi.nlm.nih.gov/9920150/ DOI: 10.1016/s0026-0495(99)90015-x
Complete structured claim and evidence
High-dose RRR-alpha-tocopherol increased PIVKA-II in both 12-week adult trials: mean values rose from 1.7 to 11.9 ng/mL and from 1.8 to 5.3 ng/mL.
RRR-alpha-tocopherol → Undercarboxylated prothrombin / PIVKA-II source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men
exposure
RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy.
limitations
Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
High-dose vitamin E altered a vitamin K-dependent clotting-protein marker.
primary_references
[e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
tissue_or_cell_type
Circulation and vitamin K-dependent carboxylation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1258–1269
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men · source_derived_draft · unverified_draft
### e-clin-vitamin-k-pivka High-dose RRR-alpha-tocopherol increased PIVKA-II in both 12-week adult trials: mean values rose from 1.7 to 11.9 ng/mL and from 1.8 to 5.3 ng/mL. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: High-dose vitamin E altered a vitamin K-dependent clotting-protein marker. organism: Homo sapiens tissue_or_cell_type: Circulation and vitamin K-dependent carboxylation experimental_model: Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men limitations: Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route. exposure: RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy. cross_nutrient: true [e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
Complete structured claim and evidence
Plasma phylloquinone and percentage undercarboxylated osteocalcin did not change significantly with vitamin E supplementation despite increased PIVKA-II.
RRR-alpha-tocopherol → Undercarboxylated osteocalcin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men
exposure
RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy.
limitations
Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The vitamin K-related markers did not all respond in the same way.
primary_references
[e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
tissue_or_cell_type
Circulation and vitamin K-dependent carboxylation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1271–1282
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men · source_derived_draft · unverified_draft
### e-clin-vitamin-k-marker-boundary Plasma phylloquinone and percentage undercarboxylated osteocalcin did not change significantly with vitamin E supplementation despite increased PIVKA-II. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The vitamin K-related markers did not all respond in the same way. organism: Homo sapiens tissue_or_cell_type: Circulation and vitamin K-dependent carboxylation experimental_model: Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men limitations: Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route. exposure: RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy. cross_nutrient: true [e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
Complete structured claim and evidence
In SELECT, vitamin E alone increased prostate-cancer incidence relative to placebo (HR 1.17, 99% CI 1.004–1.36); the absolute increase was 1.6 cases per 1000 person-years.
All-rac-alpha-tocopheryl acetate → Prostate cancer incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
SELECT randomized factorial prevention trial; 34887 men in primary analysis, 35533 originally randomized
exposure
All-rac-alpha-tocopheryl acetate 400 IU/day; selenium arm 200 micrograms/day selenium as L-selenomethionine; supplements stopped in 2008, follow-up continued to July 2011.
limitations
Trial-specific formulation, dose and population; does not establish the effect of food intake or of every vitamin E form. Group results cannot identify an intracellular mechanism.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The tested high-dose vitamin E preparation increased prostate-cancer diagnoses in this trial.
primary_references
[e-clin-select2011] Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). (2011). https://pubmed.ncbi.nlm.nih.gov/21990298/ DOI: 10.1001/jama.2011.1437
tissue_or_cell_type
Prostate and whole-person outcomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1284–1295
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SELECT randomized factorial prevention trial; 34887 men in primary analysis, 35533 originally randomized · source_derived_draft · unverified_draft
### e-clin-select-prostate-incidence In SELECT, vitamin E alone increased prostate-cancer incidence relative to placebo (HR 1.17, 99% CI 1.004–1.36); the absolute increase was 1.6 cases per 1000 person-years. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested high-dose vitamin E preparation increased prostate-cancer diagnoses in this trial. organism: Homo sapiens tissue_or_cell_type: Prostate and whole-person outcomes experimental_model: SELECT randomized factorial prevention trial; 34887 men in primary analysis, 35533 originally randomized limitations: Trial-specific formulation, dose and population; does not establish the effect of food intake or of every vitamin E form. Group results cannot identify an intracellular mechanism. exposure: All-rac-alpha-tocopheryl acetate 400 IU/day; selenium arm 200 micrograms/day selenium as L-selenomethionine; supplements stopped in 2008, follow-up continued to July 2011. cross_nutrient: true [e-clin-select2011] Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). (2011). https://pubmed.ncbi.nlm.nih.gov/21990298/ DOI: 10.1001/jama.2011.1437
Complete structured claim and evidence
SELECT did not demonstrate prostate-cancer prevention with vitamin E plus selenium (HR 1.05, 99% CI 0.89–1.22 versus placebo).
All-rac-alpha-tocopheryl acetate → Prostate cancer incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
SELECT randomized factorial prevention trial; 34887 men in primary analysis, 35533 originally randomized
exposure
All-rac-alpha-tocopheryl acetate 400 IU/day; selenium arm 200 micrograms/day selenium as L-selenomethionine; supplements stopped in 2008, follow-up continued to July 2011.
limitations
Trial-specific formulation, dose and population; does not establish the effect of food intake or of every vitamin E form. Group results cannot identify an intracellular mechanism. The nonsignificant combination estimate is not proof that selenium mechanistically neutralizes vitamin E-associated harm.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Adding selenium did not demonstrate a prostate-cancer prevention benefit.
primary_references
[e-clin-select2011] Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). (2011). https://pubmed.ncbi.nlm.nih.gov/21990298/ DOI: 10.1001/jama.2011.1437
tissue_or_cell_type
Prostate and whole-person outcomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1297–1308
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SELECT randomized factorial prevention trial; 34887 men in primary analysis, 35533 originally randomized · source_derived_draft · unverified_draft
### e-clin-select-combination-boundary SELECT did not demonstrate prostate-cancer prevention with vitamin E plus selenium (HR 1.05, 99% CI 0.89–1.22 versus placebo). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding selenium did not demonstrate a prostate-cancer prevention benefit. organism: Homo sapiens tissue_or_cell_type: Prostate and whole-person outcomes experimental_model: SELECT randomized factorial prevention trial; 34887 men in primary analysis, 35533 originally randomized limitations: Trial-specific formulation, dose and population; does not establish the effect of food intake or of every vitamin E form. Group results cannot identify an intracellular mechanism. The nonsignificant combination estimate is not proof that selenium mechanistically neutralizes vitamin E-associated harm. exposure: All-rac-alpha-tocopheryl acetate 400 IU/day; selenium arm 200 micrograms/day selenium as L-selenomethionine; supplements stopped in 2008, follow-up continued to July 2011. cross_nutrient: true [e-clin-select2011] Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). (2011). https://pubmed.ncbi.nlm.nih.gov/21990298/ DOI: 10.1001/jama.2011.1437
Complete structured claim and evidence
In the SELECT secondary analysis, vitamin E alone increased total prostate-cancer risk by 63% among men below the 40th percentile of baseline toenail selenium; a significant effect was not found above that split.
All-rac-alpha-tocopheryl acetate → Prostate cancer incidence source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Secondary case-cohort analysis nested within SELECT; 1739 total cases and 3117 sampled cohort members
exposure
Trial supplementation analyzed by baseline toenail selenium; E-alone comparison used below versus at/above the 40th percentile.
limitations
Exploratory subgroup thresholds are cohort percentiles, not deficiency thresholds; baseline selenium was not randomized. Does not justify adding selenium to make high-dose vitamin E safe.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Baseline selenium measurements helped identify different trial outcomes, but did not establish a safe supplement combination.
primary_references
[e-clin-select2014] Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk. (2014). https://pubmed.ncbi.nlm.nih.gov/24563519/ DOI: 10.1093/jnci/djt456
tissue_or_cell_type
Prostate and toenail selenium biomarker
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1310–1321
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Secondary case-cohort analysis nested within SELECT; 1739 total cases and 3117 sampled cohort members · source_derived_draft · unverified_draft
### e-clin-select-baseline-selenium In the SELECT secondary analysis, vitamin E alone increased total prostate-cancer risk by 63% among men below the 40th percentile of baseline toenail selenium; a significant effect was not found above that split. Condition category: biomarker_context nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Baseline selenium measurements helped identify different trial outcomes, but did not establish a safe supplement combination. organism: Homo sapiens tissue_or_cell_type: Prostate and toenail selenium biomarker experimental_model: Secondary case-cohort analysis nested within SELECT; 1739 total cases and 3117 sampled cohort members limitations: Exploratory subgroup thresholds are cohort percentiles, not deficiency thresholds; baseline selenium was not randomized. Does not justify adding selenium to make high-dose vitamin E safe. exposure: Trial supplementation analyzed by baseline toenail selenium; E-alone comparison used below versus at/above the 40th percentile. cross_nutrient: true [e-clin-select2014] Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk. (2014). https://pubmed.ncbi.nlm.nih.gov/24563519/ DOI: 10.1093/jnci/djt456
Complete structured claim and evidence
The ATBC secondary analysis found 32% lower prostate-cancer incidence among men assigned alpha-tocopherol versus those not assigned it.
Alpha-tocopherol → Prostate cancer incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
ATBC randomized factorial trial secondary prostate-cancer endpoint; 29133 Finnish male smokers aged 50–69
exposure
Alpha-tocopherol 50 mg/day with or without beta-carotene 20 mg/day; median 6.1 years.
limitations
Secondary cancer endpoint in male smokers; differs from SELECT in dose, population and ascertainment. An opposite trial result is not automatically a same-condition biological contradiction. This result and SELECT must retain their different populations and regimens; neither supplies the molecular explanation for their difference.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
A lower-dose trial in male smokers found fewer prostate-cancer diagnoses.
primary_references
[e-clin-atbc1998] Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. (1998). https://pubmed.ncbi.nlm.nih.gov/9521168/ DOI: 10.1093/jnci/90.6.440
tissue_or_cell_type
Prostate and whole-person outcomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1323–1334
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ATBC randomized factorial trial secondary prostate-cancer endpoint; 29133 Finnish male smokers aged 50–69 · source_derived_draft · unverified_draft
### e-clin-atbc-prostate-incidence The ATBC secondary analysis found 32% lower prostate-cancer incidence among men assigned alpha-tocopherol versus those not assigned it. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower-dose trial in male smokers found fewer prostate-cancer diagnoses. organism: Homo sapiens tissue_or_cell_type: Prostate and whole-person outcomes experimental_model: ATBC randomized factorial trial secondary prostate-cancer endpoint; 29133 Finnish male smokers aged 50–69 limitations: Secondary cancer endpoint in male smokers; differs from SELECT in dose, population and ascertainment. An opposite trial result is not automatically a same-condition biological contradiction. This result and SELECT must retain their different populations and regimens; neither supplies the molecular explanation for their difference. exposure: Alpha-tocopherol 50 mg/day with or without beta-carotene 20 mg/day; median 6.1 years. cross_nutrient: true [e-clin-atbc1998] Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. (1998). https://pubmed.ncbi.nlm.nih.gov/9521168/ DOI: 10.1093/jnci/90.6.440
Complete structured claim and evidence
Prostate-cancer mortality was 41% lower in ATBC participants assigned alpha-tocopherol, with a reported confidence interval extending from a 65% to a 1% reduction.
Alpha-tocopherol → Prostate cancer mortality source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
ATBC randomized factorial trial secondary prostate-cancer endpoint; 29133 Finnish male smokers aged 50–69
exposure
Alpha-tocopherol 50 mg/day with or without beta-carotene 20 mg/day; median 6.1 years.
limitations
Secondary cancer endpoint in male smokers; differs from SELECT in dose, population and ascertainment. An opposite trial result is not automatically a same-condition biological contradiction.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The smoker trial also reported fewer prostate-cancer deaths, with substantial uncertainty around the estimate.
primary_references
[e-clin-atbc1998] Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. (1998). https://pubmed.ncbi.nlm.nih.gov/9521168/ DOI: 10.1093/jnci/90.6.440
tissue_or_cell_type
Prostate and whole-person outcomes
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1336–1347
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ATBC randomized factorial trial secondary prostate-cancer endpoint; 29133 Finnish male smokers aged 50–69 · source_derived_draft · unverified_draft
### e-clin-atbc-prostate-mortality Prostate-cancer mortality was 41% lower in ATBC participants assigned alpha-tocopherol, with a reported confidence interval extending from a 65% to a 1% reduction. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The smoker trial also reported fewer prostate-cancer deaths, with substantial uncertainty around the estimate. organism: Homo sapiens tissue_or_cell_type: Prostate and whole-person outcomes experimental_model: ATBC randomized factorial trial secondary prostate-cancer endpoint; 29133 Finnish male smokers aged 50–69 limitations: Secondary cancer endpoint in male smokers; differs from SELECT in dose, population and ascertainment. An opposite trial result is not automatically a same-condition biological contradiction. exposure: Alpha-tocopherol 50 mg/day with or without beta-carotene 20 mg/day; median 6.1 years. cross_nutrient: false [e-clin-atbc1998] Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. (1998). https://pubmed.ncbi.nlm.nih.gov/9521168/ DOI: 10.1093/jnci/90.6.440
Complete structured claim and evidence
Vitamin E did not reduce major cardiovascular events in PHS II (HR 1.01, 95% CI 0.90–1.13).
All-rac-alpha-tocopherol → Major cardiovascular events source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50
exposure
Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years.
limitations
Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The tested vitamin E regimen did not prevent major cardiovascular events in these men.
primary_references
[e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600
tissue_or_cell_type
Cardiovascular clinical events
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1349–1360
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50 · source_derived_draft · unverified_draft
### e-clin-phs-cardiovascular Vitamin E did not reduce major cardiovascular events in PHS II (HR 1.01, 95% CI 0.90–1.13). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested vitamin E regimen did not prevent major cardiovascular events in these men. organism: Homo sapiens tissue_or_cell_type: Cardiovascular clinical events experimental_model: Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50 limitations: Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached. exposure: Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years. cross_nutrient: true [e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600
Complete structured claim and evidence
PHS II found increased hemorrhagic-stroke incidence with vitamin E assignment (HR 1.74, 95% CI 1.04–2.91).
All-rac-alpha-tocopherol → Hemorrhagic stroke incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50
exposure
Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years.
limitations
Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached. The clinical endpoint does not prove that altered vitamin K metabolism caused these events.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
A bleeding-related stroke outcome increased in this trial.
primary_references
[e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600
tissue_or_cell_type
Cardiovascular clinical events
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1362–1373
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50 · source_derived_draft · unverified_draft
### e-clin-phs-hemorrhagic-stroke PHS II found increased hemorrhagic-stroke incidence with vitamin E assignment (HR 1.74, 95% CI 1.04–2.91). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A bleeding-related stroke outcome increased in this trial. organism: Homo sapiens tissue_or_cell_type: Cardiovascular clinical events experimental_model: Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50 limitations: Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached. The clinical endpoint does not prove that altered vitamin K metabolism caused these events. exposure: Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years. cross_nutrient: false [e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600
Complete structured claim and evidence
In HOPE/HOPE-TOO, vitamin E did not reduce major cardiovascular events (RR 1.04, 95% CI 0.96–1.14).
Vitamin E → Major cardiovascular events source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
HOPE/HOPE-TOO randomized trial and extension in vascular disease or diabetes; initial n=9541
exposure
Natural-source vitamin E 400 IU/day; median follow-up 7 years; extension included ongoing treatment and passive follow-up.
limitations
High-risk population and extension participation limits. Heart failure was a secondary outcome; no specific molecular cause is established by the trial. Natural-source vitamin E is reported; an exact ester identity is not inferred from the abstract.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Longer supplementation did not lower major cardiovascular events in the studied high-risk patients.
primary_references
[e-clin-hope2005] Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/15769967/ DOI: 10.1001/jama.293.11.1338
tissue_or_cell_type
Cardiovascular clinical events
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1375–1386
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HOPE/HOPE-TOO randomized trial and extension in vascular disease or diabetes; initial n=9541 · source_derived_draft · unverified_draft
### e-clin-hope-cardiovascular In HOPE/HOPE-TOO, vitamin E did not reduce major cardiovascular events (RR 1.04, 95% CI 0.96–1.14). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Longer supplementation did not lower major cardiovascular events in the studied high-risk patients. organism: Homo sapiens tissue_or_cell_type: Cardiovascular clinical events experimental_model: HOPE/HOPE-TOO randomized trial and extension in vascular disease or diabetes; initial n=9541 limitations: High-risk population and extension participation limits. Heart failure was a secondary outcome; no specific molecular cause is established by the trial. Natural-source vitamin E is reported; an exact ester identity is not inferred from the abstract. exposure: Natural-source vitamin E 400 IU/day; median follow-up 7 years; extension included ongoing treatment and passive follow-up. cross_nutrient: false [e-clin-hope2005] Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/15769967/ DOI: 10.1001/jama.293.11.1338
Complete structured claim and evidence
Vitamin E assignment was associated with more heart failure in HOPE/HOPE-TOO (RR 1.13, 95% CI 1.01–1.26).
Vitamin E → Heart failure incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
HOPE/HOPE-TOO randomized trial and extension in vascular disease or diabetes; initial n=9541
exposure
Natural-source vitamin E 400 IU/day; median follow-up 7 years; extension included ongoing treatment and passive follow-up.
limitations
High-risk population and extension participation limits. Heart failure was a secondary outcome; no specific molecular cause is established by the trial. Natural-source vitamin E is reported; an exact ester identity is not inferred from the abstract.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Heart failure was more frequent with the tested regimen in this high-risk trial.
primary_references
[e-clin-hope2005] Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/15769967/ DOI: 10.1001/jama.293.11.1338
tissue_or_cell_type
Cardiovascular clinical events
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1388–1399
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HOPE/HOPE-TOO randomized trial and extension in vascular disease or diabetes; initial n=9541 · source_derived_draft · unverified_draft
### e-clin-hope-heart-failure Vitamin E assignment was associated with more heart failure in HOPE/HOPE-TOO (RR 1.13, 95% CI 1.01–1.26). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Heart failure was more frequent with the tested regimen in this high-risk trial. organism: Homo sapiens tissue_or_cell_type: Cardiovascular clinical events experimental_model: HOPE/HOPE-TOO randomized trial and extension in vascular disease or diabetes; initial n=9541 limitations: High-risk population and extension participation limits. Heart failure was a secondary outcome; no specific molecular cause is established by the trial. Natural-source vitamin E is reported; an exact ester identity is not inferred from the abstract. exposure: Natural-source vitamin E 400 IU/day; median follow-up 7 years; extension included ongoing treatment and passive follow-up. cross_nutrient: false [e-clin-hope2005] Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/15769967/ DOI: 10.1001/jama.293.11.1338
Complete structured claim and evidence
PIVENS met its histological improvement endpoint in 43% of vitamin E recipients versus 19% of placebo recipients (P=0.001).
RRR-alpha-tocopherol → Steatohepatitis histological improvement source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
PIVENS randomized double-blind trial; 247 adults with biopsy-confirmed NASH without diabetes
exposure
RRR-alpha-tocopherol 800 IU/day for 96 weeks; E group n=84, placebo n=83.
limitations
Histological endpoints in a defined nondiabetic NASH population, not proof of general liver benefit, fibrosis reversal, cirrhosis prevention or long-term survival benefit.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The studied vitamin E treatment improved a defined liver-biopsy outcome in adults with NASH without diabetes.
primary_references
[e-clin-pivens2010] Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. (2010). https://pubmed.ncbi.nlm.nih.gov/20427778/ DOI: 10.1056/nejmoa0907929
tissue_or_cell_type
Liver biopsy
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1401–1412
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PIVENS randomized double-blind trial; 247 adults with biopsy-confirmed NASH without diabetes · source_derived_draft · unverified_draft
### e-clin-pivens-histology PIVENS met its histological improvement endpoint in 43% of vitamin E recipients versus 19% of placebo recipients (P=0.001). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The studied vitamin E treatment improved a defined liver-biopsy outcome in adults with NASH without diabetes. organism: Homo sapiens tissue_or_cell_type: Liver biopsy experimental_model: PIVENS randomized double-blind trial; 247 adults with biopsy-confirmed NASH without diabetes limitations: Histological endpoints in a defined nondiabetic NASH population, not proof of general liver benefit, fibrosis reversal, cirrhosis prevention or long-term survival benefit. exposure: RRR-alpha-tocopherol 800 IU/day for 96 weeks; E group n=84, placebo n=83. cross_nutrient: false [e-clin-pivens2010] Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. (2010). https://pubmed.ncbi.nlm.nih.gov/20427778/ DOI: 10.1056/nejmoa0907929
Complete structured claim and evidence
Vitamin E did not significantly improve fibrosis scores in PIVENS (P=0.24 versus placebo).
RRR-alpha-tocopherol → Hepatic fibrosis score source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
PIVENS randomized double-blind trial; 247 adults with biopsy-confirmed NASH without diabetes
exposure
RRR-alpha-tocopherol 800 IU/day for 96 weeks; E group n=84, placebo n=83.
limitations
Histological endpoints in a defined nondiabetic NASH population, not proof of general liver benefit, fibrosis reversal, cirrhosis prevention or long-term survival benefit.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The liver-biopsy benefit did not establish fibrosis reversal.
primary_references
[e-clin-pivens2010] Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. (2010). https://pubmed.ncbi.nlm.nih.gov/20427778/ DOI: 10.1056/nejmoa0907929
tissue_or_cell_type
Liver biopsy
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1414–1425
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PIVENS randomized double-blind trial; 247 adults with biopsy-confirmed NASH without diabetes · source_derived_draft · unverified_draft
### e-clin-pivens-fibrosis Vitamin E did not significantly improve fibrosis scores in PIVENS (P=0.24 versus placebo). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver-biopsy benefit did not establish fibrosis reversal. organism: Homo sapiens tissue_or_cell_type: Liver biopsy experimental_model: PIVENS randomized double-blind trial; 247 adults with biopsy-confirmed NASH without diabetes limitations: Histological endpoints in a defined nondiabetic NASH population, not proof of general liver benefit, fibrosis reversal, cirrhosis prevention or long-term survival benefit. exposure: RRR-alpha-tocopherol 800 IU/day for 96 weeks; E group n=84, placebo n=83. cross_nutrient: false [e-clin-pivens2010] Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. (2010). https://pubmed.ncbi.nlm.nih.gov/20427778/ DOI: 10.1056/nejmoa0907929
Complete structured claim and evidence
TONIC did not meet its primary sustained-ALT endpoint with vitamin E: 15/58 children (26%) responded versus 10/58 (17%) with placebo (P=0.26).
RRR-alpha-tocopherol → Sustained alanine aminotransferase reduction source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD
exposure
RRR-alpha-tocopherol 400 IU twice daily for 96 weeks; E and placebo groups n=58 each.
limitations
Primary sustained-ALT endpoint and secondary histology must remain distinct. Not evidence for every child, every liver condition or long-term clinical outcome.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The pediatric trial did not achieve its primary liver-enzyme outcome.
primary_references
[e-clin-tonic2011] Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21521847/ DOI: 10.1001/jama.2011.520
tissue_or_cell_type
Liver enzymes and biopsy
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1427–1438
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD · source_derived_draft · unverified_draft
### e-clin-tonic-alt TONIC did not meet its primary sustained-ALT endpoint with vitamin E: 15/58 children (26%) responded versus 10/58 (17%) with placebo (P=0.26). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pediatric trial did not achieve its primary liver-enzyme outcome. organism: Homo sapiens tissue_or_cell_type: Liver enzymes and biopsy experimental_model: TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD limitations: Primary sustained-ALT endpoint and secondary histology must remain distinct. Not evidence for every child, every liver condition or long-term clinical outcome. exposure: RRR-alpha-tocopherol 400 IU twice daily for 96 weeks; E and placebo groups n=58 each. cross_nutrient: false [e-clin-tonic2011] Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21521847/ DOI: 10.1001/jama.2011.520
Complete structured claim and evidence
Among children with NASH in TONIC, resolution at 96 weeks occurred in 25/43 (58%) receiving vitamin E versus 11/39 (28%) receiving placebo (P=0.006).
RRR-alpha-tocopherol → Steatohepatitis resolution source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD
exposure
RRR-alpha-tocopherol 400 IU twice daily for 96 weeks; E and placebo groups n=58 each.
limitations
Primary sustained-ALT endpoint and secondary histology must remain distinct. Not evidence for every child, every liver condition or long-term clinical outcome.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
A secondary biopsy outcome improved even though the primary enzyme outcome did not.
primary_references
[e-clin-tonic2011] Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21521847/ DOI: 10.1001/jama.2011.520
tissue_or_cell_type
Liver enzymes and biopsy
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1440–1451
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD · source_derived_draft · unverified_draft
### e-clin-tonic-histology Among children with NASH in TONIC, resolution at 96 weeks occurred in 25/43 (58%) receiving vitamin E versus 11/39 (28%) receiving placebo (P=0.006). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A secondary biopsy outcome improved even though the primary enzyme outcome did not. organism: Homo sapiens tissue_or_cell_type: Liver enzymes and biopsy experimental_model: TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD limitations: Primary sustained-ALT endpoint and secondary histology must remain distinct. Not evidence for every child, every liver condition or long-term clinical outcome. exposure: RRR-alpha-tocopherol 400 IU twice daily for 96 weeks; E and placebo groups n=58 each. cross_nutrient: false [e-clin-tonic2011] Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21521847/ DOI: 10.1001/jama.2011.520
Complete structured claim and evidence
The six-patient abetalipoproteinemia report noted that vitamin A alone had not prevented or arrested the retinal lesion, whereas long-term regimens including vitamin E modified its course.
Vitamin A → Retinal function in abetalipoproteinemia source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Six-patient long-term abetalipoproteinemia case series
exposure
Large oral vitamin E doses for 12–18 years alongside low-fat diet and other fat-soluble vitamins; exact dose absent from the abstract.
limitations
Uncontrolled co-treatment series; cannot isolate vitamin E effect or demonstrate nutrient synergy. Genetic lipid transport disease differs from simple low intake.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
In this transport disease, vitamin A alone did not substitute for the broader treatment that included vitamin E.
primary_references
[e-clin-retina1986] Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia. (1986). https://pubmed.ncbi.nlm.nih.gov/3954973/ DOI: 10.1136/bjo.70.3.166
tissue_or_cell_type
Retina
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1453–1464
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-patient long-term abetalipoproteinemia case series · source_derived_draft · unverified_draft
### e-clin-abetalipo-a-alone The six-patient abetalipoproteinemia report noted that vitamin A alone had not prevented or arrested the retinal lesion, whereas long-term regimens including vitamin E modified its course. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this transport disease, vitamin A alone did not substitute for the broader treatment that included vitamin E. organism: Homo sapiens tissue_or_cell_type: Retina experimental_model: Six-patient long-term abetalipoproteinemia case series limitations: Uncontrolled co-treatment series; cannot isolate vitamin E effect or demonstrate nutrient synergy. Genetic lipid transport disease differs from simple low intake. exposure: Large oral vitamin E doses for 12–18 years alongside low-fat diet and other fat-soluble vitamins; exact dose absent from the abstract. cross_nutrient: true [e-clin-retina1986] Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia. (1986). https://pubmed.ncbi.nlm.nih.gov/3954973/ DOI: 10.1136/bjo.70.3.166
Complete structured claim and evidence
Despite combined vitamin A and E treatment, 11 of 13 ABL/HBL patients had subnormal mixed cone-rod electroretinogram amplitudes at long-term follow-up.
Vitamin E → Retinal function in abetalipoproteinemia source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Longitudinal treated cohort; 10 abetalipoproteinemia and 3 homozygous hypobetalipoproteinemia patients
exposure
Combined oral vitamins A and E; mean 11.7 years follow-up, range 4–20; exact doses unavailable in abstract.
limitations
No randomized A-only, E-only or untreated comparator. Residual retinal disease is compatible with partial benefit; it is not proof that supplementation has no effect.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
Combined treatment did not fully prevent retinal abnormalities in every patient.
primary_references
[e-clin-retina2001] Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients. (2001). https://pubmed.ncbi.nlm.nih.gov/11767031/ DOI: 10.1038/eye.2001.167
tissue_or_cell_type
Retina
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1466–1477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Longitudinal treated cohort; 10 abetalipoproteinemia and 3 homozygous hypobetalipoproteinemia patients · source_derived_draft · unverified_draft
### e-clin-abetalipo-residual-retinopathy Despite combined vitamin A and E treatment, 11 of 13 ABL/HBL patients had subnormal mixed cone-rod electroretinogram amplitudes at long-term follow-up. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Combined treatment did not fully prevent retinal abnormalities in every patient. organism: Homo sapiens tissue_or_cell_type: Retina experimental_model: Longitudinal treated cohort; 10 abetalipoproteinemia and 3 homozygous hypobetalipoproteinemia patients limitations: No randomized A-only, E-only or untreated comparator. Residual retinal disease is compatible with partial benefit; it is not proof that supplementation has no effect. exposure: Combined oral vitamins A and E; mean 11.7 years follow-up, range 4–20; exact doses unavailable in abstract. cross_nutrient: true [e-clin-retina2001] Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients. (2001). https://pubmed.ncbi.nlm.nih.gov/11767031/ DOI: 10.1038/eye.2001.167
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.

Mttp loss impairs chylomicron vitamin E export

Condition: machinery_impairment · Mttp deficiency

Normal role: MTP supports chylomicron assembly.

Recorded consequence: Reduced chylomicron-associated vitamin E secretion.

Scope: Mouse enterocytes

Nonfunctional ABCA1 impairs apoA-I-directed vitamin E export

Condition: machinery_impairment · Nonfunctional ABCA1

Normal role: ABCA1 supports transfer to apoA-I.

Recorded consequence: ApoA-I failed to remove alpha-tocopherol.

Scope: Human Tangier fibroblasts

Vitamin E depletion changes TTP localization

Condition: nutrient_deficiency · Serial passage in verified alpha-tocopherol-free medium

Normal role: TTP distribution responds to vitamin E availability.

Recorded consequence: Perinuclear puncta redistribute after repletion.

Scope: Rat hepatoma cells expressing human TTP

R221W impairs ligand-responsive TTP redistribution

Condition: machinery_impairment · Human R221W substitution

Normal role: Wild-type TTP redistributes after vitamin E supply.

Recorded consequence: Persistently punctate distribution after alpha-tocopherol.

Scope: Rat hepatoma cells expressing human TTP variants

Membrane PIP2 depletion impairs TTP-dependent reporter export

Condition: machinery_impairment · Membrane-targeted inositol 5′-phosphatase expression

Normal role: Plasma-membrane PIP2 supports TTP function.

Recorded consequence: Reduced reporter secretion.

Scope: Rat hepatoma cells with human TTP

Hepatocyte GPX4 loss and dietary vitamin E

Condition: machinery_impairment · Alb-Cre-mediated Gpx4 deletion