RRR-alpha-tocopherol

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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