Alpha-tocopherol

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

dose

Groups differing in alpha-tocopherol content; lowest 2.9 ppm, highest 28.8 ppm

duration

7 days at 2 C

evidence_access

Primary PubMed abstract; unresolved method details explicitly retained.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Rendered fat from marbled beef; bovine food matrix

limitations

Food oxidation and partitioning are not human nutrient metabolism. The abstract supports a matrix-dependent association, not an intake recommendation or gamma-nonalactone-induced vitamin E depletion.

nutrient_topic

Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone

organism

Rendered fat from marbled beef; bovine food matrix

plain_language

The lowest-alpha-tocopherol beef-fat group showed the greatest gamma-nonalactone rise during storage: 51.4 ppb, 11.7 times the prestorage level.

primary_references

Effect of α-tocopherol on lactone formation in marbled beef and changes in lactone volatility during storage. (2012). https://pubmed.ncbi.nlm.nih.gov/22583190/ DOI: 10.1111/j.1750-3841.2012.02694.x

route

Food-matrix storage; no human administration

tissue

Stored-fat headspace and lactone quantitation

Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 147–156

Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Rendered fat from marbled beef; bovine food matrix · source_derived_draft · unverified_draft

## gamma-nonalactone-vitamin-e-matrix The lowest-alpha-tocopherol beef-fat group showed the greatest gamma-nonalactone rise during storage: 51.4 ppb, 11.7 times the prestorage level. Model/species: Rendered fat from marbled beef; bovine food matrix Tissue: Stored-fat headspace and lactone quantitation Exposure: Groups differing in alpha-tocopherol content; lowest 2.9 ppm, highest 28.8 ppm Route: Food-matrix storage; no human administration Duration: 7 days at 2 C Limits: Food oxidation and partitioning are not human nutrient metabolism. The abstract supports a matrix-dependent association, not an intake recommendation or gamma-nonalactone-induced vitamin E depletion. Primary reference: Effect of α-tocopherol on lactone formation in marbled beef and changes in lactone volatility during storage. (2012). https://pubmed.ncbi.nlm.nih.gov/22583190/ DOI: 10.1111/j.1750-3841.2012.02694.x Access: Primary PubMed abstract; unresolved method details explicitly retained.

evidence_span

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experimental_model

Combined-compound proliferation assay

exposure

Lycopene below 1 micromolar and alpha-tocopherol 50 micromolar

limitations

Reported in-vitro synergy; not proof of cancer prevention or a safe/effective supplement combination.

nutrient_topic

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

organism

Human DU-145 and PC-3 prostate carcinoma cells

plain_language

A vitamin E interaction was observed, but only in the tested cancer-cell systems.

primary_references

[lycopene-p9784387] Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. (1998). https://pubmed.ncbi.nlm.nih.gov/9784387/ DOI: 10.1006/bbrc.1998.9351

tissue_or_cell_type

Cultured cell proliferation

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 871–882

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combined-compound proliferation assay · source_derived_draft · unverified_draft

### lycopene-vitamin-e-combination Combined lycopene and alpha-tocopherol inhibited proliferation by up to about 90%; lycopene alone was weak in these cultures. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin E interaction was observed, but only in the tested cancer-cell systems. organism: Human DU-145 and PC-3 prostate carcinoma cells tissue_or_cell_type: Cultured cell proliferation experimental_model: Combined-compound proliferation assay limitations: Reported in-vitro synergy; not proof of cancer prevention or a safe/effective supplement combination. exposure: Lycopene below 1 micromolar and alpha-tocopherol 50 micromolar evidence_span: {"source_cache": "artifacts/lycopene-research/9784387.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "51bb94173c1f98ab622ff028dfefaa016eb3fb5021f40f79e1d7d02bceaa7c15", "start_char": 0, "end_char": 701, "text_sha256": "51bb94173c1f98ab622ff028dfefaa016eb3fb5021f40f79e1d7d02bceaa7c15"} [lycopene-p9784387] Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. (1998). https://pubmed.ncbi.nlm.nih.gov/9784387/ DOI: 10.1006/bbrc.1998.9351

dose

Indicaxanthin 50-100 micromolar; alpha-tocopherol 100 micromolar; LPS 1 microgram/mL

duration

Indicaxanthin 1 h before LPS; lipid peroxides at 0.5 h, PGD2 at 8 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

LPS-stimulated mouse RAW 264.7 macrophages

limitations

Experimental vitamin E antagonism of this response is not evidence that vitamin E intake is harmful or that avoiding supplementation improves clinical outcomes.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

LPS-stimulated mouse RAW 264.7 macrophages

plain_language

Co-incubated alpha-tocopherol prevented the indicaxanthin-associated increase in PGD2 production in stimulated mouse macrophages.

primary_references

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004

route

In vitro co-incubation

tissue

Membrane lipid oxidation and PGD2 production

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 173–182

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · LPS-stimulated mouse RAW 264.7 macrophages · source_derived_draft · unverified_draft

## indicaxanthin-vitamin-e-pgd2-antagonism Co-incubated alpha-tocopherol prevented the indicaxanthin-associated increase in PGD2 production in stimulated mouse macrophages. Model/species: LPS-stimulated mouse RAW 264.7 macrophages Tissue: Membrane lipid oxidation and PGD2 production Exposure: Indicaxanthin 50-100 micromolar; alpha-tocopherol 100 micromolar; LPS 1 microgram/mL Route: In vitro co-incubation Duration: Indicaxanthin 1 h before LPS; lipid peroxides at 0.5 h, PGD2 at 8 h Limits: Experimental vitamin E antagonism of this response is not evidence that vitamin E intake is harmful or that avoiding supplementation improves clinical outcomes. Primary reference: Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. (2014). https://pubmed.ncbi.nlm.nih.gov/25180166/ DOI: 10.1016/j.redox.2014.07.004 Access: Primary open full text, relevant results/methods and PubMed metadata.

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

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

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

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

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

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

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

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

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

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

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

evidence_access

Primary abstract

experimental_model

Cell-free combination comparison.

limitations

Different vitamin E molecules are separate records; a null combination result does not mean either alone lacks antioxidant activity.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

The result for tocotrienols did not carry over to alpha-tocopherol.

primary_references

Synergistic antioxidative effect of astaxanthin and tocotrienol by co-encapsulated in liposomes. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27698536/ · DOI 10.3164/jcbn.15-153

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 198–204

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cell-free combination comparison. · source_derived_draft · unverified_draft

## astaxanthin-tocopherol-null The result for tocotrienols did not carry over to alpha-tocopherol. Co-encapsulating astaxanthin and alpha-tocopherol did not produce an additive antioxidative effect in the same liposome study. Model: Cell-free combination comparison. Limitations: Different vitamin E molecules are separate records; a null combination result does not mean either alone lacks antioxidant activity. Evidence access: Primary abstract Synergistic antioxidative effect of astaxanthin and tocotrienol by co-encapsulated in liposomes. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27698536/ · DOI 10.3164/jcbn.15-153

evidence_span

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experimental_model

Cell-free singlet-oxygen quenching comparison

exposure

Lycopene, beta-carotene, alpha-tocopherol and albumin-bound bilirubin

limitations

Rate constants are solvent/assay-dependent, not a clinical ranking of antioxidant supplements.

nutrient_topic

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

organism

Chemical assay and plasma-concentration comparison

plain_language

A faster molecule is not automatically the more important antioxidant in blood.

primary_references

[lycopene-p2802626] Lycopene as the most efficient biological carotenoid singlet oxygen quencher. (1989). https://pubmed.ncbi.nlm.nih.gov/2802626/ DOI: 10.1016/0003-9861(89)90467-0

tissue_or_cell_type

Solution kinetics

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 429–440

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free singlet-oxygen quenching comparison · source_derived_draft · unverified_draft

### lycopene-quenching-comparison Lycopene quenched singlet oxygen faster per molecule than alpha-tocopherol, but concentration-adjusted plasma capacities were comparable. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: A faster molecule is not automatically the more important antioxidant in blood. organism: Chemical assay and plasma-concentration comparison tissue_or_cell_type: Solution kinetics experimental_model: Cell-free singlet-oxygen quenching comparison limitations: Rate constants are solvent/assay-dependent, not a clinical ranking of antioxidant supplements. exposure: Lycopene, beta-carotene, alpha-tocopherol and albumin-bound bilirubin evidence_span: {"source_cache": "artifacts/lycopene-research/2802626.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "91ad9c300da17ee4e4c78a9ba980a7a4f05eef2328a64b5a9f75d4023abdc521", "start_char": 0, "end_char": 1046, "text_sha256": "91ad9c300da17ee4e4c78a9ba980a7a4f05eef2328a64b5a9f75d4023abdc521"} [lycopene-p2802626] Lycopene as the most efficient biological carotenoid singlet oxygen quencher. (1989). https://pubmed.ncbi.nlm.nih.gov/2802626/ DOI: 10.1016/0003-9861(89)90467-0

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

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

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

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

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

evidence_span

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experimental_model

Twelve patients sampled at the first and fifteenth hyperbaric session

exposure

Fifteen hyperbaric oxygen treatments without antioxidant supplementation

limitations

A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human

plain_language

The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell.

primary_references

[hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

tissue_or_cell_type

Plasma and erythrocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 270–281

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve patients sampled at the first and fifteenth hyperbaric session · source_derived_draft · unverified_draft

### hbot-gpx-unchanged Glutathione peroxidase activity remained almost unchanged, and no relevant differences were detected in reduced glutathione, alpha-tocopherol or retinol plasma levels. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Twelve patients sampled at the first and fifteenth hyperbaric session limitations: A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation. exposure: Fifteen hyperbaric oxygen treatments without antioxidant supplementation evidence_span: {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"} [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

evidence_access

Primary abstract

experimental_model

Radical assay and microsomal TBARS comparison; species unresolved in accessed abstract.

limitations

Synthetic lipophilic analogues in this paper are separate compounds; their activity is not assigned to myricetin.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

A chemical antioxidant ranking is not membrane protection.

primary_references

Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15080911/ · DOI 10.1016/j.bmc.2004.02.031

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 380–386

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Radical assay and microsomal TBARS comparison; species unresolved in accessed abstract. · source_derived_draft · unverified_draft

## myricetin-radical-versus-membrane A chemical antioxidant ranking is not membrane protection. Myricetin reacted with galvinoxyl radicals faster and with greater stoichiometric capacity than alpha-tocopherol, yet failed to protect the tested vitamin-E-deficient microsomes. Model: Radical assay and microsomal TBARS comparison; species unresolved in accessed abstract. Limitations: Synthetic lipophilic analogues in this paper are separate compounds; their activity is not assigned to myricetin. Evidence access: Primary abstract Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15080911/ · DOI 10.1016/j.bmc.2004.02.031

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Rats first maintained on vitamin-E-deficient diet for ten weeks.

limitations

Dose is per kg of diet, not body weight; does not establish all possible co-supplementation effects.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

Myricetin did not function as a substitute for vitamin E in this model.

primary_references

Antioxidant capacity of flavonoids in hepatic microsomes is not reflected by antioxidant effects in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22919437/ · DOI 10.1155/2012/165127

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 372–378

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rats first maintained on vitamin-E-deficient diet for ten weeks. · source_derived_draft · unverified_draft

## myricetin-vitamin-e-replacement Myricetin did not function as a substitute for vitamin E in this model. Feeding vitamin-E-deficient rats 100 mg myricetin/kg diet for two weeks did not significantly improve the reported lipid-peroxidation and tissue-damage indices, unlike alpha-tocopherol repletion. Model: Rats first maintained on vitamin-E-deficient diet for ten weeks. Limitations: Dose is per kg of diet, not body weight; does not establish all possible co-supplementation effects. Evidence access: Primary full text Antioxidant capacity of flavonoids in hepatic microsomes is not reflected by antioxidant effects in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22919437/ · DOI 10.1155/2012/165127

evidence_access

Primary abstract

experimental_model

Rat liver microsomal oxidation assay under air.

limitations

This does not support a universal potency multiplier over vitamin E or human clinical efficacy.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

It interrupted oxidation in an experimental membrane preparation.

primary_references

Astaxanthin and canthaxanthin are potent antioxidants in a membrane model. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1497349/ · DOI 10.1016/0003-9861(92)90675-m

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 150–156

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat liver microsomal oxidation assay under air. · source_derived_draft · unverified_draft

## astaxanthin-microsome-oxidation It interrupted oxidation in an experimental membrane preparation. Astaxanthin inhibited radical-induced lipid peroxidation in rat liver microsomes, with activity comparable to alpha-tocopherol under the tested conditions. Model: Rat liver microsomal oxidation assay under air. Limitations: This does not support a universal potency multiplier over vitamin E or human clinical efficacy. Evidence access: Primary abstract Astaxanthin and canthaxanthin are potent antioxidants in a membrane model. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1497349/ · DOI 10.1016/0003-9861(92)90675-m

evidence_span

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experimental_model

Combined-compound proliferation assay

exposure

Lycopene below 1 micromolar and alpha-tocopherol 50 micromolar

limitations

Reported in-vitro synergy; not proof of cancer prevention or a safe/effective supplement combination.

nutrient_topic

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

organism

Human DU-145 and PC-3 prostate carcinoma cells

plain_language

The result cannot be generalized to every antioxidant partner.

primary_references

[lycopene-p9784387] Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. (1998). https://pubmed.ncbi.nlm.nih.gov/9784387/ DOI: 10.1006/bbrc.1998.9351

tissue_or_cell_type

Cultured cell proliferation

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 884–895

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combined-compound proliferation assay · source_derived_draft · unverified_draft

### lycopene-combination-specificity The alpha-tocopherol combination effect was not reproduced with beta-tocopherol, ascorbic acid or probucol. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: The result cannot be generalized to every antioxidant partner. organism: Human DU-145 and PC-3 prostate carcinoma cells tissue_or_cell_type: Cultured cell proliferation experimental_model: Combined-compound proliferation assay limitations: Reported in-vitro synergy; not proof of cancer prevention or a safe/effective supplement combination. exposure: Lycopene below 1 micromolar and alpha-tocopherol 50 micromolar evidence_span: {"source_cache": "artifacts/lycopene-research/9784387.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "51bb94173c1f98ab622ff028dfefaa016eb3fb5021f40f79e1d7d02bceaa7c15", "start_char": 0, "end_char": 701, "text_sha256": "51bb94173c1f98ab622ff028dfefaa016eb3fb5021f40f79e1d7d02bceaa7c15"} [lycopene-p9784387] Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. (1998). https://pubmed.ncbi.nlm.nih.gov/9784387/ DOI: 10.1006/bbrc.1998.9351

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/lycopene-research/15930452.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a90148eb83ff18442e37f9fd5ed31f44acbf8d7616ef05ff1e65e6e2d64e84f", "start_char": 0, "end_char": 1595, "text_sha256": "3a90148eb83ff18442e37f9fd5ed31f44acbf8d7616ef05ff1e65e6e2d64e84f"}

experimental_model

Randomized 36-week controlled diet study

exposure

Olestra substituted for one-third of fat energy; daily multivitamin and vitamin-E-fortified olestra

limitations

Exposure-specific depletion, not an established lycopene deficiency syndrome; reference-range limits are not clinical deficiency thresholds.

nutrient_topic

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

organism

Human, 37 healthy men

plain_language

Replacing dietary fat with a nonabsorbed substitute changed carotenoid exposure.

primary_references

[lycopene-p15930452] Daily intake of multivitamins during long-term intake of olestra in men prevents declines in serum vitamins A and E but not carotenoids. (2005). https://pubmed.ncbi.nlm.nih.gov/15930452/ DOI: 10.1093/jn/135.6.1456

tissue_or_cell_type

Serum carotenoids and fat-soluble vitamins

trigger_kind

biomarker_context Imported condition classification; unverified.

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 858–869

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized 36-week controlled diet study · source_derived_draft · unverified_draft

### lycopene-olestra-lycopene Olestra lowered serum lycopene by 12 weeks, persisting after cholesterol or BMI adjustment; the multivitamin did not prevent this. Condition category: biomarker_context nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing dietary fat with a nonabsorbed substitute changed carotenoid exposure. organism: Human, 37 healthy men tissue_or_cell_type: Serum carotenoids and fat-soluble vitamins experimental_model: Randomized 36-week controlled diet study limitations: Exposure-specific depletion, not an established lycopene deficiency syndrome; reference-range limits are not clinical deficiency thresholds. exposure: Olestra substituted for one-third of fat energy; daily multivitamin and vitamin-E-fortified olestra evidence_span: {"source_cache": "artifacts/lycopene-research/15930452.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a90148eb83ff18442e37f9fd5ed31f44acbf8d7616ef05ff1e65e6e2d64e84f", "start_char": 0, "end_char": 1595, "text_sha256": "3a90148eb83ff18442e37f9fd5ed31f44acbf8d7616ef05ff1e65e6e2d64e84f"} [lycopene-p15930452] Daily intake of multivitamins during long-term intake of olestra in men prevents declines in serum vitamins A and E but not carotenoids. (2005). https://pubmed.ncbi.nlm.nih.gov/15930452/ DOI: 10.1093/jn/135.6.1456

evidence_span

{"source_cache": "artifacts/lycopene-research/2802626.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "91ad9c300da17ee4e4c78a9ba980a7a4f05eef2328a64b5a9f75d4023abdc521", "start_char": 0, "end_char": 1046, "text_sha256": "91ad9c300da17ee4e4c78a9ba980a7a4f05eef2328a64b5a9f75d4023abdc521"}

experimental_model

Cell-free singlet-oxygen quenching comparison

exposure

Lycopene, beta-carotene, alpha-tocopherol and albumin-bound bilirubin

limitations

Rate constants are solvent/assay-dependent, not a clinical ranking of antioxidant supplements.

nutrient_topic

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

organism

Chemical assay and plasma-concentration comparison

plain_language

It can remove excitation energy from this reactive oxygen species.

primary_references

[lycopene-p2802626] Lycopene as the most efficient biological carotenoid singlet oxygen quencher. (1989). https://pubmed.ncbi.nlm.nih.gov/2802626/ DOI: 10.1016/0003-9861(89)90467-0

tissue_or_cell_type

Solution kinetics

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 416–427

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free singlet-oxygen quenching comparison · source_derived_draft · unverified_draft

### lycopene-singlet-quenching Lycopene had a reported singlet-oxygen quenching constant of 31 billion per molar per second in the assay. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: It can remove excitation energy from this reactive oxygen species. organism: Chemical assay and plasma-concentration comparison tissue_or_cell_type: Solution kinetics experimental_model: Cell-free singlet-oxygen quenching comparison limitations: Rate constants are solvent/assay-dependent, not a clinical ranking of antioxidant supplements. exposure: Lycopene, beta-carotene, alpha-tocopherol and albumin-bound bilirubin evidence_span: {"source_cache": "artifacts/lycopene-research/2802626.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "91ad9c300da17ee4e4c78a9ba980a7a4f05eef2328a64b5a9f75d4023abdc521", "start_char": 0, "end_char": 1046, "text_sha256": "91ad9c300da17ee4e4c78a9ba980a7a4f05eef2328a64b5a9f75d4023abdc521"} [lycopene-p2802626] Lycopene as the most efficient biological carotenoid singlet oxygen quencher. (1989). https://pubmed.ncbi.nlm.nih.gov/2802626/ DOI: 10.1016/0003-9861(89)90467-0

dose

Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human beta-thalassemia donor erythrocytes

limitations

Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human beta-thalassemia donor erythrocytes

plain_language

Added indicaxanthin delayed vitamin E depletion during oxidative challenge of beta-thalassemic red cells.

primary_references

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228

route

Ex vivo addition

tissue

Red blood cells

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 30–39

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human beta-thalassemia donor erythrocytes · source_derived_draft · unverified_draft

## indicaxanthin-rbc-vitamin-e Added indicaxanthin delayed vitamin E depletion during oxidative challenge of beta-thalassemic red cells. Model/species: Human beta-thalassemia donor erythrocytes Tissue: Red blood cells Exposure: Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge Route: Ex vivo addition Duration: Not specified in accessed abstract Limits: Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis. Primary reference: Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228 Access: Primary PubMed abstract.

dose

25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation

duration

Kinetic oxidation assay; incubation duration not specified in accessed abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Human pooled plasma from 10 healthy donors; isolated LDL

limitations

Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human pooled plasma from 10 healthy donors; isolated LDL

plain_language

Betanin did not produce the early vitamin E preservation observed with indicaxanthin in this LDL experiment.

primary_references

Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

route

Ex vivo spiking, not oral dosing

tissue

Plasma and LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 97–105

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human pooled plasma from 10 healthy donors; isolated LDL · source_derived_draft · unverified_draft

## betalains-betanin-vitamin-e-null Betanin did not produce the early vitamin E preservation observed with indicaxanthin in this LDL experiment. Model/species: Human pooled plasma from 10 healthy donors; isolated LDL Tissue: Plasma and LDL Exposure: 25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation Route: Ex vivo spiking, not oral dosing Duration: Kinetic oxidation assay; incubation duration not specified in accessed abstract Limits: Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay. Primary reference: Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

dose

Single 500 g cactus pear pulp meal: 28 mg indicaxanthin and 16 mg betanin

duration

Plasma/urine followed for 12 h

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Eight healthy human volunteers

limitations

Whole-food exposure cannot attribute the LDL response exclusively to either pigment; urinary recovery is not absolute absorption.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Eight healthy human volunteers

plain_language

LDL isolated 3 and 5 h after cactus pear ingestion resisted ex vivo oxidation more strongly; LDL vitamin E and beta-carotene levels were unchanged.

primary_references

Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15447903/ DOI: 10.1093/ajcn/80.4.941

route

Oral whole food

tissue

Plasma, urine and isolated LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 517–525

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Eight healthy human volunteers · source_derived_draft · unverified_draft

## betalains-human-food-ldl LDL isolated 3 and 5 h after cactus pear ingestion resisted ex vivo oxidation more strongly; LDL vitamin E and beta-carotene levels were unchanged. Model/species: Eight healthy human volunteers Tissue: Plasma, urine and isolated LDL Exposure: Single 500 g cactus pear pulp meal: 28 mg indicaxanthin and 16 mg betanin Route: Oral whole food Duration: Plasma/urine followed for 12 h Limits: Whole-food exposure cannot attribute the LDL response exclusively to either pigment; urinary recovery is not absolute absorption. Primary reference: Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15447903/ DOI: 10.1093/ajcn/80.4.941

dose

25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation

duration

Kinetic oxidation assay; incubation duration not specified in accessed abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Human pooled plasma from 10 healthy donors; isolated LDL

limitations

Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay. The authors infer assay synergy; direct tocopheroxyl-radical recycling is not established.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human pooled plasma from 10 healthy donors; isolated LDL

plain_language

Indicaxanthin preserved LDL vitamin E early during oxidation; combined action protected LDL more than sequential separate action.

primary_references

Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

route

Ex vivo spiking, not oral dosing

tissue

Plasma and LDL

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 87–95

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human pooled plasma from 10 healthy donors; isolated LDL · source_derived_draft · unverified_draft

## betalains-indicaxanthin-vitamin-e Indicaxanthin preserved LDL vitamin E early during oxidation; combined action protected LDL more than sequential separate action. Model/species: Human pooled plasma from 10 healthy donors; isolated LDL Tissue: Plasma and LDL Exposure: 25-100 micromolar pigment added to plasma; copper-triggered LDL oxidation Route: Ex vivo spiking, not oral dosing Duration: Kinetic oxidation assay; incubation duration not specified in accessed abstract Limits: Plasma spiking exceeds typical dietary parent-pigment exposure; vitamin synergy refers only to this assay. The authors infer assay synergy; direct tocopheroxyl-radical recycling is not established. Primary reference: Increased resistance to oxidation of betalain-enriched human low density lipoproteins. (2003). https://pubmed.ncbi.nlm.nih.gov/12868496/ DOI: 10.1080/1071576031000097490

cross_nutrient

Clinical outcome boundary for extrapolation from vitamin C/vitamin E redox recycling.

experimental_model

Physicians Health Study II: placebo-controlled double-blind factorial trial, 14641 male physicians aged at least 50, mean eight-year follow-up.

exposure

Vitamin C 500 mg/day and separately randomized vitamin E 400 IU every other day; clinical CVD endpoints.

limitations

Older male physicians, not a selected scurvy cohort; separate vitamin E randomization is not proof of molecular synergy or antagonism.

nutrient_topic

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

organism

Homo sapiens

plain_language

A long-term supplement trial did not turn the antioxidant rationale into fewer major cardiovascular events.

primary_references

[c-sesso2008] 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

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1830–1841

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Physicians Health Study II: placebo-controlled double-blind factorial trial, 14641 male physicians aged at least 50, mean eight-year follow-up. · source_derived_draft · unverified_draft

### c-cvd-prevention-null Vitamin C assignment did not reduce major cardiovascular events (HR 0.99; 95% CI 0.89–1.11; P=0.91) over mean eight-year follow-up. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: A long-term supplement trial did not turn the antioxidant rationale into fewer major cardiovascular events. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Physicians Health Study II: placebo-controlled double-blind factorial trial, 14641 male physicians aged at least 50, mean eight-year follow-up. limitations: Older male physicians, not a selected scurvy cohort; separate vitamin E randomization is not proof of molecular synergy or antagonism. exposure: Vitamin C 500 mg/day and separately randomized vitamin E 400 IU every other day; clinical CVD endpoints. cross_nutrient: Clinical outcome boundary for extrapolation from vitamin C/vitamin E redox recycling. [c-sesso2008] 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

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

evidence_span

{"source_cache": "artifacts/lutein-research/16380385.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "410a6cc6c3325e6d2f459b06ddaf9c7b7806f9b82a918f1df02b1626f5f84074", "start_char": 0, "end_char": 1960, "text_sha256": "410a6cc6c3325e6d2f459b06ddaf9c7b7806f9b82a918f1df02b1626f5f84074"}

experimental_model

Mixed-micelle uptake in Caco-2 TC-7 cells

exposure

Alpha-tocopherol with co-incubated lutein

limitations

In vitro competition is not demonstrated vitamin E deficiency or a clinical dose-spacing rule.

nutrient_topic

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

organism

Human cell model

plain_language

Lutein and vitamin E can interact during intestinal uptake.

primary_references

[lutein-p16380385] 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 epithelium

Lutein: metabolism, signaling and nutrient connections (2026-09-17) · lines 541–552

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mixed-micelle uptake in Caco-2 TC-7 cells · source_derived_draft · unverified_draft

### lutein-vitamin-e-competition Co-incubated lutein reduced alpha-tocopherol uptake in Caco-2 TC-7 cells. Condition category: normal nutrient_topic: Lutein research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lutein and vitamin E can interact during intestinal uptake. organism: Human cell model tissue_or_cell_type: Intestinal epithelium experimental_model: Mixed-micelle uptake in Caco-2 TC-7 cells limitations: In vitro competition is not demonstrated vitamin E deficiency or a clinical dose-spacing rule. exposure: Alpha-tocopherol with co-incubated lutein evidence_span: {"source_cache": "artifacts/lutein-research/16380385.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "410a6cc6c3325e6d2f459b06ddaf9c7b7806f9b82a918f1df02b1626f5f84074", "start_char": 0, "end_char": 1960, "text_sha256": "410a6cc6c3325e6d2f459b06ddaf9c7b7806f9b82a918f1df02b1626f5f84074"} [lutein-p16380385] 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

evidence_span

{"source_cache": "artifacts/pectin-research/10573545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f0828162b0e41d10d79784cea5cc96e55409b4ee80be3afc399132a7ad087332", "start_char": 0, "end_char": 1340, "text_sha256": "f0828162b0e41d10d79784cea5cc96e55409b4ee80be3afc399132a7ad087332"}

experimental_model

Crossover mixed-carotenoid meal study in six healthy women

exposure

Pectin or other fibers at 0.15 g/kg with a carotenoid and alpha-tocopherol mixture

limitations

Reported effect-size ranges cover multiple fibers, not one pectin-specific estimate. Plasma exposure does not establish long-term deficiency.

nutrient_topic

Pectin research collection; topical membership is not evidence of a direct dietary effect. · Pectin, structurally heterogeneous plant polysaccharides

organism

Homo sapiens

plain_language

This study did not show the same reduction for vitamin E.

primary_references

[pectin-p10573545] Some dietary fibers reduce the absorption of carotenoids in women. (1999). https://pubmed.ncbi.nlm.nih.gov/10573545/ DOI: 10.1093/jn/129.12.2170

tissue_or_cell_type

Plasma 24-hour area under the curve

Pectin: metabolism, signaling and nutrient connections (2026-09-17) · lines 711–722

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover mixed-carotenoid meal study in six healthy women · source_derived_draft · unverified_draft

### pectin-vitamin-e-null Alpha-tocopherol AUC was not significantly affected by the tested fibers. Condition category: normal nutrient_topic: Pectin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This study did not show the same reduction for vitamin E. organism: Homo sapiens tissue_or_cell_type: Plasma 24-hour area under the curve experimental_model: Crossover mixed-carotenoid meal study in six healthy women limitations: Reported effect-size ranges cover multiple fibers, not one pectin-specific estimate. Plasma exposure does not establish long-term deficiency. exposure: Pectin or other fibers at 0.15 g/kg with a carotenoid and alpha-tocopherol mixture evidence_span: {"source_cache": "artifacts/pectin-research/10573545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f0828162b0e41d10d79784cea5cc96e55409b4ee80be3afc399132a7ad087332", "start_char": 0, "end_char": 1340, "text_sha256": "f0828162b0e41d10d79784cea5cc96e55409b4ee80be3afc399132a7ad087332"} [pectin-p10573545] Some dietary fibers reduce the absorption of carotenoids in women. (1999). https://pubmed.ncbi.nlm.nih.gov/10573545/ DOI: 10.1093/jn/129.12.2170

evidence_span

{"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"}

experimental_model

Retinaldehyde-liposome photosensitization with cells

exposure

4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate

limitations

Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cells and unsaturated liposomes

plain_language

A higher concentration changed the interaction.

primary_references

[zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

tissue_or_cell_type

RPE injury model

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 951–962

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

### zeaxanthin-ascorbate-high At 2 mM, ascorbate exacerbated phototoxicity; zeaxanthin or alpha-tocopherol partly ameliorated it. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher concentration changed the interaction. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

evidence_span

{"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"}

experimental_model

Retinaldehyde-liposome photosensitization with cells

exposure

4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate

limitations

Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cells and unsaturated liposomes

plain_language

Vitamin C added protection under this condition.

primary_references

[zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

tissue_or_cell_type

RPE injury model

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 938–949

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

### zeaxanthin-ascorbate-low Adding 0.5 mM ascorbate to the combination raised viability to approximately 69%. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C added protection under this condition. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

evidence_span

{"source_cache": "artifacts/zeaxanthin-research/22924673.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177", "start_char": 0, "end_char": 1415, "text_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177"}

experimental_model

Rose-bengal photosensitization with antioxidant combinations

exposure

Visible-light exposures; ascorbate 0.35–1.4 mM with lipophilic antioxidants

limitations

Different photosensitizer and exposure duration from the retinaldehyde study; do not treat this as a universal contradiction or dietary safety threshold.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cells

plain_language

Protection had limits under a different light challenge.

primary_references

[zeaxanthin-p22924673] Concentration dependence of vitamin C in combinations with vitamin E and zeaxanthin on light-induced toxicity to retinal pigment epithelial cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22924673/ DOI: 10.1111/j.1751-1097.2012.01228.x

tissue_or_cell_type

Cultured RPE model

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 964–975

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rose-bengal photosensitization with antioxidant combinations · source_derived_draft · unverified_draft

### zeaxanthin-ascorbate-rescue-limit The vitamin E–zeaxanthin combination did not prevent the deleterious high-ascorbate effect in the rose-bengal model. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection had limits under a different light challenge. organism: Human ARPE-19 cells tissue_or_cell_type: Cultured RPE model experimental_model: Rose-bengal photosensitization with antioxidant combinations limitations: Different photosensitizer and exposure duration from the retinaldehyde study; do not treat this as a universal contradiction or dietary safety threshold. exposure: Visible-light exposures; ascorbate 0.35–1.4 mM with lipophilic antioxidants evidence_span: {"source_cache": "artifacts/zeaxanthin-research/22924673.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177", "start_char": 0, "end_char": 1415, "text_sha256": "0acdf0e77d224421d61b41baeefd396ff54e53488a85dee22bfb04b0f827c177"} [zeaxanthin-p22924673] Concentration dependence of vitamin C in combinations with vitamin E and zeaxanthin on light-induced toxicity to retinal pigment epithelial cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22924673/ DOI: 10.1111/j.1751-1097.2012.01228.x

evidence_span

{"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"}

experimental_model

Retinaldehyde-liposome photosensitization with cells

exposure

4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate

limitations

Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cells and unsaturated liposomes

plain_language

The pair protected cells against this defined light challenge.

primary_references

[zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

tissue_or_cell_type

RPE injury model

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 925–936

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

### zeaxanthin-c-e-z-protection Combined zeaxanthin and alpha-tocopherol raised viability from about 26% to 63% in the tested model. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pair protected cells against this defined light challenge. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

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

experimental_model

Human stem-cell neurons/organoids.

limitations

No dietary recommendation or evidence that vitamin A replaces vitamin E in humans.

nutrient_topic

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

organism

Homo sapiens

plain_language

Suppressing ferroptosis supported this developmental model.

primary_references

[va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

tissue_or_cell_type

Human neural cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1823–1832

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human stem-cell neurons/organoids. · source_derived_draft · unverified_draft

### va-atra-neuronal-ferroptosis-rescue ATRA or ferrostatin-1 rescued differentiation under antioxidant-deprived neuronal culture conditions. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suppressing ferroptosis supported this developmental model. organism: Homo sapiens tissue_or_cell_type: Human neural cultures experimental_model: Human stem-cell neurons/organoids. limitations: No dietary recommendation or evidence that vitamin A replaces vitamin E in humans. [va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

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

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/

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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