All-trans-retinol

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Genotype-by-diet mouse comparison

exposure

Maternal vitamin A-free diet from E0.5 through lactation; neonatal endpoints through P18.

limitations

Storage-defective background accelerated depletion; this is not a knockout-only effect.

nutrient_topic

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

organism

Mus musculus

plain_language

Vitamin A shortage can stop early sperm-cell differentiation.

primary_references

[li2011] Vitamin A deficiency results in meiotic failure and accumulation of undifferentiated spermatogonia in prepubertal mouse testis. (2011). https://pubmed.ncbi.nlm.nih.gov/20881313/ DOI: 10.1095/biolreprod.110.086157

tissue_or_cell_type

prepubertal testis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 265–276

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype-by-diet mouse comparison · source_derived_draft · unverified_draft

### va-repro-vitamin-a-withdrawal Dietary vitamin A depletion caused undifferentiated spermatogonia to accumulate in prepubertal Lrat-null testes. Condition category: nutrient_deficiency nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A shortage can stop early sperm-cell differentiation. organism: Mus musculus tissue_or_cell_type: prepubertal testis experimental_model: Genotype-by-diet mouse comparison limitations: Storage-defective background accelerated depletion; this is not a knockout-only effect. exposure: Maternal vitamin A-free diet from E0.5 through lactation; neonatal endpoints through P18. cross_nutrient: false [li2011] Vitamin A deficiency results in meiotic failure and accumulation of undifferentiated spermatogonia in prepubertal mouse testis. (2011). https://pubmed.ncbi.nlm.nih.gov/20881313/ DOI: 10.1095/biolreprod.110.086157

cross_nutrient

true

evidence_location

Figure 3A–C

experimental_model

Mouse naïve ESCs in vitamin-A-free N2B27/2i medium; transcript quantification

exposure

Retinol titration 0–50 ng/mL; 8-h and 72-h transcript assays.

limitations

Retinoid signaling and response depend on culture context; no claim that vitamin A supplementation demethylates adult human tissues.

nutrient_topic

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

organism

Mus musculus

plain_language

Vitamin A raised expression of DNA-modifying enzymes through a different route from vitamin C’s iron-redox effect.

primary_references

[c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

tissue_or_cell_type

Naïve embryonic stem cells

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1047–1059

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse naïve ESCs in vitamin-A-free N2B27/2i medium; transcript quantification · source_derived_draft · unverified_draft

### c-reg-retinol-tet2-expression Retinol supplementation increased Tet2 transcription in mouse naïve ESCs within 8 h and after 72 h; Tet3 also responded, whereas evidence did not support direct retinol stimulation of TET catalytic efficiency. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A raised expression of DNA-modifying enzymes through a different route from vitamin C’s iron-redox effect. organism: Mus musculus tissue_or_cell_type: Naïve embryonic stem cells experimental_model: Mouse naïve ESCs in vitamin-A-free N2B27/2i medium; transcript quantification limitations: Retinoid signaling and response depend on culture context; no claim that vitamin A supplementation demethylates adult human tissues. exposure: Retinol titration 0–50 ng/mL; 8-h and 72-h transcript assays. cross_nutrient: true evidence_location: Figure 3A–C [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

cross_nutrient

true

experimental_model

Fluorescence competition assay, Figure 6G

exposure

5 µM NBD-alpha-tocopherol; 0.1 µM PKC alpha; retinol concentration series; 30 min at room temperature, 1% ethanol.

limitations

Exact retinol axis values were not extracted; this is direct in-vitro competition, not demonstrated competition between dietary vitamins in human tissues.

nutrient_topic

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

organism

Homo sapiens

plain_language

Vitamin A alcohol competed with the labeled vitamin E probe for association with this purified kinase.

primary_references

[mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318

tissue_or_cell_type

Cell-free enzyme

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 985–996

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fluorescence competition assay, Figure 6G · source_derived_draft · unverified_draft

### e-sig-retinol-pkc-competition Retinol competed with 5 µM NBD-alpha-tocopherol for binding to 0.1 µM recombinant PKC alpha, whereas phosphatidylserine and cholesterol did not compete in the same study. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A alcohol competed with the labeled vitamin E probe for association with this purified kinase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Fluorescence competition assay, Figure 6G limitations: Exact retinol axis values were not extracted; this is direct in-vitro competition, not demonstrated competition between dietary vitamins in human tissues. exposure: 5 µM NBD-alpha-tocopherol; 0.1 µM PKC alpha; retinol concentration series; 30 min at room temperature, 1% ethanol. cross_nutrient: true [mccary2012] Vitamin E isoforms directly bind PKCα and differentially regulate activation of PKCα. (2012). https://pubmed.ncbi.nlm.nih.gov/21933153/ DOI: 10.1042/bj20111318

experimental_model

Wild-type/Rdh8-null/Rdh12-null rod fluorescence

limitations

Residual reductases exist; this does not establish an exclusive enzyme.

nutrient_topic

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

organism

Mus musculus

plain_language

RDH8 converts the aldehyde photoproduct back to retinol in the outer segment.

primary_references

[chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

tissue_or_cell_type

Rod outer segment

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 756–765

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type/Rdh8-null/Rdh12-null rod fluorescence · source_derived_draft · unverified_draft

### a-vision-rdh8-reduction Single-cell knockout comparisons showed RDH8 supplies most reduction of bleach-generated all-trans-retinal in mouse rod outer segments. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH8 converts the aldehyde photoproduct back to retinol in the outer segment. organism: Mus musculus tissue_or_cell_type: Rod outer segment experimental_model: Wild-type/Rdh8-null/Rdh12-null rod fluorescence limitations: Residual reductases exist; this does not establish an exclusive enzyme. [chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

cross_nutrient

NADPH supports a retinoid buffering reaction.

evidence_location

Figure 5 and Table 1

experimental_model

Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos.

exposure

DHRS3 coexpressed with RDH10; retinal plus NADPH.

limitations

Cofactor dependency is not a dietary niacin intervention.

nutrient_topic

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

organism

Homo sapiens proteins in Sf9 and HEK293 systems

outcome

RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH.

plain_language

This reverse step restrains retinal available for acid production.

primary_references

[va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257

tissue_or_cell_type

Microsomal/cellular retinoid system

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 516–529

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. · source_derived_draft · unverified_draft

### va-dhrs3-retinal-reduction RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This reverse step restrains retinal available for acid production. organism: Homo sapiens proteins in Sf9 and HEK293 systems tissue_or_cell_type: Microsomal/cellular retinoid system experimental_model: Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. limitations: Cofactor dependency is not a dietary niacin intervention. exposure: DHRS3 coexpressed with RDH10; retinal plus NADPH. outcome: RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. evidence_location: Figure 5 and Table 1 cross_nutrient: NADPH supports a retinoid buffering reaction. [va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257

evidence_location

Abstract

experimental_model

Transfected-cell radioretinol uptake and real-time retinol-release assays.

exposure

Retinol-loaded RBP and STRA6 expression.

limitations

In vitro transport mechanism; no organism-wide flux estimate. Cell-line species were not resolved in the retrieved abstract/figure evidence; no species-specific extension is asserted.

nutrient_topic

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

organism

Mammalian transfected-cell preparations

outcome

STRA6 accelerated retinol release from extracellular RBP in real-time assays.

plain_language

The receptor unloads retinol from its blood carrier.

primary_references

[va-kawaguchi-2011] Receptor-mediated cellular uptake mechanism that couples to intracellular storage (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3199320/ DOI: 10.1021/cb200178w

tissue_or_cell_type

Plasma membrane

transport_direction

extracellular holo-RBP4 to membrane/cell

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 444–457

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected-cell radioretinol uptake and real-time retinol-release assays. · source_derived_draft · unverified_draft

### va-stra6-retinol-release STRA6 accelerated retinol release from extracellular RBP in real-time assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor unloads retinol from its blood carrier. organism: Mammalian transfected-cell preparations tissue_or_cell_type: Plasma membrane experimental_model: Transfected-cell radioretinol uptake and real-time retinol-release assays. limitations: In vitro transport mechanism; no organism-wide flux estimate. Cell-line species were not resolved in the retrieved abstract/figure evidence; no species-specific extension is asserted. exposure: Retinol-loaded RBP and STRA6 expression. outcome: STRA6 accelerated retinol release from extracellular RBP in real-time assays. evidence_location: Abstract transport_direction: extracellular holo-RBP4 to membrane/cell [va-kawaguchi-2011] Receptor-mediated cellular uptake mechanism that couples to intracellular storage (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3199320/ DOI: 10.1021/cb200178w

dose

Pureed labeled Moringa leaves providing 1 mg beta-carotene plus a reference retinyl-acetate dose

duration

Thirty-five-day isotope sampling

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Fifteen Mexican children aged 17-35 months

limitations

Children were well nourished with adequate vitamin A stores; the estimate may differ with deficiency, food matrix, genetics and infection.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Fifteen Mexican children aged 17-35 months

plain_language

In fifteen well-nourished young children, intrinsically labeled beta-carotene from pureed Moringa leaves had 28% relative bioefficacy and an estimated vitamin A equivalence of 3.3:1 by weight.

primary_references

Use of a "Super-child" Approach to Assess the Vitamin A Equivalence of Moringa oleifera Leaves, Develop a Compartmental Model for Vitamin A Kinetics, and Estimate Vitamin A Total Body Stores in Young Mexican Children. (2017). https://pubmed.ncbi.nlm.nih.gov/28931584/ DOI: 10.3945/jn.117.256974

route

Oral

tissue

Stable-isotope plasma retinol kinetics

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 233–242

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Fifteen Mexican children aged 17-35 months · source_derived_draft · unverified_draft

## moringa-child-vitamin-a-equivalence In fifteen well-nourished young children, intrinsically labeled beta-carotene from pureed Moringa leaves had 28% relative bioefficacy and an estimated vitamin A equivalence of 3.3:1 by weight. Model/species: Fifteen Mexican children aged 17-35 months Tissue/system: Stable-isotope plasma retinol kinetics Exposure: Pureed labeled Moringa leaves providing 1 mg beta-carotene plus a reference retinyl-acetate dose Route: Oral Duration: Thirty-five-day isotope sampling Limits: Children were well nourished with adequate vitamin A stores; the estimate may differ with deficiency, food matrix, genetics and infection. Primary reference: Use of a "Super-child" Approach to Assess the Vitamin A Equivalence of Moringa oleifera Leaves, Develop a Compartmental Model for Vitamin A Kinetics, and Estimate Vitamin A Total Body Stores in Young Mexican Children. (2017). https://pubmed.ncbi.nlm.nih.gov/28931584/ DOI: 10.3945/jn.117.256974 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Dietary rescue experiment

exposure

100 U/day maternal retinyl palmitate from P5; assessment at P10.

limitations

Rescue of early markers is not proof of adult fertility or a human dose.

nutrient_topic

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

organism

Mus musculus

plain_language

Replacing the missing nutrient restored early meiotic development.

primary_references

[li2011] Vitamin A deficiency results in meiotic failure and accumulation of undifferentiated spermatogonia in prepubertal mouse testis. (2011). https://pubmed.ncbi.nlm.nih.gov/20881313/ DOI: 10.1095/biolreprod.110.086157

tissue_or_cell_type

neonatal testis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 278–289

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary rescue experiment · source_derived_draft · unverified_draft

### va-repro-retinyl-palmitate-rescue Maternal retinyl-palmitate supplementation rescued SYCP3-positive meiotic cells in vitamin A-depleted Lrat-null pups. Condition category: nutrient_deficiency nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the missing nutrient restored early meiotic development. organism: Mus musculus tissue_or_cell_type: neonatal testis experimental_model: Dietary rescue experiment limitations: Rescue of early markers is not proof of adult fertility or a human dose. exposure: 100 U/day maternal retinyl palmitate from P5; assessment at P10. cross_nutrient: false [li2011] Vitamin A deficiency results in meiotic failure and accumulation of undifferentiated spermatogonia in prepubertal mouse testis. (2011). https://pubmed.ncbi.nlm.nih.gov/20881313/ DOI: 10.1095/biolreprod.110.086157

cross_nutrient

false

evidence_location

Figure 5b

experimental_model

Chicken CRALBP transfection into stable DES1-expressing 293T cells

exposure

All-trans-retinol substrate; CRALBP plasmid versus empty-vector comparison.

limitations

An assay yield effect does not prove physiological transport or human supplementation benefit.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Gallus gallus proteins in Homo sapiens cells

plain_language

The binding protein shifted the measured output toward the visual-cycle alcohol.

primary_references

[vav-kaylor2013] Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. (2013). https://pubmed.ncbi.nlm.nih.gov/23143414/ DOI: 10.1038/nchembio.1114

tissue_or_cell_type

cell homogenates

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 573–586

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chicken CRALBP transfection into stable DES1-expressing 293T cells · source_derived_draft · unverified_draft

### vae-cralbp-des1-isomer-yield CRALBP coexpression increased 11-cis-retinol production approximately threefold in homogenates of cells stably expressing chicken DES1. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: The binding protein shifted the measured output toward the visual-cycle alcohol. organism: Gallus gallus proteins in Homo sapiens cells tissue_or_cell_type: cell homogenates experimental_model: Chicken CRALBP transfection into stable DES1-expressing 293T cells limitations: An assay yield effect does not prove physiological transport or human supplementation benefit. exposure: All-trans-retinol substrate; CRALBP plasmid versus empty-vector comparison. cross_nutrient: false evidence_location: Figure 5b nutrient: Vitamin A [vav-kaylor2013] Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. (2013). https://pubmed.ncbi.nlm.nih.gov/23143414/ DOI: 10.1038/nchembio.1114

cross_nutrient

false

evidence_location

Figure 3a-d; Results: DES1 catalyzes equilibrium isomerization

experimental_model

Recombinant human DES1 expression; HPLC isomer analysis

exposure

Retinol isomerase assays in darkness at 37 degrees Celsius.

limitations

Activity in homogenates does not establish its quantitative contribution or necessity in an intact visual cycle.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Homo sapiens protein/cells

plain_language

DES1-associated activity made some 11-cis-retinol in biochemical assays.

primary_references

[vav-kaylor2013] Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. (2013). https://pubmed.ncbi.nlm.nih.gov/23143414/ DOI: 10.1038/nchembio.1114

tissue_or_cell_type

HEK293T homogenates

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 558–571

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DES1 expression; HPLC isomer analysis · source_derived_draft · unverified_draft

### vae-des1-retinol-isomerization Homogenates of DES1-expressing HEK293T cells formed 11-cis-retinol from all-trans-retinol, alongside more abundant alternative cis isomers. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: DES1-associated activity made some 11-cis-retinol in biochemical assays. organism: Homo sapiens protein/cells tissue_or_cell_type: HEK293T homogenates experimental_model: Recombinant human DES1 expression; HPLC isomer analysis limitations: Activity in homogenates does not establish its quantitative contribution or necessity in an intact visual cycle. exposure: Retinol isomerase assays in darkness at 37 degrees Celsius. cross_nutrient: false evidence_location: Figure 3a-d; Results: DES1 catalyzes equilibrium isomerization nutrient: Vitamin A [vav-kaylor2013] Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. (2013). https://pubmed.ncbi.nlm.nih.gov/23143414/ DOI: 10.1038/nchembio.1114

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Supplementary Figure 8; Results: RNAi knockdown

experimental_model

Targeted RNA interference with nonsilencing control

exposure

Approximately 50% DES1 expression reduction; retinol-substrate homogenate assay.

limitations

Neither complete gene deletion nor a physiological necessity test in an intact retina.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Gallus gallus

plain_language

Reducing DES1 lowered the culture preparation’s isomerase output.

primary_references

[vav-kaylor2013] Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. (2013). https://pubmed.ncbi.nlm.nih.gov/23143414/ DOI: 10.1038/nchembio.1114

tissue_or_cell_type

primary Müller cultures

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 588–601

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted RNA interference with nonsilencing control · source_derived_draft · unverified_draft

### vae-des1-sirna-isomerization DES1-targeted siRNA reduced 11-cis-retinol formation from all-trans-retinol in homogenates of primary chicken Müller cultures compared with nonsilencing RNA. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing DES1 lowered the culture preparation’s isomerase output. organism: Gallus gallus tissue_or_cell_type: primary Müller cultures experimental_model: Targeted RNA interference with nonsilencing control limitations: Neither complete gene deletion nor a physiological necessity test in an intact retina. exposure: Approximately 50% DES1 expression reduction; retinol-substrate homogenate assay. cross_nutrient: false evidence_location: Supplementary Figure 8; Results: RNAi knockdown nutrient: Vitamin A [vav-kaylor2013] Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. (2013). https://pubmed.ncbi.nlm.nih.gov/23143414/ DOI: 10.1038/nchembio.1114

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Figures 4-5; Results: RGR opsin contributes to cone visual function

experimental_model

Ex vivo cone recordings without RPE; rod transduction disabled by Gnat1 deletion

exposure

505-nm background for up to 60 minutes; 10 micromolar all-trans-retinol in perfusate; 565-nm test flashes.

limitations

Whole-retina Rgr deletion alone does not localize the responsible cells; isolated tissue and supplied substrate differ from intact vision.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Mus musculus

plain_language

Cones maintained sensitivity less well when the isolated retina lacked RGR.

primary_references

[vav-morshedian2019] Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells. (2019). https://pubmed.ncbi.nlm.nih.gov/31056353/ DOI: 10.1016/j.neuron.2019.04.004

tissue_or_cell_type

isolated neural retina

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 483–496

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ex vivo cone recordings without RPE; rod transduction disabled by Gnat1 deletion · source_derived_draft · unverified_draft

### vae-rgr-isolated-cone-sensitivity Isolated Rgr-null/Gnat1-null mouse retinas lost cone flash sensitivity faster during continuous light exposure than Rgr-intact/Gnat1-null controls. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cones maintained sensitivity less well when the isolated retina lacked RGR. organism: Mus musculus tissue_or_cell_type: isolated neural retina experimental_model: Ex vivo cone recordings without RPE; rod transduction disabled by Gnat1 deletion limitations: Whole-retina Rgr deletion alone does not localize the responsible cells; isolated tissue and supplied substrate differ from intact vision. exposure: 505-nm background for up to 60 minutes; 10 micromolar all-trans-retinol in perfusate; 565-nm test flashes. cross_nutrient: false evidence_location: Figures 4-5; Results: RGR opsin contributes to cone visual function nutrient: Vitamin A [vav-morshedian2019] Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells. (2019). https://pubmed.ncbi.nlm.nih.gov/31056353/ DOI: 10.1016/j.neuron.2019.04.004

cross_nutrient

false

evidence_location

Figure 1A; STAR Methods: Expression of RGR and RDH10

experimental_model

Recombinant bovine RGR/RDH10 coexpression

exposure

30-minute illumination; 5 micromolar all-trans-retinol; assay medium contained 250 micromolar NADPH.

limitations

Coupled output does not prove every proposed intermediate reaction or RDH10 necessity in intact retina. Added NADPH is an assay component, not a demonstrated dietary requirement.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Bos taurus proteins in Homo sapiens cells

plain_language

The two proteins supported light-dependent retinol recycling together in cultured cells.

primary_references

[vav-morshedian2019] Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells. (2019). https://pubmed.ncbi.nlm.nih.gov/31056353/ DOI: 10.1016/j.neuron.2019.04.004

tissue_or_cell_type

HEK293T culture

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 468–481

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant bovine RGR/RDH10 coexpression · source_derived_draft · unverified_draft

### vae-rgr-rdh10-coupled-retinol HEK293T cells coexpressing bovine RGR and RDH10 generated more 11-cis-retinol from all-trans-retinol during illumination than cells expressing either protein alone. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two proteins supported light-dependent retinol recycling together in cultured cells. organism: Bos taurus proteins in Homo sapiens cells tissue_or_cell_type: HEK293T culture experimental_model: Recombinant bovine RGR/RDH10 coexpression limitations: Coupled output does not prove every proposed intermediate reaction or RDH10 necessity in intact retina. Added NADPH is an assay component, not a demonstrated dietary requirement. exposure: 30-minute illumination; 5 micromolar all-trans-retinol; assay medium contained 250 micromolar NADPH. cross_nutrient: false evidence_location: Figure 1A; STAR Methods: Expression of RGR and RDH10 nutrient: Vitamin A [vav-morshedian2019] Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells. (2019). https://pubmed.ncbi.nlm.nih.gov/31056353/ DOI: 10.1016/j.neuron.2019.04.004

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"}

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

cross_nutrient

Direct clinical comparison involving B2, vitamin A, iron and folic acid.

experimental_model

366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid.

exposure

All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations.

limitations

Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone.

primary_references

[b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946

tissue_or_cell_type

Human clinical setting

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1604–1615

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. · source_derived_draft · unverified_draft

### b2-pregnancy-multiple-nutrients Adding retinol and/or riboflavin to iron-folic-acid treatment reduced anemia prevalence more than iron-folic-acid alone; the combined retinol-riboflavin arm gained 5.4±1.1 g/L more hemoglobin than the reference arm. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. limitations: Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint. exposure: All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations. cross_nutrient: Direct clinical comparison involving B2, vitamin A, iron and folic acid. [b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946

cross_nutrient

true

evidence_location

Figure 4A–C

experimental_model

KLF4-expressing OEC-2 mouse EpiSCs switched to vitamin-A-free 2i/LIF; Oct4:GFP colony counts

exposure

50 µg/mL ascorbate with 0–50 ng/mL retinol; day-6 colony endpoint; combined optimum reported near 3.13 ng/mL retinol.

limitations

Reprogramming reporter assay, not demonstrated tissue rejuvenation or therapy; relationship to DNA modification is supported by complementary experiments, not sole-cause proof.

nutrient_topic

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

organism

Mus musculus

plain_language

Vitamin A and C worked together in this stem-cell culture protocol, but more vitamin A was not always better.

primary_references

[c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

tissue_or_cell_type

Epiblast stem-cell culture

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1075–1087

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · KLF4-expressing OEC-2 mouse EpiSCs switched to vitamin-A-free 2i/LIF; Oct4:GFP colony counts · source_derived_draft · unverified_draft

### c-reg-retinol-ascorbate-reprogramming Ascorbate co-treatment increased Oct4:GFP-positive colony formation during KLF4-driven mouse EpiSC reprogramming and shifted the optimum toward lower retinol concentration; higher retinol suppressed colony formation rather than improving it indefinitely. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A and C worked together in this stem-cell culture protocol, but more vitamin A was not always better. organism: Mus musculus tissue_or_cell_type: Epiblast stem-cell culture experimental_model: KLF4-expressing OEC-2 mouse EpiSCs switched to vitamin-A-free 2i/LIF; Oct4:GFP colony counts limitations: Reprogramming reporter assay, not demonstrated tissue rejuvenation or therapy; relationship to DNA modification is supported by complementary experiments, not sole-cause proof. exposure: 50 µg/mL ascorbate with 0–50 ng/mL retinol; day-6 colony endpoint; combined optimum reported near 3.13 ng/mL retinol. cross_nutrient: true evidence_location: Figure 4A–C [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Figure 3E–F

experimental_model

CRISPR Tet2 ΔRARE naïve ESCs compared with wild type

exposure

Retinol titration as in Figure 3F; 104-bp deletion NCBI37 chr3:133197151–133197253.

limitations

Deletion tests the segment rather than one isolated nucleotide; this is engineered machinery impairment, not vitamin A deficiency.

nutrient_topic

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

organism

Mus musculus

plain_language

The vitamin A response depended on a specific DNA control sequence in the Tet2 gene.

primary_references

[c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

tissue_or_cell_type

Naïve embryonic stem cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1061–1073

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR Tet2 ΔRARE naïve ESCs compared with wild type · source_derived_draft · unverified_draft

### c-reg-tet2-rare-deletion Deleting a 104-bp intronic segment encompassing the mouse Tet2 retinoic-acid response element prevented the normal retinol-dependent Tet2 mRNA increase, supporting a cis-regulatory requirement. Condition category: machinery_impairment nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The vitamin A response depended on a specific DNA control sequence in the Tet2 gene. organism: Mus musculus tissue_or_cell_type: Naïve embryonic stem cells experimental_model: CRISPR Tet2 ΔRARE naïve ESCs compared with wild type limitations: Deletion tests the segment rather than one isolated nucleotide; this is engineered machinery impairment, not vitamin A deficiency. exposure: Retinol titration as in Figure 3F; 104-bp deletion NCBI37 chr3:133197151–133197253. cross_nutrient: true evidence_location: Figure 3E–F [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

experimental_model

2-90 micromolar IRBP; 5-180-minute incubation; HPLC

limitations

Measures release, not the entire in vivo round trip to RPE.

nutrient_topic

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

organism

Bufo marinus

plain_language

Extracellular IRBP helps remove retinol from the bleached retina.

primary_references

[qtaishat-2005] Interphotoreceptor retinoid-binding protein (IRBP) promotes the release of all-trans retinol from the isolated retina following rhodopsin bleaching illumination (2005). https://pubmed.ncbi.nlm.nih.gov/15935345/ DOI: 10.1016/j.exer.2005.03.005

tissue_or_cell_type

Isolated retina and extracellular medium

transport_direction

retina to extracellular medium

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 789–799

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 2-90 micromolar IRBP; 5-180-minute incubation; HPLC · source_derived_draft · unverified_draft

### a-vision-irbp-retinol-release IRBP at at least 10 micromolar increased all-trans-retinol release from bleached isolated toad retina during dark incubation. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extracellular IRBP helps remove retinol from the bleached retina. organism: Bufo marinus tissue_or_cell_type: Isolated retina and extracellular medium experimental_model: 2-90 micromolar IRBP; 5-180-minute incubation; HPLC limitations: Measures release, not the entire in vivo round trip to RPE. transport_direction: retina to extracellular medium [qtaishat-2005] Interphotoreceptor retinoid-binding protein (IRBP) promotes the release of all-trans retinol from the isolated retina following rhodopsin bleaching illumination (2005). https://pubmed.ncbi.nlm.nih.gov/15935345/ DOI: 10.1016/j.exer.2005.03.005

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Lrat knockout versus controls

limitations

Other tissues and dietary deficiency are separate questions.

nutrient_topic

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

organism

Mus musculus

plain_language

Without LRAT, the eye cannot maintain its normal ester reserve.

primary_references

[batten-2004] Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver (2004). https://pubmed.ncbi.nlm.nih.gov/14684738/ DOI: 10.1074/jbc.M312410200

tissue_or_cell_type

Eye/RPE

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 701–710

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lrat knockout versus controls · source_derived_draft · unverified_draft

### a-vision-lrat-esters Lrat deletion severely depleted the ocular all-trans-retinyl ester pool in mice. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without LRAT, the eye cannot maintain its normal ester reserve. organism: Mus musculus tissue_or_cell_type: Eye/RPE experimental_model: Lrat knockout versus controls limitations: Other tissues and dietary deficiency are separate questions. [batten-2004] Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver (2004). https://pubmed.ncbi.nlm.nih.gov/14684738/ DOI: 10.1074/jbc.M312410200

experimental_model

Purified-enzyme cofactor/substrate kinetics

limitations

Biochemical cofactor preference does not demonstrate a dietary niacin-deficiency visual phenotype.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

The reductase uses NADPH reducing power to convert retinal into retinol.

primary_references

[belyaeva-2005] Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids (2005). https://pubmed.ncbi.nlm.nih.gov/15865448/ DOI: 10.1021/bi050226k

tissue_or_cell_type

Recombinant enzyme preparation

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 778–787

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme cofactor/substrate kinetics · source_derived_draft · unverified_draft

### a-vision-rdh12-nadph Purified human RDH12 used NADPH for retinal reduction and had much lower apparent cofactor Km for NADP(H) than NAD(H). Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reductase uses NADPH reducing power to convert retinal into retinol. organism: Homo sapiens protein tissue_or_cell_type: Recombinant enzyme preparation experimental_model: Purified-enzyme cofactor/substrate kinetics limitations: Biochemical cofactor preference does not demonstrate a dietary niacin-deficiency visual phenotype. [belyaeva-2005] Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids (2005). https://pubmed.ncbi.nlm.nih.gov/15865448/ DOI: 10.1021/bi050226k

experimental_model

Knockout rod imaging and exogenous retinal challenge

limitations

The inferred protection of organelles is not itself a clinical outcome.

nutrient_topic

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

organism

Mus musculus

plain_language

RDH12 helps clear retinal that reaches the cell interior.

primary_references

[chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

tissue_or_cell_type

Rod inner segment

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 767–776

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Knockout rod imaging and exogenous retinal challenge · source_derived_draft · unverified_draft

### a-vision-rdh12-reduction Mouse rod imaging identified RDH12-dependent reduction of retinaldehyde entering inner segments from the outer segment or extracellular medium. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH12 helps clear retinal that reaches the cell interior. organism: Mus musculus tissue_or_cell_type: Rod inner segment experimental_model: Knockout rod imaging and exogenous retinal challenge limitations: The inferred protection of organelles is not itself a clinical outcome. [chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

experimental_model

Cell-free assay and cell lines.

limitations

ATRA direct activity was not reproduced in the 2024 assays; no clinical or nutrient-replacement inference.

nutrient_topic

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

organism

Homo sapiens

plain_language

Different vitamin A forms were protective in the tested systems.

primary_references

[va-jakaria2023] Vitamin A metabolites inhibit ferroptosis (2023). https://pubmed.ncbi.nlm.nih.gov/37236031/ DOI: 10.1016/j.biopha.2023.114930

tissue_or_cell_type

Cell-free chemistry and cell cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1789–1798

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free assay and cell lines. · source_derived_draft · unverified_draft

### va-atra-direct-radical-trapping2023 The 2023 study reported direct radical-trapping activity for retinol, retinal and ATRA alongside ferroptosis protection. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different vitamin A forms were protective in the tested systems. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry and cell cultures experimental_model: Cell-free assay and cell lines. limitations: ATRA direct activity was not reproduced in the 2024 assays; no clinical or nutrient-replacement inference. [va-jakaria2023] Vitamin A metabolites inhibit ferroptosis (2023). https://pubmed.ncbi.nlm.nih.gov/37236031/ DOI: 10.1016/j.biopha.2023.114930

experimental_model

Cell-free assays.

limitations

Does not establish universal absence of antioxidant chemistry.

nutrient_topic

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

organism

Homo sapiens

plain_language

Chemical form and assay conditions matter.

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

Cell-free chemistry

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1800–1809

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

### va-atra-no-direct-radical-trapping2024 ATRA showed no direct activity in AAPH/C11-BODIPY and DPPH assays; retinol and retinal were active in the AAPH assay. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chemical form and assay conditions matter. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry experimental_model: Cell-free assays. limitations: Does not establish universal absence of antioxidant chemistry. [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

cross_nutrient

Iron/zinc -> retinoid transport markers.

experimental_model

Same factorial trial.

limitations

Measured biomarkers do not prove the molecular mechanism.

nutrient_topic

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

organism

Homo sapiens

plain_language

The two minerals did not produce identical carrier-protein responses.

primary_references

[va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789

tissue_or_cell_type

Plasma

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1495–1505

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same factorial trial. · source_derived_draft · unverified_draft

### va-iron-improves-retinol-marker Iron increased plasma retinol, RBP and transthyretin; the combined iron/zinc arm increased retinol without significant carrier-protein increases. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two minerals did not produce identical carrier-protein responses. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Same factorial trial. limitations: Measured biomarkers do not prove the molecular mechanism. cross_nutrient: Iron/zinc -> retinoid transport markers. [va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789

availability_state

biomarker_context Imported condition classification; unverified.

experimental_model

LPS versus saline with food withdrawal.

limitations

Acute rat model; not every inflammatory illness follows the same kinetics.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

A low blood value did not mean the measured tissue stores had been emptied.

primary_references

[va-rosales1996] Effects of acute inflammation on plasma retinol, retinol-binding protein, and its mRNA in the liver and kidneys of vitamin A-sufficient rats (1996). https://pubmed.ncbi.nlm.nih.gov/8725149/ DOI: 10.1016/s0022-2275(20)42007-3

tissue_or_cell_type

Plasma, liver and kidney

trigger_kind

biomarker_context Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1674–1683

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LPS versus saline with food withdrawal. · source_derived_draft · unverified_draft

### va-lps-lowers-retinol-with-stores LPS lowered circulating retinol without a detected decrease in liver or kidney retinol in vitamin A-sufficient rats. Condition category: biomarker_context nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low blood value did not mean the measured tissue stores had been emptied. organism: Rattus norvegicus tissue_or_cell_type: Plasma, liver and kidney experimental_model: LPS versus saline with food withdrawal. limitations: Acute rat model; not every inflammatory illness follows the same kinetics. [va-rosales1996] Effects of acute inflammation on plasma retinol, retinol-binding protein, and its mRNA in the liver and kidneys of vitamin A-sufficient rats (1996). https://pubmed.ncbi.nlm.nih.gov/8725149/ DOI: 10.1016/s0022-2275(20)42007-3

availability_state

biomarker_context Imported condition classification; unverified.

experimental_model

Hepatic RNA and RBP/TTR assays.

limitations

Reduced secretion is inferred from the combined measurements, not measured as a complete flux chain.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Transport regulation helps explain why blood retinol can fall during illness.

primary_references

[va-rosales1996] Effects of acute inflammation on plasma retinol, retinol-binding protein, and its mRNA in the liver and kidneys of vitamin A-sufficient rats (1996). https://pubmed.ncbi.nlm.nih.gov/8725149/ DOI: 10.1016/s0022-2275(20)42007-3

tissue_or_cell_type

Liver and plasma

trigger_kind

biomarker_context Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1685–1694

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepatic RNA and RBP/TTR assays. · source_derived_draft · unverified_draft

### va-lps-reduces-rbp-transcript Inflammation reduced hepatic RBP mRNA and circulating transport proteins in the same rat study. Condition category: biomarker_context nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Transport regulation helps explain why blood retinol can fall during illness. organism: Rattus norvegicus tissue_or_cell_type: Liver and plasma experimental_model: Hepatic RNA and RBP/TTR assays. limitations: Reduced secretion is inferred from the combined measurements, not measured as a complete flux chain. [va-rosales1996] Effects of acute inflammation on plasma retinol, retinol-binding protein, and its mRNA in the liver and kidneys of vitamin A-sufficient rats (1996). https://pubmed.ncbi.nlm.nih.gov/8725149/ DOI: 10.1016/s0022-2275(20)42007-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Figure 3

experimental_model

Lrat-knockout mice; retinol gavage and one-month retinoid-deficient diet.

exposure

6 micrograms retinol in peanut oil; P-407 clearance blockade; sampling at three hours.

limitations

Clearance was pharmacologically blocked; remaining enzyme identity was not established here.

nutrient_topic

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

organism

Mus musculus

outcome

Lrat-null mice still secreted chylomicron retinyl esters whose acyl composition reflected the gavage oil.

plain_language

Alternative esterification partly handles absorbed retinol when LRAT is missing.

primary_references

[va-obyrne-2005] Retinoid Absorption and Storage Is Impaired in Mice Lacking Lecithin:Retinol Acyltransferase (LRAT) (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC1352312/ DOI: 10.1074/jbc.M507924200

tissue_or_cell_type

Intestine and isolated chylomicrons

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 346–358

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lrat-knockout mice; retinol gavage and one-month retinoid-deficient diet. · source_derived_draft · unverified_draft

### va-lrat-chylomicron-retinoids Lrat-null mice still secreted chylomicron retinyl esters whose acyl composition reflected the gavage oil. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Alternative esterification partly handles absorbed retinol when LRAT is missing. organism: Mus musculus tissue_or_cell_type: Intestine and isolated chylomicrons experimental_model: Lrat-knockout mice; retinol gavage and one-month retinoid-deficient diet. limitations: Clearance was pharmacologically blocked; remaining enzyme identity was not established here. exposure: 6 micrograms retinol in peanut oil; P-407 clearance blockade; sampling at three hours. outcome: Lrat-null mice still secreted chylomicron retinyl esters whose acyl composition reflected the gavage oil. evidence_location: Figure 3 [va-obyrne-2005] Retinoid Absorption and Storage Is Impaired in Mice Lacking Lecithin:Retinol Acyltransferase (LRAT) (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC1352312/ DOI: 10.1074/jbc.M507924200

evidence_location

Figure 1

experimental_model

Transfected-cell radioretinol uptake and real-time retinol-release assays.

exposure

STRA6 with or without LRAT; radiolabeled holo-RBP uptake.

limitations

No single intracellular protein was absolutely required for STRA6 activity. Cell-line species were not resolved in the retrieved abstract/figure evidence; no species-specific extension is asserted.

nutrient_topic

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

organism

Mammalian transfected cells

outcome

Coexpression of LRAT enhanced STRA6-mediated retinol uptake by coupling transport to ester storage.

plain_language

Retinol esterification helps keep inward uptake moving.

primary_references

[va-kawaguchi-2011] Receptor-mediated cellular uptake mechanism that couples to intracellular storage (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3199320/ DOI: 10.1021/cb200178w

tissue_or_cell_type

Plasma membrane and intracellular retinoid compartment

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 459–471

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected-cell radioretinol uptake and real-time retinol-release assays. · source_derived_draft · unverified_draft

### va-lrat-couples-stra6 Coexpression of LRAT enhanced STRA6-mediated retinol uptake by coupling transport to ester storage. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Retinol esterification helps keep inward uptake moving. organism: Mammalian transfected cells tissue_or_cell_type: Plasma membrane and intracellular retinoid compartment experimental_model: Transfected-cell radioretinol uptake and real-time retinol-release assays. limitations: No single intracellular protein was absolutely required for STRA6 activity. Cell-line species were not resolved in the retrieved abstract/figure evidence; no species-specific extension is asserted. exposure: STRA6 with or without LRAT; radiolabeled holo-RBP uptake. outcome: Coexpression of LRAT enhanced STRA6-mediated retinol uptake by coupling transport to ester storage. evidence_location: Figure 1 [va-kawaguchi-2011] Receptor-mediated cellular uptake mechanism that couples to intracellular storage (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3199320/ DOI: 10.1021/cb200178w

cross_nutrient

Phosphatidylcholine-dependent retinol storage links retinoid metabolism to choline-containing phospholipid availability.

evidence_location

Abstract

experimental_model

Human and rat liver microsomes supplied phosphatidylcholine and CRBP-bound retinol.

exposure

Exogenous phosphatidylcholine plus CRBP-bound retinol.

limitations

Biochemical donor requirement; dietary choline deficiency was not tested.

nutrient_topic

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

organism

Homo sapiens and Rattus norvegicus

outcome

Human and rat liver LRAT activity transferred the sn-1 acyl group of phosphatidylcholine to CRBP-bound retinol.

plain_language

A membrane choline phospholipid supplies the fatty-acid group used to store vitamin A.

primary_references

[va-macdonald-1988] A lecithin:retinol acyltransferase activity in human and rat liver (1988). https://pubmed.ncbi.nlm.nih.gov/3178828/ DOI: 10.1016/S0006-291X(88)80818-0

tissue_or_cell_type

Liver microsomes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 317–330

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and rat liver microsomes supplied phosphatidylcholine and CRBP-bound retinol. · source_derived_draft · unverified_draft

### va-lrat-phosphatidylcholine-donor Human and rat liver LRAT activity transferred the sn-1 acyl group of phosphatidylcholine to CRBP-bound retinol. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane choline phospholipid supplies the fatty-acid group used to store vitamin A. organism: Homo sapiens and Rattus norvegicus tissue_or_cell_type: Liver microsomes experimental_model: Human and rat liver microsomes supplied phosphatidylcholine and CRBP-bound retinol. limitations: Biochemical donor requirement; dietary choline deficiency was not tested. exposure: Exogenous phosphatidylcholine plus CRBP-bound retinol. outcome: Human and rat liver LRAT activity transferred the sn-1 acyl group of phosphatidylcholine to CRBP-bound retinol. evidence_location: Abstract cross_nutrient: Phosphatidylcholine-dependent retinol storage links retinoid metabolism to choline-containing phospholipid availability. [va-macdonald-1988] A lecithin:retinol acyltransferase activity in human and rat liver (1988). https://pubmed.ncbi.nlm.nih.gov/3178828/ DOI: 10.1016/S0006-291X(88)80818-0

experimental_model

189 hospitalized children; randomized trial.

limitations

No specific immune pathway was proven as mediator; not evidence for preventing all infections or replacing vaccination.

nutrient_topic

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

organism

Homo sapiens

plain_language

A clinical benefit was demonstrated in a defined illness setting.

primary_references

[va-hussey1990] A randomized, controlled trial of vitamin A in children with severe measles (1990). https://pubmed.ncbi.nlm.nih.gov/2194128/ DOI: 10.1056/nejm199007193230304

tissue_or_cell_type

Clinical outcome

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1707–1716

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 189 hospitalized children; randomized trial. · source_derived_draft · unverified_draft

### va-measles-clinical-endpoint Vitamin A reduced the combined risk of death or major complications during severe-measles hospitalization in the trial. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A clinical benefit was demonstrated in a defined illness setting. organism: Homo sapiens tissue_or_cell_type: Clinical outcome experimental_model: 189 hospitalized children; randomized trial. limitations: No specific immune pathway was proven as mediator; not evidence for preventing all infections or replacing vaccination. [va-hussey1990] A randomized, controlled trial of vitamin A in children with severe measles (1990). https://pubmed.ncbi.nlm.nih.gov/2194128/ DOI: 10.1056/nejm199007193230304

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Abstract

experimental_model

Rbp4-knockout mice on vitamin A-sufficient and deficient diets.

exposure

Rbp4 knockout under sufficient and deficient feeding.

limitations

Alternative delivery operates with adequate intake; RBP4 is not the sole tissue supply route.

nutrient_topic

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

organism

Mus musculus

outcome

Rbp4-null mice acquired hepatic vitamin A stores but could not mobilize them normally.

plain_language

Stored vitamin A can remain inaccessible when its transport protein is absent.

primary_references

[va-quadro-1999] Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein (1999). https://pmc.ncbi.nlm.nih.gov/articles/PMC1171537/ DOI: 10.1093/emboj/18.17.4633

tissue_or_cell_type

Liver and circulation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 374–386

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rbp4-knockout mice on vitamin A-sufficient and deficient diets. · source_derived_draft · unverified_draft

### va-rbp4-store-mobilization Rbp4-null mice acquired hepatic vitamin A stores but could not mobilize them normally. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stored vitamin A can remain inaccessible when its transport protein is absent. organism: Mus musculus tissue_or_cell_type: Liver and circulation experimental_model: Rbp4-knockout mice on vitamin A-sufficient and deficient diets. limitations: Alternative delivery operates with adequate intake; RBP4 is not the sole tissue supply route. exposure: Rbp4 knockout under sufficient and deficient feeding. outcome: Rbp4-null mice acquired hepatic vitamin A stores but could not mobilize them normally. evidence_location: Abstract [va-quadro-1999] Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein (1999). https://pmc.ncbi.nlm.nih.gov/articles/PMC1171537/ DOI: 10.1093/emboj/18.17.4633

cross_nutrient

NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability.

evidence_location

Results: cofactor preference

experimental_model

Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells.

exposure

1 micromolar retinol and 1 millimolar NAD+ versus NADP+.

limitations

Cofactor specificity does not establish an effect of dietary niacin deficiency.

nutrient_topic

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

organism

Homo sapiens protein in Spodoptera frugiperda Sf9 cells

outcome

Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays.

plain_language

RDH10 uses the oxidized nicotinamide cofactor to make retinal.

primary_references

[va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

tissue_or_cell_type

Microsomes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 487–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. · source_derived_draft · unverified_draft

### va-rdh10-retinol-oxidation Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH10 uses the oxidized nicotinamide cofactor to make retinal. organism: Homo sapiens protein in Spodoptera frugiperda Sf9 cells tissue_or_cell_type: Microsomes experimental_model: Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. limitations: Cofactor specificity does not establish an effect of dietary niacin deficiency. exposure: 1 micromolar retinol and 1 millimolar NAD+ versus NADP+. outcome: Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. evidence_location: Results: cofactor preference cross_nutrient: NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability. [va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Experimental Procedures: siRNA-mediated Knockdowns; Results: endogenous SDR silencing

experimental_model

Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells.

exposure

RDH10 siRNA at 100 nanomolar, two transfections 24 hours apart; 10 micromolar retinol for 24 hours after silencing.

limitations

Residual activity and other enzymes prevent an exclusive RDH10 interpretation.

nutrient_topic

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

organism

Homo sapiens

outcome

Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells.

plain_language

Reducing precursor oxidation lowered downstream active retinoid production.

primary_references

[va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

tissue_or_cell_type

HEK293 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 502–514

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. · source_derived_draft · unverified_draft

### va-rdh10-silencing-ra Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing precursor oxidation lowered downstream active retinoid production. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. limitations: Residual activity and other enzymes prevent an exclusive RDH10 interpretation. exposure: RDH10 siRNA at 100 nanomolar, two transfections 24 hours apart; 10 micromolar retinol for 24 hours after silencing. outcome: Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells. evidence_location: Experimental Procedures: siRNA-mediated Knockdowns; Results: endogenous SDR silencing [va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

availability_state

biomarker_context Imported condition classification; unverified.

experimental_model

37 Thai and 128 Zambian children.

limitations

Isotope-derived liver reserves are model estimates; these data do not establish universal diagnostic performance.

nutrient_topic

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

organism

Homo sapiens

plain_language

Neither a normal nor a low serum result fully described reserves in these cohorts.

primary_references

[va-suri2015] Serum retinol concentrations demonstrate high specificity after correcting for inflammation but questionable sensitivity compared with liver stores calculated from isotope dilution in determining vitamin A deficiency in Thai and Zambian children (2015). https://pubmed.ncbi.nlm.nih.gov/26447158/ DOI: 10.3945/ajcn.115.113050

tissue_or_cell_type

Serum and inferred liver stores

trigger_kind

biomarker_context Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1696–1705

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 37 Thai and 128 Zambian children. · source_derived_draft · unverified_draft

### va-serum-versus-isotope-classification Serum-retinol and isotope-modelled liver-store classifications disagreed in Thai and Zambian children; inflammation adjustment reduced false positives in the latter. Condition category: biomarker_context nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Neither a normal nor a low serum result fully described reserves in these cohorts. organism: Homo sapiens tissue_or_cell_type: Serum and inferred liver stores experimental_model: 37 Thai and 128 Zambian children. limitations: Isotope-derived liver reserves are model estimates; these data do not establish universal diagnostic performance. [va-suri2015] Serum retinol concentrations demonstrate high specificity after correcting for inflammation but questionable sensitivity compared with liver stores calculated from isotope dilution in determining vitamin A deficiency in Thai and Zambian children (2015). https://pubmed.ncbi.nlm.nih.gov/26447158/ DOI: 10.3945/ajcn.115.113050

evidence_locator

Figure 2; Methods

experimental_model

Mouse MODE-K cells and intestinal epithelial Rarb deletion.

exposure

100 nM retinol plus 100 ng/mL LPS for 24 h

limitations

Direct binding to Saa1/Saa2 was predicted, not demonstrated here.

nutrient_topic

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

organism

Mus musculus

plain_language

Epithelial retinoid sensing directly controls this mouse immune gene.

primary_references

[va-gattu-2019] Epithelial retinoic acid receptor beta regulates serum amyloid A expression and vitamin A-dependent intestinal immunity (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6561173/ DOI: 10.1073/pnas.1812069116

tissue_or_cell_type

MODE-K intestinal epithelial cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1318–1329

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse MODE-K cells and intestinal epithelial Rarb deletion. · source_derived_draft · unverified_draft

### va-sig-rarb-saa3-promoter RAR beta occupied the mouse Saa3 promoter; mutation of RARE -224 abolished reporter activity. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Epithelial retinoid sensing directly controls this mouse immune gene. organism: Mus musculus tissue_or_cell_type: MODE-K intestinal epithelial cells experimental_model: Mouse MODE-K cells and intestinal epithelial Rarb deletion. limitations: Direct binding to Saa1/Saa2 was predicted, not demonstrated here. evidence_locator: Figure 2; Methods exposure: 100 nM retinol plus 100 ng/mL LPS for 24 h [va-gattu-2019] Epithelial retinoic acid receptor beta regulates serum amyloid A expression and vitamin A-dependent intestinal immunity (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6561173/ DOI: 10.1073/pnas.1812069116

evidence_location

Abstract

experimental_model

Receptor isolation from bovine retinal pigment epithelium and cellular uptake assays.

exposure

RBP-binding purification and receptor-expression assays.

limitations

Identification in RPE does not make STRA6 mandatory for every tissue.

nutrient_topic

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

organism

Bos taurus receptor-isolation material and transfected cells

outcome

STRA6 was identified as a high-affinity membrane receptor for retinol-binding protein.

plain_language

Cells recognize circulating retinol through its carrier protein.

primary_references

[va-kawaguchi-2007] A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A (2007). https://pubmed.ncbi.nlm.nih.gov/17255476/ DOI: 10.1126/science.1136244

tissue_or_cell_type

Retinal pigment epithelium and plasma membrane

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 430–442

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor isolation from bovine retinal pigment epithelium and cellular uptake assays. · source_derived_draft · unverified_draft

### va-stra6-rbp-binding STRA6 was identified as a high-affinity membrane receptor for retinol-binding protein. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells recognize circulating retinol through its carrier protein. organism: Bos taurus receptor-isolation material and transfected cells tissue_or_cell_type: Retinal pigment epithelium and plasma membrane experimental_model: Receptor isolation from bovine retinal pigment epithelium and cellular uptake assays. limitations: Identification in RPE does not make STRA6 mandatory for every tissue. exposure: RBP-binding purification and receptor-expression assays. outcome: STRA6 was identified as a high-affinity membrane receptor for retinol-binding protein. evidence_location: Abstract [va-kawaguchi-2007] A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A (2007). https://pubmed.ncbi.nlm.nih.gov/17255476/ DOI: 10.1126/science.1136244

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Zinc -> hepatic retinoid metabolism.

experimental_model

Pair-feeding controls; three weeks.

limitations

Does not show that every retinol dehydrogenase is a zinc enzyme.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Zinc depletion changed retinoid handling in the liver.

primary_references

[va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995

tissue_or_cell_type

Liver

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1519–1529

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pair-feeding controls; three weeks. · source_derived_draft · unverified_draft

### va-zinc-deficiency-adh-decrease Zinc-deficient rats had lower hepatic retinol-oxidizing ADH activity and greater hepatic vitamin A content. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc depletion changed retinoid handling in the liver. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Pair-feeding controls; three weeks. limitations: Does not show that every retinol dehydrogenase is a zinc enzyme. cross_nutrient: Zinc -> hepatic retinoid metabolism. [va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995

cross_nutrient

Zinc -> vitamin A biomarkers.

experimental_model

Six-month preschool trial.

limitations

No direct proof of restored liver release or increased RBP synthesis.

nutrient_topic

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

organism

Homo sapiens

plain_language

Zinc status can influence vitamin A transport-related blood measurements.

primary_references

[va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789

tissue_or_cell_type

Plasma

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1483–1493

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month preschool trial. · source_derived_draft · unverified_draft

### va-zinc-improves-retinol-marker Zinc increased plasma retinol and transthyretin versus placebo; the RBP increase was not significant. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc status can influence vitamin A transport-related blood measurements. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Six-month preschool trial. limitations: No direct proof of restored liver release or increased RBP synthesis. cross_nutrient: Zinc -> vitamin A biomarkers. [va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789

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

evidence_access

Primary abstract

experimental_model

RBP-loss mouse comparison with t10,c12 supplementation.

limitations

Genetic model, not evidence that RBP abundance alone predicts a human response.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

A transport protein helped determine where vitamin A went.

primary_references

Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 262–268

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · RBP-loss mouse comparison with t10,c12 supplementation. · source_derived_draft · unverified_draft

## cla-rbp-loss A transport protein helped determine where vitamin A went. RBP-deficient mice supported an RBP-dependent mechanism for CLA-induced hepatic retinol secretion and redistribution toward adipose tissue. Model: RBP-loss mouse comparison with t10,c12 supplementation. Limitations: Genetic model, not evidence that RBP abundance alone predicts a human response. Evidence access: Primary abstract Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

evidence_access

Primary abstract

experimental_model

Mouse dietary comparison.

limitations

Retinoid oxidation was only proposed; no demonstrated human deficiency or toxicity.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

Vitamin A distribution changed beyond liver storage.

primary_references

Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 254–260

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

## cla-retinol-release Vitamin A distribution changed beyond liver storage. Only the t10,c12 preparation increased hepatic retinol secretion and serum retinol/RBP. Model: Mouse dietary comparison. Limitations: Retinoid oxidation was only proposed; no demonstrated human deficiency or toxicity. Evidence access: Primary abstract Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

evidence_access

Primary abstract

experimental_model

Mouse dietary isomer comparison.

limitations

Accumulation does not establish improved vitamin A function.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

CLA altered a vitamin A storage compartment.

primary_references

Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 238–244

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

## cla-retinyl-c9 CLA altered a vitamin A storage compartment. Feeding the enriched isomer preparation increased hepatic retinyl ester accumulation. Model: Mouse dietary isomer comparison. Limitations: Accumulation does not establish improved vitamin A function. Evidence access: Primary abstract Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

evidence_access

Primary abstract

experimental_model

Mouse dietary isomer comparison.

limitations

Accumulation does not establish improved vitamin A function.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

CLA altered a vitamin A storage compartment.

primary_references

Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 246–252

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

## cla-retinyl-t10 CLA altered a vitamin A storage compartment. Feeding the enriched isomer preparation increased hepatic retinyl ester accumulation. Model: Mouse dietary isomer comparison. Limitations: Accumulation does not establish improved vitamin A function. Evidence access: Primary abstract Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19454764/ · DOI 10.1194/jlr.M900054-JLR200

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges

exposure

Intoxicating ethanol dose, formaldehyde LD50, and retinol administration

limitations

A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one.

nutrient_topic

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

organism

Mouse

plain_language

The same enzymes that clear alcohol also turn vitamin A into its signalling form.

primary_references

[alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796

tissue_or_cell_type

Liver and embryo

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 241–252

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges · source_derived_draft · unverified_draft

### alcohol-adh-retinoic-acid Retinoic acid production following retinol administration was reduced 8.5-fold in Adh4-null mice and 4.8-fold in Adh1-null mice, showing overlapping roles for Adh1 and Adh4 in both ethanol and retinol metabolism. Condition category: machinery_impairment nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: The same enzymes that clear alcohol also turn vitamin A into its signalling form. organism: Mouse tissue_or_cell_type: Liver and embryo experimental_model: Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges limitations: A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one. exposure: Intoxicating ethanol dose, formaldehyde LD50, and retinol administration evidence_span: {"source_cache": "artifacts/alcohol-research/10358022.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305", "start_char": 0, "end_char": 1272, "text_sha256": "c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305"} [alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796