Calcitriol

cross_nutrient

false

experimental_model

Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison

exposure

Murine cell response and comparative promoter analysis.

limitations

Species boundary, not proof that vitamin D has no immune actions in rodents.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus; comparative mammalian DNA

plain_language

This human antimicrobial gene-control route cannot simply be copied into a mouse model.

primary_references

[gombart2005] Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. (2005). https://pubmed.ncbi.nlm.nih.gov/15985530/ DOI: 10.1096/fj.04-3284com

tissue_or_cell_type

Murine cells and comparative promoter sequences

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 931–942

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison · source_derived_draft · unverified_draft

### vd-camp-mouse-boundary CAMP induction was not observed in the tested murine cells; the primate-conserved promoter VDRE was absent from mouse, rat and canine genomes. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This human antimicrobial gene-control route cannot simply be copied into a mouse model. organism: Mus musculus; comparative mammalian DNA tissue_or_cell_type: Murine cells and comparative promoter sequences experimental_model: Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison limitations: Species boundary, not proof that vitamin D has no immune actions in rodents. exposure: Murine cell response and comparative promoter analysis. cross_nutrient: false [gombart2005] Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. (2005). https://pubmed.ncbi.nlm.nih.gov/15985530/ DOI: 10.1096/fj.04-3284com

cross_nutrient

false

experimental_model

Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison

exposure

Calcitriol-treated primary cells and cell lines; concentrations not recovered from the abstract.

limitations

Human cell and promoter experiments; no oral D2/D3 efficacy or infection-incidence trial.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

The active D3 hormone increased the instructions for an antimicrobial protein.

primary_references

[gombart2005] Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. (2005). https://pubmed.ncbi.nlm.nih.gov/15985530/ DOI: 10.1096/fj.04-3284com

tissue_or_cell_type

Human myeloid and epithelial cells

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 905–916

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison · source_derived_draft · unverified_draft

### vd-camp-transcription Calcitriol induced CAMP expression in tested human myeloid, keratinocyte and colon cell models and bone-marrow-derived cells. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active D3 hormone increased the instructions for an antimicrobial protein. organism: Homo sapiens tissue_or_cell_type: Human myeloid and epithelial cells experimental_model: Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison limitations: Human cell and promoter experiments; no oral D2/D3 efficacy or infection-incidence trial. exposure: Calcitriol-treated primary cells and cell lines; concentrations not recovered from the abstract. cross_nutrient: false [gombart2005] Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. (2005). https://pubmed.ncbi.nlm.nih.gov/15985530/ DOI: 10.1096/fj.04-3284com

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Calcitriol-injected mice; bone Fgf23 transcript assay and circulating FGF23 measurement

exposure

Calcitriol administration; circulating FGF23 rose by 8 hours. Dose and transcript collection time not specified in the retrieved abstract.

limitations

The mRNA result is distinguished from circulating hormone and renal action; the separate cell reporter experiment supports receptor dependence but is not inferred to prove every bone enhancer.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Active vitamin D induced a bone hormone that feeds back on vitamin D activation and phosphate handling.

primary_references

[vdm-liu2006] Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. (2006). https://pubmed.ncbi.nlm.nih.gov/16597685/ DOI: 10.1681/asn.2005111185

tissue_or_cell_type

Bone

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 729–743

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Calcitriol-injected mice; bone Fgf23 transcript assay and circulating FGF23 measurement · source_derived_draft · unverified_draft

### vdm-calcitriol-increases-bone-fgf23-transcripts Calcitriol administration produced about a fourfold increase in bone Fgf23 transcripts in the Liu mouse study. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D induced a bone hormone that feeds back on vitamin D activation and phosphate handling. organism: Mus musculus tissue_or_cell_type: Bone experimental_model: Calcitriol-injected mice; bone Fgf23 transcript assay and circulating FGF23 measurement limitations: The mRNA result is distinguished from circulating hormone and renal action; the separate cell reporter experiment supports receptor dependence but is not inferred to prove every bone enhancer. exposure: Calcitriol administration; circulating FGF23 rose by 8 hours. Dose and transcript collection time not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-liu2006] Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. (2006). https://pubmed.ncbi.nlm.nih.gov/16597685/ DOI: 10.1681/asn.2005111185

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Figure 6; Results: Increased circulating 1,25(OH)2D levels impair mineralization by upregulating mineralization inhibitors

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Differentiated primary Vdr-intact mouse osteoblasts; conditioned-medium pyrophosphate normalized to DNA

exposure

10^-8 M calcitriol for 4 days after osteogenic differentiation.

limitations

Direct culture result does not imply that usual dietary vitamin D damages bone; physiological outcome also depends on intestinal mineral delivery.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

In this model, active vitamin D increased a molecule that restrains mineral deposition.

primary_references

[vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

tissue_or_cell_type

Osteoblast culture

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 809–823

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated primary Vdr-intact mouse osteoblasts; conditioned-medium pyrophosphate normalized to DNA · source_derived_draft · unverified_draft

### vdm-calcitriol-increases-extracellular-ppi Calcitriol treatment increased extracellular pyrophosphate in differentiated Vdr-intact mouse osteoblast cultures. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this model, active vitamin D increased a molecule that restrains mineral deposition. organism: Mus musculus tissue_or_cell_type: Osteoblast culture experimental_model: Differentiated primary Vdr-intact mouse osteoblasts; conditioned-medium pyrophosphate normalized to DNA limitations: Direct culture result does not imply that usual dietary vitamin D damages bone; physiological outcome also depends on intestinal mineral delivery. exposure: 10^-8 M calcitriol for 4 days after osteogenic differentiation. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Figure 6; Results: Increased circulating 1,25(OH)2D levels impair mineralization by upregulating mineralization inhibitors nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays

exposure

Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.

limitations

Stimulation was segment-specific: increased transporter protein in ileum did not establish the same active-flux response there. No human dietary-dose inference.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Active vitamin D increased the intestine’s sodium-coupled phosphate uptake in the responsive segment.

primary_references

[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

tissue_or_cell_type

Jejunum

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 665–679

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft

### vdm-calcitriol-increases-jejunal-phosphate-transport Two daily calcitriol injections increased active phosphate transport in wild-type mouse jejunum. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D increased the intestine’s sodium-coupled phosphate uptake in the responsive segment. organism: Mus musculus tissue_or_cell_type: Jejunum experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: Stimulation was segment-specific: increased transporter protein in ileum did not establish the same active-flux response there. No human dietary-dose inference. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Primary abstract and Results/Discussion on calcitriol-induced claudin expression; cached web-primary-excerpts.json

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Human Caco-2 cells; RT-PCR, immunoblotting and junctional localization

exposure

Calcitriol-treated versus vehicle Caco-2 cultures; exact hormone dose/time not recovered in the primary passages used.

limitations

Cell-line expression response; the separately reused permeability experiments support function, but neither establishes a universal fraction of human dietary calcium absorption.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

Active vitamin D can increase a tight-junction protein involved in calcium movement between intestinal cells.

primary_references

[vdm-fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18287530/ DOI: 10.1091/mbc.e07-09-0973

tissue_or_cell_type

Intestinal epithelial cell model

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 633–647

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human Caco-2 cells; RT-PCR, immunoblotting and junctional localization · source_derived_draft · unverified_draft

### vdm-calcitriol-induces-cldn12 Calcitriol increased Claudin-12 expression in human Caco-2 intestinal epithelial cells. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D can increase a tight-junction protein involved in calcium movement between intestinal cells. organism: Homo sapiens tissue_or_cell_type: Intestinal epithelial cell model experimental_model: Human Caco-2 cells; RT-PCR, immunoblotting and junctional localization limitations: Cell-line expression response; the separately reused permeability experiments support function, but neither establishes a universal fraction of human dietary calcium absorption. exposure: Calcitriol-treated versus vehicle Caco-2 cultures; exact hormone dose/time not recovered in the primary passages used. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Primary abstract and Results/Discussion on calcitriol-induced claudin expression; cached web-primary-excerpts.json nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18287530/ DOI: 10.1091/mbc.e07-09-0973

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Primary abstract and Results/Discussion on calcitriol-induced claudin expression; cached web-primary-excerpts.json

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Human Caco-2 cells; RT-PCR, immunoblotting and junctional localization

exposure

Calcitriol-treated versus vehicle Caco-2 cultures; exact hormone dose/time not recovered in the primary passages used.

limitations

Cell-line expression response; the separately reused permeability experiments support function, but neither establishes a universal fraction of human dietary calcium absorption.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

Active vitamin D can increase a tight-junction protein involved in calcium movement between intestinal cells.

primary_references

[vdm-fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18287530/ DOI: 10.1091/mbc.e07-09-0973

tissue_or_cell_type

Intestinal epithelial cell model

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 617–631

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human Caco-2 cells; RT-PCR, immunoblotting and junctional localization · source_derived_draft · unverified_draft

### vdm-calcitriol-induces-cldn2 Calcitriol increased Claudin-2 expression in human Caco-2 intestinal epithelial cells. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D can increase a tight-junction protein involved in calcium movement between intestinal cells. organism: Homo sapiens tissue_or_cell_type: Intestinal epithelial cell model experimental_model: Human Caco-2 cells; RT-PCR, immunoblotting and junctional localization limitations: Cell-line expression response; the separately reused permeability experiments support function, but neither establishes a universal fraction of human dietary calcium absorption. exposure: Calcitriol-treated versus vehicle Caco-2 cultures; exact hormone dose/time not recovered in the primary passages used. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Primary abstract and Results/Discussion on calcitriol-induced claudin expression; cached web-primary-excerpts.json nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18287530/ DOI: 10.1091/mbc.e07-09-0973

cross_nutrient

Vitamin D–vitamin K boundary: vitamin D-regulated osteocalcin expression is distinct from subsequent vitamin K-dependent carboxylation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Human osteocalcin genomic transgene in mice; calvarial mRNA analysis

exposure

Repeated calcitriol administration; exact dose and calvarial mRNA collection time not specified in the retrieved abstract.

limitations

Human transgene in mouse tissue is not a human supplementation trial. Transcript induction does not measure vitamin K-dependent carboxylation.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus with human BGLAP transgene

plain_language

The human osteocalcin gene responded to active vitamin D in this engineered mouse model.

primary_references

[vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570

tissue_or_cell_type

Calvaria

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 857–871

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human osteocalcin genomic transgene in mice; calvarial mRNA analysis · source_derived_draft · unverified_draft

### vdm-calcitriol-induces-human-osteocalcin-transgene Calcitriol increased human osteocalcin mRNA about 1.8-fold in calvaria of mice carrying the human osteocalcin genomic transgene. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human osteocalcin gene responded to active vitamin D in this engineered mouse model. organism: Mus musculus with human BGLAP transgene tissue_or_cell_type: Calvaria experimental_model: Human osteocalcin genomic transgene in mice; calvarial mRNA analysis limitations: Human transgene in mouse tissue is not a human supplementation trial. Transcript induction does not measure vitamin K-dependent carboxylation. exposure: Repeated calcitriol administration; exact dose and calvarial mRNA collection time not specified in the retrieved abstract. cross_nutrient: Vitamin D–vitamin K boundary: vitamin D-regulated osteocalcin expression is distinct from subsequent vitamin K-dependent carboxylation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570

cross_nutrient

Vitamin D–vitamin K boundary: gene expression and carboxylation are distinct, and osteocalcin transcription is species-dependent.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Primary calvarial osteoblasts from human-osteocalcin-transgenic mice; species-specific protein assays

exposure

Calcitriol exposure of primary cultures; exact culture dose/time not given in the retrieved abstract.

limitations

Species and gene-regulatory context explain the difference; this is not an orange scientific conflict and does not predict human fracture outcomes.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus with human BGLAP transgene

plain_language

Mouse and human osteocalcin genes responded differently in the same experimental setting.

primary_references

[vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570

tissue_or_cell_type

Calvarial osteoblast culture

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 873–887

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary calvarial osteoblasts from human-osteocalcin-transgenic mice; species-specific protein assays · source_derived_draft · unverified_draft

### vdm-calcitriol-mouse-osteocalcin-culture-scope In primary calvarial osteoblast cultures from the same transgenic mice, calcitriol inhibited endogenous mouse osteocalcin accumulation while increasing human osteocalcin production. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse and human osteocalcin genes responded differently in the same experimental setting. organism: Mus musculus with human BGLAP transgene tissue_or_cell_type: Calvarial osteoblast culture experimental_model: Primary calvarial osteoblasts from human-osteocalcin-transgenic mice; species-specific protein assays limitations: Species and gene-regulatory context explain the difference; this is not an orange scientific conflict and does not predict human fracture outcomes. exposure: Calcitriol exposure of primary cultures; exact culture dose/time not given in the retrieved abstract. cross_nutrient: Vitamin D–vitamin K boundary: gene expression and carboxylation are distinct, and osteocalcin transcription is species-dependent. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays

exposure

Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.

limitations

A negative result for this assay and regimen does not exclude other doses, durations, species or intestinal segments.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

The measured phosphate response involved transport through cells; the route between cells did not show the same increase.

primary_references

[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

tissue_or_cell_type

Intestinal epithelium

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 681–695

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft

### vdm-calcitriol-no-detected-paracellular-phosphate-response The two-day calcitriol regimen did not detectably increase paracellular phosphate flux in the mouse intestine. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured phosphate response involved transport through cells; the route between cells did not show the same increase. organism: Mus musculus tissue_or_cell_type: Intestinal epithelium experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: A negative result for this assay and regimen does not exclude other doses, durations, species or intestinal segments. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays

exposure

Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract.

limitations

Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions.

primary_references

[vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06

tissue_or_cell_type

Osteoblastic cell chromatin

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 841–855

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays · source_derived_draft · unverified_draft

### vdm-calcitriol-rankl-distal-enhancer Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions. organism: Mus musculus tissue_or_cell_type: Osteoblastic cell chromatin experimental_model: Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays limitations: Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical. exposure: Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Vitamin-D-deficient wild-type mice; everted duodenal gut-sac calcium transport

exposure

Diet-induced vitamin D deficiency followed by calcitriol administration; exact replacement dose/time not reported in the retrieved abstract.

limitations

Wild-type arm is separated from the knockout arms; this is active-hormone replacement, not a D2/D3 oral-dose equivalence test.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Providing the active hormone restored part of the intestinal calcium-transport response after vitamin D deprivation.

primary_references

[vdm-benn2008] Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k. (2008). https://pubmed.ncbi.nlm.nih.gov/18325990/ DOI: 10.1210/en.2007-1655

tissue_or_cell_type

Duodenum

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 649–663

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vitamin-D-deficient wild-type mice; everted duodenal gut-sac calcium transport · source_derived_draft · unverified_draft

### vdm-calcitriol-restores-transport-after-d-deficiency Calcitriol administration increased active duodenal calcium transport in vitamin-D-deficient wild-type mice in the Benn study. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the active hormone restored part of the intestinal calcium-transport response after vitamin D deprivation. organism: Mus musculus tissue_or_cell_type: Duodenum experimental_model: Vitamin-D-deficient wild-type mice; everted duodenal gut-sac calcium transport limitations: Wild-type arm is separated from the knockout arms; this is active-hormone replacement, not a D2/D3 oral-dose equivalence test. exposure: Diet-induced vitamin D deficiency followed by calcitriol administration; exact replacement dose/time not reported in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-benn2008] Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k. (2008). https://pubmed.ncbi.nlm.nih.gov/18325990/ DOI: 10.1210/en.2007-1655

evidence_access

Primary abstract

experimental_model

Small before/after subgroup within the dual-tracer study.

limitations

Four patients, active hormone and renal impairment; not a universal effect of vitamin D3 supplementation.

nutrient_topic

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

plain_language

Active vitamin D changed the two absorption responses by different amounts.

primary_references

Stable strontium absorption as a measure of intestinal calcium absorption: comparison with the double-radiotracer calcium absorption test. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7955914/ · DOI 10.1042/cs0870363

Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 54–60

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small before/after subgroup within the dual-tracer study. · source_derived_draft · unverified_draft

## strontium-calcitriol-absorption Active vitamin D changed the two absorption responses by different amounts. In four renal-failure patients retested after calcitriol 1 microgram/day for ten days, six-hour strontium absorption increased 4.29-fold and calcium absorption 2.4-fold. Model: Small before/after subgroup within the dual-tracer study. Limitations: Four patients, active hormone and renal impairment; not a universal effect of vitamin D3 supplementation. Evidence access: Primary abstract Stable strontium absorption as a measure of intestinal calcium absorption: comparison with the double-radiotracer calcium absorption test. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7955914/ · DOI 10.1042/cs0870363

experimental_model

Vitamin D metabolite administration to rats; parathyroid RNA and nuclear transcription assays

limitations

Administered hormone and transcription assay; does not resolve every promoter mechanism.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Active vitamin D feeds back on hormone production.

primary_references

[silver1986] Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat (1986). https://pubmed.ncbi.nlm.nih.gov/3771798/ DOI: 10.1172/JCI112714

tissue_or_cell_type

Parathyroid

Calcium: mechanism-first literature curation (2026-09-17) · lines 80–89

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vitamin D metabolite administration to rats; parathyroid RNA and nuclear transcription assays · source_derived_draft · unverified_draft

### calcitriol-suppresses-pth-transcription Calcitriol administration suppresses parathyroid PTH transcription in rats without a measured rise in serum calcium. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D feeds back on hormone production. organism: Rattus norvegicus tissue_or_cell_type: Parathyroid experimental_model: Vitamin D metabolite administration to rats; parathyroid RNA and nuclear transcription assays limitations: Administered hormone and transcription assay; does not resolve every promoter mechanism. [silver1986] Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat (1986). https://pubmed.ncbi.nlm.nih.gov/3771798/ DOI: 10.1172/JCI112714

experimental_model

Human intestinal cell lines; chromatin immunoprecipitation, promoter reporters and regulatory-element mutagenesis

limitations

Promoter activity and receptor occupancy do not establish an exclusive transport route or whole-body calcium flux.

nutrient_topic

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

organism

Homo sapiens cell lines

plain_language

Active vitamin D increases a calcium-entry channel.

primary_references

[meyer2006] The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells (2006). https://pubmed.ncbi.nlm.nih.gov/16574738/ DOI: 10.1210/me.2006-0031

tissue_or_cell_type

Intestinal cell transcriptional regulation

Calcium: mechanism-first literature curation (2026-09-17) · lines 181–190

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human intestinal cell lines; chromatin immunoprecipitation, promoter reporters and regulatory-element mutagenesis · source_derived_draft · unverified_draft

### calcitriol-vdr-induces-trpv6 Calcitriol induces human TRPV6 transcription through VDR/RXR-associated regulatory elements in intestinal cell models. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D increases a calcium-entry channel. organism: Homo sapiens cell lines tissue_or_cell_type: Intestinal cell transcriptional regulation experimental_model: Human intestinal cell lines; chromatin immunoprecipitation, promoter reporters and regulatory-element mutagenesis limitations: Promoter activity and receptor occupancy do not establish an exclusive transport route or whole-body calcium flux. [meyer2006] The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells (2006). https://pubmed.ncbi.nlm.nih.gov/16574738/ DOI: 10.1210/me.2006-0031

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH response -> vitamin D/calcium

experimental_model

26 initially normal adults before/after three-week low-Mg diet

limitations

Circulating metabolite response does not identify CYP27B1 as a directly Mg-dependent enzyme or distinguish all production/clearance effects.

nutrient_topic

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

organism

Homo sapiens

plain_language

Even when PTH was supplied directly, the downstream vitamin-D response was reduced, supporting a target-organ component beyond reduced hormone release.

primary_references

[fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

tissue_or_cell_type

Blood; parathyroid and renal mineral axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 385–395

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26 initially normal adults before/after three-week low-Mg diet · source_derived_draft · unverified_draft

### selective-mg-depletion-blunts-pth-calcitriol-response The rise in circulating calcitriol during a six-hour human PTH(1-34) infusion was smaller after dietary Mg depletion. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Even when PTH was supplied directly, the downstream vitamin-D response was reduced, supporting a target-organ component beyond reduced hormone release. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid and renal mineral axis experimental_model: 26 initially normal adults before/after three-week low-Mg diet limitations: Circulating metabolite response does not identify CYP27B1 as a directly Mg-dependent enzyme or distinguish all production/clearance effects. cross_nutrient: magnesium -> PTH response -> vitamin D/calcium [fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

cross_nutrient

false

evidence_location

Primary abstract: identified C24R products and comparative initial-rate kinetics.

experimental_model

Matched recombinant human CYP24A1 kinetics

exposure

Comparison of kcat/Km; low-substrate limit.

limitations

This observation does not establish longer in-vivo D2 hormone exposure or negate clinical differences between parent vitamin dosing regimens.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens protein

plain_language

Active D2 was initially oxidized more slowly than active D3 in this assay.

primary_references

[li2023] Inactivation of vitamin D2 metabolites by human CYP24A1. (2023). https://pubmed.ncbi.nlm.nih.gov/37495192/ DOI: 10.1016/j.jsbmb.2023.106368

tissue_or_cell_type

phospholipid-vesicle membrane

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 557–570

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched recombinant human CYP24A1 kinetics · source_derived_draft · unverified_draft

### vd-act-cyp24a1-hormone-selectivity Human CYP24A1 initial catalytic efficiency for calcitriol was almost twice that for the active D2 hormone in the matched vesicle experiment. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active D2 was initially oxidized more slowly than active D3 in this assay. organism: Homo sapiens protein tissue_or_cell_type: phospholipid-vesicle membrane experimental_model: Matched recombinant human CYP24A1 kinetics limitations: This observation does not establish longer in-vivo D2 hormone exposure or negate clinical differences between parent vitamin dosing regimens. exposure: Comparison of kcat/Km; low-substrate limit. cross_nutrient: false evidence_location: Primary abstract: identified C24R products and comparative initial-rate kinetics. nutrient: Vitamin D2 and D3 [li2023] Inactivation of vitamin D2 metabolites by human CYP24A1. (2023). https://pubmed.ncbi.nlm.nih.gov/37495192/ DOI: 10.1016/j.jsbmb.2023.106368

cross_nutrient

false

experimental_model

Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum

exposure

Human monocytes, 24 hours, 100 nMadded 25(OH)D3; Fig 3C.

limitations

Ex-vivo monocytes in 10% serum, not a whole-person infection endpoint. Low-substrate medium is not a validated universal blood threshold.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

These immune cells could activate the precursor locally.

primary_references

[adams2009] Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. (2009). https://pubmed.ncbi.nlm.nih.gov/19299728/ DOI: 10.4049/jimmunol.0803736

tissue_or_cell_type

Human monocytes

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 996–1007

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum · source_derived_draft · unverified_draft

### vd-adams-local-conversion Adding 100 nM 25(OH)D3 increased detectable 1, 25(OH)2D in conditioned monocyte medium even without TLR induction. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: These immune cells could activate the precursor locally. organism: Homo sapiens tissue_or_cell_type: Human monocytes experimental_model: Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum limitations: Ex-vivo monocytes in 10% serum, not a whole-person infection endpoint. Low-substrate medium is not a validated universal blood threshold. exposure: Human monocytes, 24 hours, 100 nMadded 25(OH)D3; Fig 3C. cross_nutrient: false [adams2009] Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. (2009). https://pubmed.ncbi.nlm.nih.gov/19299728/ DOI: 10.4049/jimmunol.0803736

experimental_model

Recombinant human CYP27B1 expressed in bacteria and reconstituted with phospholipids and electron-transfer partners

limitations

Activity requires electron-transfer support; this assay does not measure endocrine flux in an intact kidney.

nutrient_topic

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

organism

Homo sapiens enzyme

plain_language

CYP27B1 activates the vitamin D precursor.

primary_references

[tang2012cyp27b1] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles (2012). https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2012.08736.x DOI: 10.1111/j.1742-4658.2012.08736.x

research_relationship_category

biochemical_reaction

tissue_or_cell_type

Reconstituted membrane system

transport_or_reaction_direction

forward

Calcium: mechanism-first literature curation (2026-09-17) · lines 349–360

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP27B1 expressed in bacteria and reconstituted with phospholipids and electron-transfer partners · source_derived_draft · unverified_draft

### cyp27b1-produces-calcitriol Recombinant human CYP27B1 converts calcifediol to calcitriol by 1-alpha-hydroxylation in reconstituted enzyme systems. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP27B1 activates the vitamin D precursor. organism: Homo sapiens enzyme tissue_or_cell_type: Reconstituted membrane system experimental_model: Recombinant human CYP27B1 expressed in bacteria and reconstituted with phospholipids and electron-transfer partners limitations: Activity requires electron-transfer support; this assay does not measure endocrine flux in an intact kidney. research_relationship_category: biochemical_reaction transport_or_reaction_direction: forward [tang2012cyp27b1] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles (2012). https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2012.08736.x DOI: 10.1111/j.1742-4658.2012.08736.x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Magnesium -> calcium response; vitamin D normalization is not obligatory in this cohort.

experimental_model

Five to thirteen days of parenteral Mg.

limitations

Nonrandomized clinical response; calcium recovery does not prove that calcitriol rose.

nutrient_topic

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

organism

Homo sapiens

plain_language

Restoring magnesium did not automatically normalize every vitamin D result.

primary_references

[mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933

tissue_or_cell_type

Human serum; circulating mineral and vitamin D metabolites

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1358–1368

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five to thirteen days of parenteral Mg. · source_derived_draft · unverified_draft

### mg-calcium-recovery-precedes-calcitriol Magnesium treatment normalized mean serum calcium, while calcitriol rose into or above normal in only five of the 23 patients. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring magnesium did not automatically normalize every vitamin D result. organism: Homo sapiens tissue_or_cell_type: Human serum; circulating mineral and vitamin D metabolites experimental_model: Five to thirteen days of parenteral Mg. limitations: Nonrandomized clinical response; calcium recovery does not prove that calcitriol rose. cross_nutrient: Magnesium -> calcium response; vitamin D normalization is not obligatory in this cohort. [mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Magnesium -> vitamin D/calcium regulation; direct CYP cofactor step not established.

experimental_model

Clinical metabolite measurements.

limitations

Association within an affected cohort; substrate supply, PTH and other illness can contribute.

nutrient_topic

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

organism

Homo sapiens

plain_language

Magnesium depletion can accompany low active vitamin D.

primary_references

[mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933

tissue_or_cell_type

Human serum; circulating mineral and vitamin D metabolites

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1346–1356

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

### mg-deficient-human-low-calcitriol Sixteen of 23 hypocalcemic magnesium-deficient patients had low circulating calcitriol. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium depletion can accompany low active vitamin D. organism: Homo sapiens tissue_or_cell_type: Human serum; circulating mineral and vitamin D metabolites experimental_model: Clinical metabolite measurements. limitations: Association within an affected cohort; substrate supply, PTH and other illness can contribute. cross_nutrient: Magnesium -> vitamin D/calcium regulation; direct CYP cofactor step not established. [mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Magnesium/vitamin D: qualify a universal CYP27B1 shutdown claim.

experimental_model

In-vivo tracer and isolated mitochondrial assays.

limitations

No-added-Mg buffer does not prove a metal-free preparation. This result cannot be generalized to every species or illness.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Low magnesium did not switch off vitamin D activation in this rat experiment.

primary_references

[mg-carpenter1987] Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats (1987). https://pubmed.ncbi.nlm.nih.gov/3605332/ DOI: 10.1152/ajpendo.1987.253.1.e106

tissue_or_cell_type

Rat circulation and isolated kidney mitochondria

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1370–1380

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vivo tracer and isolated mitochondrial assays. · source_derived_draft · unverified_draft

### mg-rat-calcitriol-conversion-preserved Magnesium depletion did not impair measured calcifediol-to-calcitriol conversion in these rats; isolated renal activity persisted without added Mg. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low magnesium did not switch off vitamin D activation in this rat experiment. organism: Rattus norvegicus tissue_or_cell_type: Rat circulation and isolated kidney mitochondria experimental_model: In-vivo tracer and isolated mitochondrial assays. limitations: No-added-Mg buffer does not prove a metal-free preparation. This result cannot be generalized to every species or illness. cross_nutrient: Magnesium/vitamin D: qualify a universal CYP27B1 shutdown claim. [mg-carpenter1987] Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats (1987). https://pubmed.ncbi.nlm.nih.gov/3605332/ DOI: 10.1152/ajpendo.1987.253.1.e106

cross_nutrient

Magnesium/vitamin D: distinguish 25(OH)D from 1,25(OH)2D.

experimental_model

Same randomized ancillary analysis.

limitations

No significant interaction is not proof of no possible effect.

nutrient_topic

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

organism

Homo sapiens

plain_language

A change in stored vitamin D did not establish the same pattern for its active form.

primary_references

[mg-dai2018] Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial (2018). https://pubmed.ncbi.nlm.nih.gov/30541089/ DOI: 10.1093/ajcn/nqy274

tissue_or_cell_type

Human plasma

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1443–1453

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

### mg-supplement-calcitriol-no-baseline-interaction The trial did not detect a treatment-by-baseline-25(OH)D interaction for plasma calcitriol. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A change in stored vitamin D did not establish the same pattern for its active form. organism: Homo sapiens tissue_or_cell_type: Human plasma experimental_model: Same randomized ancillary analysis. limitations: No significant interaction is not proof of no possible effect. cross_nutrient: Magnesium/vitamin D: distinguish 25(OH)D from 1,25(OH)2D. [mg-dai2018] Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial (2018). https://pubmed.ncbi.nlm.nih.gov/30541089/ DOI: 10.1093/ajcn/nqy274

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria

exposure

SLC34A3 disease-associated mutations in five families

limitations

Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention.

nutrient_topic

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

organism

Human

plain_language

A phosphate-handling defect can change the vitamin D environment.

primary_references

[sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410

tissue_or_cell_type

Renal proximal tubule and systemic mineral phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 681–692

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria · source_derived_draft · unverified_draft

### sodium-napi2c-calcitriol The HHRH phenotype included elevated circulating 1,25-dihydroxyvitamin D with normal or low-normal FGF23. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A phosphate-handling defect can change the vitamin D environment. organism: Human tissue_or_cell_type: Renal proximal tubule and systemic mineral phenotype experimental_model: Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria limitations: Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention. exposure: SLC34A3 disease-associated mutations in five families evidence_span: {"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"} [sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"}

experimental_model

Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria

exposure

SLC34A3 disease-associated mutations in five families

limitations

Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention.

nutrient_topic

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

organism

Human

plain_language

This phosphate disorder can also increase calcium loss into urine.

primary_references

[sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410

tissue_or_cell_type

Renal proximal tubule and systemic mineral phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 694–705

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria · source_derived_draft · unverified_draft

### sodium-napi2c-calcium The sodium/phosphate-transporter-associated HHRH phenotype included hypercalciuria. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This phosphate disorder can also increase calcium loss into urine. organism: Human tissue_or_cell_type: Renal proximal tubule and systemic mineral phenotype experimental_model: Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria limitations: Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention. exposure: SLC34A3 disease-associated mutations in five families evidence_span: {"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"} [sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410

cross_nutrient

false

evidence_location

Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion.

experimental_model

Human CYP24A1 expressed in V79-4 cells

exposure

Calcitriol 0.003-9 micromolar across transient/stable systems; Figure 4.

limitations

Aqueous radioactivity measures the terminal catabolic fraction; not every oxidation intermediate is individually isolated in this record.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens protein in hamster-derived cells

plain_language

CYP24A1 carries active D3 through a multistep breakdown pathway.

primary_references

[schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864

tissue_or_cell_type

cellular vitamin D catabolic assay

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 497–510

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP24A1 expressed in V79-4 cells · source_derived_draft · unverified_draft

### vd-act-cyp24a1-calcitroic Wild-type human CYP24A1 expressed in V79-4 cells metabolized calcitriol through C24-pathway intermediates to a water-soluble fraction assigned to calcitroic acid. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP24A1 carries active D3 through a multistep breakdown pathway. organism: Homo sapiens protein in hamster-derived cells tissue_or_cell_type: cellular vitamin D catabolic assay experimental_model: Human CYP24A1 expressed in V79-4 cells limitations: Aqueous radioactivity measures the terminal catabolic fraction; not every oxidation intermediate is individually isolated in this record. exposure: Calcitriol 0.003-9 micromolar across transient/stable systems; Figure 4. cross_nutrient: false evidence_location: Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion. nutrient: Vitamin D2 and D3 [schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion.

experimental_model

Human candidate-gene study with supporting enzyme assays

exposure

First cohort received 500 IU/day; second cohort became symptomatic 2-3 weeks after intermittent high-dose prophylaxis.

limitations

Selected families do not estimate population risk. Genotype, dose and penetrance matter; this is not a universal safe/unsafe serum or dose threshold.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

Defective vitamin D breakdown can make infants unusually sensitive to supplementation.

primary_references

[schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864

tissue_or_cell_type

systemic calcium handling

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 602–615

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human candidate-gene study with supporting enzyme assays · source_derived_draft · unverified_draft

### vd-act-cyp24a1-hypercalcemia Recessive CYP24A1 variants were identified in infants with hypercalcemia, including a second group whose illness followed high-dose vitamin D prophylaxis. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Defective vitamin D breakdown can make infants unusually sensitive to supplementation. organism: Homo sapiens tissue_or_cell_type: systemic calcium handling experimental_model: Human candidate-gene study with supporting enzyme assays limitations: Selected families do not estimate population risk. Genotype, dose and penetrance matter; this is not a universal safe/unsafe serum or dose threshold. exposure: First cohort received 500 IU/day; second cohort became symptomatic 2-3 weeks after intermittent high-dose prophylaxis. cross_nutrient: true evidence_location: Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion. nutrient: Vitamin D2 and D3 [schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion.

experimental_model

Patient variants expressed in V79-4 cells

exposure

Transient/stable transfection; calcitriol 0.003-9 micromolar depending on system.

limitations

The full text qualifies its abstract: L409S retained small measurable activity, so not all variants were absolutely inactive.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens protein in hamster-derived cells

plain_language

Some inherited defects prevent normal removal of active vitamin D.

primary_references

[schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864

tissue_or_cell_type

cellular catabolic assay

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 587–600

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient variants expressed in V79-4 cells · source_derived_draft · unverified_draft

### vd-act-cyp24a1-loss Patient-derived CYP24A1 variants severely impaired calcitriol catabolism in expression assays; L409S retained 5.3% of wild-type activity in the detailed results. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some inherited defects prevent normal removal of active vitamin D. organism: Homo sapiens protein in hamster-derived cells tissue_or_cell_type: cellular catabolic assay experimental_model: Patient variants expressed in V79-4 cells limitations: The full text qualifies its abstract: L409S retained small measurable activity, so not all variants were absolutely inactive. exposure: Transient/stable transfection; calcitriol 0.003-9 micromolar depending on system. cross_nutrient: false evidence_location: Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion. nutrient: Vitamin D2 and D3 [schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Primary abstract, Methods and Results.

experimental_model

Patient sequencing and heterologous functional assays

exposure

Four patient-derived variants versus normal enzyme; dose/time not specified in abstract.

limitations

Functional loss is experimentally supported; clinical severity cannot be predicted solely from this assay.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens proteins in COS-1 cells

plain_language

An inherited enzyme defect can block the final activation step.

primary_references

[kitanaka1998] Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. (1998). https://pubmed.ncbi.nlm.nih.gov/9486994/ DOI: 10.1056/NEJM199803053381004

tissue_or_cell_type

renal activation machinery modeled in cultured cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 482–495

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

### vd-act-cyp27b1-mutations All four homozygous CYP27B1 missense variants identified in four unrelated rickets patients abolished measured 1alpha-hydroxylase activity when expressed in COS-1 cells. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited enzyme defect can block the final activation step. organism: Homo sapiens proteins in COS-1 cells tissue_or_cell_type: renal activation machinery modeled in cultured cells experimental_model: Patient sequencing and heterologous functional assays limitations: Functional loss is experimentally supported; clinical severity cannot be predicted solely from this assay. exposure: Four patient-derived variants versus normal enzyme; dose/time not specified in abstract. cross_nutrient: false evidence_location: Primary abstract, Methods and Results. nutrient: Vitamin D2 and D3 [kitanaka1998] Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. (1998). https://pubmed.ncbi.nlm.nih.gov/9486994/ DOI: 10.1056/NEJM199803053381004

cross_nutrient

true

evidence_location

Primary Tables 3-5, Figure 6A and Experimental procedures; full text retrieved.

experimental_model

Human CYP27B1/FDX1/FDXR kinetic reconstitution

exposure

FDX1 1-30 micromolar; 2-min incubations with calcifediol; Table 4.

limitations

The experiment varies intact FDX1, not dietary iron. Reciprocal changes of apparent Km and turnover prevent interpreting FDX1 level as a universal limiting factor.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens proteins

plain_language

An iron-sulfur electron carrier supports the final D3 activation step.

primary_references

[tang2012] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. (2012). https://pubmed.ncbi.nlm.nih.gov/22862690/ DOI: 10.1111/j.1742-4658.2012.08736.x

tissue_or_cell_type

reconstituted mitochondrial membrane

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 452–465

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP27B1/FDX1/FDXR kinetic reconstitution · source_derived_draft · unverified_draft

### vd-act-fdx1-cyp27b1 Human adrenodoxin supported CYP27B1 activity in reconstituted vesicles; varying adrenodoxin changed apparent kinetic parameters for calcifediol hydroxylation. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An iron-sulfur electron carrier supports the final D3 activation step. organism: Homo sapiens proteins tissue_or_cell_type: reconstituted mitochondrial membrane experimental_model: Human CYP27B1/FDX1/FDXR kinetic reconstitution limitations: The experiment varies intact FDX1, not dietary iron. Reciprocal changes of apparent Km and turnover prevent interpreting FDX1 level as a universal limiting factor. exposure: FDX1 1-30 micromolar; 2-min incubations with calcifediol; Table 4. cross_nutrient: true evidence_location: Primary Tables 3-5, Figure 6A and Experimental procedures; full text retrieved. nutrient: Vitamin D2 and D3 [tang2012] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. (2012). https://pubmed.ncbi.nlm.nih.gov/22862690/ DOI: 10.1111/j.1742-4658.2012.08736.x

cross_nutrient

false

evidence_location

Primary abstract, purified-enzyme HPLC results.

experimental_model

Purified rat CYP24A1 with HPLC product analysis

exposure

Active D2 versus D3 substrates; detailed dose/time unavailable in abstract.

limitations

Negative detection is assay-specific. Rat enzyme behavior is not a claim that humans cannot metabolize D2 further.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Rattus norvegicus protein

plain_language

A rat enzyme experiment found different terminal breakdown products for D2 and D3.

primary_references

[horst2003] Rat cytochrome P450C24 (CYP24) does not metabolize 1,25-dihydroxyvitamin D2 to calcitroic acid. (2003). https://pubmed.ncbi.nlm.nih.gov/12520527/ DOI: 10.1002/jcb.10359

tissue_or_cell_type

cell-free enzyme system

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 572–585

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat CYP24A1 with HPLC product analysis · source_derived_draft · unverified_draft

### vd-act-rat-cyp24-d2-boundary Purified rat CYP24A1 produced a C24R-hydroxylated metabolite from active D2 but no detectable calcitroic acid under conditions that generated calcitroic acid from calcitriol. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A rat enzyme experiment found different terminal breakdown products for D2 and D3. organism: Rattus norvegicus protein tissue_or_cell_type: cell-free enzyme system experimental_model: Purified rat CYP24A1 with HPLC product analysis limitations: Negative detection is assay-specific. Rat enzyme behavior is not a claim that humans cannot metabolize D2 further. exposure: Active D2 versus D3 substrates; detailed dose/time unavailable in abstract. cross_nutrient: false evidence_location: Primary abstract, purified-enzyme HPLC results. nutrient: Vitamin D2 and D3 [horst2003] Rat cytochrome P450C24 (CYP24) does not metabolize 1,25-dihydroxyvitamin D2 to calcitroic acid. (2003). https://pubmed.ncbi.nlm.nih.gov/12520527/ DOI: 10.1002/jcb.10359

cross_nutrient

false

experimental_model

Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison

exposure

Promoter binding and functional response-element experiments.

limitations

Human cell and promoter experiments; no oral D2/D3 efficacy or infection-incidence trial.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

The receptor connects the active hormone to a specific DNA control element.

primary_references

[gombart2005] Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. (2005). https://pubmed.ncbi.nlm.nih.gov/15985530/ DOI: 10.1096/fj.04-3284com

tissue_or_cell_type

Human CAMP promoter

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 918–929

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison · source_derived_draft · unverified_draft

### vd-camp-vdre VDR bound a consensus vitamin D response element in the human CAMP promoter; this element mediated the observed induction. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects the active hormone to a specific DNA control element. organism: Homo sapiens tissue_or_cell_type: Human CAMP promoter experimental_model: Human cell lines and bone-marrow-derived cells; promoter studies and mouse comparison limitations: Human cell and promoter experiments; no oral D2/D3 efficacy or infection-incidence trial. exposure: Promoter binding and functional response-element experiments. cross_nutrient: false [gombart2005] Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. (2005). https://pubmed.ncbi.nlm.nih.gov/15985530/ DOI: 10.1096/fj.04-3284com

cross_nutrient

false

experimental_model

52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months

exposure

Four oral 2.5 mg D2 or D3 bolus doses over 4 months.

limitations

Metabolite-to-parent ratios integrate production, binding, distribution and clearance; they are not an isolated CYP activity assay.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

The active-D3 to precursor ratio also fell under this bolus regimen.

primary_references

[martineau2019] Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31199458/ DOI: 10.1210/jc.2019-00207

tissue_or_cell_type

Human circulating measurements

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1444–1455

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months · source_derived_draft · unverified_draft

### vd-martineau-1alpha-ratio After D2, the mean 1, 25(OH)2D3: 25(OH)D3 ratio decreased and was lower than after D3. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active-D3 to precursor ratio also fell under this bolus regimen. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: 52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months limitations: Metabolite-to-parent ratios integrate production, binding, distribution and clearance; they are not an isolated CYP activity assay. exposure: Four oral 2.5 mg D2 or D3 bolus doses over 4 months. cross_nutrient: false [martineau2019] Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31199458/ DOI: 10.1210/jc.2019-00207

cross_nutrient

false

experimental_model

52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months

exposure

Four oral 2.5 mg D2 or D3 bolus doses over 4 months.

limitations

Metabolite-to-parent ratios integrate production, binding, distribution and clearance; they are not an isolated CYP activity assay.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

Both groups showed a catabolic-ratio increase; the between-form difference was not detected.

primary_references

[martineau2019] Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31199458/ DOI: 10.1210/jc.2019-00207

tissue_or_cell_type

Human circulating measurements

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1457–1468

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months · source_derived_draft · unverified_draft

### vd-martineau-24-ratio The 24R, 25(OH)2D3: 25(OH)D3 ratio rose within both D2 and D3 groups, but their postsupplementation ratios did not differ significantly. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both groups showed a catabolic-ratio increase; the between-form difference was not detected. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: 52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months limitations: Metabolite-to-parent ratios integrate production, binding, distribution and clearance; they are not an isolated CYP activity assay. exposure: Four oral 2.5 mg D2 or D3 bolus doses over 4 months. cross_nutrient: false [martineau2019] Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31199458/ DOI: 10.1210/jc.2019-00207

cross_nutrient

false

experimental_model

52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months

exposure

Four oral 2.5 mg D2 or D3 bolus doses over 4 months.

limitations

Metabolite-to-parent ratios integrate production, binding, distribution and clearance; they are not an isolated CYP activity assay.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

The metabolite-to-parent ratio changed, suggesting altered handling of D3.

primary_references

[martineau2019] Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31199458/ DOI: 10.1210/jc.2019-00207

tissue_or_cell_type

Human circulating measurements

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1431–1442

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months · source_derived_draft · unverified_draft

### vd-martineau-25-ratio After D2, the mean 25(OH)D3: D3 ratio decreased and was lower than after D3. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The metabolite-to-parent ratio changed, suggesting altered handling of D3. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: 52-person metabolite-profile subset of a 340-person randomized trial; four 2.5 mg oral D2/D3 boluses over 4 months limitations: Metabolite-to-parent ratios integrate production, binding, distribution and clearance; they are not an isolated CYP activity assay. exposure: Four oral 2.5 mg D2 or D3 bolus doses over 4 months. cross_nutrient: false [martineau2019] Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31199458/ DOI: 10.1210/jc.2019-00207

cross_nutrient

false

experimental_model

Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay

exposure

TLR activation in cultured human monocytes/macrophages.

limitations

Gene-expression result; does not mean any dietary D dose reproduces pathogen-triggered signaling.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

A pathogen-sensing signal increased part of the local vitamin D machinery.

primary_references

[liu2006] Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. (2006). https://pubmed.ncbi.nlm.nih.gov/16497887/ DOI: 10.1126/science.1123933

tissue_or_cell_type

Human monocytes/macrophages

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 957–968

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay · source_derived_draft · unverified_draft

### vd-tlr-cyp27b1 TLR activation increased vitamin D1-alpha-hydroxylase gene expression in human macrophages. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A pathogen-sensing signal increased part of the local vitamin D machinery. organism: Homo sapiens tissue_or_cell_type: Human monocytes/macrophages experimental_model: Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay limitations: Gene-expression result; does not mean any dietary D dose reproduces pathogen-triggered signaling. exposure: TLR activation in cultured human monocytes/macrophages. cross_nutrient: false [liu2006] Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. (2006). https://pubmed.ncbi.nlm.nih.gov/16497887/ DOI: 10.1126/science.1123933

cross_nutrient

false

experimental_model

Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay

exposure

Cultured human macrophages with intracellular M. tuberculosis.

limitations

Cellular experimental result, not a human tuberculosis-treatment trial; infection response depends on more than vitamin D.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

The cell experiment linked local vitamin D signaling to bacterial killing.

primary_references

[liu2006] Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. (2006). https://pubmed.ncbi.nlm.nih.gov/16497887/ DOI: 10.1126/science.1123933

tissue_or_cell_type

Human macrophages

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 970–981

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay · source_derived_draft · unverified_draft

### vd-tlr-mycobacteria TLR activation coupled vitamin D pathway induction to cathelicidin expression and killing of intracellular M. tuberculosis in the human macrophage experiments. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell experiment linked local vitamin D signaling to bacterial killing. organism: Homo sapiens tissue_or_cell_type: Human macrophages experimental_model: Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay limitations: Cellular experimental result, not a human tuberculosis-treatment trial; infection response depends on more than vitamin D. exposure: Cultured human macrophages with intracellular M. tuberculosis. cross_nutrient: false [liu2006] Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. (2006). https://pubmed.ncbi.nlm.nih.gov/16497887/ DOI: 10.1126/science.1123933

cross_nutrient

false

experimental_model

Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay

exposure

TLR activation in cultured human monocytes/macrophages.

limitations

Gene-expression result; does not mean any dietary D dose reproduces pathogen-triggered signaling.

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens

plain_language

A pathogen-sensing signal increased part of the local vitamin D machinery.

primary_references

[liu2006] Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. (2006). https://pubmed.ncbi.nlm.nih.gov/16497887/ DOI: 10.1126/science.1123933

tissue_or_cell_type

Human monocytes/macrophages

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 944–955

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay · source_derived_draft · unverified_draft

### vd-tlr-vdr TLR activation increased VDR gene expression in human macrophages. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A pathogen-sensing signal increased part of the local vitamin D machinery. organism: Homo sapiens tissue_or_cell_type: Human monocytes/macrophages experimental_model: Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay limitations: Gene-expression result; does not mean any dietary D dose reproduces pathogen-triggered signaling. exposure: TLR activation in cultured human monocytes/macrophages. cross_nutrient: false [liu2006] Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. (2006). https://pubmed.ncbi.nlm.nih.gov/16497887/ DOI: 10.1126/science.1123933

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays

exposure

Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.

limitations

Conditional transporter loss removes the measured hormonal increment; it does not prove that all baseline phosphate absorption is absent.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Without this intestinal transporter, active vitamin D failed to produce its usual phosphate-uptake increment.

primary_references

[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

tissue_or_cell_type

Intestinal epithelium

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 697–711

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft

### vdm-slc34a2-deletion-removes-calcitriol-phosphate-increment Intestine-specific Slc34a2 deletion eliminated the phosphate-transport increase induced by the tested calcitriol regimen. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without this intestinal transporter, active vitamin D failed to produce its usual phosphate-uptake increment. organism: Mus musculus tissue_or_cell_type: Intestinal epithelium experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: Conditional transporter loss removes the measured hormonal increment; it does not prove that all baseline phosphate absorption is absent. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Figure 6 and adjacent Results: mineralization restored by TNAP

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays

exposure

10^-8 M calcitriol and 1 U/mL added TNAP for 4 days; companion cultures tested 5 x 10^-6 M pyrophosphate.

limitations

Enzyme-addition culture rescue supports pyrophosphate involvement; it does not quantify human bone outcomes or establish the contribution of each calcitriol-regulated gene.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Removing the pyrophosphate brake restored mineral deposition in the treated cultures.

primary_references

[vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

tissue_or_cell_type

Osteoblast extracellular matrix

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 825–839

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays · source_derived_draft · unverified_draft

### vdm-tnap-rescues-calcitriol-culture-mineralization Added TNAP restored mineralization in calcitriol-treated differentiated mouse osteoblast cultures while lowering extracellular pyrophosphate. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the pyrophosphate brake restored mineral deposition in the treated cultures. organism: Mus musculus tissue_or_cell_type: Osteoblast extracellular matrix experimental_model: Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays limitations: Enzyme-addition culture rescue supports pyrophosphate involvement; it does not quantify human bone outcomes or establish the contribution of each calcitriol-regulated gene. exposure: 10^-8 M calcitriol and 1 U/mL added TNAP for 4 days; companion cultures tested 5 x 10^-6 M pyrophosphate. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Figure 6 and adjacent Results: mineralization restored by TNAP nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

experimental_model

Human CYP24A1 expressed in E. coli, partially purified and reconstituted in phospholipid vesicles

limitations

This is a C24-pathway intermediate, not a final inactive product. Further oxidation and the distinct C23 route are not represented by this single edge.

nutrient_topic

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

organism

Homo sapiens enzyme

plain_language

CYP24A1 begins a defined calcitriol breakdown route.

primary_references

[tieu2014] Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-oxidation pathway (2014). https://pubmed.ncbi.nlm.nih.gov/24893882/ DOI: 10.1111/febs.12862

research_relationship_category

biochemical_reaction

tissue_or_cell_type

Reconstituted enzyme/membrane system

transport_or_reaction_direction

forward

Calcium: mechanism-first literature curation (2026-09-17) · lines 362–373

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP24A1 expressed in E. coli, partially purified and reconstituted in phospholipid vesicles · source_derived_draft · unverified_draft

### cyp24a1-calcitriol-c24-hydroxylation Human CYP24A1 hydroxylates calcitriol to 1-alpha,24,25-trihydroxyvitamin D3 in the first C24-oxidation step. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP24A1 begins a defined calcitriol breakdown route. organism: Homo sapiens enzyme tissue_or_cell_type: Reconstituted enzyme/membrane system experimental_model: Human CYP24A1 expressed in E. coli, partially purified and reconstituted in phospholipid vesicles limitations: This is a C24-pathway intermediate, not a final inactive product. Further oxidation and the distinct C23 route are not represented by this single edge. research_relationship_category: biochemical_reaction transport_or_reaction_direction: forward [tieu2014] Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-oxidation pathway (2014). https://pubmed.ncbi.nlm.nih.gov/24893882/ DOI: 10.1111/febs.12862

experimental_model

Recombinant FGF23 injections in normal and parathyroidectomized rodents

limitations

Acute rodent transcript response; does not quantify human calcium balance.

nutrient_topic

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

organism

Mus musculus; Rattus norvegicus

plain_language

FGF23 increases vitamin D inactivation machinery.

primary_references

[shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264

tissue_or_cell_type

Kidney

Calcium: mechanism-first literature curation (2026-09-17) · lines 102–111

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FGF23 injections in normal and parathyroidectomized rodents · source_derived_draft · unverified_draft

### fgf23-increases-cyp24a1-expression Recombinant FGF23 raises renal CYP24A1 mRNA as circulating calcitriol declines. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 increases vitamin D inactivation machinery. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Recombinant FGF23 injections in normal and parathyroidectomized rodents limitations: Acute rodent transcript response; does not quantify human calcium balance. [shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264

experimental_model

Recombinant FGF23 injections in normal and parathyroidectomized rodents

limitations

Injection study; transcript change is not direct enzyme inhibition.

nutrient_topic

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

organism

Mus musculus; Rattus norvegicus

plain_language

FGF23 restrains a vitamin D activation enzyme.

primary_references

[shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264

tissue_or_cell_type

Kidney

Calcium: mechanism-first literature curation (2026-09-17) · lines 91–100

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FGF23 injections in normal and parathyroidectomized rodents · source_derived_draft · unverified_draft

### fgf23-reduces-cyp27b1-expression Recombinant FGF23 lowers renal CYP27B1 mRNA before the fall in serum phosphate. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 restrains a vitamin D activation enzyme. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Recombinant FGF23 injections in normal and parathyroidectomized rodents limitations: Injection study; transcript change is not direct enzyme inhibition. [shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Villin-Cre intestine-specific Atp2b1 deletion in mice

limitations

Conditional deletion and administered calcitriol; basal absorption was not shown to be zero.

nutrient_topic

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

organism

Mus musculus

plain_language

A calcium pump is needed for this hormone response.

primary_references

[ryan2015] Deletion of the intestinal plasma membrane calcium pump, isoform 1, Atp2b1, in mice is associated with decreased bone mineral density and impaired responsiveness to 1, 25-dihydroxyvitamin D3 (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4772868/ DOI: 10.1016/j.bbrc.2015.09.087

tissue_or_cell_type

Intestinal absorptive cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 280–289

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Villin-Cre intestine-specific Atp2b1 deletion in mice · source_derived_draft · unverified_draft

### intestinal-pmca1-loss-calcitriol-response Intestinal Atp2b1 deletion prevented the active-calcium-transport increase elicited by calcitriol in control mice. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A calcium pump is needed for this hormone response. organism: Mus musculus tissue_or_cell_type: Intestinal absorptive cells experimental_model: Villin-Cre intestine-specific Atp2b1 deletion in mice limitations: Conditional deletion and administered calcitriol; basal absorption was not shown to be zero. [ryan2015] Deletion of the intestinal plasma membrane calcium pump, isoform 1, Atp2b1, in mice is associated with decreased bone mineral density and impaired responsiveness to 1, 25-dihydroxyvitamin D3 (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4772868/ DOI: 10.1016/j.bbrc.2015.09.087

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Low-calcium-fed rats; thyroparathyroidectomy and parathyroid-extract replacement

limitations

Surgical removal plus extract replacement; not a purified-enzyme assay.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Hormonal support helps activate vitamin D during calcium restriction.

primary_references

[garabedian1972] Control of 25-hydroxycholecalciferol metabolism by parathyroid glands (1972). https://pubmed.ncbi.nlm.nih.gov/4340153/ DOI: 10.1073/pnas.69.7.1673

tissue_or_cell_type

Systemic vitamin D metabolism

trigger_kind

machinery_impairment Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 69–78

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Low-calcium-fed rats; thyroparathyroidectomy and parathyroid-extract replacement · source_derived_draft · unverified_draft

### parathyroid-loss-calcitriol-production Thyroparathyroidectomy nearly abolished calcitriol production in low-calcium-fed rats; parathyroid extract restored it. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hormonal support helps activate vitamin D during calcium restriction. organism: Rattus norvegicus tissue_or_cell_type: Systemic vitamin D metabolism experimental_model: Low-calcium-fed rats; thyroparathyroidectomy and parathyroid-extract replacement limitations: Surgical removal plus extract replacement; not a purified-enzyme assay. [garabedian1972] Control of 25-hydroxycholecalciferol metabolism by parathyroid glands (1972). https://pubmed.ncbi.nlm.nih.gov/4340153/ DOI: 10.1073/pnas.69.7.1673

cross_nutrient

Retinyl ester/calcitriol/calcium interaction.

experimental_model

Nine adults; acute blinded crossover.

exposure

15 mg retinyl palmitate and/or 2 micrograms calcitriol; historical experiment, not advice.

limitations

Serum response is not a direct isotope absorption measurement, long-term fracture outcome or universal vitamin A:D ratio.

nutrient_topic

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

organism

Homo sapiens

plain_language

Vitamin A form and exposure changed a measured vitamin D/calcium response.

primary_references

[va-johansson2001] Vitamin A antagonizes calcium response to vitamin D in man (2001). https://pubmed.ncbi.nlm.nih.gov/11585356/ DOI: 10.1359/jbmr.2001.16.10.1899

tissue_or_cell_type

Serum

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1601–1612

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine adults; acute blinded crossover. · source_derived_draft · unverified_draft

### va-retinyl-palmitate-calcitriol-calcium Retinyl palmitate attenuated the serum-calcium rise after calcitriol in the small crossover. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A form and exposure changed a measured vitamin D/calcium response. organism: Homo sapiens tissue_or_cell_type: Serum experimental_model: Nine adults; acute blinded crossover. limitations: Serum response is not a direct isotope absorption measurement, long-term fracture outcome or universal vitamin A:D ratio. cross_nutrient: Retinyl ester/calcitriol/calcium interaction. exposure: 15 mg retinyl palmitate and/or 2 micrograms calcitriol; historical experiment, not advice. [va-johansson2001] Vitamin A antagonizes calcium response to vitamin D in man (2001). https://pubmed.ncbi.nlm.nih.gov/11585356/ DOI: 10.1359/jbmr.2001.16.10.1899

cross_nutrient

Vitamin A-vitamin D: shared receptor partner; no supplementation or deficiency rescue tested.

evidence_locator

Figure 3

experimental_model

Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters.

exposure

Reconstituted VDR/RXRA

limitations

Does not prove vitamin A intake enhances calcium absorption.

nutrient_topic

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

organism

Recombinant receptors

plain_language

Vitamin D signaling shares RXRA receptor machinery with retinoid pathways.

primary_references

[va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

tissue_or_cell_type

Cell-free DNA-binding assay

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1095–1107

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. · source_derived_draft · unverified_draft

### va-sig-rxra-vdr-partnership RXRA formed a VDR complex and enhanced binding to the osteopontin vitamin D response element. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin D signaling shares RXRA receptor machinery with retinoid pathways. organism: Recombinant receptors tissue_or_cell_type: Cell-free DNA-binding assay experimental_model: Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. limitations: Does not prove vitamin A intake enhances calcium absorption. evidence_locator: Figure 3 cross_nutrient: Vitamin A-vitamin D: shared receptor partner; no supplementation or deficiency rescue tested. exposure: Reconstituted VDR/RXRA [va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}

experimental_model

Double-blind randomized comparison with physiological substudy

exposure

One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up

limitations

Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.

nutrient_topic

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

organism

1997 adults with iron-deficiency anemia; 185 in substudy

plain_language

The phosphate disturbance connected to active vitamin D and calcium-regulating hormones.

primary_references

[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486

tissue_or_cell_type

Blood and renal phosphate handling

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 979–990

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft

### iron-fgf23-vitamin-d-calcium The FGF23 rise was associated with lower calcitriol and serum calcium and higher PTH concentrations. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate disturbance connected to active vitamin D and calcium-regulating hormones. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486