Nutrient chapter

Vitamin D2 and D3

Two vitamin forms feed a regulated hormone system. Follow their activation, cellular responses, and links to calcium, phosphate and magnesium. D2, D3, their metabolites and blood measurements have separate records. Combined nutritional chapter covering ergocalciferol and cholecalciferol; chemically distinct metabolites remain separate.

135 recorded mechanisms · 18 availability situations · 4 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Recombinant human CYP27B1 converts calcifediol to calcitriol by 1-alpha-hydroxylation in reconstituted enzyme systems.
Vitamin D 1-alpha-hydroxylase / CYP27B1 → Calcitriol source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human CYP24A1 hydroxylates calcitriol to 1-alpha,24,25-trihydroxyvitamin D3 in the first C24-oxidation step.
Vitamin D 24-hydroxylase / CYP24A1 → 1-alpha,24,25-Trihydroxyvitamin D3 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Calcitriol induces human TRPV6 transcription through VDR/RXR-associated regulatory elements in intestinal cell models.
Calcitriol → TRPV6 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Claudin-2 manipulation changes calcium permeability across Caco-2 epithelial monolayers.
Claudin-2 → Paracellular calcium permeability source_derived_draftungraded
Experimental context and source evidence
experimental_model
Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression
limitations
Cell-line permeability; not an obligatory route in every intestinal segment.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens cell line
plain_language
Claudin-2 supports calcium movement between cells.
primary_references
[fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973
tissue_or_cell_type
Caco-2 epithelial tight junctions
Calcium: mechanism-first literature curation (2026-09-17) · lines 192–201
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression · source_derived_draft · unverified_draft
### cldn2-calcium-permeability Claudin-2 manipulation changes calcium permeability across Caco-2 epithelial monolayers. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Claudin-2 supports calcium movement between cells. organism: Homo sapiens cell line tissue_or_cell_type: Caco-2 epithelial tight junctions experimental_model: Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression limitations: Cell-line permeability; not an obligatory route in every intestinal segment. [fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973
Complete structured claim and evidence
Claudin-12 knockdown/overexpression alters calcium permeability in Caco-2 monolayers.
Claudin-12 → Paracellular calcium permeability source_derived_draftungraded
Experimental context and source evidence
experimental_model
Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression
limitations
Assay context matters; this does not prove a mandatory claudin-2/12 complex.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens cell line
plain_language
Claudin-12 contributes another between-cell route.
primary_references
[fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973
tissue_or_cell_type
Caco-2 epithelial tight junctions
Calcium: mechanism-first literature curation (2026-09-17) · lines 203–212
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression · source_derived_draft · unverified_draft
### cldn12-calcium-permeability Claudin-12 knockdown/overexpression alters calcium permeability in Caco-2 monolayers. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Claudin-12 contributes another between-cell route. organism: Homo sapiens cell line tissue_or_cell_type: Caco-2 epithelial tight junctions experimental_model: Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression limitations: Assay context matters; this does not prove a mandatory claudin-2/12 complex. [fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973
Complete structured claim and evidence
Intestinal Atp2b1 deletion prevented the active-calcium-transport increase elicited by calcitriol in control mice.
Plasma membrane calcium ATPase 1 / ATP2B1 → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Trpv6 deletion reduced intestinal calcium absorption by about 60% in the Bianco mouse model.
TRPV6 → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Whole-body Trpv6 knockout mice under regular and low-calcium diets
limitations
Whole-body deletion; diet and assay matter; residual absorption remained.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus
plain_language
TRPV6 materially supports calcium uptake in this model.
primary_references
[bianco2007] Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene (2007). https://pubmed.ncbi.nlm.nih.gov/17129178/ DOI: 10.1359/jbmr.061110
tissue_or_cell_type
Intestine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Calcium: mechanism-first literature curation (2026-09-17) · lines 158–167
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body Trpv6 knockout mice under regular and low-calcium diets · source_derived_draft · unverified_draft
### trpv6-loss-reduces-absorption Trpv6 deletion reduced intestinal calcium absorption by about 60% in the Bianco mouse model. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: TRPV6 materially supports calcium uptake in this model. organism: Mus musculus tissue_or_cell_type: Intestine experimental_model: Whole-body Trpv6 knockout mice under regular and low-calcium diets limitations: Whole-body deletion; diet and assay matter; residual absorption remained. [bianco2007] Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene (2007). https://pubmed.ncbi.nlm.nih.gov/17129178/ DOI: 10.1359/jbmr.061110
Complete structured claim and evidence
Significant active duodenal calcium transport persists in Trpv6/calbindin-D9k double-null mice under the tested stimulation conditions.
TRPV6 and calbindin-D9k → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Trpv6 and calbindin-D9k single/double knockout mice; duodenal transport assays
limitations
Residual transport does not establish dispensability under every diet or life stage.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus
plain_language
Other routes can support active calcium absorption.
primary_references
[benn2008] Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2408805/ DOI: 10.1210/en.2007-1655
reported_effect
retained
tissue_or_cell_type
Duodenum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Calcium: mechanism-first literature curation (2026-09-17) · lines 169–179
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Trpv6 and calbindin-D9k single/double knockout mice; duodenal transport assays · source_derived_draft · unverified_draft
### trpv6-calbindin-independent-active-transport Significant active duodenal calcium transport persists in Trpv6/calbindin-D9k double-null mice under the tested stimulation conditions. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Other routes can support active calcium absorption. organism: Mus musculus tissue_or_cell_type: Duodenum experimental_model: Trpv6 and calbindin-D9k single/double knockout mice; duodenal transport assays limitations: Residual transport does not establish dispensability under every diet or life stage. reported_effect: retained [benn2008] Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2408805/ DOI: 10.1210/en.2007-1655
Complete structured claim and evidence
Thyroparathyroidectomy nearly abolished calcitriol production in low-calcium-fed rats; parathyroid extract restored it.
Parathyroid hormone / PTH → Calcitriol production source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Calcitriol administration suppresses parathyroid PTH transcription in rats without a measured rise in serum calcium.
Calcitriol → Parathyroid hormone gene transcription source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant FGF23 lowers renal CYP27B1 mRNA before the fall in serum phosphate.
Fibroblast growth factor 23 / FGF23 → Vitamin D 1-alpha-hydroxylase / CYP27B1 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant FGF23 raises renal CYP24A1 mRNA as circulating calcitriol declines.
Fibroblast growth factor 23 / FGF23 → Vitamin D 24-hydroxylase / CYP24A1 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Alpha-Klotho cooperates with FGFR1(IIIc) to confer high-affinity binding and signaling by FGF23.
Alpha-Klotho / KL → Fibroblast growth factor receptor 1 / FGFR1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Renal homogenates, receptor-reconstitution cell assays and anti-Klotho antibody in mice
limitations
Specifically FGFR1(IIIc) reconstitution; not all FGFR1 splice forms are equivalent.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mammalian cell systems; Mus musculus
plain_language
FGF23 needs a suitable receptor partnership.
primary_references
[urakawa2006] Klotho converts canonical FGF receptor into a specific receptor for FGF23 (2006). https://pubmed.ncbi.nlm.nih.gov/17086194/ DOI: 10.1038/nature05315
tissue_or_cell_type
Kidney receptor system
Calcium: mechanism-first literature curation (2026-09-17) · lines 113–122
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Renal homogenates, receptor-reconstitution cell assays and anti-Klotho antibody in mice · source_derived_draft · unverified_draft
### klotho-fgfr1-fgf23-receptor Alpha-Klotho cooperates with FGFR1(IIIc) to confer high-affinity binding and signaling by FGF23. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 needs a suitable receptor partnership. organism: Mammalian cell systems; Mus musculus tissue_or_cell_type: Kidney receptor system experimental_model: Renal homogenates, receptor-reconstitution cell assays and anti-Klotho antibody in mice limitations: Specifically FGFR1(IIIc) reconstitution; not all FGFR1 splice forms are equivalent. [urakawa2006] Klotho converts canonical FGF receptor into a specific receptor for FGF23 (2006). https://pubmed.ncbi.nlm.nih.gov/17086194/ DOI: 10.1038/nature05315
Complete structured claim and evidence
VDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH.
Vitamin D receptor / VDR → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Mice with targeted disruption of the VDR DNA-binding domain
limitations
Global receptor deletion; not isolated dietary calcium shortage.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus
plain_language
Vitamin D receptor failure disrupts calcium regulation.
primary_references
[li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831
tissue_or_cell_type
Systemic mineral metabolism
trigger_kind
machinery_impairment Imported condition classification; unverified.
Calcium: mechanism-first literature curation (2026-09-17) · lines 135–144
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice with targeted disruption of the VDR DNA-binding domain · source_derived_draft · unverified_draft
### vdr-loss-hypocalcemia VDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin D receptor failure disrupts calcium regulation. organism: Mus musculus tissue_or_cell_type: Systemic mineral metabolism experimental_model: Mice with targeted disruption of the VDR DNA-binding domain limitations: Global receptor deletion; not isolated dietary calcium shortage. [li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831
Complete structured claim and evidence
A mineral/lactose rescue diet normalizes ionized calcium in VDR-ablated mice.
Calcium → Serum ionized calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
VDR-ablated mice and controls fed a mineral/lactose rescue diet
limitations
Combined dietary intervention; cannot attribute rescue to calcium alone.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus
plain_language
Dietary mineral delivery can bypass part of receptor failure.
primary_references
[li1998] Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice (1998). https://pubmed.ncbi.nlm.nih.gov/9751523/ DOI: 10.1210/endo.139.10.6262
reported_effect
normalizing
tissue_or_cell_type
Intestine and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Calcium: mechanism-first literature curation (2026-09-17) · lines 146–156
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VDR-ablated mice and controls fed a mineral/lactose rescue diet · source_derived_draft · unverified_draft
### vdr-null-mineral-diet-rescue A mineral/lactose rescue diet normalizes ionized calcium in VDR-ablated mice. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary mineral delivery can bypass part of receptor failure. organism: Mus musculus tissue_or_cell_type: Intestine and blood experimental_model: VDR-ablated mice and controls fed a mineral/lactose rescue diet limitations: Combined dietary intervention; cannot attribute rescue to calcium alone. reported_effect: normalizing [li1998] Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice (1998). https://pubmed.ncbi.nlm.nih.gov/9751523/ DOI: 10.1210/endo.139.10.6262
Complete structured claim and evidence
Mice with intestinal Vdr deletion maintained serum calcium despite calcium malabsorption and impaired skeletal mineral storage.
Serum calcium concentration → Calcium nutritional status source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Intestinal and osteoblast Vdr deletion, low-calcium diets, and skeletal assays in growing mice
limitations
Growing-mouse genetic model; not a validated human dietary diagnostic.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus
plain_language
Normal blood calcium can coexist with inadequate skeletal supply.
primary_references
[lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3336970/ DOI: 10.1172/JCI45890
research_relationship_category
biomarker
tissue_or_cell_type
Blood, intestine and skeleton
trigger_kind
biomarker_context Imported condition classification; unverified.
Calcium: mechanism-first literature curation (2026-09-17) · lines 337–347
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal and osteoblast Vdr deletion, low-calcium diets, and skeletal assays in growing mice · source_derived_draft · unverified_draft
### normal-serum-calcium-does-not-establish-sufficiency Mice with intestinal Vdr deletion maintained serum calcium despite calcium malabsorption and impaired skeletal mineral storage. Condition category: biomarker_context nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Normal blood calcium can coexist with inadequate skeletal supply. organism: Mus musculus tissue_or_cell_type: Blood, intestine and skeleton experimental_model: Intestinal and osteoblast Vdr deletion, low-calcium diets, and skeletal assays in growing mice limitations: Growing-mouse genetic model; not a validated human dietary diagnostic. research_relationship_category: biomarker [lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3336970/ DOI: 10.1172/JCI45890
Complete structured claim and evidence
The rise in circulating calcitriol during a six-hour human PTH(1-34) infusion was smaller after dietary Mg depletion.
Parathyroid hormone / PTH → Calcitriol source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Sixteen of 23 hypocalcemic magnesium-deficient patients had low circulating calcitriol.
Magnesium → Serum calcitriol concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Magnesium treatment normalized mean serum calcium, while calcitriol rose into or above normal in only five of the 23 patients.
Magnesium → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Magnesium depletion did not impair measured calcifediol-to-calcitriol conversion in these rats; isolated renal activity persisted without added Mg.
Magnesium → Calcitriol production source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Magnesium assignment altered plasma 25(OH)D3 differently by baseline vitamin D: an increase near 30 ng/mL and a decrease at higher baseline concentrations.
Magnesium → Plasma calcifediol concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium <-> vitamin D status; baseline-dependent clinical endpoint.
experimental_model
Randomized 12-week ancillary analysis, 180 adults.
exposure
Personalized Mg supplementation; baseline calcium:magnesium intake ratio at least 2.6. Ratios describe enrollment, not a recommended target.
limitations
Only two participants had overt vitamin D deficiency; the trial does not show universal deficiency rescue or identify the responsible enzyme.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The vitamin D response depended on the starting level.
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 1430–1441
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized 12-week ancillary analysis, 180 adults. · source_derived_draft · unverified_draft
### mg-supplement-calcifediol-baseline-dependent Magnesium assignment altered plasma 25(OH)D3 differently by baseline vitamin D: an increase near 30 ng/mL and a decrease at higher baseline concentrations. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The vitamin D response depended on the starting level. organism: Homo sapiens tissue_or_cell_type: Human plasma experimental_model: Randomized 12-week ancillary analysis, 180 adults. limitations: Only two participants had overt vitamin D deficiency; the trial does not show universal deficiency rescue or identify the responsible enzyme. cross_nutrient: Magnesium <-> vitamin D status; baseline-dependent clinical endpoint. exposure: Personalized Mg supplementation; baseline calcium:magnesium intake ratio at least 2.6. Ratios describe enrollment, not a recommended target. [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
Complete structured claim and evidence
The trial did not detect a treatment-by-baseline-25(OH)D interaction for plasma calcitriol.
Magnesium → Plasma calcitriol concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
RXRA formed a VDR complex and enhanced binding to the osteopontin vitamin D response element.
Retinoid X receptor alpha → Vitamin D receptor / VDR source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Narrow-band ultraviolet irradiation converted cutaneous 7-dehydrocholesterol to previtamin D3; 295-300 nm was the most effective tested range.
7-Dehydrocholesterol → Previtamin D3 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract: optimal 295-300 nm; up to 65% conversion under 295-nm radiation.
experimental_model
Human skin irradiation with chemical product measurements
exposure
Narrow-band radiation; up to 65% conversion at 295 nm; fluence/time not in retrieved abstract.
limitations
Controlled photochemistry; no safe or universally effective sunlight duration follows.
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
UVB starts the skin pathway that makes vitamin D3.
primary_references
[maclaughlin1982] Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. (1982). https://pubmed.ncbi.nlm.nih.gov/6281884/ DOI: 10.1126/science.6281884
tissue_or_cell_type
skin
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 91–104
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human skin irradiation with chemical product measurements · source_derived_draft · unverified_draft
### vd-act-skin-photoconversion Narrow-band ultraviolet irradiation converted cutaneous 7-dehydrocholesterol to previtamin D3; 295-300 nm was the most effective tested range. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: UVB starts the skin pathway that makes vitamin D3. organism: Homo sapiens tissue_or_cell_type: skin experimental_model: Human skin irradiation with chemical product measurements limitations: Controlled photochemistry; no safe or universally effective sunlight duration follows. exposure: Narrow-band radiation; up to 65% conversion at 295 nm; fluence/time not in retrieved abstract. cross_nutrient: false evidence_location: Primary abstract: optimal 295-300 nm; up to 65% conversion under 295-nm radiation. nutrient: Vitamin D2 and D3 [maclaughlin1982] Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. (1982). https://pubmed.ncbi.nlm.nih.gov/6281884/ DOI: 10.1126/science.6281884
Complete structured claim and evidence
Skin-generated previtamin D3 underwent temperature-dependent isomerization to cholecalciferol, taking at least three days to complete under the reported conditions.
Previtamin D3 → Cholecalciferol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract; skin photochemistry and transport experiments.
experimental_model
Human skin photochemistry
exposure
Solar UV exposure followed by thermal conversion; at least 3 days for completion.
limitations
Completion time is experiment-specific and is not an absorption half-life.
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
The first skin photoproduct rearranges into vitamin D3.
primary_references
[holick1980] Photosynthesis of previtamin D3 in human skin and the physiologic consequences. (1980). https://pubmed.ncbi.nlm.nih.gov/6251551/ DOI: 10.1126/science.6251551
tissue_or_cell_type
skin
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 106–119
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human skin photochemistry · source_derived_draft · unverified_draft
### vd-act-skin-thermal-isomerization Skin-generated previtamin D3 underwent temperature-dependent isomerization to cholecalciferol, taking at least three days to complete under the reported conditions. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first skin photoproduct rearranges into vitamin D3. organism: Homo sapiens tissue_or_cell_type: skin experimental_model: Human skin photochemistry limitations: Completion time is experiment-specific and is not an absorption half-life. exposure: Solar UV exposure followed by thermal conversion; at least 3 days for completion. cross_nutrient: false evidence_location: Primary abstract; skin photochemistry and transport experiments. nutrient: Vitamin D2 and D3 [holick1980] Photosynthesis of previtamin D3 in human skin and the physiologic consequences. (1980). https://pubmed.ncbi.nlm.nih.gov/6251551/ DOI: 10.1126/science.6251551
Complete structured claim and evidence
Vitamin D-binding protein preferentially translocated thermally formed cholecalciferol from the skin into circulation in the reported photochemistry experiments.
Human vitamin D-binding protein / GC → Entry of skin-generated cholecalciferol into circulation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract; skin photochemistry and transport experiments.
experimental_model
Human skin-to-circulation vitamin transport
exposure
After UV generation and thermal conversion; quantitative carrier concentrations unavailable in abstract.
limitations
Preferential transport is not proof that every route of D3 entry requires DBP.
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
A carrier helps newly made D3 enter the blood.
primary_references
[holick1980] Photosynthesis of previtamin D3 in human skin and the physiologic consequences. (1980). https://pubmed.ncbi.nlm.nih.gov/6251551/ DOI: 10.1126/science.6251551
tissue_or_cell_type
skin and circulation
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 121–134
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human skin-to-circulation vitamin transport · source_derived_draft · unverified_draft
### vd-act-dbp-skin-export Vitamin D-binding protein preferentially translocated thermally formed cholecalciferol from the skin into circulation in the reported photochemistry experiments. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A carrier helps newly made D3 enter the blood. organism: Homo sapiens tissue_or_cell_type: skin and circulation experimental_model: Human skin-to-circulation vitamin transport limitations: Preferential transport is not proof that every route of D3 entry requires DBP. exposure: After UV generation and thermal conversion; quantitative carrier concentrations unavailable in abstract. cross_nutrient: false evidence_location: Primary abstract; skin photochemistry and transport experiments. nutrient: Vitamin D2 and D3 [holick1980] Photosynthesis of previtamin D3 in human skin and the physiologic consequences. (1980). https://pubmed.ncbi.nlm.nih.gov/6251551/ DOI: 10.1126/science.6251551
Complete structured claim and evidence
Ultraviolet irradiation of white button mushrooms generated previtamin D2 from ergosterol, identified by chromatographic analysis.
Ergosterol → Previtamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary Results: Photoproduction of previtamin D2 and its conversion to vitamin D2; Figures 2-5.
experimental_model
White button mushroom and ergosterol photochemistry
exposure
UV-irradiated preparations; protocol varied with irradiation experiment.
limitations
This is fungal/ex-vivo photochemistry; human skin D3 photochemistry is a separate route.
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
Agaricus bisporus
plain_language
UV converts a fungal sterol into the precursor of vitamin D2.
primary_references
[keegan2013] Photobiology of vitamin D in mushrooms and its bioavailability in humans. (2013). https://pubmed.ncbi.nlm.nih.gov/24494050/ DOI: 10.4161/derm.23321
tissue_or_cell_type
mushroom tissue
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 136–149
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · White button mushroom and ergosterol photochemistry · source_derived_draft · unverified_draft
### vd-act-ergosterol-photoconversion Ultraviolet irradiation of white button mushrooms generated previtamin D2 from ergosterol, identified by chromatographic analysis. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: UV converts a fungal sterol into the precursor of vitamin D2. organism: Agaricus bisporus tissue_or_cell_type: mushroom tissue experimental_model: White button mushroom and ergosterol photochemistry limitations: This is fungal/ex-vivo photochemistry; human skin D3 photochemistry is a separate route. exposure: UV-irradiated preparations; protocol varied with irradiation experiment. cross_nutrient: false evidence_location: Primary Results: Photoproduction of previtamin D2 and its conversion to vitamin D2; Figures 2-5. nutrient: Vitamin D2 and D3 [keegan2013] Photobiology of vitamin D in mushrooms and its bioavailability in humans. (2013). https://pubmed.ncbi.nlm.nih.gov/24494050/ DOI: 10.4161/derm.23321
Complete structured claim and evidence
Previtamin D2 generated in irradiated mushrooms converted thermally to ergocalciferol; mushroom conversion was faster than in methanol in the compared preparations.
Previtamin D2 → Ergocalciferol / vitamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary Results: Photoproduction of previtamin D2 and its conversion to vitamin D2; Figures 2-5.
experimental_model
Mushroom-versus-solution HPLC time course
exposure
Post-irradiation time course at 25 C; approximately half converted after 11.5 hours in mushrooms.
limitations
Matrix and temperature affect rate; no metabolic activation enzyme is implied.
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
Agaricus bisporus
plain_language
The fungal photoproduct rearranges into vitamin D2.
primary_references
[keegan2013] Photobiology of vitamin D in mushrooms and its bioavailability in humans. (2013). https://pubmed.ncbi.nlm.nih.gov/24494050/ DOI: 10.4161/derm.23321
tissue_or_cell_type
mushroom tissue
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 151–164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mushroom-versus-solution HPLC time course · source_derived_draft · unverified_draft
### vd-act-previtamin-d2-isomerization Previtamin D2 generated in irradiated mushrooms converted thermally to ergocalciferol; mushroom conversion was faster than in methanol in the compared preparations. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fungal photoproduct rearranges into vitamin D2. organism: Agaricus bisporus tissue_or_cell_type: mushroom tissue experimental_model: Mushroom-versus-solution HPLC time course limitations: Matrix and temperature affect rate; no metabolic activation enzyme is implied. exposure: Post-irradiation time course at 25 C; approximately half converted after 11.5 hours in mushrooms. cross_nutrient: false evidence_location: Primary Results: Photoproduction of previtamin D2 and its conversion to vitamin D2; Figures 2-5. nutrient: Vitamin D2 and D3 [keegan2013] Photobiology of vitamin D in mushrooms and its bioavailability in humans. (2013). https://pubmed.ncbi.nlm.nih.gov/24494050/ DOI: 10.4161/derm.23321
Complete structured claim and evidence
Expression of SR-BI in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake.
Scavenger receptor class B type 1 / SCARB1 → Intestinal cholecalciferol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract.
experimental_model
Transfected HEK-cell uptake assay; intestinal relevance tested separately
exposure
Transporter transfection and selective-inhibitor co-incubation; exact dose/time absent from abstract.
limitations
HEK overexpression is not intact human intestine; inhibitors and uptake assays do not establish clinical deficiency. In-vivo ezetimibe effect in mice was nonsignificant.
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
SR-BI can contribute to vitamin D3 entry into cells.
primary_references
[reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553
tissue_or_cell_type
HEK cell model of a candidate intestinal uptake mechanism
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 166–179
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected HEK-cell uptake assay; intestinal relevance tested separately · source_derived_draft · unverified_draft
### vd-act-scarb1-uptake Expression of SR-BI in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: SR-BI can contribute to vitamin D3 entry into cells. organism: Homo sapiens tissue_or_cell_type: HEK cell model of a candidate intestinal uptake mechanism experimental_model: Transfected HEK-cell uptake assay; intestinal relevance tested separately limitations: HEK overexpression is not intact human intestine; inhibitors and uptake assays do not establish clinical deficiency. In-vivo ezetimibe effect in mice was nonsignificant. exposure: Transporter transfection and selective-inhibitor co-incubation; exact dose/time absent from abstract. cross_nutrient: false evidence_location: Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract. nutrient: Vitamin D2 and D3 [reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553
Complete structured claim and evidence
Expression of CD36 in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake.
Human CD36 scavenger receptor → Intestinal cholecalciferol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract.
experimental_model
Transfected HEK-cell uptake assay; intestinal relevance tested separately
exposure
Transporter transfection and selective-inhibitor co-incubation; exact dose/time absent from abstract.
limitations
HEK overexpression is not intact human intestine; inhibitors and uptake assays do not establish clinical deficiency. In-vivo ezetimibe effect in mice was nonsignificant.
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
CD36 can contribute to vitamin D3 entry into cells.
primary_references
[reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553
tissue_or_cell_type
HEK cell model of a candidate intestinal uptake mechanism
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 181–194
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected HEK-cell uptake assay; intestinal relevance tested separately · source_derived_draft · unverified_draft
### vd-act-cd36-uptake Expression of CD36 in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CD36 can contribute to vitamin D3 entry into cells. organism: Homo sapiens tissue_or_cell_type: HEK cell model of a candidate intestinal uptake mechanism experimental_model: Transfected HEK-cell uptake assay; intestinal relevance tested separately limitations: HEK overexpression is not intact human intestine; inhibitors and uptake assays do not establish clinical deficiency. In-vivo ezetimibe effect in mice was nonsignificant. exposure: Transporter transfection and selective-inhibitor co-incubation; exact dose/time absent from abstract. cross_nutrient: false evidence_location: Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract. nutrient: Vitamin D2 and D3 [reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553
Complete structured claim and evidence
Expression of NPC1L1 in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake.
Human Niemann-Pick C1-like protein 1 / NPC1L1 → Intestinal cholecalciferol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract.
experimental_model
Transfected HEK-cell uptake assay; intestinal relevance tested separately
exposure
Transporter transfection and selective-inhibitor co-incubation; exact dose/time absent from abstract.
limitations
HEK overexpression is not intact human intestine; inhibitors and uptake assays do not establish clinical deficiency. In-vivo ezetimibe effect in mice was nonsignificant.
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
NPC1L1 can contribute to vitamin D3 entry into cells.
primary_references
[reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553
tissue_or_cell_type
HEK cell model of a candidate intestinal uptake mechanism
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 196–209
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected HEK-cell uptake assay; intestinal relevance tested separately · source_derived_draft · unverified_draft
### vd-act-npc1l1-uptake Expression of NPC1L1 in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: NPC1L1 can contribute to vitamin D3 entry into cells. organism: Homo sapiens tissue_or_cell_type: HEK cell model of a candidate intestinal uptake mechanism experimental_model: Transfected HEK-cell uptake assay; intestinal relevance tested separately limitations: HEK overexpression is not intact human intestine; inhibitors and uptake assays do not establish clinical deficiency. In-vivo ezetimibe effect in mice was nonsignificant. exposure: Transporter transfection and selective-inhibitor co-incubation; exact dose/time absent from abstract. cross_nutrient: false evidence_location: Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract. nutrient: Vitamin D2 and D3 [reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553
Complete structured claim and evidence
Co-incubation with tocopherol significantly impaired cholecalciferol uptake in Caco-2 cells.
Alpha-tocopherol → Intestinal cholecalciferol uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract.
experimental_model
Caco-2 apical uptake assay
exposure
Tocopherol and cholecalciferol co-incubation; dose/time unavailable in primary abstract.
limitations
The primary abstract says tocopherol; the authors' subsequent primary paper identifies it as alpha-tocopherol. No evidence here warrants separating normal oral supplements or diagnosing D malabsorption.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens
plain_language
Vitamin E competed with D3 uptake in an intestinal cell model.
primary_references
[reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553 [goncalves2015] Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption. (2015). https://pubmed.ncbi.nlm.nih.gov/25442537/ DOI: 10.1016/j.foodchem.2014.09.021
tissue_or_cell_type
Caco-2 intestinal epithelial model
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 211–225
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Caco-2 apical uptake assay · source_derived_draft · unverified_draft
### vd-act-tocopherol-uptake-competition Co-incubation with tocopherol significantly impaired cholecalciferol uptake in Caco-2 cells. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E competed with D3 uptake in an intestinal cell model. organism: Homo sapiens tissue_or_cell_type: Caco-2 intestinal epithelial model experimental_model: Caco-2 apical uptake assay limitations: The primary abstract says tocopherol; the authors' subsequent primary paper identifies it as alpha-tocopherol. No evidence here warrants separating normal oral supplements or diagnosing D malabsorption. exposure: Tocopherol and cholecalciferol co-incubation; dose/time unavailable in primary abstract. cross_nutrient: true evidence_location: Primary abstract, Methods and results; exact incubation concentrations/durations unavailable in abstract. nutrient: Vitamin D2 and D3 [reboul2011] Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. (2011). https://pubmed.ncbi.nlm.nih.gov/21280209/ DOI: 10.1002/mnfr.201000553 [goncalves2015] Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption. (2015). https://pubmed.ncbi.nlm.nih.gov/25442537/ DOI: 10.1016/j.foodchem.2014.09.021
Complete structured claim and evidence
Megalin-mediated endocytosis retrieved filtered vitamin D-binding-protein/calcifediol complexes in proximal tubules.
Mouse megalin / Lrp2 → Renal reclamation of filtered calcifediol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, receptor-mediated uptake and knockout phenotype.
experimental_model
Mouse renal endocytosis experiments
exposure
Endogenous carrier complexes and uptake assays; timing not specified in abstract.
limitations
Renal endocytosis finding does not exclude free-hormone uptake elsewhere.
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
Kidney cells reclaim carrier-bound D3 precursor from the filtrate.
primary_references
[nykjaer1999] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (1999). https://pubmed.ncbi.nlm.nih.gov/10052453/ DOI: 10.1016/s0092-8674(00)80655-8
tissue_or_cell_type
kidney proximal tubule
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 227–240
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse renal endocytosis experiments · source_derived_draft · unverified_draft
### vd-act-megalin-retrieval Megalin-mediated endocytosis retrieved filtered vitamin D-binding-protein/calcifediol complexes in proximal tubules. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kidney cells reclaim carrier-bound D3 precursor from the filtrate. organism: Mus musculus tissue_or_cell_type: kidney proximal tubule experimental_model: Mouse renal endocytosis experiments limitations: Renal endocytosis finding does not exclude free-hormone uptake elsewhere. exposure: Endogenous carrier complexes and uptake assays; timing not specified in abstract. cross_nutrient: false evidence_location: Primary abstract, receptor-mediated uptake and knockout phenotype. nutrient: Vitamin D2 and D3 [nykjaer1999] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (1999). https://pubmed.ncbi.nlm.nih.gov/10052453/ DOI: 10.1016/s0092-8674(00)80655-8
Complete structured claim and evidence
Megalin-null mice failed to retrieve filtered calcifediol and lost the vitamin D precursor in urine.
Mouse Lrp2 gene → Urinary loss of calcifediol source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary abstract, receptor-mediated uptake and knockout phenotype.
experimental_model
Targeted megalin knockout versus controls
exposure
Lrp2 gene disruption; no dietary restriction inferred.
limitations
The knockout affects other filtered ligands too; it is machinery impairment.
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
A broken kidney uptake receptor wastes vitamin D precursor.
primary_references
[nykjaer1999] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (1999). https://pubmed.ncbi.nlm.nih.gov/10052453/ DOI: 10.1016/s0092-8674(00)80655-8
tissue_or_cell_type
kidney and urine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 242–255
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted megalin knockout versus controls · source_derived_draft · unverified_draft
### vd-act-megalin-knockout-loss Megalin-null mice failed to retrieve filtered calcifediol and lost the vitamin D precursor in urine. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A broken kidney uptake receptor wastes vitamin D precursor. organism: Mus musculus tissue_or_cell_type: kidney and urine experimental_model: Targeted megalin knockout versus controls limitations: The knockout affects other filtered ligands too; it is machinery impairment. exposure: Lrp2 gene disruption; no dietary restriction inferred. cross_nutrient: false evidence_location: Primary abstract, receptor-mediated uptake and knockout phenotype. nutrient: Vitamin D2 and D3 [nykjaer1999] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (1999). https://pubmed.ncbi.nlm.nih.gov/10052453/ DOI: 10.1016/s0092-8674(00)80655-8
Complete structured claim and evidence
Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway.
Human CUBN gene → Urinary loss of calcifediol source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract, cubilin sequestration and human urinary loss.
experimental_model
Human inherited cubilin dysfunction; supporting receptor experiments
exposure
Inherited CUBN dysfunction; patient details/doses not specified in retrieved abstract.
limitations
This shared B12/D transport machinery does not mean dietary B12 deficiency causes urinary D loss. Genotype-phenotype evidence is observational.
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
Cubilin defects can cause loss of vitamin D precursor through urine.
primary_references
[nykjaer2001] Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). (2001). https://pubmed.ncbi.nlm.nih.gov/11717447/ DOI: 10.1073/pnas.241516998
tissue_or_cell_type
kidney proximal tubule and urine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 257–270
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human inherited cubilin dysfunction; supporting receptor experiments · source_derived_draft · unverified_draft
### vd-act-cubilin-human-loss Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cubilin defects can cause loss of vitamin D precursor through urine. organism: Homo sapiens tissue_or_cell_type: kidney proximal tubule and urine experimental_model: Human inherited cubilin dysfunction; supporting receptor experiments limitations: This shared B12/D transport machinery does not mean dietary B12 deficiency causes urinary D loss. Genotype-phenotype evidence is observational. exposure: Inherited CUBN dysfunction; patient details/doses not specified in retrieved abstract. cross_nutrient: true evidence_location: Primary abstract, cubilin sequestration and human urinary loss. nutrient: Vitamin D2 and D3 [nykjaer2001] Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). (2001). https://pubmed.ncbi.nlm.nih.gov/11717447/ DOI: 10.1073/pnas.241516998
Complete structured claim and evidence
Deletion of mouse vitamin D-binding protein accelerated the loss of injected radiolabeled calcifediol from plasma.
Mouse Gc gene → Circulating calcifediol retention source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Full primary Methods, Vitamin D kinetics; Results, kinetics of 25(OH)D3; abstract.
experimental_model
Radiotracer kinetics in Gc-null and wild-type mice
exposure
After 4-6 weeks on D3-deficient diet, 0.5 microCi or 100000 cpm tracer in homologous serum was injected intravenously; sampling over 24 h.
limitations
Both genotypes experienced dietary depletion; the comparison isolates an additional carrier defect. Tracer plasma residence is not a human dietary-dose trial.
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 blood carrier helps vitamin D precursor stay in circulation.
primary_references
[safadi1999] Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. (1999). https://pubmed.ncbi.nlm.nih.gov/9916136/ DOI: 10.1172/jci5244
tissue_or_cell_type
plasma and liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 272–285
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer kinetics in Gc-null and wild-type mice · source_derived_draft · unverified_draft
### vd-act-dbp-null-retention Deletion of mouse vitamin D-binding protein accelerated the loss of injected radiolabeled calcifediol from plasma. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood carrier helps vitamin D precursor stay in circulation. organism: Mus musculus tissue_or_cell_type: plasma and liver experimental_model: Radiotracer kinetics in Gc-null and wild-type mice limitations: Both genotypes experienced dietary depletion; the comparison isolates an additional carrier defect. Tracer plasma residence is not a human dietary-dose trial. exposure: After 4-6 weeks on D3-deficient diet, 0.5 microCi or 100000 cpm tracer in homologous serum was injected intravenously; sampling over 24 h. cross_nutrient: false evidence_location: Full primary Methods, Vitamin D kinetics; Results, kinetics of 25(OH)D3; abstract. nutrient: Vitamin D2 and D3 [safadi1999] Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. (1999). https://pubmed.ncbi.nlm.nih.gov/9916136/ DOI: 10.1172/jci5244
Complete structured claim and evidence
Recombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol.
Human vitamin D 25-hydroxylase / CYP2R1 → Calcifediol / 25-hydroxyvitamin D3 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, substrate product positions and kinetic comparison.
experimental_model
Recombinant human enzyme metabolism
exposure
D3 substrate series; reported Km 0.45 micromolar and kcat 0.97 per minute.
limitations
In-vitro kinetics depend on assay setup and are not serum cutoffs.
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
CYP2R1 performs the first activation step for D3.
primary_references
[shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
tissue_or_cell_type
microsomal enzyme preparation
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 287–300
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme metabolism · source_derived_draft · unverified_draft
### vd-act-cyp2r1-d3 Recombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2R1 performs the first activation step for D3. organism: Homo sapiens protein tissue_or_cell_type: microsomal enzyme preparation experimental_model: Recombinant human enzyme metabolism limitations: In-vitro kinetics depend on assay setup and are not serum cutoffs. exposure: D3 substrate series; reported Km 0.45 micromolar and kcat 0.97 per minute. cross_nutrient: false evidence_location: Primary abstract, substrate product positions and kinetic comparison. nutrient: Vitamin D2 and D3 [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
Complete structured claim and evidence
Recombinant human CYP2R1 hydroxylated ergocalciferol at C25 to form 25-hydroxyvitamin D2.
Human vitamin D 25-hydroxylase / CYP2R1 → 25-Hydroxyvitamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, substrate product positions and kinetic comparison.
experimental_model
Recombinant human enzyme product identification
exposure
D2 substrate incubations; detailed concentration/time not available in abstract.
limitations
A shared enzyme does not by itself prove equal long-term serum responses to all D2 and D3 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
The same first-step enzyme also activates D2.
primary_references
[shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
tissue_or_cell_type
microsomal enzyme preparation
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 302–315
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme product identification · source_derived_draft · unverified_draft
### vd-act-cyp2r1-d2 Recombinant human CYP2R1 hydroxylated ergocalciferol at C25 to form 25-hydroxyvitamin D2. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same first-step enzyme also activates D2. organism: Homo sapiens protein tissue_or_cell_type: microsomal enzyme preparation experimental_model: Recombinant human enzyme product identification limitations: A shared enzyme does not by itself prove equal long-term serum responses to all D2 and D3 dosing regimens. exposure: D2 substrate incubations; detailed concentration/time not available in abstract. cross_nutrient: false evidence_location: Primary abstract, substrate product positions and kinetic comparison. nutrient: Vitamin D2 and D3 [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
Complete structured claim and evidence
Human CYP27A1 catalyzed D3 25-hydroxylation in the recombinant comparison, with lower catalytic efficiency than CYP2R1.
Human sterol 27-hydroxylase / CYP27A1 → Calcifediol / 25-hydroxyvitamin D3 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, substrate product positions and kinetic comparison.
experimental_model
Recombinant human CYP27A1/CYP2R1 comparison
exposure
Kinetic substrate comparison; CYP2R1 kcat/Km was reported 26-fold higher in this assay.
limitations
Does not establish CYP27A1 as the dominant human liver D3 25-hydroxylase.
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
A second enzyme can 25-hydroxylate D3 in laboratory assays.
primary_references
[shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
tissue_or_cell_type
mitochondrial enzyme preparation
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 317–330
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP27A1/CYP2R1 comparison · source_derived_draft · unverified_draft
### vd-act-cyp27a1-d3 Human CYP27A1 catalyzed D3 25-hydroxylation in the recombinant comparison, with lower catalytic efficiency than CYP2R1. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second enzyme can 25-hydroxylate D3 in laboratory assays. organism: Homo sapiens protein tissue_or_cell_type: mitochondrial enzyme preparation experimental_model: Recombinant human CYP27A1/CYP2R1 comparison limitations: Does not establish CYP27A1 as the dominant human liver D3 25-hydroxylase. exposure: Kinetic substrate comparison; CYP2R1 kcat/Km was reported 26-fold higher in this assay. cross_nutrient: false evidence_location: Primary abstract, substrate product positions and kinetic comparison. nutrient: Vitamin D2 and D3 [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
Complete structured claim and evidence
Human CYP27A1 hydroxylated ergocalciferol at C24 in the reported D2 substrate analysis.
Human sterol 27-hydroxylase / CYP27A1 → 24-Hydroxyvitamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, substrate product positions and kinetic comparison.
experimental_model
Recombinant human CYP27A1 product identification
exposure
D2 incubation; concentration/time not reported in retrieved abstract.
limitations
D2 C24/C27 hydroxylation must not be mislabeled as C25 activation or assumed to be the main route in vivo.
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
CYP27A1 modifies D2 at carbon 24.
primary_references
[shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
tissue_or_cell_type
mitochondrial enzyme preparation
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 332–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP27A1 product identification · source_derived_draft · unverified_draft
### vd-act-cyp27a1-d2-c24 Human CYP27A1 hydroxylated ergocalciferol at C24 in the reported D2 substrate analysis. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP27A1 modifies D2 at carbon 24. organism: Homo sapiens protein tissue_or_cell_type: mitochondrial enzyme preparation experimental_model: Recombinant human CYP27A1 product identification limitations: D2 C24/C27 hydroxylation must not be mislabeled as C25 activation or assumed to be the main route in vivo. exposure: D2 incubation; concentration/time not reported in retrieved abstract. cross_nutrient: false evidence_location: Primary abstract, substrate product positions and kinetic comparison. nutrient: Vitamin D2 and D3 [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
Complete structured claim and evidence
Human CYP27A1 hydroxylated ergocalciferol at C27 in the reported D2 substrate analysis.
Human sterol 27-hydroxylase / CYP27A1 → 27-Hydroxyvitamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract, substrate product positions and kinetic comparison.
experimental_model
Recombinant human CYP27A1 product identification
exposure
D2 incubation; concentration/time not reported in retrieved abstract.
limitations
D2 C24/C27 hydroxylation must not be mislabeled as C25 activation or assumed to be the main route in vivo.
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
CYP27A1 modifies D2 at carbon 27.
primary_references
[shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
tissue_or_cell_type
mitochondrial enzyme preparation
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 347–360
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP27A1 product identification · source_derived_draft · unverified_draft
### vd-act-cyp27a1-d2-c27 Human CYP27A1 hydroxylated ergocalciferol at C27 in the reported D2 substrate analysis. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP27A1 modifies D2 at carbon 27. organism: Homo sapiens protein tissue_or_cell_type: mitochondrial enzyme preparation experimental_model: Recombinant human CYP27A1 product identification limitations: D2 C24/C27 hydroxylation must not be mislabeled as C25 activation or assumed to be the main route in vivo. exposure: D2 incubation; concentration/time not reported in retrieved abstract. cross_nutrient: false evidence_location: Primary abstract, substrate product positions and kinetic comparison. nutrient: Vitamin D2 and D3 [shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073
Complete structured claim and evidence
The patient-derived human CYP2R1 Leu99Pro variant lost detectable D3 25-hydroxylase activity in the expression assays.
Human CYP2R1 L99P variant → Calcifediol / 25-hydroxyvitamin D3 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Results, Figures 3-5 and primary abstract.
experimental_model
Patient-derived allele expressed in cells
exposure
L99P versus wild-type CYP2R1; D3 biochemical/reporting assays.
limitations
The patient had residual circulating metabolites and responded to D2 treatment; this does not prove zero whole-body activation or zero residual D2 activity.
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
A CYP2R1 mutation can break the first D3 activation step.
primary_references
[cheng2004] Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. (2004). https://pubmed.ncbi.nlm.nih.gov/15128933/ DOI: 10.1073/pnas.0402490101
tissue_or_cell_type
heterologous expression model
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 362–375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived allele expressed in cells · source_derived_draft · unverified_draft
### vd-act-cyp2r1-l99p The patient-derived human CYP2R1 Leu99Pro variant lost detectable D3 25-hydroxylase activity in the expression assays. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A CYP2R1 mutation can break the first D3 activation step. organism: Homo sapiens protein tissue_or_cell_type: heterologous expression model experimental_model: Patient-derived allele expressed in cells limitations: The patient had residual circulating metabolites and responded to D2 treatment; this does not prove zero whole-body activation or zero residual D2 activity. exposure: L99P versus wild-type CYP2R1; D3 biochemical/reporting assays. cross_nutrient: false evidence_location: Results, Figures 3-5 and primary abstract. nutrient: Vitamin D2 and D3 [cheng2004] Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. (2004). https://pubmed.ncbi.nlm.nih.gov/15128933/ DOI: 10.1073/pnas.0402490101
Complete structured claim and evidence
The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group.
Human vitamin D 25-hydroxylase / CYP2R1 → Heme source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract and structure PDB 3C6G.
experimental_model
Purified human enzyme crystallography
exposure
CYP2R1-D3 crystal complex; PDB 3C6G.
limitations
A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people.
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
D3 activation uses an iron-containing heme enzyme.
primary_references
[strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065
tissue_or_cell_type
CYP2R1 active site
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 377–390
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme crystallography · source_derived_draft · unverified_draft
### vd-act-cyp2r1-heme The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D3 activation uses an iron-containing heme enzyme. organism: Homo sapiens protein tissue_or_cell_type: CYP2R1 active site experimental_model: Purified human enzyme crystallography limitations: A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people. exposure: CYP2R1-D3 crystal complex; PDB 3C6G. cross_nutrient: true evidence_location: Primary abstract and structure PDB 3C6G. nutrient: Vitamin D2 and D3 [strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065
Complete structured claim and evidence
Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.
NADPH-cytochrome P450 oxidoreductase / POR → Human vitamin D 25-hydroxylase / CYP2R1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Figure 2C; Methods 2.3 and reconstitution assays.
experimental_model
Purified enzyme and phospholipid-vesicle reconstitution
exposure
0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C.
limitations
Assay optimum is not a tissue expression target or a vitamin dosing requirement.
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
CYP2R1 needs an electron-supplying partner.
primary_references
[cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
tissue_or_cell_type
reconstituted membrane
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 392–405
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme and phospholipid-vesicle reconstitution · source_derived_draft · unverified_draft
### vd-act-por-support Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2R1 needs an electron-supplying partner. organism: Homo sapiens proteins tissue_or_cell_type: reconstituted membrane experimental_model: Purified enzyme and phospholipid-vesicle reconstitution limitations: Assay optimum is not a tissue expression target or a vitamin dosing requirement. exposure: 0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C. cross_nutrient: true evidence_location: Primary Figure 2C; Methods 2.3 and reconstitution assays. nutrient: Vitamin D2 and D3 [cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution 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
plain_language
POR carries a FAD cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 407–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fad Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FAD cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR.
NADPH-cytochrome P450 oxidoreductase / POR → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.
experimental_model
Human POR structure and flavin-content analysis
exposure
Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.
limitations
The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution 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
plain_language
POR carries a FMN cofactor derived from vitamin B2.
primary_references
[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
tissue_or_cell_type
POR cofactor-binding domain
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 422–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft
### vd-act-por-fmn Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FMN cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108
Complete structured claim and evidence
Human CYP27B1 1alpha-hydroxylated 25-hydroxyvitamin D2 in phospholipid vesicles; low-substrate catalytic efficiency was similar to that measured for calcifediol.
Vitamin D 1-alpha-hydroxylase / CYP27B1 → 1-alpha,25-Dihydroxyvitamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary Tables 3-5, Figure 6A and Experimental procedures; full text retrieved.
experimental_model
Partially purified human CYP27B1 membrane assay
exposure
5-40 nM CYP27B1; 15 micromolar FDX1, 0.4 micromolar FDXR, 50 micromolar NADPH; 2 min at 37 C. Table 5/Figure 6A.
limitations
D2 kinetic data came from one experiment; results do not establish human dosing equivalence.
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
CYP27B1 completes activation of the D2 precursor.
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 inner-mitochondrial-membrane model
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 437–450
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified human CYP27B1 membrane assay · source_derived_draft · unverified_draft
### vd-act-cyp27b1-d2 Human CYP27B1 1alpha-hydroxylated 25-hydroxyvitamin D2 in phospholipid vesicles; low-substrate catalytic efficiency was similar to that measured for calcifediol. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP27B1 completes activation of the D2 precursor. organism: Homo sapiens proteins tissue_or_cell_type: reconstituted inner-mitochondrial-membrane model experimental_model: Partially purified human CYP27B1 membrane assay limitations: D2 kinetic data came from one experiment; results do not establish human dosing equivalence. exposure: 5-40 nM CYP27B1; 15 micromolar FDX1, 0.4 micromolar FDXR, 50 micromolar NADPH; 2 min at 37 C. Table 5/Figure 6A. cross_nutrient: false 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
Complete structured claim and evidence
Human adrenodoxin supported CYP27B1 activity in reconstituted vesicles; varying adrenodoxin changed apparent kinetic parameters for calcifediol hydroxylation.
Human adrenodoxin / FDX1 → Vitamin D 1-alpha-hydroxylase / CYP27B1 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The active human CYP27B1 reconstitution supplied human adrenodoxin reductase and NADPH upstream of human adrenodoxin.
Human ferredoxin reductase / FDXR → Human adrenodoxin / FDX1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Tables 3-5, Figure 6A and Experimental procedures; full text retrieved.
experimental_model
Human protein reconstitution and substrate turnover
exposure
0.4 micromolar FDXR, 15 micromolar FDX1 and 50 micromolar NADPH; Experimental procedures.
limitations
This record reports the supported redox chain; FDXR omission or dietary niacin/riboflavin intervention was not reported in the extracted experiment.
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
A reductase feeds the electron carrier used during vitamin D activation.
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
mitochondrial redox-partner assay
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 467–480
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human protein reconstitution and substrate turnover · source_derived_draft · unverified_draft
### vd-act-fdxr-cyp27b1-system The active human CYP27B1 reconstitution supplied human adrenodoxin reductase and NADPH upstream of human adrenodoxin. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A reductase feeds the electron carrier used during vitamin D activation. organism: Homo sapiens proteins tissue_or_cell_type: mitochondrial redox-partner assay experimental_model: Human protein reconstitution and substrate turnover limitations: This record reports the supported redox chain; FDXR omission or dietary niacin/riboflavin intervention was not reported in the extracted experiment. exposure: 0.4 micromolar FDXR, 15 micromolar FDX1 and 50 micromolar NADPH; Experimental procedures. 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
Complete structured claim and evidence
All four homozygous CYP27B1 missense variants identified in four unrelated rickets patients abolished measured 1alpha-hydroxylase activity when expressed in COS-1 cells.
Human CYP27B1 gene → Calcitriol production source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Wild-type human CYP24A1 expressed in V79-4 cells metabolized calcitriol through C24-pathway intermediates to a water-soluble fraction assigned to calcitroic acid.
Vitamin D 24-hydroxylase / CYP24A1 → Calcitroic acid source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human CYP24A1 initiated 25-hydroxyvitamin D2 oxidation by hydroxylation at C24R in the vesicle-reconstituted enzyme system.
Vitamin D 24-hydroxylase / CYP24A1 → 24R,25-Dihydroxyvitamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract: identified C24R products and comparative initial-rate kinetics.
experimental_model
Partially purified human CYP24A1 product analysis
exposure
25(OH)D2 substrate; concentration/time not specified in retrieved primary abstract.
limitations
Additional oxidation sites and products were not all fully identified; this is one identified initial route.
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
CYP24A1 begins one breakdown route for the D2 precursor.
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 512–525
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified human CYP24A1 product analysis · source_derived_draft · unverified_draft
### vd-act-cyp24a1-25d2 Human CYP24A1 initiated 25-hydroxyvitamin D2 oxidation by hydroxylation at C24R in the vesicle-reconstituted enzyme system. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP24A1 begins one breakdown route for the D2 precursor. organism: Homo sapiens protein tissue_or_cell_type: phospholipid-vesicle membrane experimental_model: Partially purified human CYP24A1 product analysis limitations: Additional oxidation sites and products were not all fully identified; this is one identified initial route. exposure: 25(OH)D2 substrate; concentration/time not specified in retrieved primary abstract. 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
Complete structured claim and evidence
Human CYP24A1 initiated active 1alpha,25-dihydroxyvitamin D2 oxidation through C24R hydroxylation.
Vitamin D 24-hydroxylase / CYP24A1 → 1-alpha,24R,25-Trihydroxyvitamin D2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract: identified C24R products and comparative initial-rate kinetics.
experimental_model
Partially purified human CYP24A1 product analysis
exposure
1,25(OH)2D2 substrate; concentration/time not specified in abstract.
limitations
Product profile is human enzyme-specific; active D2 is not calcitriol.
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
CYP24A1 also starts breaking down the active D2 hormone.
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 527–540
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified human CYP24A1 product analysis · source_derived_draft · unverified_draft
### vd-act-cyp24a1-active-d2 Human CYP24A1 initiated active 1alpha,25-dihydroxyvitamin D2 oxidation through C24R hydroxylation. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP24A1 also starts breaking down the active D2 hormone. organism: Homo sapiens protein tissue_or_cell_type: phospholipid-vesicle membrane experimental_model: Partially purified human CYP24A1 product analysis limitations: Product profile is human enzyme-specific; active D2 is not calcitriol. exposure: 1,25(OH)2D2 substrate; concentration/time not specified in abstract. 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
Complete structured claim and evidence
Human CYP24A1 had similar initial hydroxylation catalytic efficiencies for 25-hydroxyvitamin D2 and calcifediol in the matched vesicle assay.
25-Hydroxyvitamin D2 → Calcifediol / 25-hydroxyvitamin D3 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary abstract: identified C24R products and comparative initial-rate kinetics.
experimental_model
Matched recombinant human CYP24A1 initial-rate kinetics
exposure
Comparative kcat/Km at low substrate availability; exact substrate range not reported in abstract.
limitations
This is an enzyme comparison; it does not measure binding-protein clearance, repeated dosing, or whole-person serum responses.
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
The two 25-hydroxy precursors were initially oxidized with similar enzyme efficiency.
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 542–555
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched recombinant human CYP24A1 initial-rate kinetics · source_derived_draft · unverified_draft
### vd-act-cyp24a1-precursor-selectivity Human CYP24A1 had similar initial hydroxylation catalytic efficiencies for 25-hydroxyvitamin D2 and calcifediol in the matched vesicle assay. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two 25-hydroxy precursors were initially oxidized with similar enzyme efficiency. organism: Homo sapiens protein tissue_or_cell_type: phospholipid-vesicle membrane experimental_model: Matched recombinant human CYP24A1 initial-rate kinetics limitations: This is an enzyme comparison; it does not measure binding-protein clearance, repeated dosing, or whole-person serum responses. exposure: Comparative kcat/Km at low substrate availability; exact substrate range not reported in abstract. 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
Complete structured claim and evidence
Human CYP24A1 initial catalytic efficiency for calcitriol was almost twice that for the active D2 hormone in the matched vesicle experiment.
1-alpha,25-Dihydroxyvitamin D2 → Calcitriol source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified rat CYP24A1 produced a C24R-hydroxylated metabolite from active D2 but no detectable calcitroic acid under conditions that generated calcitroic acid from calcitriol.
Rat vitamin D 24-hydroxylase / Cyp24a1 → Calcitroic acid source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Patient-derived CYP24A1 variants severely impaired calcitriol catabolism in expression assays; L409S retained 5.3% of wild-type activity in the detailed results.
Human CYP24A1 gene → Calcitriol catabolism source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recessive CYP24A1 variants were identified in infants with hypercalcemia, including a second group whose illness followed high-dose vitamin D prophylaxis.
Human CYP24A1 gene → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Calcitriol increased Claudin-2 expression in human Caco-2 intestinal epithelial cells.
Calcitriol → Claudin-2 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Calcitriol increased Claudin-12 expression in human Caco-2 intestinal epithelial cells.
Calcitriol → Claudin-12 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Calcitriol administration increased active duodenal calcium transport in vitamin-D-deficient wild-type mice in the Benn study.
Calcitriol → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Two daily calcitriol injections increased active phosphate transport in wild-type mouse jejunum.
Calcitriol → Active intestinal phosphate absorption source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The two-day calcitriol regimen did not detectably increase paracellular phosphate flux in the mouse intestine.
Calcitriol → Paracellular intestinal phosphate flux source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Intestine-specific Slc34a2 deletion eliminated the phosphate-transport increase induced by the tested calcitriol regimen.
Intestine-specific Slc34a2-null mouse genotype → Active intestinal phosphate absorption source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
A low-phosphate diet increased intestinal NaPi-IIb protein expression even in Vdr-null mice.
Vdr-null mouse genotype → Sodium-phosphate cotransporter NaPi-IIb / SLC34A2 source_derived_draftungraded
Experimental context and source evidence
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
Vdr-null and wild-type mice; intestinal brush-border transporter immunodetection
exposure
Vdr deletion plus dietary phosphate restriction; exact dietary percentage and duration not given in the retrieved abstract.
limitations
Baseline NaPi-IIb protein and sodium-dependent phosphate transport were lower in knockout mice; preserved adaptation does not imply normal baseline transport.
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 intestine retained a phosphate-conservation response despite loss of vitamin D receptor signaling.
primary_references
[vdm-segawa2004] Intestinal Na-P(i) cotransporter adaptation to dietary P(i) content in vitamin D receptor null mice. (2004). https://pubmed.ncbi.nlm.nih.gov/14996670/ DOI: 10.1152/ajprenal.00375.2003
tissue_or_cell_type
Intestinal brush-border membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 713–727
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vdr-null and wild-type mice; intestinal brush-border transporter immunodetection · source_derived_draft · unverified_draft
### vdm-low-phosphate-adaptation-persists-without-vdr A low-phosphate diet increased intestinal NaPi-IIb protein expression even in Vdr-null mice. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intestine retained a phosphate-conservation response despite loss of vitamin D receptor signaling. organism: Mus musculus tissue_or_cell_type: Intestinal brush-border membrane experimental_model: Vdr-null and wild-type mice; intestinal brush-border transporter immunodetection limitations: Baseline NaPi-IIb protein and sodium-dependent phosphate transport were lower in knockout mice; preserved adaptation does not imply normal baseline transport. exposure: Vdr deletion plus dietary phosphate restriction; exact dietary percentage and duration not given 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-segawa2004] Intestinal Na-P(i) cotransporter adaptation to dietary P(i) content in vitamin D receptor null mice. (2004). https://pubmed.ncbi.nlm.nih.gov/14996670/ DOI: 10.1152/ajprenal.00375.2003
Complete structured claim and evidence
Calcitriol administration produced about a fourfold increase in bone Fgf23 transcripts in the Liu mouse study.
Calcitriol → FGF23 mRNA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant FGF23 reduced renal NaPi-IIa mRNA and protein abundance in the acute rodent injection study.
Fibroblast growth factor 23 / FGF23 → Sodium-phosphate cotransporter NaPi-IIa / SLC34A1 source_derived_draftungraded
Experimental context and source evidence
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
Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements
exposure
Single recombinant FGF23 injection; serum phosphate reduction was first observed at 9 hours; dose not recovered in the primary abstract.
limitations
Transporter abundance is not itself a flux measurement. Lack of a PTH rise and parathyroidectomized-rat responses support a PTH-independent action in this experiment.
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; Rattus norvegicus
plain_language
FGF23 reduced a kidney transporter that normally helps retain phosphate.
primary_references
[vdm-shimada2004] 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
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 745–759
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements · source_derived_draft · unverified_draft
### vdm-fgf23-reduces-renal-napi2a Recombinant FGF23 reduced renal NaPi-IIa mRNA and protein abundance in the acute rodent injection study. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 reduced a kidney transporter that normally helps retain phosphate. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements limitations: Transporter abundance is not itself a flux measurement. Lack of a PTH rise and parathyroidectomized-rat responses support a PTH-independent action in this experiment. exposure: Single recombinant FGF23 injection; serum phosphate reduction was first observed at 9 hours; dose not recovered in the primary 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-shimada2004] 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
Complete structured claim and evidence
The combined mineral/lactose rescue diet prevented rickets and osteomalacia in VDR-ablated mice.
Inorganic phosphate → Skeletal matrix mineralization source_derived_draftungraded
Experimental context and source evidence
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
VDR-ablated mice and control littermates receiving a mineral/lactose rescue diet
exposure
Combined mineral/lactose rescue diet; individual ingredient contributions and exact formulation are not resolved by the retrieved abstract.
limitations
This is a combined dietary rescue of receptor-deficient mice, not phosphate monotherapy, not a D2/D3 trial, and not evidence that VDR has no direct skeletal functions.
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
Improving mineral delivery protected the skeleton even when the vitamin D receptor was missing.
primary_references
[vdm-li1998] Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. (1998). https://pubmed.ncbi.nlm.nih.gov/9751523/ DOI: 10.1210/endo.139.10.6262
tissue_or_cell_type
Skeleton
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 761–775
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VDR-ablated mice and control littermates receiving a mineral/lactose rescue diet · source_derived_draft · unverified_draft
### vdm-mineral-rescue-prevents-vdr-null-skeletal-defects The combined mineral/lactose rescue diet prevented rickets and osteomalacia in VDR-ablated mice. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improving mineral delivery protected the skeleton even when the vitamin D receptor was missing. organism: Mus musculus tissue_or_cell_type: Skeleton experimental_model: VDR-ablated mice and control littermates receiving a mineral/lactose rescue diet limitations: This is a combined dietary rescue of receptor-deficient mice, not phosphate monotherapy, not a D2/D3 trial, and not evidence that VDR has no direct skeletal functions. exposure: Combined mineral/lactose rescue diet; individual ingredient contributions and exact formulation are not resolved by 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-li1998] Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. (1998). https://pubmed.ncbi.nlm.nih.gov/9751523/ DOI: 10.1210/endo.139.10.6262
Complete structured claim and evidence
Diet-induced hypophosphatemic mice had impaired late hypertrophic-chondrocyte apoptosis and rachitic growth-plate expansion despite hypercalcemia and suppressed PTH.
Inorganic phosphate → Hypertrophic chondrocyte apoptosis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin D–calcium–phosphate regulation.
evidence_locator
Results: biochemical parameters, growth-plate histology and TUNEL; primary text excerpts cached in web-assay-excerpts.json
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Wild-type mice fed high-calcium/low-phosphate diet; growth-plate histology and TUNEL assay
exposure
High-calcium/low-phosphate diet; biochemical comparisons at 24 days of age in Figure 2. Exact diet duration/formulation not resolved in retrieved passages.
limitations
The diet arm is separated from Vdr-null and Phex-mutant models. No single human serum threshold or claim that every rachitic disorder has one mechanism is inferred.
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
Low phosphate disrupted maturation of growth-plate cartilage even when calcium was high.
primary_references
[vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. (2005). https://pubmed.ncbi.nlm.nih.gov/15976027/ DOI: 10.1073/pnas.0502249102
tissue_or_cell_type
Growth-plate hypertrophic chondrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 777–791
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type mice fed high-calcium/low-phosphate diet; growth-plate histology and TUNEL assay · source_derived_draft · unverified_draft
### vdm-phosphate-restriction-reduces-growth-plate-apoptosis Diet-induced hypophosphatemic mice had impaired late hypertrophic-chondrocyte apoptosis and rachitic growth-plate expansion despite hypercalcemia and suppressed PTH. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low phosphate disrupted maturation of growth-plate cartilage even when calcium was high. organism: Mus musculus tissue_or_cell_type: Growth-plate hypertrophic chondrocytes experimental_model: Wild-type mice fed high-calcium/low-phosphate diet; growth-plate histology and TUNEL assay limitations: The diet arm is separated from Vdr-null and Phex-mutant models. No single human serum threshold or claim that every rachitic disorder has one mechanism is inferred. exposure: High-calcium/low-phosphate diet; biochemical comparisons at 24 days of age in Figure 2. Exact diet duration/formulation not resolved in retrieved passages. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Results: biochemical parameters, growth-plate histology and TUNEL; primary text excerpts cached in web-assay-excerpts.json nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. (2005). https://pubmed.ncbi.nlm.nih.gov/15976027/ DOI: 10.1073/pnas.0502249102
Complete structured claim and evidence
Phosphate exposure activated the caspase-9-dependent mitochondrial apoptotic pathway in cultured primary mouse hypertrophic chondrocytes.
Inorganic phosphate → Caspase-9 / CASP9 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D–calcium–phosphate regulation.
evidence_locator
Primary abstract and opening experimental-results summary; web-assay-excerpts.json
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Primary mouse chondrocytes; caspase-9 pathway and apoptosis assays
exposure
Inorganic phosphate exposure in differentiated primary cultures; exact dose/time not recovered in the primary passages used.
limitations
Cell differentiation and exposure conditions matter; no nutrient dose recommendation, universal phosphate sensor or human serum threshold is established.
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
Phosphate served as a signal for a cartilage-cell maturation pathway in this culture system.
primary_references
[vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. (2005). https://pubmed.ncbi.nlm.nih.gov/15976027/ DOI: 10.1073/pnas.0502249102
tissue_or_cell_type
Cultured hypertrophic chondrocytes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 793–807
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary mouse chondrocytes; caspase-9 pathway and apoptosis assays · source_derived_draft · unverified_draft
### vdm-phosphate-activates-chondrocyte-caspase9 Phosphate exposure activated the caspase-9-dependent mitochondrial apoptotic pathway in cultured primary mouse hypertrophic chondrocytes. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate served as a signal for a cartilage-cell maturation pathway in this culture system. organism: Mus musculus tissue_or_cell_type: Cultured hypertrophic chondrocytes experimental_model: Primary mouse chondrocytes; caspase-9 pathway and apoptosis assays limitations: Cell differentiation and exposure conditions matter; no nutrient dose recommendation, universal phosphate sensor or human serum threshold is established. exposure: Inorganic phosphate exposure in differentiated primary cultures; exact dose/time not recovered in the primary passages used. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Primary abstract and opening experimental-results summary; web-assay-excerpts.json nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. (2005). https://pubmed.ncbi.nlm.nih.gov/15976027/ DOI: 10.1073/pnas.0502249102
Complete structured claim and evidence
Calcitriol treatment increased extracellular pyrophosphate in differentiated Vdr-intact mouse osteoblast cultures.
Calcitriol → Extracellular pyrophosphate concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Added TNAP restored mineralization in calcitriol-treated differentiated mouse osteoblast cultures while lowering extracellular pyrophosphate.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Osteoblast mineralization source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream.
Calcitriol → RANK ligand / TNFSF11 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Calcitriol increased human osteocalcin mRNA about 1.8-fold in calvaria of mice carrying the human osteocalcin genomic transgene.
Calcitriol → Human BGLAP mRNA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
In primary calvarial osteoblast cultures from the same transgenic mice, calcitriol inhibited endogenous mouse osteocalcin accumulation while increasing human osteocalcin production.
Calcitriol → Osteocalcin / BGLAP source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
A concentrated vitamin K-dependent carboxylase preparation converted glutamate residues of decarboxylated bovine osteocalcin into gamma-carboxyglutamate in vitro.
Gamma-glutamyl carboxylase / GGCX → Decarboxylated osteocalcin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction.
evidence_locator
Abstract: reported experimental results
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay
exposure
50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions.
limitations
In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested.
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
Bos taurus osteocalcin; liver-derived enzyme preparation
plain_language
Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction.
primary_references
[vdm-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066
tissue_or_cell_type
Cell-free enzyme assay
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 889–903
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay · source_derived_draft · unverified_draft
### vdm-vitamin-k-carboxylase-modifies-osteocalcin A concentrated vitamin K-dependent carboxylase preparation converted glutamate residues of decarboxylated bovine osteocalcin into gamma-carboxyglutamate in vitro. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction. organism: Bos taurus osteocalcin; liver-derived enzyme preparation tissue_or_cell_type: Cell-free enzyme assay experimental_model: Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay limitations: In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested. exposure: 50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions. cross_nutrient: Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction. 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-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066
Complete structured claim and evidence
Calcitriol induced CAMP expression in tested human myeloid, keratinocyte and colon cell models and bone-marrow-derived cells.
Calcitriol → Human CAMP mRNA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
VDR bound a consensus vitamin D response element in the human CAMP promoter; this element mediated the observed induction.
Vitamin D receptor / VDR → Human CAMP promoter vitamin D response element source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
CAMP induction was not observed in the tested murine cells; the primate-conserved promoter VDRE was absent from mouse, rat and canine genomes.
Calcitriol → Mouse Camp mRNA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
TLR activation increased VDR gene expression in human macrophages.
TLR2-TLR1 receptor complex → Human VDR mRNA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
TLR activation increased vitamin D1-alpha-hydroxylase gene expression in human macrophages.
TLR2-TLR1 receptor complex → CYP27B1 mRNA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
TLR activation coupled vitamin D pathway induction to cathelicidin expression and killing of intracellular M. tuberculosis in the human macrophage experiments.
TLR2-TLR1 receptor complex → Intracellular Mycobacterium tuberculosis viability source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
In monocytes cultured with 10% autologous serum, 19 kDa TLR2/1 agonist increased CYP27B1 yet reduced hCAP transcript; expression was enhanced by adding 5 nM 25(OH)D3.
Mycobacterial 19 kDa lipopeptide TLR agonist → Human CAMP mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum
exposure
24-hour ex-vivo culture; 10% autologous serum, with or without added 5 nM 25(OH)D3.
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
Making more activation machinery did not guarantee an antimicrobial response when substrate supply was limited.
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
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 983–994
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-low-substrate In monocytes cultured with 10% autologous serum, 19 kDa TLR2/1 agonist increased CYP27B1 yet reduced hCAP transcript; expression was enhanced by adding 5 nM 25(OH)D3. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making more activation machinery did not guarantee an antimicrobial response when substrate supply was limited. 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: 24-hour ex-vivo culture; 10% autologous serum, with or without added 5 nM 25(OH)D3. 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
Complete structured claim and evidence
Adding 100 nM 25(OH)D3 increased detectable 1, 25(OH)2D in conditioned monocyte medium even without TLR induction.
Calcifediol / 25-hydroxyvitamin D3 → Calcitriol source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Serum collected after D2 treatment of low-status patients better supported TLR-triggered monocyte hCAP expression ex vivo.
Ergocalciferol / vitamin D2 → Human CAMP mRNA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum
exposure
D2 50, 000 IU twice weekly 5 weeks in low-status patients; paired serum used for ex-vivo assays.
limitations
Before/after serum comparison; no randomized D2/D3 head-to-head or demonstrated reduction of infections.
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
D2 treatment changed serum support for a local cell response.
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
Patient serum and ex-vivo monocytes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1009–1020
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-d2-serum-rescue Serum collected after D2 treatment of low-status patients better supported TLR-triggered monocyte hCAP expression ex vivo. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D2 treatment changed serum support for a local cell response. organism: Homo sapiens tissue_or_cell_type: Patient serum and ex-vivo monocytes experimental_model: Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum limitations: Before/after serum comparison; no randomized D2/D3 head-to-head or demonstrated reduction of infections. exposure: D2 50, 000 IU twice weekly 5 weeks in low-status patients; paired serum used for ex-vivo assays. 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
Complete structured claim and evidence
The patient D2 supplementation course did not change circulating hCAP concentration, despite improved serum support for the ex-vivo transcript response.
Ergocalciferol / vitamin D2 → Circulating hCAP18 concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum
exposure
D2 treatment and paired circulating hCAP assay in the bone-clinic cohort.
limitations
Circulating protein and stimulated local transcription are different readouts, so this is not a contradiction.
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 better local cell response did not translate into a higher circulating protein measurement.
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 serum
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1022–1033
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-circulating-hcap-null The patient D2 supplementation course did not change circulating hCAP concentration, despite improved serum support for the ex-vivo transcript response. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A better local cell response did not translate into a higher circulating protein measurement. organism: Homo sapiens tissue_or_cell_type: Human serum experimental_model: Human bone-clinic cohort and ex-vivo monocytes in 10% autologous serum limitations: Circulating protein and stimulated local transcription are different readouts, so this is not a contradiction. exposure: D2 treatment and paired circulating hCAP assay in the bone-clinic cohort. 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
Complete structured claim and evidence
Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced antimicrobial peptide expression.
Calcifediol / 25-hydroxyvitamin D3 → Human CAMP mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human macrophage IFN-gamma experiments with sera of differing 25OHD content
exposure
IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract.
limitations
Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred.
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
Adding precursor restored the antimicrobial gene response.
primary_references
[fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
tissue_or_cell_type
Human macrophages
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1035–1046
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human macrophage IFN-gamma experiments with sera of differing 25OHD content · source_derived_draft · unverified_draft
### vd-fabri-camp Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced antimicrobial peptide expression. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding precursor restored the antimicrobial gene response. organism: Homo sapiens tissue_or_cell_type: Human macrophages experimental_model: Human macrophage IFN-gamma experiments with sera of differing 25OHD content limitations: Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred. exposure: IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract. cross_nutrient: false [fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
Complete structured claim and evidence
Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced macrophage autophagy.
Calcifediol / 25-hydroxyvitamin D3 → Macrophage autophagy source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human macrophage IFN-gamma experiments with sera of differing 25OHD content
exposure
IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract.
limitations
Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred.
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 cells recovered a recycling and defense process called autophagy.
primary_references
[fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
tissue_or_cell_type
Human macrophages
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1048–1059
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human macrophage IFN-gamma experiments with sera of differing 25OHD content · source_derived_draft · unverified_draft
### vd-fabri-autophagy Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced macrophage autophagy. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells recovered a recycling and defense process called autophagy. organism: Homo sapiens tissue_or_cell_type: Human macrophages experimental_model: Human macrophage IFN-gamma experiments with sera of differing 25OHD content limitations: Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred. exposure: IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract. cross_nutrient: false [fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
Complete structured claim and evidence
Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced phagosome-lysosome fusion.
Calcifediol / 25-hydroxyvitamin D3 → Macrophage phagosome-lysosome fusion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human macrophage IFN-gamma experiments with sera of differing 25OHD content
exposure
IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract.
limitations
Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred.
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 compartment holding the pathogen could fuse with a degradative compartment.
primary_references
[fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
tissue_or_cell_type
Human macrophages
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1061–1072
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human macrophage IFN-gamma experiments with sera of differing 25OHD content · source_derived_draft · unverified_draft
### vd-fabri-fusion Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced phagosome-lysosome fusion. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The compartment holding the pathogen could fuse with a degradative compartment. organism: Homo sapiens tissue_or_cell_type: Human macrophages experimental_model: Human macrophage IFN-gamma experiments with sera of differing 25OHD content limitations: Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred. exposure: IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract. cross_nutrient: false [fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
Complete structured claim and evidence
Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced antimicrobial activity against intracellularM. tuberculosis.
Calcifediol / 25-hydroxyvitamin D3 → Intracellular Mycobacterium tuberculosis viability source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human macrophage IFN-gamma experiments with sera of differing 25OHD content
exposure
IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract.
limitations
Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred.
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 also recovered antimicrobial activity.
primary_references
[fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
tissue_or_cell_type
Human macrophages
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1074–1085
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human macrophage IFN-gamma experiments with sera of differing 25OHD content · source_derived_draft · unverified_draft
### vd-fabri-killing Adding 25(OH)D3 to low-vitamin-D serum restored IFN-gamma -induced antimicrobial activity against intracellularM. tuberculosis. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell experiment also recovered antimicrobial activity. organism: Homo sapiens tissue_or_cell_type: Human macrophages experimental_model: Human macrophage IFN-gamma experiments with sera of differing 25OHD content limitations: Cultured human macrophages and selected serum pools; no universal serum threshold or clinical tuberculosis cure inferred. exposure: IFN-gamma -stimulated human macrophages; low-vitamin-D serum with 25(OH)D3 add-back; dose/time not recovered from abstract. cross_nutrient: false [fabri2011] Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. (2011). https://pubmed.ncbi.nlm.nih.gov/21998409/ DOI: 10.1126/scitranslmed.3003045
Complete structured claim and evidence
Difference-in-difference testing found no significant probe changes in the white-European cohort or pooled D2/D3-versus-placebo analyses; five were found specifically for D3 versus placebo in the South-Asian cohort, largely driven by placebo-group changes.
Matched-dose D2 versus D3 comparison → Placebo-adjusted whole-blood transcriptome contrast source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women
exposure
15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end.
limitations
Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint.
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 strongest direct comparisons were much less conclusive than the within-group gene-change lists.
primary_references
[durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
tissue_or_cell_type
Whole blood
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1087–1098
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women · source_derived_draft · unverified_draft
### vd-durrant-direct-contrast Difference-in-difference testing found no significant probe changes in the white-European cohort or pooled D2/D3-versus-placebo analyses; five were found specifically for D3 versus placebo in the South-Asian cohort, largely driven by placebo-group changes. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The strongest direct comparisons were much less conclusive than the within-group gene-change lists. organism: Homo sapiens tissue_or_cell_type: Whole blood experimental_model: 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women limitations: Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint. exposure: 15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end. cross_nutrient: false [durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
Complete structured claim and evidence
The interferon-alpha response gene set was positively enriched at week 12 versus baseline within the white-European D3 group (GSEA adjusted P≤ 0.05).
Cholecalciferol → Whole-blood interferon alpha response gene-set expression source_derived_draftungraded
Experimental context and source evidence
analysis_scope
Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast.
cross_nutrient
false
experimental_model
97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women
exposure
15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end.
limitations
Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint.
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
This was a time trend in a gene set within one study group, not proof of improved infection resistance.
primary_references
[durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
tissue_or_cell_type
Whole blood
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1100–1112
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women · source_derived_draft · unverified_draft
### vd-durrant-d3-white-european-alpha The interferon-alpha response gene set was positively enriched at week 12 versus baseline within the white-European D3 group (GSEA adjusted P≤ 0.05). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This was a time trend in a gene set within one study group, not proof of improved infection resistance. organism: Homo sapiens tissue_or_cell_type: Whole blood experimental_model: 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women limitations: Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint. exposure: 15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end. cross_nutrient: false analysis_scope: Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast. [durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
Complete structured claim and evidence
The interferon-gamma response gene set was positively enriched at week 12 versus baseline within the white-European D3 group (GSEA adjusted P≤ 0.05).
Cholecalciferol → Whole-blood interferon gamma response gene-set expression source_derived_draftungraded
Experimental context and source evidence
analysis_scope
Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast.
cross_nutrient
false
experimental_model
97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women
exposure
15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end.
limitations
Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint.
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
This was a time trend in a gene set within one study group, not proof of improved infection resistance.
primary_references
[durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
tissue_or_cell_type
Whole blood
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1114–1126
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women · source_derived_draft · unverified_draft
### vd-durrant-d3-white-european-gamma The interferon-gamma response gene set was positively enriched at week 12 versus baseline within the white-European D3 group (GSEA adjusted P≤ 0.05). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This was a time trend in a gene set within one study group, not proof of improved infection resistance. organism: Homo sapiens tissue_or_cell_type: Whole blood experimental_model: 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women limitations: Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint. exposure: 15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end. cross_nutrient: false analysis_scope: Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast. [durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
Complete structured claim and evidence
The interferon-alpha response gene set was negatively enriched at week 12 versus baseline within the white-European D2 group (GSEA adjusted P≤ 0.05).
Ergocalciferol / vitamin D2 → Whole-blood interferon alpha response gene-set expression source_derived_draftungraded
Experimental context and source evidence
analysis_scope
Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast.
cross_nutrient
false
experimental_model
97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women
exposure
15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end.
limitations
Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint.
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
This was a time trend in a gene set within one study group, not proof of improved infection resistance.
primary_references
[durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
tissue_or_cell_type
Whole blood
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1128–1140
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women · source_derived_draft · unverified_draft
### vd-durrant-d2-white-european-alpha The interferon-alpha response gene set was negatively enriched at week 12 versus baseline within the white-European D2 group (GSEA adjusted P≤ 0.05). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This was a time trend in a gene set within one study group, not proof of improved infection resistance. organism: Homo sapiens tissue_or_cell_type: Whole blood experimental_model: 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women limitations: Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint. exposure: 15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end. cross_nutrient: false analysis_scope: Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast. [durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
Complete structured claim and evidence
The interferon-gamma response gene set was negatively enriched at week 12 versus baseline within the white-European D2 group (GSEA adjusted P≤ 0.05).
Ergocalciferol / vitamin D2 → Whole-blood interferon gamma response gene-set expression source_derived_draftungraded
Experimental context and source evidence
analysis_scope
Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast.
cross_nutrient
false
experimental_model
97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women
exposure
15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end.
limitations
Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint.
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
This was a time trend in a gene set within one study group, not proof of improved infection resistance.
primary_references
[durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
tissue_or_cell_type
Whole blood
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1142–1154
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women · source_derived_draft · unverified_draft
### vd-durrant-d2-white-european-gamma The interferon-gamma response gene set was negatively enriched at week 12 versus baseline within the white-European D2 group (GSEA adjusted P≤ 0.05). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This was a time trend in a gene set within one study group, not proof of improved infection resistance. organism: Homo sapiens tissue_or_cell_type: Whole blood experimental_model: 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women limitations: Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint. exposure: 15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end. cross_nutrient: false analysis_scope: Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast. [durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
Complete structured claim and evidence
The interferon-alpha response gene set was negatively enriched at week 12 versus baseline within the South-Asian D3 group (GSEA adjusted P≤ 0.05).
Cholecalciferol → Whole-blood interferon alpha response gene-set expression source_derived_draftungraded
Experimental context and source evidence
analysis_scope
Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast.
cross_nutrient
false
experimental_model
97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women
exposure
15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end.
limitations
Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint.
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
This was a time trend in a gene set within one study group, not proof of improved infection resistance.
primary_references
[durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
tissue_or_cell_type
Whole blood
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1156–1168
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women · source_derived_draft · unverified_draft
### vd-durrant-d3-south-asian-alpha The interferon-alpha response gene set was negatively enriched at week 12 versus baseline within the South-Asian D3 group (GSEA adjusted P≤ 0.05). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This was a time trend in a gene set within one study group, not proof of improved infection resistance. organism: Homo sapiens tissue_or_cell_type: Whole blood experimental_model: 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women limitations: Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint. exposure: 15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end. cross_nutrient: false analysis_scope: Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast. [durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
Complete structured claim and evidence
The interferon-gamma response gene set was negatively enriched at week 12 versus baseline within the South-Asian D3 group (GSEA adjusted P≤ 0.05).
Cholecalciferol → Whole-blood interferon gamma response gene-set expression source_derived_draftungraded
Experimental context and source evidence
analysis_scope
Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast.
cross_nutrient
false
experimental_model
97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women
exposure
15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end.
limitations
Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint.
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
This was a time trend in a gene set within one study group, not proof of improved infection resistance.
primary_references
[durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
tissue_or_cell_type
Whole blood
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1170–1182
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women · source_derived_draft · unverified_draft
### vd-durrant-d3-south-asian-gamma The interferon-gamma response gene set was negatively enriched at week 12 versus baseline within the South-Asian D3 group (GSEA adjusted P≤ 0.05). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This was a time trend in a gene set within one study group, not proof of improved infection resistance. organism: Homo sapiens tissue_or_cell_type: Whole blood experimental_model: 97 participant transcriptomic subset of Tripkovic 2017; 67 white-European and 30 South-Asian women limitations: Exploratory selected trial subset; differences in baseline status, season and whole-blood cell composition may matter. Within-group significance is not a significant difference between groups; no infection endpoint. exposure: 15 micrograms/day D2 or D3 or placebo for 12 winter weeks; blood microarrays at baseline/end. cross_nutrient: false analysis_scope: Within-group baseline-to-week 12 GSEA; not a randomized treatment-versus-placebo contrast. [durrant2022] Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. (2022). https://pubmed.ncbi.nlm.nih.gov/35281034/ DOI: 10.3389/fimmu.2022.790444
Complete structured claim and evidence
Keratinocyte-targeted ligand-binding-defective VDR restored normal hair cycling in VDR-null mice.
Keratinocyte-targeted ligand-binding-defective VDR transgene → Hair follicle cycling source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays
exposure
Keratinocyte-specific mutant VDR transgenes in VDR-null mice.
limitations
Engineered mouse VDR system; does not establish a vitamin D supplement as treatment for human hair loss.
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
A receptor defect and a vitamin shortage are different problems.
primary_references
[skorija2005] Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. (2005). https://pubmed.ncbi.nlm.nih.gov/15591533/ DOI: 10.1210/me.2004-0415
tissue_or_cell_type
Keratinocytes/hair follicles
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1184–1195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays · source_derived_draft · unverified_draft
### vd-hair-binding Keratinocyte-targeted ligand-binding-defective VDR restored normal hair cycling in VDR-null mice. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor defect and a vitamin shortage are different problems. organism: Mus musculus tissue_or_cell_type: Keratinocytes/hair follicles experimental_model: Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays limitations: Engineered mouse VDR system; does not establish a vitamin D supplement as treatment for human hair loss. exposure: Keratinocyte-specific mutant VDR transgenes in VDR-null mice. cross_nutrient: false [skorija2005] Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. (2005). https://pubmed.ncbi.nlm.nih.gov/15591533/ DOI: 10.1210/me.2004-0415
Complete structured claim and evidence
Keratinocyte-targeted AF2-mutant VDR only partly restored hair cycling in VDR-null mice.
Keratinocyte-targeted AF2-mutant VDR transgene → Hair follicle cycling source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays
exposure
Keratinocyte-specific mutant VDR transgenes in VDR-null mice.
limitations
Engineered mouse VDR system; does not establish a vitamin D supplement as treatment for human hair loss.
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
A receptor defect and a vitamin shortage are different problems.
primary_references
[skorija2005] Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. (2005). https://pubmed.ncbi.nlm.nih.gov/15591533/ DOI: 10.1210/me.2004-0415
tissue_or_cell_type
Keratinocytes/hair follicles
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1197–1208
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays · source_derived_draft · unverified_draft
### vd-hair-af2 Keratinocyte-targeted AF2-mutant VDR only partly restored hair cycling in VDR-null mice. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor defect and a vitamin shortage are different problems. organism: Mus musculus tissue_or_cell_type: Keratinocytes/hair follicles experimental_model: Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays limitations: Engineered mouse VDR system; does not establish a vitamin D supplement as treatment for human hair loss. exposure: Keratinocyte-specific mutant VDR transgenes in VDR-null mice. cross_nutrient: false [skorija2005] Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. (2005). https://pubmed.ncbi.nlm.nih.gov/15591533/ DOI: 10.1210/me.2004-0415
Complete structured claim and evidence
Hairless bound VDR and supported transcriptional repression; the tested ligand-binding and AF2 mutations did not abolish those interactions.
Hairless nuclear receptor corepressor → Vitamin D receptor / VDR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays
exposure
VDR-Hairless interaction/repression assays accompanying transgenic studies.
limitations
Engineered mouse VDR system; does not establish a vitamin D supplement as treatment for human hair loss.
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Mouse-model-associated molecular assays
plain_language
The receptor also interacts with a gene-silencing partner, independently of normal hormone binding.
primary_references
[skorija2005] Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. (2005). https://pubmed.ncbi.nlm.nih.gov/15591533/ DOI: 10.1210/me.2004-0415
tissue_or_cell_type
Experimental receptor/corepressor system
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1210–1221
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays · source_derived_draft · unverified_draft
### vd-hairless-vdr Hairless bound VDR and supported transcriptional repression; the tested ligand-binding and AF2 mutations did not abolish those interactions. 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 also interacts with a gene-silencing partner, independently of normal hormone binding. organism: Mouse-model-associated molecular assays tissue_or_cell_type: Experimental receptor/corepressor system experimental_model: Keratinocyte-targeted mutant VDR transgenes in VDR-null mice; binding/repression assays limitations: Engineered mouse VDR system; does not establish a vitamin D supplement as treatment for human hair loss. exposure: VDR-Hairless interaction/repression assays accompanying transgenic studies. cross_nutrient: false [skorija2005] Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. (2005). https://pubmed.ncbi.nlm.nih.gov/15591533/ DOI: 10.1210/me.2004-0415
Complete structured claim and evidence
The administered D2 and D3 produced similar initial rises in their respective parent calciferol serum concentrations.
Matched-dose D2 versus D3 comparison → Serum administered parent calciferol concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human single-dose comparison; 20 healthy men; 28-day follow-up
exposure
One oral 50, 000-IU dose of D2 or D3; serial serum measures for 28 days.
limitations
Single 50, 000-IU dose in healthy men; biochemical response, not fracture efficacy. Model-extrapolated potency is not a universal IU conversion.
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 two forms entered the circulation similarly in this single-dose experiment.
primary_references
[armas2004] Vitamin D2 is much less effective than vitamin D3 in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15531486/ DOI: 10.1210/jc.2004-0360
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1223–1234
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human single-dose comparison; 20 healthy men; 28-day follow-up · source_derived_draft · unverified_draft
### vd-armas-parent-appearance The administered D2 and D3 produced similar initial rises in their respective parent calciferol serum concentrations. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two forms entered the circulation similarly in this single-dose experiment. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Human single-dose comparison; 20 healthy men; 28-day follow-up limitations: Single 50, 000-IU dose in healthy men; biochemical response, not fracture efficacy. Model-extrapolated potency is not a universal IU conversion. exposure: One oral 50, 000-IU dose of D2 or D3; serial serum measures for 28 days. cross_nutrient: false [armas2004] Vitamin D2 is much less effective than vitamin D3 in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15531486/ DOI: 10.1210/jc.2004-0360
Complete structured claim and evidence
Initial total 25(OH)D rises were similar through day 3; D3-associated levels peaked at day 14 while the D2-associated level had returned to baseline by then.
Cholecalciferol → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human single-dose comparison; 20 healthy men; 28-day follow-up
exposure
One oral 50, 000-IU dose of D2 or D3; serial serum measures for 28 days.
limitations
Single 50, 000-IU dose in healthy men; biochemical response, not fracture efficacy. Model-extrapolated potency is not a universal IU conversion.
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
Similar early responses did not mean equally long-lasting blood-level responses.
primary_references
[armas2004] Vitamin D2 is much less effective than vitamin D3 in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15531486/ DOI: 10.1210/jc.2004-0360
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1236–1247
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human single-dose comparison; 20 healthy men; 28-day follow-up · source_derived_draft · unverified_draft
### vd-armas-total25-timecourse Initial total 25(OH)D rises were similar through day 3; D3-associated levels peaked at day 14 while the D2-associated level had returned to baseline by then. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Similar early responses did not mean equally long-lasting blood-level responses. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Human single-dose comparison; 20 healthy men; 28-day follow-up limitations: Single 50, 000-IU dose in healthy men; biochemical response, not fracture efficacy. Model-extrapolated potency is not a universal IU conversion. exposure: One oral 50, 000-IU dose of D2 or D3; serial serum measures for 28 days. cross_nutrient: false [armas2004] Vitamin D2 is much less effective than vitamin D3 in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15531486/ DOI: 10.1210/jc.2004-0360
Complete structured claim and evidence
Measured incremental 25(OH)D AUC through day 28 was 204.7 ng·day/mL for D3 versus 60.2 for D2 (P<0.002); the reported 9.5: 1 ratio instead came from extrapolation to infinite time.
Cholecalciferol → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human single-dose comparison; 20 healthy men; 28-day follow-up
exposure
One oral 50, 000-IU dose of D2 or D3; serial serum measures for 28 days.
limitations
Single 50, 000-IU dose in healthy men; biochemical response, not fracture efficacy. Model-extrapolated potency is not a universal IU conversion.
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 measured difference and the extrapolated difference are separate results.
primary_references
[armas2004] Vitamin D2 is much less effective than vitamin D3 in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15531486/ DOI: 10.1210/jc.2004-0360
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1249–1260
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human single-dose comparison; 20 healthy men; 28-day follow-up · source_derived_draft · unverified_draft
### vd-armas-auc Measured incremental 25(OH)D AUC through day 28 was 204.7 ng·day/mL for D3 versus 60.2 for D2 (P<0.002); the reported 9.5: 1 ratio instead came from extrapolation to infinite time. 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 difference and the extrapolated difference are separate results. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Human single-dose comparison; 20 healthy men; 28-day follow-up limitations: Single 50, 000-IU dose in healthy men; biochemical response, not fracture efficacy. Model-extrapolated potency is not a universal IU conversion. exposure: One oral 50, 000-IU dose of D2 or D3; serial serum measures for 28 days. cross_nutrient: false [armas2004] Vitamin D2 is much less effective than vitamin D3 in humans. (2004). https://pubmed.ncbi.nlm.nih.gov/15531486/ DOI: 10.1210/jc.2004-0360
Complete structured claim and evidence
Mean serum total 25(OH)D rose from 16.9 to 26.8 ng/mL with daily D2; the study reported a comparable response to D3, which rose from 19.6 to 28.9 ng/mL.
Ergocalciferol / vitamin D2 → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks
exposure
Daily D2 1000 IU, D3 1000 IU, mixed 500+500 IU or placebo; 11 winter weeks.
limitations
Small groups and biochemical endpoints; authors reported comparable responses. Daily regimen differs from single-dose and food-fortification studies.
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 forms increased the blood marker in this daily-dose trial.
primary_references
[holick2008] Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. (2008). https://pubmed.ncbi.nlm.nih.gov/18089691/ DOI: 10.1210/jc.2007-2308
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1262–1273
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks · source_derived_draft · unverified_draft
### vd-holick-daily-d2 Mean serum total 25(OH)D rose from 16.9 to 26.8 ng/mL with daily D2; the study reported a comparable response to D3, which rose from 19.6 to 28.9 ng/mL. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both forms increased the blood marker in this daily-dose trial. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks limitations: Small groups and biochemical endpoints; authors reported comparable responses. Daily regimen differs from single-dose and food-fortification studies. exposure: Daily D2 1000 IU, D3 1000 IU, mixed 500+500 IU or placebo; 11 winter weeks. cross_nutrient: false [holick2008] Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. (2008). https://pubmed.ncbi.nlm.nih.gov/18089691/ DOI: 10.1210/jc.2007-2308
Complete structured claim and evidence
With the 500-IU D2 plus 500-IU D3 daily combination, mean total 25(OH)D rose from 20.2 to 28.4 ng/mL.
Matched-dose D2 versus D3 comparison → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks
exposure
Daily D2 1000 IU, D3 1000 IU, mixed 500+500 IU or placebo; 11 winter weeks.
limitations
Small groups and biochemical endpoints; authors reported comparable responses. Daily regimen differs from single-dose and food-fortification studies.
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 mixture also raised the marker; this was not a test proving synergy.
primary_references
[holick2008] Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. (2008). https://pubmed.ncbi.nlm.nih.gov/18089691/ DOI: 10.1210/jc.2007-2308
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1275–1286
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks · source_derived_draft · unverified_draft
### vd-holick-mixed With the 500-IU D2 plus 500-IU D3 daily combination, mean total 25(OH)D rose from 20.2 to 28.4 ng/mL. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mixture also raised the marker; this was not a test proving synergy. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks limitations: Small groups and biochemical endpoints; authors reported comparable responses. Daily regimen differs from single-dose and food-fortification studies. exposure: Daily D2 1000 IU, D3 1000 IU, mixed 500+500 IU or placebo; 11 winter weeks. cross_nutrient: false [holick2008] Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. (2008). https://pubmed.ncbi.nlm.nih.gov/18089691/ DOI: 10.1210/jc.2007-2308
Complete structured claim and evidence
The D2-only daily group did not show a change in serum 25(OH)D3 over the 11-week study.
Ergocalciferol / vitamin D2 → Serum 25-hydroxyvitamin D3 concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks
exposure
Daily D2 1000 IU, D3 1000 IU, mixed 500+500 IU or placebo; 11 winter weeks.
limitations
Small groups and biochemical endpoints; authors reported comparable responses. Daily regimen differs from single-dose and food-fortification studies.
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 fall in the D3-derived fraction was not detected in every D2 regimen.
primary_references
[holick2008] Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. (2008). https://pubmed.ncbi.nlm.nih.gov/18089691/ DOI: 10.1210/jc.2007-2308
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1288–1299
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks · source_derived_draft · unverified_draft
### vd-holick-d2-d3-fraction The D2-only daily group did not show a change in serum 25(OH)D3 over the 11-week study. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A fall in the D3-derived fraction was not detected in every D2 regimen. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Double-blind placebo-controlled daily D2/D3/mixed trial; 68 adults represented in Fig.1; 11 weeks limitations: Small groups and biochemical endpoints; authors reported comparable responses. Daily regimen differs from single-dose and food-fortification studies. exposure: Daily D2 1000 IU, D3 1000 IU, mixed 500+500 IU or placebo; 11 winter weeks. cross_nutrient: false [holick2008] Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. (2008). https://pubmed.ncbi.nlm.nih.gov/18089691/ DOI: 10.1210/jc.2007-2308
Complete structured claim and evidence
Incremental 12-week 25(OH)D AUC averaged 2136 ng·day/mL for D3 versus 1366 for D2 (P<0.001).
Cholecalciferol → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks
exposure
D2 or D3 50, 000 IU orally each week for 12 weeks.
limitations
This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint.
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
D3 produced the larger accumulated blood-marker response during weekly dosing.
primary_references
[heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1301–1312
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks · source_derived_draft · unverified_draft
### vd-heaney-auc Incremental 12-week 25(OH)D AUC averaged 2136 ng·day/mL for D3 versus 1366 for D2 (P<0.001). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D3 produced the larger accumulated blood-marker response during weekly dosing. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks limitations: This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint. exposure: D2 or D3 50, 000 IU orally each week for 12 weeks. cross_nutrient: false [heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
Complete structured claim and evidence
Mean steady-state total 25(OH)D increments were 45 ng/mL with D3 and 24 ng/mL with D2 (P<0.001).
Cholecalciferol → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks
exposure
D2 or D3 50, 000 IU orally each week for 12 weeks.
limitations
This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint.
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 later steady blood-level rise also differed between the forms.
primary_references
[heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1314–1325
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks · source_derived_draft · unverified_draft
### vd-heaney-steady-state Mean steady-state total 25(OH)D increments were 45 ng/mL with D3 and 24 ng/mL with D2 (P<0.001). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The later steady blood-level rise also differed between the forms. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks limitations: This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint. exposure: D2 or D3 50, 000 IU orally each week for 12 weeks. cross_nutrient: false [heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
Complete structured claim and evidence
Subcutaneous adipose content of the administered D2 increased by 50 micrograms/kg.
Ergocalciferol / vitamin D2 → Subcutaneous adipose vitamin D2 content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks
exposure
D2 or D3 50, 000 IU orally each week for 12 weeks.
limitations
This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint. This is vitamer-specific content, not the disputed total-fat unit in the abstract.
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 administered form was also measured in fat tissue.
primary_references
[heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
tissue_or_cell_type
Subcutaneous adipose tissue
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1327–1338
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks · source_derived_draft · unverified_draft
### vd-heaney-fat-d2 Subcutaneous adipose content of the administered D2 increased by 50 micrograms/kg. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The administered form was also measured in fat tissue. organism: Homo sapiens tissue_or_cell_type: Subcutaneous adipose tissue experimental_model: Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks limitations: This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint. This is vitamer-specific content, not the disputed total-fat unit in the abstract. exposure: D2 or D3 50, 000 IU orally each week for 12 weeks. cross_nutrient: false [heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
Complete structured claim and evidence
Subcutaneous adipose content of the administered D3 increased by 104 micrograms/kg.
Cholecalciferol → Subcutaneous adipose vitamin D3 content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks
exposure
D2 or D3 50, 000 IU orally each week for 12 weeks.
limitations
This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint. This is vitamer-specific content, not the disputed total-fat unit in the abstract.
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 administered form was also measured in fat tissue.
primary_references
[heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
tissue_or_cell_type
Subcutaneous adipose tissue
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1340–1351
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks · source_derived_draft · unverified_draft
### vd-heaney-fat-d3 Subcutaneous adipose content of the administered D3 increased by 104 micrograms/kg. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The administered form was also measured in fat tissue. organism: Homo sapiens tissue_or_cell_type: Subcutaneous adipose tissue experimental_model: Single-blind randomized D2/D3 comparison in 33 adults; weekly dosing for 12 weeks limitations: This weekly regimen and marker response do not establish a universal conversion factor or superiority for every clinical endpoint. This is vitamer-specific content, not the disputed total-fat unit in the abstract. exposure: D2 or D3 50, 000 IU orally each week for 12 weeks. cross_nutrient: false [heaney2011] Vitamin D(3) is more potent than vitamin D(2) in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21177785/ DOI: 10.1210/jc.2010-2230
Complete structured claim and evidence
The D3-biscuit group had a 15.3 nmol/L greater incremental total 25(OH)D change than D2-biscuit (95% CI7.4–23.3; P<0.0003).
Cholecalciferol → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Randomized double-blind five-group food-fortification trial; 335 South Asian and white European women
exposure
Daily 15 micrograms D2 or D3 in juice or biscuits versus placebo; 12 winter weeks.
limitations
Women aged 20–64 in the UK; food vehicles and dose differ from other trials. Marker superiority is not proof of better disease outcomes.
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
With matched fortified biscuits, D3 produced a larger marker increase.
primary_references
[tripkovic2017] Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28679555/ DOI: 10.3945/ajcn.116.138693
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1353–1364
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind five-group food-fortification trial; 335 South Asian and white European women · source_derived_draft · unverified_draft
### vd-tripkovic-biscuit The D3-biscuit group had a 15.3 nmol/L greater incremental total 25(OH)D change than D2-biscuit (95% CI7.4–23.3; P<0.0003). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: With matched fortified biscuits, D3 produced a larger marker increase. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Randomized double-blind five-group food-fortification trial; 335 South Asian and white European women limitations: Women aged 20–64 in the UK; food vehicles and dose differ from other trials. Marker superiority is not proof of better disease outcomes. exposure: Daily 15 micrograms D2 or D3 in juice or biscuits versus placebo; 12 winter weeks. cross_nutrient: false [tripkovic2017] Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28679555/ DOI: 10.3945/ajcn.116.138693
Complete structured claim and evidence
The D3-juice group had a 16.9 nmol/L greater incremental total 25(OH)D change than D2-juice (95% CI9.0–24.8; P<0.0001).
Cholecalciferol → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Randomized double-blind five-group food-fortification trial; 335 South Asian and white European women
exposure
Daily 15 micrograms D2 or D3 in juice or biscuits versus placebo; 12 winter weeks.
limitations
Women aged 20–64 in the UK; food vehicles and dose differ from other trials. Marker superiority is not proof of better disease outcomes.
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 matched-juice comparison also favored D3 for this blood marker.
primary_references
[tripkovic2017] Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28679555/ DOI: 10.3945/ajcn.116.138693
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1366–1377
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind five-group food-fortification trial; 335 South Asian and white European women · source_derived_draft · unverified_draft
### vd-tripkovic-juice The D3-juice group had a 16.9 nmol/L greater incremental total 25(OH)D change than D2-juice (95% CI9.0–24.8; P<0.0001). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The matched-juice comparison also favored D3 for this blood marker. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Randomized double-blind five-group food-fortification trial; 335 South Asian and white European women limitations: Women aged 20–64 in the UK; food vehicles and dose differ from other trials. Marker superiority is not proof of better disease outcomes. exposure: Daily 15 micrograms D2 or D3 in juice or biscuits versus placebo; 12 winter weeks. cross_nutrient: false [tripkovic2017] Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28679555/ DOI: 10.3945/ajcn.116.138693
Complete structured claim and evidence
Across both countries, mean tracer half-life was 13.9 days for 25(OH)D2 versus 15.1 days for 25(OH)D3 (P=0.001); the difference was significant in Gambians but not the UK subgroup.
25-Hydroxyvitamin D2 → Plasma 25-hydroxyvitamin D2 tracer half-life source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Oral deuterated 25(OH)D2 and 25(OH)D3 tracer study; 18 Gambian and 18 UK healthy men
exposure
Oral deuterated 25(OH)D2 and 25(OH)D3, 40 nmol each; sampling 33 days.
limitations
Measured metabolites rather than parent supplements; country subgroup and DBP associations do not provide a universal whole-body storage half-life.
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 circulating D2-derived metabolite cleared somewhat faster overall, with variation between groups.
primary_references
[jones2014] 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. (2014). https://pubmed.ncbi.nlm.nih.gov/24885631/ DOI: 10.1210/jc.2014-1714
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1379–1390
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral deuterated 25(OH)D2 and 25(OH)D3 tracer study; 18 Gambian and 18 UK healthy men · source_derived_draft · unverified_draft
### vd-jones-half-life Across both countries, mean tracer half-life was 13.9 days for 25(OH)D2 versus 15.1 days for 25(OH)D3 (P=0.001); the difference was significant in Gambians but not the UK subgroup. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The circulating D2-derived metabolite cleared somewhat faster overall, with variation between groups. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Oral deuterated 25(OH)D2 and 25(OH)D3 tracer study; 18 Gambian and 18 UK healthy men limitations: Measured metabolites rather than parent supplements; country subgroup and DBP associations do not provide a universal whole-body storage half-life. exposure: Oral deuterated 25(OH)D2 and 25(OH)D3, 40 nmol each; sampling 33 days. cross_nutrient: false [jones2014] 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. (2014). https://pubmed.ncbi.nlm.nih.gov/24885631/ DOI: 10.1210/jc.2014-1714
Complete structured claim and evidence
Higher plasma DBP concentration was associated with longer 25(OH)D3 half-life in the combined model (0.04 days per 1 mg/L DBP; P=0.02); the corresponding 25(OH)D2 association was 0.03 days (P=0.03).
Plasma vitamin D binding protein concentration → Plasma 25-hydroxyvitamin D3 tracer half-life source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Oral deuterated 25(OH)D2 and 25(OH)D3 tracer study; 18 Gambian and 18 UK healthy men
exposure
Oral deuterated 25(OH)D2 and 25(OH)D3, 40 nmol each; sampling 33 days.
limitations
Measured metabolites rather than parent supplements; country subgroup and DBP associations do not provide a universal whole-body storage half-life.
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
Carrier abundance was associated with metabolite persistence; it was not experimentally assigned.
primary_references
[jones2014] 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. (2014). https://pubmed.ncbi.nlm.nih.gov/24885631/ DOI: 10.1210/jc.2014-1714
tissue_or_cell_type
Human circulating measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1392–1403
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral deuterated 25(OH)D2 and 25(OH)D3 tracer study; 18 Gambian and 18 UK healthy men · source_derived_draft · unverified_draft
### vd-jones-dbp-half-life Higher plasma DBP concentration was associated with longer 25(OH)D3 half-life in the combined model (0.04 days per 1 mg/L DBP; P=0.02); the corresponding 25(OH)D2 association was 0.03 days (P=0.03). Condition category: biomarker_context nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carrier abundance was associated with metabolite persistence; it was not experimentally assigned. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Oral deuterated 25(OH)D2 and 25(OH)D3 tracer study; 18 Gambian and 18 UK healthy men limitations: Measured metabolites rather than parent supplements; country subgroup and DBP associations do not provide a universal whole-body storage half-life. exposure: Oral deuterated 25(OH)D2 and 25(OH)D3, 40 nmol each; sampling 33 days. cross_nutrient: false [jones2014] 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. (2014). https://pubmed.ncbi.nlm.nih.gov/24885631/ DOI: 10.1210/jc.2014-1714
Complete structured claim and evidence
At day 28, the D2 arm showed a 13.2 nmol/L greater decline in 25(OH)D3 than placebo (95% CI9.7–16.6).
Ergocalciferol / vitamin D2 → Serum 25-hydroxyvitamin D3 concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Two randomized single-dose experiments; 100 volunteers, 97 analyzed
exposure
Study 1: one 50, 000 IU oral D2 dose versus placebo.
limitations
No direct enzyme-flux assay. Reciprocal fraction changes are not proof that D2 is toxic or that net total vitamin D falls.
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 large D2 dose lowered the measured D3-derived fraction in this experiment.
primary_references
[hammami2019] Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30658603/ DOI: 10.1186/s12902-019-0337-8
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1405–1416
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two randomized single-dose experiments; 100 volunteers, 97 analyzed · source_derived_draft · unverified_draft
### vd-hammami-d2-decreases-d3 At day 28, the D2 arm showed a 13.2 nmol/L greater decline in 25(OH)D3 than placebo (95% CI9.7–16.6). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A large D2 dose lowered the measured D3-derived fraction in this experiment. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Two randomized single-dose experiments; 100 volunteers, 97 analyzed limitations: No direct enzyme-flux assay. Reciprocal fraction changes are not proof that D2 is toxic or that net total vitamin D falls. exposure: Study 1: one 50, 000 IU oral D2 dose versus placebo. cross_nutrient: false [hammami2019] Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30658603/ DOI: 10.1186/s12902-019-0337-8
Complete structured claim and evidence
At day 28, D3 produced a 9.8 nmol/L greater decline in 25(OH)D2 than placebo (95% CI5.2–14.4); by day 56 the 1.7 nmol/L difference was not significant (CI−7.6–11.1).
Cholecalciferol → Serum 25-hydroxyvitamin D2 concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Two randomized single-dose experiments; 100 volunteers, 97 analyzed
exposure
Study 2: D2 50, 000 IU preload; four days later D3 50, 000 IU or placebo.
limitations
No direct enzyme-flux assay. Reciprocal fraction changes are not proof that D2 is toxic or that net total vitamin D falls.
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 reverse effect also occurred after D3, and its between-group difference was shorter-lived.
primary_references
[hammami2019] Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30658603/ DOI: 10.1186/s12902-019-0337-8
tissue_or_cell_type
Human circulating measurements
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1418–1429
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two randomized single-dose experiments; 100 volunteers, 97 analyzed · source_derived_draft · unverified_draft
### vd-hammami-d3-decreases-d2 At day 28, D3 produced a 9.8 nmol/L greater decline in 25(OH)D2 than placebo (95% CI5.2–14.4); by day 56 the 1.7 nmol/L difference was not significant (CI−7.6–11.1). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reverse effect also occurred after D3, and its between-group difference was shorter-lived. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Two randomized single-dose experiments; 100 volunteers, 97 analyzed limitations: No direct enzyme-flux assay. Reciprocal fraction changes are not proof that D2 is toxic or that net total vitamin D falls. exposure: Study 2: D2 50, 000 IU preload; four days later D3 50, 000 IU or placebo. cross_nutrient: false [hammami2019] Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30658603/ DOI: 10.1186/s12902-019-0337-8
Complete structured claim and evidence
After D2, the mean 25(OH)D3: D3 ratio decreased and was lower than after D3.
Ergocalciferol / vitamin D2 → Serum 25(OH)D3 to D3 ratio source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
After D2, the mean 1, 25(OH)2D3: 25(OH)D3 ratio decreased and was lower than after D3.
Ergocalciferol / vitamin D2 → Serum 1,25(OH)2D3 to 25(OH)D3 ratio source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The 24R, 25(OH)2D3: 25(OH)D3 ratio rose within both D2 and D3 groups, but their postsupplementation ratios did not differ significantly.
Ergocalciferol / vitamin D2 → Serum 24R,25(OH)2D3 to 25(OH)D3 ratio source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
All three regimens approximately tripled total 25(OH)D; daily D2 versus daily D3 differed by 7% with P=0.82.
Matched-dose D2 versus D3 comparison → Serum total 25-hydroxyvitamin D concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Six-week randomized comparison in 40 infants/toddlers with 25(OH)D<20 ng/mL; all prescribed calcium
exposure
D2 2000 IU/day, D2 50, 000 IU/week or D3 2000 IU/day for 6 weeks; all also 50 mg/kg/day elemental calcium.
limitations
Small pediatric trial; D and calcium effects cannot be separated; biochemical outcomes do not establish long-term comparative safety.
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
D2 could correct the low marker too in this short pediatric study.
primary_references
[gordon2008] Treatment of hypovitaminosis D in infants and toddlers. (2008). https://pubmed.ncbi.nlm.nih.gov/18413426/ DOI: 10.1210/jc.2007-2790
tissue_or_cell_type
Human circulating measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1470–1481
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-week randomized comparison in 40 infants/toddlers with 25(OH)D<20 ng/mL; all prescribed calcium · source_derived_draft · unverified_draft
### vd-gordon-25-response All three regimens approximately tripled total 25(OH)D; daily D2 versus daily D3 differed by 7% with P=0.82. Condition category: biomarker_context nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D2 could correct the low marker too in this short pediatric study. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Six-week randomized comparison in 40 infants/toddlers with 25(OH)D<20 ng/mL; all prescribed calcium limitations: Small pediatric trial; D and calcium effects cannot be separated; biochemical outcomes do not establish long-term comparative safety. exposure: D2 2000 IU/day, D2 50, 000 IU/week or D3 2000 IU/day for 6 weeks; all also 50 mg/kg/day elemental calcium. cross_nutrient: true [gordon2008] Treatment of hypovitaminosis D in infants and toddlers. (2008). https://pubmed.ncbi.nlm.nih.gov/18413426/ DOI: 10.1210/jc.2007-2790
Complete structured claim and evidence
PTH suppression did not differ significantly among the three vitamin D regimens given with calcium.
Matched-dose D2 versus D3 comparison → Serum PTH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Six-week randomized comparison in 40 infants/toddlers with 25(OH)D<20 ng/mL; all prescribed calcium
exposure
D2 2000 IU/day, D2 50, 000 IU/week or D3 2000 IU/day for 6 weeks; all also 50 mg/kg/day elemental calcium.
limitations
Small pediatric trial; D and calcium effects cannot be separated; biochemical outcomes do not establish long-term comparative safety.
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 hormone response was not detectably different between these treatment groups.
primary_references
[gordon2008] Treatment of hypovitaminosis D in infants and toddlers. (2008). https://pubmed.ncbi.nlm.nih.gov/18413426/ DOI: 10.1210/jc.2007-2790
tissue_or_cell_type
Human circulating measurements
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1483–1494
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-week randomized comparison in 40 infants/toddlers with 25(OH)D<20 ng/mL; all prescribed calcium · source_derived_draft · unverified_draft
### vd-gordon-pth PTH suppression did not differ significantly among the three vitamin D regimens given with calcium. Condition category: biomarker_context nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone response was not detectably different between these treatment groups. organism: Homo sapiens tissue_or_cell_type: Human circulating measurements experimental_model: Six-week randomized comparison in 40 infants/toddlers with 25(OH)D<20 ng/mL; all prescribed calcium limitations: Small pediatric trial; D and calcium effects cannot be separated; biochemical outcomes do not establish long-term comparative safety. exposure: D2 2000 IU/day, D2 50, 000 IU/week or D3 2000 IU/day for 6 weeks; all also 50 mg/kg/day elemental calcium. cross_nutrient: true [gordon2008] Treatment of hypovitaminosis D in infants and toddlers. (2008). https://pubmed.ncbi.nlm.nih.gov/18413426/ DOI: 10.1210/jc.2007-2790
Complete structured claim and evidence
D3 assignment did not significantly reduce total fractures (HR0.98; 95% CI0.89–1.08; P=0.70).
Cholecalciferol → Total fracture incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years
exposure
D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years.
limitations
Generally healthy midlife/older adults not selected for deficiency. Does not test treatment of established deficiency rickets or osteomalacia.
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
Extra D3 did not reduce this fracture endpoint in the population studied.
primary_references
[leboff2022] Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35939577/ DOI: 10.1056/nejmoa2202106
tissue_or_cell_type
Clinical skeletal outcomes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1496–1507
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years · source_derived_draft · unverified_draft
### vd-vital-fracture-total D3 assignment did not significantly reduce total fractures (HR0.98; 95% CI0.89–1.08; P=0.70). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra D3 did not reduce this fracture endpoint in the population studied. organism: Homo sapiens tissue_or_cell_type: Clinical skeletal outcomes experimental_model: VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years limitations: Generally healthy midlife/older adults not selected for deficiency. Does not test treatment of established deficiency rickets or osteomalacia. exposure: D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years. cross_nutrient: false [leboff2022] Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35939577/ DOI: 10.1056/nejmoa2202106
Complete structured claim and evidence
D3 assignment did not significantly reduce nonvertebral fractures (HR0.97; 95% CI0.87–1.07; P=0.50).
Cholecalciferol → Nonvertebral fracture incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years
exposure
D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years.
limitations
Generally healthy midlife/older adults not selected for deficiency. Does not test treatment of established deficiency rickets or osteomalacia.
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
Extra D3 did not reduce this fracture endpoint in the population studied.
primary_references
[leboff2022] Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35939577/ DOI: 10.1056/nejmoa2202106
tissue_or_cell_type
Clinical skeletal outcomes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1509–1520
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years · source_derived_draft · unverified_draft
### vd-vital-fracture-nonvertebral D3 assignment did not significantly reduce nonvertebral fractures (HR0.97; 95% CI0.87–1.07; P=0.50). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra D3 did not reduce this fracture endpoint in the population studied. organism: Homo sapiens tissue_or_cell_type: Clinical skeletal outcomes experimental_model: VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years limitations: Generally healthy midlife/older adults not selected for deficiency. Does not test treatment of established deficiency rickets or osteomalacia. exposure: D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years. cross_nutrient: false [leboff2022] Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35939577/ DOI: 10.1056/nejmoa2202106
Complete structured claim and evidence
D3 assignment did not significantly reduce hip fractures (HR1.01; 95% CI0.70–1.47; P=0.96).
Cholecalciferol → Hip fracture incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years
exposure
D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years.
limitations
Generally healthy midlife/older adults not selected for deficiency. Does not test treatment of established deficiency rickets or osteomalacia.
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
Extra D3 did not reduce this fracture endpoint in the population studied.
primary_references
[leboff2022] Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35939577/ DOI: 10.1056/nejmoa2202106
tissue_or_cell_type
Clinical skeletal outcomes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1522–1533
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years · source_derived_draft · unverified_draft
### vd-vital-fracture-hip D3 assignment did not significantly reduce hip fractures (HR1.01; 95% CI0.70–1.47; P=0.96). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra D3 did not reduce this fracture endpoint in the population studied. organism: Homo sapiens tissue_or_cell_type: Clinical skeletal outcomes experimental_model: VITAL ancillary fracture trial; 25, 871 adults; median 5.3 years limitations: Generally healthy midlife/older adults not selected for deficiency. Does not test treatment of established deficiency rickets or osteomalacia. exposure: D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years. cross_nutrient: false [leboff2022] Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35939577/ DOI: 10.1056/nejmoa2202106
Complete structured claim and evidence
D3 versus placebo estimate: HR0.96; 95% CI0.88–1.06; P=0.47.
Cholecalciferol → Incidence of invasive cancer source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
VITAL primary prevention RCT; 25, 871 adults; median 5.3 years
exposure
D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years.
limitations
Primary prevention population; secondary mortality finding is not the primary cancer-incidence endpoint. This record does not summarize later pooled analyses.
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 supplement did not significantly lower invasive cancer incidence.
primary_references
[manson2019] Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. (2019). https://pubmed.ncbi.nlm.nih.gov/30415629/ DOI: 10.1056/nejmoa1809944
tissue_or_cell_type
Human clinical events
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1535–1546
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VITAL primary prevention RCT; 25, 871 adults; median 5.3 years · source_derived_draft · unverified_draft
### vd-vital-cancer D3 versus placebo estimate: HR0.96; 95% CI0.88–1.06; P=0.47. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The supplement did not significantly lower invasive cancer incidence. organism: Homo sapiens tissue_or_cell_type: Human clinical events experimental_model: VITAL primary prevention RCT; 25, 871 adults; median 5.3 years limitations: Primary prevention population; secondary mortality finding is not the primary cancer-incidence endpoint. This record does not summarize later pooled analyses. exposure: D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years. cross_nutrient: false [manson2019] Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. (2019). https://pubmed.ncbi.nlm.nih.gov/30415629/ DOI: 10.1056/nejmoa1809944
Complete structured claim and evidence
D3 versus placebo estimate: HR0.97; 95% CI0.85–1.12; P=0.69.
Cholecalciferol → Major cardiovascular event incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
VITAL primary prevention RCT; 25, 871 adults; median 5.3 years
exposure
D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years.
limitations
Primary prevention population; secondary mortality finding is not the primary cancer-incidence endpoint. This record does not summarize later pooled analyses.
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 supplement did not significantly lower the main cardiovascular outcome.
primary_references
[manson2019] Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. (2019). https://pubmed.ncbi.nlm.nih.gov/30415629/ DOI: 10.1056/nejmoa1809944
tissue_or_cell_type
Human clinical events
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1548–1559
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VITAL primary prevention RCT; 25, 871 adults; median 5.3 years · source_derived_draft · unverified_draft
### vd-vital-cvd D3 versus placebo estimate: HR0.97; 95% CI0.85–1.12; P=0.69. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The supplement did not significantly lower the main cardiovascular outcome. organism: Homo sapiens tissue_or_cell_type: Human clinical events experimental_model: VITAL primary prevention RCT; 25, 871 adults; median 5.3 years limitations: Primary prevention population; secondary mortality finding is not the primary cancer-incidence endpoint. This record does not summarize later pooled analyses. exposure: D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years. cross_nutrient: false [manson2019] Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. (2019). https://pubmed.ncbi.nlm.nih.gov/30415629/ DOI: 10.1056/nejmoa1809944
Complete structured claim and evidence
D3 versus placebo estimate: HR0.83; 95% CI0.67–1.02.
Cholecalciferol → Cancer mortality source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
VITAL primary prevention RCT; 25, 871 adults; median 5.3 years
exposure
D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years.
limitations
Primary prevention population; secondary mortality finding is not the primary cancer-incidence endpoint. This record does not summarize later pooled analyses.
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 secondary cancer-mortality estimate suggested possible benefit but included no effect.
primary_references
[manson2019] Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. (2019). https://pubmed.ncbi.nlm.nih.gov/30415629/ DOI: 10.1056/nejmoa1809944
tissue_or_cell_type
Human clinical events
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1561–1572
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · VITAL primary prevention RCT; 25, 871 adults; median 5.3 years · source_derived_draft · unverified_draft
### vd-vital-cancer-death D3 versus placebo estimate: HR0.83; 95% CI0.67–1.02. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The secondary cancer-mortality estimate suggested possible benefit but included no effect. organism: Homo sapiens tissue_or_cell_type: Human clinical events experimental_model: VITAL primary prevention RCT; 25, 871 adults; median 5.3 years limitations: Primary prevention population; secondary mortality finding is not the primary cancer-incidence endpoint. This record does not summarize later pooled analyses. exposure: D3 2000 IU/day versus placebo; randomized factorial omega 3 allocation; median 5.3 years. cross_nutrient: false [manson2019] Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. (2019). https://pubmed.ncbi.nlm.nih.gov/30415629/ DOI: 10.1056/nejmoa1809944
Complete structured claim and evidence
Fall incidence was higher with annual D3 (rate ratio 1.15; 95% CI1.02–1.30; P=0.03).
Cholecalciferol → Incidence of falls source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
2256 community-dwelling women aged≥ 70; annual-bolus randomized placebo-controlled trial
exposure
500, 000 IU oral D3 each autumn/winter for 3–5 years.
limitations
Annual very large bolus in older women; does not demonstrate that all D3 regimens raise risk.
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 annual megadose increased falls rather than preventing them.
primary_references
[sanders2010] Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. (2010). https://pubmed.ncbi.nlm.nih.gov/20460620/ DOI: 10.1001/jama.2010.594
tissue_or_cell_type
Clinical falls
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1574–1585
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 2256 community-dwelling women aged≥ 70; annual-bolus randomized placebo-controlled trial · source_derived_draft · unverified_draft
### vd-sanders-falls Fall incidence was higher with annual D3 (rate ratio 1.15; 95% CI1.02–1.30; P=0.03). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The annual megadose increased falls rather than preventing them. organism: Homo sapiens tissue_or_cell_type: Clinical falls experimental_model: 2256 community-dwelling women aged≥ 70; annual-bolus randomized placebo-controlled trial limitations: Annual very large bolus in older women; does not demonstrate that all D3 regimens raise risk. exposure: 500, 000 IU oral D3 each autumn/winter for 3–5 years. cross_nutrient: false [sanders2010] Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. (2010). https://pubmed.ncbi.nlm.nih.gov/20460620/ DOI: 10.1001/jama.2010.594
Complete structured claim and evidence
There were 171 versus 135 fractures; fracture rate ratio 1.26 (95% CI1.00–1.59; P=0.047) for annual D3 versus placebo.
Cholecalciferol → Total fracture incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
2256 community-dwelling women aged≥ 70; annual-bolus randomized placebo-controlled trial
exposure
500, 000 IU oral D3 each autumn/winter for 3–5 years.
limitations
Annual very large bolus in older women; does not demonstrate that all D3 regimens raise risk.
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
Fractures were also more frequent under that specific regimen.
primary_references
[sanders2010] Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. (2010). https://pubmed.ncbi.nlm.nih.gov/20460620/ DOI: 10.1001/jama.2010.594
tissue_or_cell_type
Clinical skeletal outcomes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1587–1598
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 2256 community-dwelling women aged≥ 70; annual-bolus randomized placebo-controlled trial · source_derived_draft · unverified_draft
### vd-sanders-fractures There were 171 versus 135 fractures; fracture rate ratio 1.26 (95% CI1.00–1.59; P=0.047) for annual D3 versus placebo. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Fractures were also more frequent under that specific regimen. organism: Homo sapiens tissue_or_cell_type: Clinical skeletal outcomes experimental_model: 2256 community-dwelling women aged≥ 70; annual-bolus randomized placebo-controlled trial limitations: Annual very large bolus in older women; does not demonstrate that all D3 regimens raise risk. exposure: 500, 000 IU oral D3 each autumn/winter for 3–5 years. cross_nutrient: false [sanders2010] Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. (2010). https://pubmed.ncbi.nlm.nih.gov/20460620/ DOI: 10.1001/jama.2010.594
Complete structured claim and evidence
Relative to 400 IU/day, final radial volumetric BMD was lower by 3.9 mgHA/cm³ with 4000 IU (95% CI−6.5 to−1.3) and 7.5 mgHA/cm³ with 10000 IU (CI−10.1 to−5.0).
Cholecalciferol → Radial volumetric bone mineral density source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed
exposure
D3 400, 4000 or 10000 IU/day for 3 years; calcium added for dietary intake<1200 mg/day.
limitations
Adults without osteoporosis, baseline 25(OH)D30–125 nmol/L; surrogate outcomes, not a deficiency-repletion trial or fracture endpoint.
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
More vitamin D did not produce denser bone at the forearm in this trial.
primary_references
[burt2019] Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31454046/ DOI: 10.1001/jama.2019.11889
tissue_or_cell_type
Radius
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1600–1611
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed · source_derived_draft · unverified_draft
### vd-burt-radius Relative to 400 IU/day, final radial volumetric BMD was lower by 3.9 mgHA/cm³ with 4000 IU (95% CI−6.5 to−1.3) and 7.5 mgHA/cm³ with 10000 IU (CI−10.1 to−5.0). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: More vitamin D did not produce denser bone at the forearm in this trial. organism: Homo sapiens tissue_or_cell_type: Radius experimental_model: 311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed limitations: Adults without osteoporosis, baseline 25(OH)D30–125 nmol/L; surrogate outcomes, not a deficiency-repletion trial or fracture endpoint. exposure: D3 400, 4000 or 10000 IU/day for 3 years; calcium added for dietary intake<1200 mg/day. cross_nutrient: true [burt2019] Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31454046/ DOI: 10.1001/jama.2019.11889
Complete structured claim and evidence
Tibial BMD differences versus 400 IU/day were−1.8 mgHA/cm³ with 4000 IU (95% CI−3.7 to 0.1; not significant) and−4.1 mgHA/cm³ with 10000 IU (CI−6.0 to−2.2).
Cholecalciferol → Tibial volumetric bone mineral density source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed
exposure
D3 400, 4000 or 10000 IU/day for 3 years; calcium added for dietary intake<1200 mg/day.
limitations
Adults without osteoporosis, baseline 25(OH)D30–125 nmol/L; surrogate outcomes, not a deficiency-repletion trial or fracture endpoint.
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 tibial result depended on dose; the lower comparison included no difference.
primary_references
[burt2019] Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31454046/ DOI: 10.1001/jama.2019.11889
tissue_or_cell_type
Tibia
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1613–1624
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed · source_derived_draft · unverified_draft
### vd-burt-tibia Tibial BMD differences versus 400 IU/day were−1.8 mgHA/cm³ with 4000 IU (95% CI−3.7 to 0.1; not significant) and−4.1 mgHA/cm³ with 10000 IU (CI−6.0 to−2.2). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tibial result depended on dose; the lower comparison included no difference. organism: Homo sapiens tissue_or_cell_type: Tibia experimental_model: 311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed limitations: Adults without osteoporosis, baseline 25(OH)D30–125 nmol/L; surrogate outcomes, not a deficiency-repletion trial or fracture endpoint. exposure: D3 400, 4000 or 10000 IU/day for 3 years; calcium added for dietary intake<1200 mg/day. cross_nutrient: true [burt2019] Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31454046/ DOI: 10.1001/jama.2019.11889
Complete structured claim and evidence
Estimated failure-load changes did not significantly differ across groups at the radius(P=0.06) or tibia(P=0.12).
Cholecalciferol → Estimated bone failure load source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed
exposure
D3 400, 4000 or 10000 IU/day for 3 years; calcium added for dietary intake<1200 mg/day.
limitations
Adults without osteoporosis, baseline 25(OH)D30–125 nmol/L; surrogate outcomes, not a deficiency-repletion trial or fracture endpoint.
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 estimated strength result was separate from the bone-density findings.
primary_references
[burt2019] Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31454046/ DOI: 10.1001/jama.2019.11889
tissue_or_cell_type
Radius and tibia
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1626–1637
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed · source_derived_draft · unverified_draft
### vd-burt-strength Estimated failure-load changes did not significantly differ across groups at the radius(P=0.06) or tibia(P=0.12). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The estimated strength result was separate from the bone-density findings. organism: Homo sapiens tissue_or_cell_type: Radius and tibia experimental_model: 311 healthy adults 55–70 randomized to daily 400, 4000, 10000 IU D3 for 3 years; 287 completed limitations: Adults without osteoporosis, baseline 25(OH)D30–125 nmol/L; surrogate outcomes, not a deficiency-repletion trial or fracture endpoint. exposure: D3 400, 4000 or 10000 IU/day for 3 years; calcium added for dietary intake<1200 mg/day. cross_nutrient: false [burt2019] Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31454046/ DOI: 10.1001/jama.2019.11889
Complete structured claim and evidence
Diabetes developed in 293 D3 recipients and 323 placebo recipients; HR0.88 (95% CI0.75–1.04; P=0.12).
Cholecalciferol → Incidence of type 2 diabetes source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
D2 d randomized trial; 2423 adults with prediabetes; median 2.5 years
exposure
D3 4000 IU/day versus placebo; participants met≥ 2 of 3 prediabetes criteria.
limitations
Individual-trial estimate is compatible with modest benefit and no effect; not a claim that pooled prevention evidence is negative.
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
This individual D3 trial did not meet statistical significance for preventing diabetes.
primary_references
[pittas2019] Vitamin D Supplementation and Prevention of Type 2 Diabetes. (2019). https://pubmed.ncbi.nlm.nih.gov/31173679/ DOI: 10.1056/nejmoa1900906
tissue_or_cell_type
Clinical glucose outcomes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1639–1650
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · D2 d randomized trial; 2423 adults with prediabetes; median 2.5 years · source_derived_draft · unverified_draft
### vd-d2d-diabetes Diabetes developed in 293 D3 recipients and 323 placebo recipients; HR0.88 (95% CI0.75–1.04; P=0.12). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This individual D3 trial did not meet statistical significance for preventing diabetes. organism: Homo sapiens tissue_or_cell_type: Clinical glucose outcomes experimental_model: D2 d randomized trial; 2423 adults with prediabetes; median 2.5 years limitations: Individual-trial estimate is compatible with modest benefit and no effect; not a claim that pooled prevention evidence is negative. exposure: D3 4000 IU/day versus placebo; participants met≥ 2 of 3 prediabetes criteria. cross_nutrient: false [pittas2019] Vitamin D Supplementation and Prevention of Type 2 Diabetes. (2019). https://pubmed.ncbi.nlm.nih.gov/31173679/ DOI: 10.1056/nejmoa1900906
Complete structured claim and evidence
At least one confirmed respiratory infection occurred in 4.6% of no-offer, 5.7% of lower-dose-offer and 5.0% of higher-dose-offer participants; ORs 1.26 (95% CI0.96–1.66) and 1.09 (0.82–1.46).
Vitamin D testing and conditional supplementation offer → Acute respiratory tract infection incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
CORONAVIT pragmatic randomized open-label offer-to-test-and-treat trial; 6200UKadults≥ 16
exposure
Offer 800 or 3200 IU/day vitamin D for 6 months if 25(OH)D<75 nmol/L versus no offer; 2674 of 3100 offered received supplements.
limitations
Open-label strategy trial; receipt, outside supplementation and pandemic context limit inference about specific cellular mechanisms or all dosing regimens.
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
Offering this test-and-supplement strategy did not reduce confirmed respiratory infections.
primary_references
[jolliffe2022] Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). (2022). https://pubmed.ncbi.nlm.nih.gov/36215226/ DOI: 10.1136/bmj-2022-071230
tissue_or_cell_type
Clinical respiratory outcomes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1652–1663
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CORONAVIT pragmatic randomized open-label offer-to-test-and-treat trial; 6200UKadults≥ 16 · source_derived_draft · unverified_draft
### vd-coronavit-ari At least one confirmed respiratory infection occurred in 4.6% of no-offer, 5.7% of lower-dose-offer and 5.0% of higher-dose-offer participants; ORs 1.26 (95% CI0.96–1.66) and 1.09 (0.82–1.46). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Offering this test-and-supplement strategy did not reduce confirmed respiratory infections. organism: Homo sapiens tissue_or_cell_type: Clinical respiratory outcomes experimental_model: CORONAVIT pragmatic randomized open-label offer-to-test-and-treat trial; 6200UKadults≥ 16 limitations: Open-label strategy trial; receipt, outside supplementation and pandemic context limit inference about specific cellular mechanisms or all dosing regimens. exposure: Offer 800 or 3200 IU/day vitamin D for 6 months if 25(OH)D<75 nmol/L versus no offer; 2674 of 3100 offered received supplements. cross_nutrient: false [jolliffe2022] Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). (2022). https://pubmed.ncbi.nlm.nih.gov/36215226/ DOI: 10.1136/bmj-2022-071230
Complete structured claim and evidence
COVID-19 occurred in 2.6% of no-offer, 3.6% of lower-dose-offer and 3.0% of higher-dose-offer participants; ORs 1.39 (95% CI0.98–1.97) and 1.13 (0.78–1.63).
Vitamin D testing and conditional supplementation offer → Laboratory-confirmed COVID-19 incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
CORONAVIT pragmatic randomized open-label offer-to-test-and-treat trial; 6200UKadults≥ 16
exposure
Offer 800 or 3200 IU/day vitamin D for 6 months if 25(OH)D<75 nmol/L versus no offer; 2674 of 3100 offered received supplements.
limitations
Open-label strategy trial; receipt, outside supplementation and pandemic context limit inference about specific cellular mechanisms or all dosing regimens.
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 COVID-19 endpoint likewise showed no statistically clear protection.
primary_references
[jolliffe2022] Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). (2022). https://pubmed.ncbi.nlm.nih.gov/36215226/ DOI: 10.1136/bmj-2022-071230
tissue_or_cell_type
Clinical respiratory outcomes
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1665–1676
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CORONAVIT pragmatic randomized open-label offer-to-test-and-treat trial; 6200UKadults≥ 16 · source_derived_draft · unverified_draft
### vd-coronavit-covid COVID-19 occurred in 2.6% of no-offer, 3.6% of lower-dose-offer and 3.0% of higher-dose-offer participants; ORs 1.39 (95% CI0.98–1.97) and 1.13 (0.78–1.63). Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The COVID-19 endpoint likewise showed no statistically clear protection. organism: Homo sapiens tissue_or_cell_type: Clinical respiratory outcomes experimental_model: CORONAVIT pragmatic randomized open-label offer-to-test-and-treat trial; 6200UKadults≥ 16 limitations: Open-label strategy trial; receipt, outside supplementation and pandemic context limit inference about specific cellular mechanisms or all dosing regimens. exposure: Offer 800 or 3200 IU/day vitamin D for 6 months if 25(OH)D<75 nmol/L versus no offer; 2674 of 3100 offered received supplements. cross_nutrient: false [jolliffe2022] Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). (2022). https://pubmed.ncbi.nlm.nih.gov/36215226/ DOI: 10.1136/bmj-2022-071230
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

A broken kidney uptake receptor wastes vitamin D precursor.

Condition: machinery_impairment · Targeted disruption of mouse Lrp2.

Normal role: Megalin reclaims filtered DBP-bound calcifediol.

Recorded consequence: Megalin-null mice failed to retrieve filtered calcifediol and lost the vitamin D precursor in urine.

Scope: Targeted megalin knockout versus controls

Cubilin defects can cause loss of vitamin D precursor through urine.

Condition: machinery_impairment · Inherited cubilin dysfunction.

Normal role: Cubilin captures carrier complexes for endocytosis and also participates in intestinal intrinsic-factor/B12 uptake.

Recorded consequence: Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway.

Scope: Human inherited cubilin dysfunction; supporting receptor experiments

The blood carrier helps vitamin D precursor stay in circulation.

Condition: machinery_impairment · Gc gene deletion superimposed on the same D3-depleted tracer protocol.

Normal role: DBP binds circulating calcifediol and slows its clearance.

Recorded consequence: Deletion of mouse vitamin D-binding protein accelerated the loss of injected radiolabeled calcifediol from plasma.

Scope: Radiotracer kinetics in Gc-null and wild-type mice

A CYP2R1 mutation can break the first D3 activation step.

Condition: machinery_impairment · Homozygous CYP2R1 L99P substitution.

Normal role: CYP2R1 performs C25 hydroxylation of D3 and D2.

Recorded consequence: The patient-derived human CYP2R1 Leu99Pro variant lost detectable D3 25-hydroxylase activity in the expression assays.

Scope: Patient-derived allele expressed in cells

An inherited enzyme defect can block the final activation step.

Condition: machinery_impairment · Inherited homozygous CYP27B1 missense variants.

Normal role: CYP27B1 generates calcitriol from calcifediol.

Recorded consequence: All four homozygous CYP27B1 missense variants identified in four unrelated rickets patients abolished measured 1alpha-hydroxylase activity when expressed in COS-1 cells.

Scope: Patient sequencing and heterologous functional assays

Some inherited defects prevent normal removal of active vitamin D.

Condition: machinery_impairment · Patient-derived CYP24A1 loss-of-function variants.

Normal role: CYP24A1 normally limits active-vitamin-D persistence by catalysis.

Recorded consequence: Patient-derived CYP24A1 variants severely impaired calcitriol catabolism in expression assays; L409S retained 5.3% of wild-type activity in the detailed results.

Scope: Patient variants expressed in V79-4 cells

Boron changes some outcomes during animal vitamin D restriction

Condition: nutrient_deficiency · Experimental vitamin D deprivation or inadequate vitamin D3 feeding in animals.

Normal role: Vitamin D supports calcium and phosphate handling and skeletal development.

Recorded consequence: Boron altered some mineral-balance, metabolic and growth-plate endpoints.

Scope: Rat and chick studies retain separate exposures in each claim. These are not trials of treating human vitamin D deficiency.

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

Condition: machinery_impairment · Inherited CYP24A1 dysfunction in the reported prophylaxis settings.

Normal role: Vitamin D catabolism restrains hormonal stimulation of calcium availability.

Recorded consequence: Recessive CYP24A1 variants were identified in infants with hypercalcemia, including a second group whose illness followed high-dose vitamin D prophylaxis.

Scope: Human candidate-gene study with supporting enzyme assays

Vitamin D deprivation lowers the inducible calcium-transport state

Condition: nutrient_deficiency · Experimental dietary vitamin D deprivation in wild-type mice

Normal role: Vitamin D metabolites support intestinal calcium transport.

Recorded consequence: Calcitriol replacement increased duodenal transport

Scope: Wild-type arm of dietary-deficiency mouse study

Missing NaPi-IIb prevents the measured phosphate response

Condition: machinery_impairment · Intestinal Slc34a2 deletion

Normal role: NaPi-IIb couples sodium entry to active phosphate transport.

Recorded consequence: Loss of calcitriol-stimulated active phosphate-transport increment

Scope: Mouse intestine

A phosphate response persists without VDR

Condition: machinery_impairment · Vdr deletion, followed by low-phosphate diet

Normal role: Vitamin D signaling and additional dietary signals both regulate phosphate transport.

Recorded consequence: NaPi-IIb protein still increased despite lower baseline transport

Scope: Mouse intestine

Mineral delivery protects the VDR-null skeleton

Condition: machinery_impairment · Vdr ablation with impaired mineral homeostasis

Normal role: Vitamin D signaling supports mineral availability for skeletal mineralization.

Recorded consequence: Combined dietary mineral rescue prevented rachitic and osteomalacic changes

Scope: VDR-ablated mice

Local substrate can limit the antimicrobial response

Condition: nutrient_deficiency · TLR stimulation under the tested diluted-serum culture conditions.

Normal role: Macrophages can convert 25(OH)D3 into local hormone to support VDR-regulated CAMP.

Recorded consequence: Adding 25(OH)D3 restored/enhanced the local transcript response.

Scope: Human monocyte culture

Low-substrate serum impaired an IFN-gamma-triggered cell-defense pathway

Condition: nutrient_deficiency · IFN-gamma stimulation in low-vitamin-D serum culture.

Normal role: Local conversion and VDR signaling can support antimicrobial responses to IFN-gamma .

Recorded consequence: Adding 25(OH)D3 restored the tested cellular response.

Scope: Human macrophage culture

Receptor structure and hair cycling

Condition: machinery_impairment · VDR-null mice carrying a keratinocyte-targeted mutant VDR transgene.

Normal role: VDR has ligand-independent functions that help maintain hair cycling.

Recorded consequence: Restored normal hair cycling in the studied model.

Scope: Mouse keratinocytes/hair follicles

Receptor structure and hair cycling

Condition: machinery_impairment · VDR-null mice carrying a keratinocyte-targeted mutant VDR transgene.

Normal role: VDR has ligand-independent functions that help maintain hair cycling.

Recorded consequence: Only partly restored hair cycling in the studied model.

Scope: Mouse keratinocytes/hair follicles

Carrier concentration and metabolite persistence

Condition: biomarker_context · Measured variation in plasma DBP concentration; no randomized assignment of DBP.

Normal role: DBP binds circulating vitamin D metabolites and changes their transport and retention.

Recorded consequence: Higher plasma DBP was associated with longer tracer half-life.

Scope: Healthy Gambian and UK men in a tracer study

D2 and D3 regimens during treatment of low vitamin D status

Condition: biomarker_context · Trial enrollment with serum 25(OH)D<20 ng/mL; assigned D regimen plus calcium.

Normal role: Vitamin D metabolites support receptor-dependent mineral and cellular responses.

Recorded consequence: Total 25(OH)D rose and PTH responses were comparable between groups.

Scope: Infants/toddlers, six-week biochemical trial

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

How much clinically important vitamin D malabsorption results from competition with ordinary vitamin E intakes?Caco-2 competition does not determine ordinary dietary effects, and study concentrations are absent from the retrieved abstract.
Do low iron, riboflavin or niacin intake limit these vitamin D redox reactions in a particular human population?Heme, flavins and NADPH participate biochemically, but the cited structure/reconstitution studies do not test nutrient-depletion or repletion outcomes.
What is the whole-body quantitative contribution of each D2 catabolic product and alternative hydroxylase?Cell-free substrate selectivity cannot resolve tissue expression, carrier binding, clearance or regimen effects.
Does high-substrate inhibition of CYP27B1 occur at relevant intracellular membrane concentrations in vivo?The inhibition depends on substrate and membrane composition; aqueous or serum 25(OH)D is not the measured membrane-phase concentration.
How much of D2/D3 comparative clinical benefit is explained by circulating 25(OH)D differences?Most direct form comparisons measured metabolites, not fractures or disease outcomes; a marker difference does not answer the clinical question.
Which mechanisms cause reciprocal reductions of the other 25(OH)D fraction?Reciprocal changes and metabolite ratios constrain explanations, but do not isolate enzyme flux from binding/distribution/clearance.
What is the appropriate response for an individual with deficient intake, malabsorption, altered binding protein or kidney disease?These are different biological contexts. The selected trials do not establish an individualized regimen or a universal serum cutoff.
What do newer pooled trials conclude about diabetes prevention and other clinical endpoints?This collection preserves selected original experiments and does not substitute for a current systematic review or guideline.
What quantitatively explains residual calcium transport without TRPV6 and calbindin across different diets, ages and human tissues?Knockout models show contribution and compensation; they do not establish one universal transcellular chain. Different mouse results are context, not automatically contradictory.
How much do acute calcitriol-dependent intestinal phosphate changes contribute to long-term phosphate balance in people?Mouse segment-specific flux assays do not establish a human chronic dietary response or a fixed contribution of paracellular transport.
Which molecular steps mediate magnesium-dependent vitamin D responses in humans?The human depletion and repletion studies do not isolate a direct Mg cofactor role for each CYP. The rat conversion study retained activation, and the randomized trial measured circulating metabolites rather than enzyme activities.
Does pairing a particular vitamin K supplement with vitamin D improve clinical outcomes in a given population?Human-gene induction and a vitamin K-dependent enzyme assay establish distinct biochemical steps; they do not establish obligatory D-plus-K supplementation, a specific K2 requirement, or fracture benefit.
How do direct skeletal VDR actions and intestinal mineral supply interact across disease states and treatment regimens?Combined dietary rescue and the calcitriol/pyrophosphate culture pathway concern different models and cannot be collapsed into either universally anabolic or universally harmful vitamin D.
Do the exploratory D2/D3 whole-blood gene-set trajectories cause differences in infection outcomes?Small selected transcriptomic subset; direct contrasts largely null and no clinical infection endpoint. Requires adequately powered form comparison with prespecified outcomes.
Which local-cell vitamin D effects are reproduced by ordinary oral D2 versus D3 exposure?Calcitriol or 25(OH)D3 culture exposures do not directly establish equivalent tissue delivery from the parent supplements.
Does maintaining ligand-independent VDR function explain any common human hair-loss phenotype?Mutant-receptor mouse rescue is not a supplement trial in common hair loss.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Vitamin D2 and D3

The mechanisms

Recombinant human CYP27B1 converts calcifediol to calcitriol by 1-alpha-hydroxylation in reconstituted enzyme systems.

Human CYP24A1 hydroxylates calcitriol to 1-alpha,24,25-trihydroxyvitamin D3 in the first C24-oxidation step.

Calcitriol induces human TRPV6 transcription through VDR/RXR-associated regulatory elements in intestinal cell models.

Claudin-2 manipulation changes calcium permeability across Caco-2 epithelial monolayers.

Claudin-12 knockdown/overexpression alters calcium permeability in Caco-2 monolayers.

Intestinal Atp2b1 deletion prevented the active-calcium-transport increase elicited by calcitriol in control mice.

Trpv6 deletion reduced intestinal calcium absorption by about 60% in the Bianco mouse model.

Significant active duodenal calcium transport persists in Trpv6/calbindin-D9k double-null mice under the tested stimulation conditions.

Thyroparathyroidectomy nearly abolished calcitriol production in low-calcium-fed rats; parathyroid extract restored it.

Calcitriol administration suppresses parathyroid PTH transcription in rats without a measured rise in serum calcium.

Recombinant FGF23 lowers renal CYP27B1 mRNA before the fall in serum phosphate.

Recombinant FGF23 raises renal CYP24A1 mRNA as circulating calcitriol declines.

Alpha-Klotho cooperates with FGFR1(IIIc) to confer high-affinity binding and signaling by FGF23.

VDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH.

A mineral/lactose rescue diet normalizes ionized calcium in VDR-ablated mice.

Mice with intestinal Vdr deletion maintained serum calcium despite calcium malabsorption and impaired skeletal mineral storage.

The rise in circulating calcitriol during a six-hour human PTH(1-34) infusion was smaller after dietary Mg depletion.

Sixteen of 23 hypocalcemic magnesium-deficient patients had low circulating calcitriol.

Magnesium treatment normalized mean serum calcium, while calcitriol rose into or above normal in only five of the 23 patients.

Magnesium depletion did not impair measured calcifediol-to-calcitriol conversion in these rats; isolated renal activity persisted without added Mg.

Magnesium assignment altered plasma 25(OH)D3 differently by baseline vitamin D: an increase near 30 ng/mL and a decrease at higher baseline concentrations.

The trial did not detect a treatment-by-baseline-25(OH)D interaction for plasma calcitriol.

RXRA formed a VDR complex and enhanced binding to the osteopontin vitamin D response element.

Narrow-band ultraviolet irradiation converted cutaneous 7-dehydrocholesterol to previtamin D3; 295-300 nm was the most effective tested range.

Skin-generated previtamin D3 underwent temperature-dependent isomerization to cholecalciferol, taking at least three days to complete under the reported conditions.

Vitamin D-binding protein preferentially translocated thermally formed cholecalciferol from the skin into circulation in the reported photochemistry experiments.

Ultraviolet irradiation of white button mushrooms generated previtamin D2 from ergosterol, identified by chromatographic analysis.

Previtamin D2 generated in irradiated mushrooms converted thermally to ergocalciferol; mushroom conversion was faster than in methanol in the compared preparations.

Expression of SR-BI in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake.

Expression of CD36 in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake.

Expression of NPC1L1 in HEK cells increased cholecalciferol uptake, and its corresponding inhibitor reduced this uptake.

Co-incubation with tocopherol significantly impaired cholecalciferol uptake in Caco-2 cells.

Megalin-mediated endocytosis retrieved filtered vitamin D-binding-protein/calcifediol complexes in proximal tubules.

Megalin-null mice failed to retrieve filtered calcifediol and lost the vitamin D precursor in urine.

Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway.

Deletion of mouse vitamin D-binding protein accelerated the loss of injected radiolabeled calcifediol from plasma.

Recombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol.

Recombinant human CYP2R1 hydroxylated ergocalciferol at C25 to form 25-hydroxyvitamin D2.

Human CYP27A1 catalyzed D3 25-hydroxylation in the recombinant comparison, with lower catalytic efficiency than CYP2R1.

Human CYP27A1 hydroxylated ergocalciferol at C24 in the reported D2 substrate analysis.

Human CYP27A1 hydroxylated ergocalciferol at C27 in the reported D2 substrate analysis.

The patient-derived human CYP2R1 Leu99Pro variant lost detectable D3 25-hydroxylase activity in the expression assays.

The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group.

Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.

Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR.

Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR.

Human CYP27B1 1alpha-hydroxylated 25-hydroxyvitamin D2 in phospholipid vesicles; low-substrate catalytic efficiency was similar to that measured for calcifediol.

Human adrenodoxin supported CYP27B1 activity in reconstituted vesicles; varying adrenodoxin changed apparent kinetic parameters for calcifediol hydroxylation.

The active human CYP27B1 reconstitution supplied human adrenodoxin reductase and NADPH upstream of human adrenodoxin.

All four homozygous CYP27B1 missense variants identified in four unrelated rickets patients abolished measured 1alpha-hydroxylase activity when expressed in COS-1 cells.

Wild-type human CYP24A1 expressed in V79-4 cells metabolized calcitriol through C24-pathway intermediates to a water-soluble fraction assigned to calcitroic acid.

Human CYP24A1 initiated 25-hydroxyvitamin D2 oxidation by hydroxylation at C24R in the vesicle-reconstituted enzyme system.

Human CYP24A1 initiated active 1alpha,25-dihydroxyvitamin D2 oxidation through C24R hydroxylation.

Human CYP24A1 had similar initial hydroxylation catalytic efficiencies for 25-hydroxyvitamin D2 and calcifediol in the matched vesicle assay.

Human CYP24A1 initial catalytic efficiency for calcitriol was almost twice that for the active D2 hormone in the matched vesicle experiment.

Purified rat CYP24A1 produced a C24R-hydroxylated metabolite from active D2 but no detectable calcitroic acid under conditions that generated calcitroic acid from calcitriol.

Patient-derived CYP24A1 variants severely impaired calcitriol catabolism in expression assays; L409S retained 5.3% of wild-type activity in the detailed results.

Recessive CYP24A1 variants were identified in infants with hypercalcemia, including a second group whose illness followed high-dose vitamin D prophylaxis.

Calcitriol increased Claudin-2 expression in human Caco-2 intestinal epithelial cells.

Calcitriol increased Claudin-12 expression in human Caco-2 intestinal epithelial cells.

Calcitriol administration increased active duodenal calcium transport in vitamin-D-deficient wild-type mice in the Benn study.

Two daily calcitriol injections increased active phosphate transport in wild-type mouse jejunum.

The two-day calcitriol regimen did not detectably increase paracellular phosphate flux in the mouse intestine.

Intestine-specific Slc34a2 deletion eliminated the phosphate-transport increase induced by the tested calcitriol regimen.

A low-phosphate diet increased intestinal NaPi-IIb protein expression even in Vdr-null mice.

Calcitriol administration produced about a fourfold increase in bone Fgf23 transcripts in the Liu mouse study.

Recombinant FGF23 reduced renal NaPi-IIa mRNA and protein abundance in the acute rodent injection study.

The combined mineral/lactose rescue diet prevented rickets and osteomalacia in VDR-ablated mice.

Diet-induced hypophosphatemic mice had impaired late hypertrophic-chondrocyte apoptosis and rachitic growth-plate expansion despite hypercalcemia and suppressed PTH.

Phosphate exposure activated the caspase-9-dependent mitochondrial apoptotic pathway in cultured primary mouse hypertrophic chondrocytes.

Calcitriol treatment increased extracellular pyrophosphate in differentiated Vdr-intact mouse osteoblast cultures.

Added TNAP restored mineralization in calcitriol-treated differentiated mouse osteoblast cultures while lowering extracellular pyrophosphate.

Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream.

Calcitriol increased human osteocalcin mRNA about 1.8-fold in calvaria of mice carrying the human osteocalcin genomic transgene.

In primary calvarial osteoblast cultures from the same transgenic mice, calcitriol inhibited endogenous mouse osteocalcin accumulation while increasing human osteocalcin production.

A concentrated vitamin K-dependent carboxylase preparation converted glutamate residues of decarboxylated bovine osteocalcin into gamma-carboxyglutamate in vitro.

Calcitriol induced CAMP expression in tested human myeloid, keratinocyte and colon cell models and bone-marrow-derived cells.

VDR bound a consensus vitamin D response element in the human CAMP promoter; this element mediated the observed induction.