Calcifediol / 25-hydroxyvitamin D3

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

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

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

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

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

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

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

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

experimental_model

In-vivo tracer and isolated mitochondrial assays.

limitations

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

nutrient_topic

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

organism

Rattus norvegicus

plain_language

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

primary_references

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

tissue_or_cell_type

Rat circulation and isolated kidney mitochondria

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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

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

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

cross_nutrient

Magnesium <-> vitamin D 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

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

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

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

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

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

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

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

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

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

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

cross_nutrient

false

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Human circulating measurements

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

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

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

cross_nutrient

false

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Human circulating measurements

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

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

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

cross_nutrient

false

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Human circulating measurements

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

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

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

cross_nutrient

false

experimental_model

Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay

exposure

TLR activation in cultured human monocytes/macrophages.

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Human monocytes/macrophages

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

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

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

cross_nutrient

false

experimental_model

Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay

exposure

Cultured human macrophages with intracellular M. tuberculosis.

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Human macrophages

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

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

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

cross_nutrient

false

experimental_model

Human monocyte/macrophage TLR stimulation and intracellular mycobacterial assay

exposure

TLR activation in cultured human monocytes/macrophages.

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

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

primary_references

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

tissue_or_cell_type

Human monocytes/macrophages

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

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

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

experimental_model

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

limitations

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

nutrient_topic

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

organism

Homo sapiens enzyme

plain_language

CYP27B1 activates the vitamin D precursor.

primary_references

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

research_relationship_category

biochemical_reaction

tissue_or_cell_type

Reconstituted membrane system

transport_or_reaction_direction

forward

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

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

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

availability_state

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Clcn5 knockout and uptake measurements

exposure

Clcn5 disruption

limitations

The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.

nutrient_topic

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

organism

Mouse

plain_language

The transporter defect connects chloride machinery to vitamin D handling.

primary_references

[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597

tissue_or_cell_type

Proximal renal tubule

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 692–703

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft

### chloride-clc5-vitd-loss The Clcn5-null model lost 25-hydroxyvitamin D3 in urine. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter defect connects chloride machinery to vitamin D handling. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597