Cholecalciferol

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

evidence_access

Primary abstract

experimental_model

25 women below 50 nmol/L 25(OH)D and 25 above 75 nmol/L; deficient group retested after repletion.

limitations

Mild deficiency, oral overload test and D3 intervention differ from the four-patient calcitriol experiment; not a scientific contradiction or evidence against treating vitamin D deficiency.

nutrient_topic

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

plain_language

Improving vitamin D status did not automatically improve strontium absorption.

primary_references

Vitamin D supplementation and strontium ranelate absorption in postmenopausal women with low bone mass. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24394724/ · DOI 10.1530/EJE-13-0899

Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 62–68

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 25 women below 50 nmol/L 25(OH)D and 25 above 75 nmol/L; deficient group retested after repletion. · source_derived_draft · unverified_draft

## strontium-vitamin-d3-null Improving vitamin D status did not automatically improve strontium absorption. Correcting vitamin D deficiency with vitamin D3 did not increase the measured strontium-ranelate absorption in the study of postmenopausal women with low bone mass. Model: 25 women below 50 nmol/L 25(OH)D and 25 above 75 nmol/L; deficient group retested after repletion. Limitations: Mild deficiency, oral overload test and D3 intervention differ from the four-patient calcitriol experiment; not a scientific contradiction or evidence against treating vitamin D deficiency. Evidence access: Primary abstract Vitamin D supplementation and strontium ranelate absorption in postmenopausal women with low bone mass. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24394724/ · DOI 10.1530/EJE-13-0899

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

evidence_access

Primary abstract

experimental_model

Randomized placebo-controlled SOTI trial; both groups received calcium and vitamin D.

limitations

Specific drug, population and co-treatment; no equivalent efficacy established for dietary strontium or strontium citrate. Trial mechanisms are not identified by the fracture endpoint.

nutrient_topic

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

plain_language

A clinical trial measured fewer fractures, separately from density scans.

primary_references

The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14749454/ · DOI 10.1056/NEJMoa022436

Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 422–428

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized placebo-controlled SOTI trial; both groups received calcium and vitamin D. · source_derived_draft · unverified_draft

## strontium-soti-fractures A clinical trial measured fewer fractures, separately from density scans. In 1,649 postmenopausal women with osteoporosis and a prior vertebral fracture, 2 g/day ranelate reduced new vertebral-fracture risk over three years: relative risk 0.59, 95% CI 0.48–0.73. Model: Randomized placebo-controlled SOTI trial; both groups received calcium and vitamin D. Limitations: Specific drug, population and co-treatment; no equivalent efficacy established for dietary strontium or strontium citrate. Trial mechanisms are not identified by the fracture endpoint. Evidence access: Primary abstract The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14749454/ · DOI 10.1056/NEJMoa022436

evidence_access

Primary abstract

experimental_model

Same 12-month calcium/D3-background trial.

limitations

Post-hoc subgroup findings are exploratory; not independent replication.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A matrix marker and bone-density outcome did not provide equivalent evidence.

primary_references

Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18547426/ · DOI 10.1186/1471-2474-9-85

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 384–390

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same 12-month calcium/D3-background trial. · source_derived_draft · unverified_draft

## silica-human-bmd-null A matrix marker and bone-density outcome did not provide equivalent evidence. Lumbar spine BMD did not significantly change; a femoral-neck signal arose in a post-hoc subgroup. Model: Same 12-month calcium/D3-background trial. Limitations: Post-hoc subgroup findings are exploratory; not independent replication. Evidence access: Primary abstract Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18547426/ · DOI 10.1186/1471-2474-9-85

evidence_access

Primary abstract

experimental_model

184 women randomized; 136 completed; all received 1,000 mg calcium and 20 micrograms D3 daily.

limitations

Marker result is not fracture prevention; attrition and multiple endpoints matter.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A collagen-formation marker changed on top of calcium and vitamin D.

primary_references

Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18547426/ · DOI 10.1186/1471-2474-9-85

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 376–382

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 184 women randomized; 136 completed; all received 1,000 mg calcium and 20 micrograms D3 daily. · source_derived_draft · unverified_draft

## silica-human-pinp A collagen-formation marker changed on top of calcium and vitamin D. PINP differed from placebo at 12 months in the 6- and 12-mg Si groups without a clear dose response. Model: 184 women randomized; 136 completed; all received 1,000 mg calcium and 20 micrograms D3 daily. Limitations: Marker result is not fracture prevention; attrition and multiple endpoints matter. Evidence access: Primary abstract Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18547426/ · DOI 10.1186/1471-2474-9-85

experimental_model

2259 participants randomized in partial factorial design, 3-5-year follow-up.

exposure

1200 mg calcium/day; calcium versus no-calcium adjusted RR 0.95 (95% CI 0.85-1.06).

limitations

Trial contexts differ; mechanism of between-trial disagreement remains unproven.

nutrient_topic

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

organism

Homo sapiens

plain_language

A later trial did not confirm the earlier polyp benefit.

primary_references

[cal-clin-baron2015] A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas (2015). https://pubmed.ncbi.nlm.nih.gov/26465985/ DOI: 10.1056/NEJMoa1500409

tissue_or_cell_type

Human clinical or absorption endpoint

Calcium: mechanism-first literature curation (2026-09-17) · lines 1317–1327

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 2259 participants randomized in partial factorial design, 3-5-year follow-up. · source_derived_draft · unverified_draft

### cal-baron2015-adenomas The 2015 trial found no significant reduction in recurrent adenomas with assigned calcium. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later trial did not confirm the earlier polyp benefit. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: 2259 participants randomized in partial factorial design, 3-5-year follow-up. limitations: Trial contexts differ; mechanism of between-trial disagreement remains unproven. exposure: 1200 mg calcium/day; calcium versus no-calcium adjusted RR 0.95 (95% CI 0.85-1.06). [cal-clin-baron2015] A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas (2015). https://pubmed.ncbi.nlm.nih.gov/26465985/ DOI: 10.1056/NEJMoa1500409

experimental_model

3270 elderly women; mean age 84; 18-month randomized trial.

exposure

1.2 g elemental calcium as tricalcium phosphate plus 800 IU vitamin D3/day; 43% lower hip-fracture count among completers, with similar direction in intention-to-treat analysis.

limitations

Calcium-specific attribution is impossible because vitamin D was coadministered. Completer and intention-to-treat analyses must be distinguished.

nutrient_topic

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

organism

Homo sapiens

plain_language

A combined intervention reduced fractures in this older population.

primary_references

[cal-clin-chapuy1992] Vitamin D3 and calcium to prevent hip fractures in elderly women (1992). https://pubmed.ncbi.nlm.nih.gov/1331788/ DOI: 10.1056/NEJM199212033272305

tissue_or_cell_type

Human clinical or absorption endpoint

Calcium: mechanism-first literature curation (2026-09-17) · lines 1199–1209

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 3270 elderly women; mean age 84; 18-month randomized trial. · source_derived_draft · unverified_draft

### cal-chapuy-hip-fractures Combined calcium and vitamin D lowered hip-fracture occurrence in the elderly-women trial. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A combined intervention reduced fractures in this older population. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: 3270 elderly women; mean age 84; 18-month randomized trial. limitations: Calcium-specific attribution is impossible because vitamin D was coadministered. Completer and intention-to-treat analyses must be distinguished. exposure: 1.2 g elemental calcium as tricalcium phosphate plus 800 IU vitamin D3/day; 43% lower hip-fracture count among completers, with similar direction in intention-to-treat analysis. [cal-clin-chapuy1992] Vitamin D3 and calcium to prevent hip fractures in elderly women (1992). https://pubmed.ncbi.nlm.nih.gov/1331788/ DOI: 10.1056/NEJM199212033272305

experimental_model

Prespecified secondary WHI outcome; seven years.

exposure

MI/coronary-death HR 1.04, 95% CI 0.92-1.18.

limitations

Different cointervention, participants and ascertainment from the calcium-only trial; absence of significance does not prove universal safety.

nutrient_topic

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

organism

Homo sapiens

plain_language

This trial did not reproduce a clear increase in coronary events.

primary_references

[cal-clin-hsia2007] Calcium/vitamin D supplementation and cardiovascular events (2007). https://pubmed.ncbi.nlm.nih.gov/17309935/ DOI: 10.1161/CIRCULATIONAHA.106.673491

tissue_or_cell_type

Human clinical or absorption endpoint

Calcium: mechanism-first literature curation (2026-09-17) · lines 1293–1303

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prespecified secondary WHI outcome; seven years. · source_derived_draft · unverified_draft

### cal-whi-coronary-events WHI found no significant effect of calcium plus vitamin D on myocardial infarction or coronary death. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This trial did not reproduce a clear increase in coronary events. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Prespecified secondary WHI outcome; seven years. limitations: Different cointervention, participants and ascertainment from the calcium-only trial; absence of significance does not prove universal safety. exposure: MI/coronary-death HR 1.04, 95% CI 0.92-1.18. [cal-clin-hsia2007] Calcium/vitamin D supplementation and cardiovascular events (2007). https://pubmed.ncbi.nlm.nih.gov/17309935/ DOI: 10.1161/CIRCULATIONAHA.106.673491

experimental_model

36,282 postmenopausal women; seven-year mean follow-up.

exposure

1000 mg elemental calcium as carbonate plus 400 IU vitamin D3/day; hip-fracture HR 0.88, 95% CI 0.72-1.08.

limitations

Adherence and background supplement use complicate comparison; a nonsignificant result is not proof of zero effect.

nutrient_topic

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

organism

Homo sapiens

plain_language

A larger trial did not establish a hip-fracture benefit for its overall assigned-treatment groups.

primary_references

[cal-clin-jackson2006] Calcium plus vitamin D supplementation and the risk of fractures (2006). https://pubmed.ncbi.nlm.nih.gov/16481635/ DOI: 10.1056/NEJMoa055218

tissue_or_cell_type

Human clinical or absorption endpoint

Calcium: mechanism-first literature curation (2026-09-17) · lines 1211–1221

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 36,282 postmenopausal women; seven-year mean follow-up. · source_derived_draft · unverified_draft

### cal-whi-hip-fractures WHI calcium plus vitamin D did not significantly reduce hip fractures in the intention-to-treat analysis. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A larger trial did not establish a hip-fracture benefit for its overall assigned-treatment groups. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: 36,282 postmenopausal women; seven-year mean follow-up. limitations: Adherence and background supplement use complicate comparison; a nonsignificant result is not proof of zero effect. exposure: 1000 mg elemental calcium as carbonate plus 400 IU vitamin D3/day; hip-fracture HR 0.88, 95% CI 0.72-1.08. [cal-clin-jackson2006] Calcium plus vitamin D supplementation and the risk of fractures (2006). https://pubmed.ncbi.nlm.nih.gov/16481635/ DOI: 10.1056/NEJMoa055218

experimental_model

Randomized WHI safety outcome.

exposure

Renal-calculus HR 1.17, 95% CI 1.02-1.34; same assigned regimen as the fracture analysis.

limitations

Combined intervention; cannot attribute the whole effect to calcium or identify every stone composition.

nutrient_topic

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

organism

Homo sapiens

plain_language

The same trial recorded more kidney-stone events with the combined supplements.

primary_references

[cal-clin-jackson2006] Calcium plus vitamin D supplementation and the risk of fractures (2006). https://pubmed.ncbi.nlm.nih.gov/16481635/ DOI: 10.1056/NEJMoa055218

tissue_or_cell_type

Human clinical or absorption endpoint

Calcium: mechanism-first literature curation (2026-09-17) · lines 1223–1233

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized WHI safety outcome. · source_derived_draft · unverified_draft

### cal-whi-urinary-stones WHI assigned calcium plus vitamin D increased reported renal-calculus events relative to placebo. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same trial recorded more kidney-stone events with the combined supplements. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Randomized WHI safety outcome. limitations: Combined intervention; cannot attribute the whole effect to calcium or identify every stone composition. exposure: Renal-calculus HR 1.17, 95% CI 1.02-1.34; same assigned regimen as the fracture analysis. [cal-clin-jackson2006] Calcium plus vitamin D supplementation and the risk of fractures (2006). https://pubmed.ncbi.nlm.nih.gov/16481635/ DOI: 10.1056/NEJMoa055218

evidence_span

{"source_cache": "artifacts/chromium-research/31593637.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9", "start_char": 0, "end_char": 1523, "text_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9"}

experimental_model

Four-arm randomized supplementation trial; 92 participants

exposure

Four months; vitamin D3 50,000 IU/week, chromium picolinate reported as 500 µg/day, both or placebo

limitations

Study regimens are historical exposures, not recommendations. Stable versus rising HOMA-IR does not show direct mediation by TNF-alpha; no molecular target was tested.

nutrient_topic

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

organism

Human with type 2 diabetes

plain_language

The reported HOMA-IR pattern did not translate into a demonstrated HbA1c improvement.

primary_references

[chromium-p31593637] The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31593637/ DOI: 10.1139/apnm-2019-0113

tissue_or_cell_type

Blood glycemia, HOMA-IR and TNF-alpha

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 679–690

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-arm randomized supplementation trial; 92 participants · source_derived_draft · unverified_draft

### chromium-vitd-hba1c-null HbA1c, fasting glucose and the lipid profile did not change significantly across the study’s groups. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reported HOMA-IR pattern did not translate into a demonstrated HbA1c improvement. organism: Human with type 2 diabetes tissue_or_cell_type: Blood glycemia, HOMA-IR and TNF-alpha experimental_model: Four-arm randomized supplementation trial; 92 participants limitations: Study regimens are historical exposures, not recommendations. Stable versus rising HOMA-IR does not show direct mediation by TNF-alpha; no molecular target was tested. exposure: Four months; vitamin D3 50,000 IU/week, chromium picolinate reported as 500 µg/day, both or placebo evidence_span: {"source_cache": "artifacts/chromium-research/31593637.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9", "start_char": 0, "end_char": 1523, "text_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9"} [chromium-p31593637] The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31593637/ DOI: 10.1139/apnm-2019-0113

evidence_span

{"source_cache": "artifacts/chromium-research/31593637.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9", "start_char": 0, "end_char": 1523, "text_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9"}

experimental_model

Four-arm randomized supplementation trial; 92 participants

exposure

Four months; vitamin D3 50,000 IU/week, chromium picolinate reported as 500 µg/day, both or placebo

limitations

Study regimens are historical exposures, not recommendations. Stable versus rising HOMA-IR does not show direct mediation by TNF-alpha; no molecular target was tested.

nutrient_topic

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

organism

Human with type 2 diabetes

plain_language

The chromium-containing groups avoided the increase seen in other arms of this trial.

primary_references

[chromium-p31593637] The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31593637/ DOI: 10.1139/apnm-2019-0113

tissue_or_cell_type

Blood glycemia, HOMA-IR and TNF-alpha

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 653–664

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-arm randomized supplementation trial; 92 participants · source_derived_draft · unverified_draft

### chromium-vitd-homa HOMA-IR rose in the placebo and vitamin-D3-only groups but was controlled in the chromium and chromium-plus-vitamin-D3 groups. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chromium-containing groups avoided the increase seen in other arms of this trial. organism: Human with type 2 diabetes tissue_or_cell_type: Blood glycemia, HOMA-IR and TNF-alpha experimental_model: Four-arm randomized supplementation trial; 92 participants limitations: Study regimens are historical exposures, not recommendations. Stable versus rising HOMA-IR does not show direct mediation by TNF-alpha; no molecular target was tested. exposure: Four months; vitamin D3 50,000 IU/week, chromium picolinate reported as 500 µg/day, both or placebo evidence_span: {"source_cache": "artifacts/chromium-research/31593637.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9", "start_char": 0, "end_char": 1523, "text_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9"} [chromium-p31593637] The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31593637/ DOI: 10.1139/apnm-2019-0113

evidence_span

{"source_cache": "artifacts/chromium-research/31593637.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9", "start_char": 0, "end_char": 1523, "text_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9"}

experimental_model

Four-arm randomized supplementation trial; 92 participants

exposure

Four months; vitamin D3 50,000 IU/week, chromium picolinate reported as 500 µg/day, both or placebo

limitations

Study regimens are historical exposures, not recommendations. Stable versus rising HOMA-IR does not show direct mediation by TNF-alpha; no molecular target was tested.

nutrient_topic

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

organism

Human with type 2 diabetes

plain_language

The inflammatory marker changed in several active-treatment groups; this does not establish why HOMA-IR differed.

primary_references

[chromium-p31593637] The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31593637/ DOI: 10.1139/apnm-2019-0113

tissue_or_cell_type

Blood glycemia, HOMA-IR and TNF-alpha

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 666–677

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-arm randomized supplementation trial; 92 participants · source_derived_draft · unverified_draft

### chromium-vitd-tnf TNF-alpha decreased in the vitamin-D3, chromium and combined-treatment groups. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inflammatory marker changed in several active-treatment groups; this does not establish why HOMA-IR differed. organism: Human with type 2 diabetes tissue_or_cell_type: Blood glycemia, HOMA-IR and TNF-alpha experimental_model: Four-arm randomized supplementation trial; 92 participants limitations: Study regimens are historical exposures, not recommendations. Stable versus rising HOMA-IR does not show direct mediation by TNF-alpha; no molecular target was tested. exposure: Four months; vitamin D3 50,000 IU/week, chromium picolinate reported as 500 µg/day, both or placebo evidence_span: {"source_cache": "artifacts/chromium-research/31593637.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9", "start_char": 0, "end_char": 1523, "text_sha256": "9815b482cfc5655a11a3192ca21b47c903e8722a3b9b9e7d770e92e9fb94bfa9"} [chromium-p31593637] The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31593637/ DOI: 10.1139/apnm-2019-0113

evidence_span

{"source_cache": "artifacts/k2-research/33030563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138", "start_char": 0, "end_char": 2370, "text_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138"}

experimental_model

Three-year double-blind randomized add-on trial

exposure

MK-7 375 micrograms/day versus placebo; both groups D3 38 micrograms/day and calcium 800 mg/day

limitations

Different population, dose and background supplementation from the 180-microgram trial; the one-year and three-year reports are not independent cohorts.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

142 postmenopausal women with osteopenia

plain_language

Improved carboxylation did not translate into a demonstrated bone-density benefit in this trial.

primary_references

[k2-p33030563] The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33030563/ DOI: 10.1007/s00198-020-05638-z

tissue_or_cell_type

Osteocalcin, DXA and bone microarchitecture

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1098–1109

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-year double-blind randomized add-on trial · source_derived_draft · unverified_draft

### k2-mk7-cad-bone-null After three years, BMD declined without significant between-group differences, and microarchitecture and turnover changes were also similar. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improved carboxylation did not translate into a demonstrated bone-density benefit in this trial. organism: 142 postmenopausal women with osteopenia tissue_or_cell_type: Osteocalcin, DXA and bone microarchitecture experimental_model: Three-year double-blind randomized add-on trial limitations: Different population, dose and background supplementation from the 180-microgram trial; the one-year and three-year reports are not independent cohorts. exposure: MK-7 375 micrograms/day versus placebo; both groups D3 38 micrograms/day and calcium 800 mg/day evidence_span: {"source_cache": "artifacts/k2-research/33030563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138", "start_char": 0, "end_char": 2370, "text_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138"} [k2-p33030563] The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33030563/ DOI: 10.1007/s00198-020-05638-z

evidence_span

{"source_cache": "artifacts/k2-research/33030563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138", "start_char": 0, "end_char": 2370, "text_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138"}

experimental_model

Three-year double-blind randomized add-on trial

exposure

MK-7 375 micrograms/day versus placebo; both groups D3 38 micrograms/day and calcium 800 mg/day

limitations

Different population, dose and background supplementation from the 180-microgram trial; the one-year and three-year reports are not independent cohorts.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

142 postmenopausal women with osteopenia

plain_language

Adding K2 changed the protein marker even with calcium and vitamin D already supplied.

primary_references

[k2-p33030563] The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33030563/ DOI: 10.1007/s00198-020-05638-z

tissue_or_cell_type

Osteocalcin, DXA and bone microarchitecture

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1085–1096

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-year double-blind randomized add-on trial · source_derived_draft · unverified_draft

### k2-mk7-cad-carboxylation With calcium and D3 in both groups, MK-7 reduced ucOC by about 65% after one year. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding K2 changed the protein marker even with calcium and vitamin D already supplied. organism: 142 postmenopausal women with osteopenia tissue_or_cell_type: Osteocalcin, DXA and bone microarchitecture experimental_model: Three-year double-blind randomized add-on trial limitations: Different population, dose and background supplementation from the 180-microgram trial; the one-year and three-year reports are not independent cohorts. exposure: MK-7 375 micrograms/day versus placebo; both groups D3 38 micrograms/day and calcium 800 mg/day evidence_span: {"source_cache": "artifacts/k2-research/33030563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138", "start_char": 0, "end_char": 2370, "text_sha256": "008ef1b176a3f718d923eea696a7a97b09d64e3079e57c997beaf485153ca138"} [k2-p33030563] The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33030563/ DOI: 10.1007/s00198-020-05638-z

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/boron-research/8140930.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc", "start_char": 0, "end_char": 1621, "text_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc"}

experimental_model

Factorial boron/vitamin-D3 feeding experiment in chicks

exposure

26 days; basal boron ≤0.18 mg/kg with 0 or 1.4 mg/kg orthoboric acid supplement; vitamin D3 3.13 or 15.6 µg/kg

limitations

Animal developmental experiment. It did not demonstrate direct CYP24A1 inhibition or that boron replaces vitamin D in humans.

nutrient_topic

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

organism

Day-old cockerel chicks

plain_language

Some metabolic changes from inadequate vitamin D improved in this chick experiment.

primary_references

[boron-p8140930] Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick. (1994). https://pubmed.ncbi.nlm.nih.gov/8140930/ DOI: 10.1002/jbmr.5650090206

tissue_or_cell_type

Plasma metabolism and growth plates

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 846–857

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial boron/vitamin-D3 feeding experiment in chicks · source_derived_draft · unverified_draft

### boron-chick-glucose Boron supplementation returned elevated plasma glucose concentrations in vitamin-D3-inadequate chicks toward those in vitamin-D3-adequate chicks. Condition category: nutrient_deficiency nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some metabolic changes from inadequate vitamin D improved in this chick experiment. organism: Day-old cockerel chicks tissue_or_cell_type: Plasma metabolism and growth plates experimental_model: Factorial boron/vitamin-D3 feeding experiment in chicks limitations: Animal developmental experiment. It did not demonstrate direct CYP24A1 inhibition or that boron replaces vitamin D in humans. exposure: 26 days; basal boron ≤0.18 mg/kg with 0 or 1.4 mg/kg orthoboric acid supplement; vitamin D3 3.13 or 15.6 µg/kg evidence_span: {"source_cache": "artifacts/boron-research/8140930.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc", "start_char": 0, "end_char": 1621, "text_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc"} [boron-p8140930] Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick. (1994). https://pubmed.ncbi.nlm.nih.gov/8140930/ DOI: 10.1002/jbmr.5650090206

evidence_span

{"source_cache": "artifacts/boron-research/8140930.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc", "start_char": 0, "end_char": 1621, "text_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc"}

experimental_model

Factorial boron/vitamin-D3 feeding experiment in chicks

exposure

26 days; basal boron ≤0.18 mg/kg with 0 or 1.4 mg/kg orthoboric acid supplement; vitamin D3 3.13 or 15.6 µg/kg

limitations

Animal developmental experiment. It did not demonstrate direct CYP24A1 inhibition or that boron replaces vitamin D in humans.

nutrient_topic

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

organism

Day-old cockerel chicks

plain_language

The developing growth plate appeared to mature differently; this is an animal histology finding.

primary_references

[boron-p8140930] Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick. (1994). https://pubmed.ncbi.nlm.nih.gov/8140930/ DOI: 10.1002/jbmr.5650090206

tissue_or_cell_type

Plasma metabolism and growth plates

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 872–883

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial boron/vitamin-D3 feeding experiment in chicks · source_derived_draft · unverified_draft

### boron-chick-growth-plate Growth-plate histology suggested enhanced maturation with boron supplementation in the chick feeding experiment. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The developing growth plate appeared to mature differently; this is an animal histology finding. organism: Day-old cockerel chicks tissue_or_cell_type: Plasma metabolism and growth plates experimental_model: Factorial boron/vitamin-D3 feeding experiment in chicks limitations: Animal developmental experiment. It did not demonstrate direct CYP24A1 inhibition or that boron replaces vitamin D in humans. exposure: 26 days; basal boron ≤0.18 mg/kg with 0 or 1.4 mg/kg orthoboric acid supplement; vitamin D3 3.13 or 15.6 µg/kg evidence_span: {"source_cache": "artifacts/boron-research/8140930.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc", "start_char": 0, "end_char": 1621, "text_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc"} [boron-p8140930] Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick. (1994). https://pubmed.ncbi.nlm.nih.gov/8140930/ DOI: 10.1002/jbmr.5650090206

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/boron-research/8140930.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc", "start_char": 0, "end_char": 1621, "text_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc"}

experimental_model

Factorial boron/vitamin-D3 feeding experiment in chicks

exposure

26 days; basal boron ≤0.18 mg/kg with 0 or 1.4 mg/kg orthoboric acid supplement; vitamin D3 3.13 or 15.6 µg/kg

limitations

Animal developmental experiment. It did not demonstrate direct CYP24A1 inhibition or that boron replaces vitamin D in humans.

nutrient_topic

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

organism

Day-old cockerel chicks

plain_language

Some metabolic changes from inadequate vitamin D improved in this chick experiment.

primary_references

[boron-p8140930] Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick. (1994). https://pubmed.ncbi.nlm.nih.gov/8140930/ DOI: 10.1002/jbmr.5650090206

tissue_or_cell_type

Plasma metabolism and growth plates

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 859–870

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial boron/vitamin-D3 feeding experiment in chicks · source_derived_draft · unverified_draft

### boron-chick-triglycerides Boron supplementation returned elevated plasma triglyceride concentrations in vitamin-D3-inadequate chicks toward those in vitamin-D3-adequate chicks. Condition category: nutrient_deficiency nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some metabolic changes from inadequate vitamin D improved in this chick experiment. organism: Day-old cockerel chicks tissue_or_cell_type: Plasma metabolism and growth plates experimental_model: Factorial boron/vitamin-D3 feeding experiment in chicks limitations: Animal developmental experiment. It did not demonstrate direct CYP24A1 inhibition or that boron replaces vitamin D in humans. exposure: 26 days; basal boron ≤0.18 mg/kg with 0 or 1.4 mg/kg orthoboric acid supplement; vitamin D3 3.13 or 15.6 µg/kg evidence_span: {"source_cache": "artifacts/boron-research/8140930.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc", "start_char": 0, "end_char": 1621, "text_sha256": "6f8776234acbd0efd282761bbbcb0f51b39d8882c651b3f64686a890f646d4fc"} [boron-p8140930] Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick. (1994). https://pubmed.ncbi.nlm.nih.gov/8140930/ DOI: 10.1002/jbmr.5650090206

evidence_span

{"source_cache": "artifacts/boron-research/35571926.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30", "start_char": 0, "end_char": 2097, "text_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30"}

experimental_model

Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters

exposure

Waterborne boron 10 or 100 ng/mL, vitamin D3 10 pg/mL and combinations; developmental time points

limitations

Fish water exposure cannot be translated directly into human supplement intake. Combination superiority alone is not proof of a formal statistical interaction; pathway enrichment is not proof of direct molecular activation.

nutrient_topic

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

organism

Danio rerio

plain_language

The combination outperformed vitamin D alone in developing fish.

primary_references

[boron-p35571926] Zebrafish as a Model to Unveil the Pro-Osteogenic Effects of Boron-Vitamin D3 Synergism. (2022). https://pubmed.ncbi.nlm.nih.gov/35571926/ DOI: 10.3389/fnut.2022.868805

tissue_or_cell_type

Opercular bone and osteoblast development

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 885–896

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters · source_derived_draft · unverified_draft

### boron-zebrafish-bone-combination Boron plus vitamin D3 increased opercular bone growth more than vitamin D3 alone in zebrafish larvae. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combination outperformed vitamin D alone in developing fish. organism: Danio rerio tissue_or_cell_type: Opercular bone and osteoblast development experimental_model: Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters limitations: Fish water exposure cannot be translated directly into human supplement intake. Combination superiority alone is not proof of a formal statistical interaction; pathway enrichment is not proof of direct molecular activation. exposure: Waterborne boron 10 or 100 ng/mL, vitamin D3 10 pg/mL and combinations; developmental time points evidence_span: {"source_cache": "artifacts/boron-research/35571926.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30", "start_char": 0, "end_char": 2097, "text_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30"} [boron-p35571926] Zebrafish as a Model to Unveil the Pro-Osteogenic Effects of Boron-Vitamin D3 Synergism. (2022). https://pubmed.ncbi.nlm.nih.gov/35571926/ DOI: 10.3389/fnut.2022.868805

evidence_span

{"source_cache": "artifacts/boron-research/35571926.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30", "start_char": 0, "end_char": 2097, "text_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30"}

experimental_model

Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters

exposure

Waterborne boron 10 or 100 ng/mL, vitamin D3 10 pg/mL and combinations; developmental time points

limitations

Fish water exposure cannot be translated directly into human supplement intake. Combination superiority alone is not proof of a formal statistical interaction; pathway enrichment is not proof of direct molecular activation.

nutrient_topic

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

organism

Danio rerio

plain_language

Earlier bone-building cells increased at these stages in the fish experiment.

primary_references

[boron-p35571926] Zebrafish as a Model to Unveil the Pro-Osteogenic Effects of Boron-Vitamin D3 Synergism. (2022). https://pubmed.ncbi.nlm.nih.gov/35571926/ DOI: 10.3389/fnut.2022.868805

tissue_or_cell_type

Opercular bone and osteoblast development

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 898–909

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters · source_derived_draft · unverified_draft

### boron-zebrafish-intermediate-osteoblasts The 10 ng/mL boron plus 10 pg/mL vitamin D3 condition enriched sp7-positive intermediate osteoblasts at 6 and 9 days post-fertilization. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Earlier bone-building cells increased at these stages in the fish experiment. organism: Danio rerio tissue_or_cell_type: Opercular bone and osteoblast development experimental_model: Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters limitations: Fish water exposure cannot be translated directly into human supplement intake. Combination superiority alone is not proof of a formal statistical interaction; pathway enrichment is not proof of direct molecular activation. exposure: Waterborne boron 10 or 100 ng/mL, vitamin D3 10 pg/mL and combinations; developmental time points evidence_span: {"source_cache": "artifacts/boron-research/35571926.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30", "start_char": 0, "end_char": 2097, "text_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30"} [boron-p35571926] Zebrafish as a Model to Unveil the Pro-Osteogenic Effects of Boron-Vitamin D3 Synergism. (2022). https://pubmed.ncbi.nlm.nih.gov/35571926/ DOI: 10.3389/fnut.2022.868805

evidence_span

{"source_cache": "artifacts/boron-research/35571926.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30", "start_char": 0, "end_char": 2097, "text_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30"}

experimental_model

Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters

exposure

Waterborne boron 10 or 100 ng/mL, vitamin D3 10 pg/mL and combinations; developmental time points

limitations

Fish water exposure cannot be translated directly into human supplement intake. Combination superiority alone is not proof of a formal statistical interaction; pathway enrichment is not proof of direct molecular activation.

nutrient_topic

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

organism

Danio rerio

plain_language

More mature bone-building cells appeared later in the fish experiment.

primary_references

[boron-p35571926] Zebrafish as a Model to Unveil the Pro-Osteogenic Effects of Boron-Vitamin D3 Synergism. (2022). https://pubmed.ncbi.nlm.nih.gov/35571926/ DOI: 10.3389/fnut.2022.868805

tissue_or_cell_type

Opercular bone and osteoblast development

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 911–922

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters · source_derived_draft · unverified_draft

### boron-zebrafish-mature-osteoblasts The 10 ng/mL boron plus 10 pg/mL vitamin D3 condition enriched bglap-positive mature osteoblasts at 15 days post-fertilization. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: More mature bone-building cells appeared later in the fish experiment. organism: Danio rerio tissue_or_cell_type: Opercular bone and osteoblast development experimental_model: Larval zebrafish morphology, transcriptomics and fluorescent osteoblast reporters limitations: Fish water exposure cannot be translated directly into human supplement intake. Combination superiority alone is not proof of a formal statistical interaction; pathway enrichment is not proof of direct molecular activation. exposure: Waterborne boron 10 or 100 ng/mL, vitamin D3 10 pg/mL and combinations; developmental time points evidence_span: {"source_cache": "artifacts/boron-research/35571926.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30", "start_char": 0, "end_char": 2097, "text_sha256": "cf22409e40b52d79a9f1738a942771e626afdb39fce0e8bc16cbf877cdf7ea30"} [boron-p35571926] Zebrafish as a Model to Unveil the Pro-Osteogenic Effects of Boron-Vitamin D3 Synergism. (2022). https://pubmed.ncbi.nlm.nih.gov/35571926/ DOI: 10.3389/fnut.2022.868805